TY - BOOK T1 - The Maudsley Prescribing Guidelines 9th Edition A1 - Taylor D A1 - Paton C A1 - Kerwin R ED - Taylor D, Paton C, Kerwin R Y1 - 2007/// VL - 9th PB - Informa Healthcare CY - UK SP - 1 EP - 543 N2 - - ER - TY - BOOK T1 - Atlas of Tropical Medicine and Parasitology A1 - Wallace Peters A1 - Geoffrey Pasvol Y1 - 2007/// VL - 6th PB - Elsevier CY - Philadelphia SP - 1 EP - 429 N2 - - ER - TY - BOOK T1 - Cardiovascular Medicine. Chapter 28 Global differences in atherosclerosis 653-658 A1 - Poole-Wilson, PA ED - Willerson JT, Cohn JN, Wellens HJJ, Holmes DR Y1 - 2007/// VL - 3rd PB - Springer-Verlag CY - London SN - 1-84628-188-1 SP - 1 EP - 2926 N2 - - L1 - http://springer.com ER - TY - BOOK T1 - Working with children and adolescents: an evidence-based approach to risk and resilience. A1 - Garralda ME A1 - Flament M ED - Garralda ME Flament M Y1 - 2006/// VL - First PB - Rowman and Littlefield CY - New York N2 - - ER - TY - BOOK T1 - What can primary care do to improve health outcomes in diabetes and cardiovascular disease for ethnic minority groups in the UK? A1 - Misra T A1 - Saxena S A1 - Car J A1 - Smith R Y1 - 2006/// PB - Report for United Health Europe CY - London N2 - - ER - TY - BOOK T1 - Coronary Heart Disease Epidemiology: From Aetiology to Public Health A1 - Elliott P ED - Marmot M; Elliott P Y1 - 2005/06// PB - Oxford University Press CY - Oxford, UK SN - 0-1985-6806-1 SP - 1 EP - 932 N2 - - ER - TY - BOOK T1 - Report of the royal society working group on the health hazards of depleted uranium munitions, part II - chemical toxicity and environmental effects A1 - Spratt BG A1 - Bailey MR A1 - Beral V A1 - Clayton B A1 - Goodhead DT A1 - Darby SC A1 - Hendry J A1 - MArsh C A1 - Murray V A1 - Smith B A1 - Stoneham M Y1 - 2005/06// SN - 0-8540-3574-5 N2 - - UR - http://www.royalsoc.ac.uk/document.asp?id=1401 ER - TY - BOOK T1 - Viral Hepatitis A1 - Thomas HC A1 - Lemon S A1 - Zuckerman AJ ED - Thomas HC; Lemon S; Zuckerman AJ Y1 - 2005/// VL - Third Edition PB - Blackwell Publishing CY - Oxford; UK SP - 1 EP - 876 N2 - - ER - TY - BOOK T1 - The Maudsley Prescribing Guidelines 2005/6 A1 - Taylor D A1 - Paton C A1 - Kerwin R ED - David Taylor, Carol Paton, Robert Kerwin Y1 - 2005/// VL - 8th PB - Martin Dunitz CY - UK SN - 1 84184 500 0 N2 - - ER - TY - BOOK T1 - Viral Hepatitis A1 - Thomas HC, A1 - Lemon.S A1 - Zuckerman A ED - Thomas HC, Lemon S; and Zuckerman A Y1 - 2005/// VL - Third Edition PB - Blackwell Publishing CY - Oxford, UK SN - 1-4051-3005-9 SP - 3 EP - 876 N2 - - ER - TY - BOOK T1 - The importance of school health and nutrition in achieving Education for All A1 - Jukes, MCH A1 - Drake, LJ A1 - Bundy, DAP Y1 - 2005/// PB - World Bank N2 - - ER - TY - BOOK T1 - A Guide to the MRCP Part 2 Written Paper A1 - Warrens, A N A1 - Persey, M A1 - Fertleman, M A1 - Powis, S H A1 - Zumla, A Y1 - 2005/// VL - Second Edition PB - Hodder Arnold CY - London SN - 0-340-80658-3 N2 - - ER - TY - BOOK T1 - Weight-of-evidence for forensic DNA profiles A1 - Balding DJ Y1 - 2005/01// PB - Wiley CY - Chichester UK SN - 0-470-86764-7 N2 - - ER - TY - BOOK T1 - Sex work, mobility and health in Europe A1 - Ward H ED - Day S; Ward H Y1 - 2004/09// PB - Kegan Paul CY - London SN - 0-7103-0942-2 N2 - - ER - TY - BOOK T1 - Oxford handbook of tropical medicine A1 - Eddleston M A1 - Davidson RN A1 - Wilkinson RJ A1 - Pierini S Y1 - 2004/// VL - 2 PB - Oxford University Press SN - 0-1985-2509-5 SP - 1 EP - 712 N2 - - ER - TY - BOOK T1 - Building a European Information Capacity for Environment and Security. A Contribution to the Initial Period of the GMES Action Plan (2002-2003). A1 - Wyatt BK A1 - Briggs DJ A1 - Ryder P Y1 - 2004/// PB - European Commission. Directorate General for Research SP - 1 EP - 237 N2 - - ER - TY - BOOK T1 - Malaria A hematological perspective A1 - Pasvol G ED - Abdalla SH; Pasvol G Y1 - 2004/// PB - Imperial College Press SN - 1-86094-357-8 N2 - - ER - TY - BOOK T1 - Complete Medicine and Surgery A1 - Kendall G A1 - Shiu KY A1 - Johnston SL Y1 - 2004/// PB - Blackwell Science N2 - - ER - TY - BOOK T1 - Child Public Health A1 - Blair M A1 - Waterston T A1 - Stewart Brown S A1 - Crowther R Y1 - 2003/11// IS - 1 PB - Oxford University Press SN - 0-19-263192-6 SP - 1 EP - 256 N2 - - UR - http://www.oup.com ER - TY - BOOK T1 - Living with heart failure - a guide for patients A1 - Cowie MR Y1 - 2003/// PB - Bladon Medical Publishing CY - Chipping Norton, Oxfordshire SN - 1-904218-22-9 N2 - - ER - TY - BOOK T1 - Exposure assessment in Occupational and Environmental Epidemiology A1 - Niuewenhuijsen MJ ED - Nieuwenhuijsen MJ Y1 - 2003/// PB - Oxford University Press SN - 0-19-852861-2 N2 - - ER - TY - BOOK T1 - Managing Children with Psychiatric Problems A1 - Garralda Hualde ME ED - Garralda ME; Hyde C Y1 - 2003/// PB - BMJ N2 - - ER - TY - BOOK T1 - Infection and Immunity A1 - Friedland JS A1 - Lightstone L Y1 - 2003/// PB - Martin Dunitz CY - London, UK SN - 1 84184 373 3 N2 - - ER - TY - BOOK T1 - Key Advances in the Clinical Management of Ovarian Cancer A1 - Ghaem-Maghami S A1 - Orton K A1 - Soutter P ED - Ghaem-Maghami S; Orton K; Soutter P Y1 - 2003/// PB - Royal Society of Medicine Press CY - London N2 - - ER - TY - BOOK T1 - Making a Difference. Indicators to Improve Children's Environmental Health. A1 - Briggs DJ Y1 - 2003/// PB - World Health Organisation CY - Geneva. N2 - - ER - TY - BOOK T1 - Gynaecology A1 - Shaw RW A1 - Soutter WP A1 - Stanton SL ED - Shaw RW; Soutter WP; Stanton SL Y1 - 2003/// PB - Churchill Livingstone CY - Edinburgh N2 - - ER - TY - BOOK T1 - Impact of Environmental Pollution on Health: Balancing Risk A1 - Briggs DJ ED - Briggs DJ; Joffe M; Elliott PE Y1 - 2003/// IS - 68 PB - British Medical Bulletin SP - 1 EP - 282 N2 - - ER - TY - BOOK T1 - Infection and Immunity A1 - Lightstone EB ED - Friedland JS; Lightstone EB Y1 - 2003/// PB - Martin Dunitz CY - 11 New Fetter Lane, London EC4P 4EE SN - 1 84184 373 3 N2 - - UR - http://www.dunitz.co.uk ER - TY - BOOK T1 - Highly Structured Stochastic Systems A1 - Richardson S ED - Green PJ; Hjort NL; Richardson S Y1 - 2003/// PB - Oxford University Press N2 - - ER - TY - BOOK T1 - Handbook of Statistical Genetics, 2nd edition A1 - n. ED - Balding DJ; Bishop M; Cannings C Y1 - 2003/// PB - Wiley CY - Chichester SN - 0-470-84829-4 N2 - - ER - TY - BOOK T1 - Respiratory infections in allergy and asthma A1 - Johnston SL ED - Papadopoulos NG; Johnston SL Y1 - 2003/// PB - Marcell Dekker CY - New York N2 - - ER - TY - BOOK T1 - Managing heart failure in primary care - a practical guide A1 - Cowie MR A1 - Kirby M Y1 - 2003/// PB - Bladon Medical Publishing SN - 1-904218-20-2 N2 - - ER - TY - BOOK T1 - The Maudsley Prescribing Guidelines 2003 A1 - Taylor D A1 - Paton C A1 - Kerwin R ED - David Taylor, Carol Paton, Robert Kerwin Y1 - 2003/// VL - 7th PB - Martin Dunitz CY - London, UK SN - 1 84184 176 5 N2 - - ER - TY - BOOK T1 - The effective management of asthma. U.K. Key advances in clinical practice series A1 - Partridge MR ED - Partridge MR; Miles A Y1 - 2003/// PB - Aesculapius Medical Press SN - 1-9030-4426-X N2 - - ER - TY - BOOK T1 - Mosby's Colour Atlas and Text of Gastroenterology and Liver Disease A1 - Aspinall RJ A1 - Taylor-Robinson SD Y1 - 2002/// SN - 0-7234-3103-5 N2 - - ER - TY - BOOK T1 - GIS for emergency preparedness and health risk reduction (NATO advanced research workshop: 2001 Apr: Budapest) A1 - Jarup L Y1 - 2002/// SN - 1-4020-0798-1 N2 - - ER - TY - BOOK T1 - Outcome of psychiatric admission through the courts. A1 - James D A1 - Farnham F A1 - Moorey H A1 - Lloyd H A1 - Hill K A1 - Blizard R A1 - Barnes TRE Y1 - 2002/// PB - RDS Occasional Paper No. 79. Home Office CY - London SN - 1-84082-804-8 N2 - - ER - TY - BOOK T1 - GIS for emergency preparedness and health risk reduction A1 - Briggs DJ ED - Briggs DJ; Forer P; Jarup L; Stern R Y1 - 2002/// PB - Kluwer Academic SN - 1-4020-0798-1 SP - 1 EP - 326 N2 - - ER - TY - BOOK T1 - WHO-UNAIDS Guidelines for Standard HIV Isolation and Characterisation Procedures A1 - Weber JN A1 - Fenyo EM Y1 - 2002/// SN - 9-2415-9021-1 N2 - - ER - TY - BOOK T1 - Hypertension: A guide to assessment and management A1 - Poulter N A1 - Kirby M Y1 - 2002/// SN - 1-9042-1801-6 N2 - - ER - TY - BOOK T1 - Education and HIV/AIDS; a window of hope A1 - Drake L Y1 - 2002/// SN - 0-8213-5117-6 N2 - - ER - TY - BOOK T1 - Preventing kidney disease: the ethnic challenge in Brent A1 - Lightstone L A1 - Woolnough L Y1 - 2002/// PB - National Kidney Research Fund SN - 1-9042-2704-X N2 - - ER - TY - BOOK T1 - Environmental Health Hazard Mapping A1 - Briggs DJ Y1 - 2002/// PB - WHO- Afro CY - Nairobi SP - 1 EP - 140 N2 - - ER - TY - BOOK T1 - Tropical medicine and parasitology A1 - Peters W A1 - Pasvol G Y1 - 2002/// SN - 0-7234-3191-4 N2 - - ER - TY - BOOK T1 - Case Studies in Psychopharmacology A1 - Taylor D A1 - Paton C ED - David Taylor, Carol Paton Y1 - 2002/// VL - 2nd PB - Martin Dunitz CY - London, UK SN - 1 84184 154 4 N2 - - ER - TY - BOOK T1 - Learning from Bristol: report of the Public Enquiry into Children's Heart Surgery at Bristol Royal Infirmary 1984-1995: summary and recommendations A1 - Dept. of Health Y1 - 2001/// PB - Bristol Royal Infirmary Inquiry CY - London SN - 0-1015-2073-5 SP - 1 EP - 48 N2 - - ER - TY - BOOK T1 - Infection and pregnancy. Proceedings of the 40th RCOG study group on infection and pregnancy A1 - Regan L A1 - Jivraj S Y1 - 2001/// SN - 1-9003-6444-1 N2 - - ER - TY - BOOK T1 - Shared care for hypertension A1 - Poulter N A1 - Thom S A1 - Kirby M Y1 - 2001/// SN - 1-8990-6680-2 N2 - - ER - TY - BOOK T1 - Handbook of statistical genetics, 1st edition A1 - n. ED - Balding DJ; Bishop M; Cannings C Y1 - 2001/// PB - Wiley CY - Chichester UK SN - 0-4718-6094-8 N2 - - ER - TY - BOOK T1 - Psychiatric Intensive Care A1 - Beer MD A1 - Pereira SM A1 - Paton C ED - Dominic Beer, Stephen Pereira, Carol Paton Y1 - 2001/// VL - 1st PB - Greenwich Medical Media Ltd CY - London, UK SN - 1 900151 87 1 N2 - - ER - TY - BOOK T1 - Preventing kidney disease: the ethnic challenge A1 - Lightstone E Y1 - 2001/// PB - National Kidney Research Fund CY - Peterborough, England SN - 1-9042-2700-7 N2 - - ER - TY - BOOK T1 - Shared care for hypertension A1 - Poulter N A1 - Thom S A1 - Kirby M Y1 - 2001/// SN - 1-8990-6680-2 N2 - - ER - TY - BOOK T1 - Asthma: critical debates A1 - Johnston SL ED - Johnston SL; Holgate ST Y1 - 2001/// SN - 0-6320-5721-1 N2 - - ER - TY - BOOK T1 - Spatial Epidemiology: Methods and Applications A1 - Best NG ED - Elliott P; Wakefield JC; Best NG; Briggs DJ Y1 - 2000/// PB - Oxford University Press SN - 0-19-851532-4 N2 - - UR - http://www.oup.co.uk/isbn/0-19-851532-4 ER - TY - BOOK T1 - Accounting for Nature: Assessing Habitats in the UK Countryside A1 - Haines-Young RH A1 - Barr CJ A1 - Black HIJ A1 - Briggs DJ A1 - Bunce RGH A1 - Clarke RT A1 - Cooper A A1 - Dawson FH A1 - Firbank LG A1 - Fuller RM A1 - Furse MT A1 - Gillespie MK A1 - Hill R A1 - Hornung M A1 - Howard DC A1 - McCann T A1 - Morecroft MD A1 - Petit S A1 - Sie Y1 - 2000/// PB - DETR CY - London N2 - - ER - TY - BOOK T1 - Decision-making in Environmenal Health: from Evidence to Action A1 - Briggs DJ ED - Corvalan C; Briggs D; Zielhuis G Y1 - 2000/// PB - SPON Routledge CY - London N2 - - ER - TY - BOOK T1 - HLA in Health and Disease A1 - Warrens AN ED - Lechler RI ; Warrens AN Y1 - 2000/// PB - Academic Press CY - London SN - 0-12-440315-8 N2 - - ER - TY - BOOK T1 - Spatial Epidemiology: Methods and Applications A1 - Briggs DJ ED - Elliott P; Wakefield J; Best N; Briggs DJ Y1 - 2000/// PB - Oxford University Press CY - Oxford SP - 1 EP - 475 N2 - - ER - TY - BOOK T1 - Report into the Removal and Retention of Human Material A1 - Howard R A1 - Jarman B A1 - Kennedy I A1 - Maclean M Y1 - 2000/// PB - Department of Health CY - London N2 - - ER - TY - BOOK T1 - Nel crepuscolo della probabilita' A1 - Vineis P Y1 - 1999/// PB - Einaudi N2 - - ER - TY - BOOK T1 - Metabolic Polymorphisms and Susceptibility to Cancer A1 - Vineis P A1 - et al Y1 - 1999/// IS - 48 PB - INTERNATIONAL AGENCY FOR RESEARCH ON CANCER N2 - - ER - TY - BOOK T1 - Gynaecology A1 - Soutter WP ED - Shaw RW; Soutter WP; Stanton SL Y1 - 1997/// PB - Churchill Livingstone CY - Edinburgh N2 - - ER - TY - CHAP T1 - Sex-specific aspects of dyslipidaemia and atherosclerosis A1 - Godsland, I F ED - Packard, C J T2 - The Year in Lipid Disorders Y1 - 2007/// M2 - 1 PB - Clinical Publishing CY - Oxford N2 - - ER - TY - CHAP T1 - The Heart and the kidney A1 - Cowie, MR ED - Willerson, JT, Cohn, JN, Wellens, HJJ, Holmes, DR Jr. T2 - Cardiovascular medicine Y1 - 2007/// VL - 3rd PB - Verlag CY - London SN - 1-84628-188-1 SP - 2819 EP - 2837 N2 - - ER - TY - CHAP T1 - The epidemiology and diagnosis of heart failure A1 - Dar, O A1 - Cowie, MR ED - Fuster, V T2 - Hurst's The Heart Y1 - 2007/// VL - 12th PB - Andover Publishing SP - 713 EP - 723 N2 - - ER - TY - CHAP T1 - Treatment options for young people and refugees with posttraumatic stress disorder A1 - Hodes M A1 - Diaz-Caneja A ED - Hosin A T2 - Children, Families and Refugees of Multiple Traumas: Contemporary Issues in Mental Health Y1 - 2006/11// PB - Palgrave Macmillan CY - Basingstoke, Hampshire SN - 1403996806 N2 - - ER - TY - CHAP T1 - Health Hazards of Depleted Uranium Munitions: Estimatesof Exposures and Risks in the Gulf War, the Balkans, and Iraq. A1 - Spratt, BG ED - A.C. Miller T2 - Depleted Uranium: Properties, Uses, and Health Consequences Y1 - 2006/// PB - CRC Press CY - USA SN - 0849330475 SP - 121 EP - 141 N2 - - ER - TY - CHAP T1 - Using Transmission Dynamics Models to Validate Vaccine Efficacy Measures Prior to Conducting HIV Vaccine Efficacy Trials. A1 - Desai K, A1 - Boily MC, A1 - Masse B, ED - James Abello and Graham Cormode V Eds T2 - Discrete Epidemiology Y1 - 2006/// VL - DIMACS Special Volume PB - AMS(American Mathematical Society)- N2 - - ER - TY - CHAP T1 - Immunosuppressive drugs in renal transplantation - 2006 A1 - Warrens, A N ED - Haskard, D O T2 - Horizons in Medicine - 17 Y1 - 2006/// PB - Royal College of Physicians of London SN - 1-86016-253-3 SP - 71 EP - 77 N2 - - ER - TY - CHAP T1 - Epidemiology. A1 - Crawford M ED - C. Freeman, P. Tyrer T2 - Research Methods in Psychiatry Y1 - 2006/// VL - 3rd Edition PB - Gaskell CY - London SP - 53 EP - 72 N2 - - ER - TY - CHAP T1 - Functional somatic symptoms and somatoform disorders in children A1 - Garralda ME ED - C Gillberg, R Harrington, HC Steinhausen T2 - A Clinician's Handbook of Child and Adolescent Psychiatry Y1 - 2006/// PB - Cambridge University Press SP - 246 EP - 271 N2 - - ER - TY - CHAP T1 - Point sources of air pollution - Investigation of possible health effects using small area methods A1 - Elliott, P ED - Ayres J, Maynard R, Richards R T2 - Air Pollution and Health Y1 - 2006/// M2 - 3 (Air Pollution Reviews) PB - Imperial College Press CY - Singapore SN - 1-86094-191-5 SP - 49 EP - 67 N2 - - ER - TY - CHAP T1 - Models for the study of infection in populations A1 - John R Williams ED - P Michael Conn T2 - Handbook of models for human aging Y1 - 2006/// PB - Academic Press CY - San Diego, CA SN - 0-12-369391-8 SP - 165 EP - 182 N2 - - UR - http://www.elsevier.com/wps/find/bookdescription.cws_home/707448/description#description ER - TY - CHAP T1 - Host Genetics and Susceptibility to infection A1 - Wilkinson RJ A1 - Levin M ED - Guerrant R.L, Walker, D.H. and Weller, P.F. T2 - Tropical Infectious Diseases: Principles, pathogens and practice Y1 - 2006/// VL - 2 M2 - 1 PB - Churchill Livingstone CY - Philadelphia SN - 0-443-06668-X SP - 53 EP - 67 N2 - - ER - TY - CHAP T1 - Spatial epidemiology: methods and applications. A1 - Elliott P A1 - Wakefield JC A1 - Nest NG A1 - Briggs DJ ED - Elliott P; Best N; Wakefield J; Briggs DJ T2 - Spatial epidemiology: methods and applications Y1 - 2005/// PB - Oxford University Press CY - Oxford SP - 3 EP - 14 N2 - - ER - TY - CHAP T1 - Seasonal variations in all-cause and cardiovascular mortality and the role of temperature A1 - Toledano M A1 - Shaddick G A1 - Elliott P ED - Marmot M; Elliott P T2 - Coronary Heart Disease Epidemiology: From Aetiology to Public Health Y1 - 2005/06/30/ M2 - 2nd PB - Oxford University Press CY - Oxford, UK SN - 0-1985-6806-1 SP - 495 EP - 527 N2 - - ER - TY - CHAP T1 - Primary prevention of high blood pressure A1 - Elliott P A1 - Stamler J ED - Marmot M; Elliott P T2 - Coronary Heart Disease Epidemiology: From Aetiology to Public Health Y1 - 2005/06/30/ M2 - 2nd PB - Oxford University Press CY - Oxford, UK SN - 0-1985-6806-1 SP - 751 EP - 768 N2 - - ER - TY - CHAP T1 - Coronary heart disease epidemiology: from aetiology to public health A1 - Marmot M A1 - Elliott P ED - Marmot M; Elliott P T2 - Coronary Heart Disease Epidemiology: From Aetiology to Public Health Y1 - 2005/06/30/ M2 - 2nd PB - Oxford University Press CY - Oxford, UK SN - 0-1985-6806-1 SP - 3 EP - 7 N2 - - ER - TY - CHAP T1 - Seasonal variations in all cause and cardiovascular mortality and the role of temperature A1 - Toledano MB A1 - Shaddick G A1 - Elliott P ED - Marmot M and Elliott P T2 - Coronary Heart Disease Epidemiology: from aetiology to public health. Second edition. Y1 - 2005/06/30/ PB - Oxford University Press CY - Oxford SN - 0-19-856806-1 N2 - - ER - TY - CHAP T1 - Blood pressure and the burden of coronary heart disease A1 - Lawes,CMM A1 - Vander Hoorn S A1 - Law MR A1 - Elliott P A1 - MacMahon S A1 - Rodgers A. ED - Marmot M; Elliott P T2 - Coronary Heart Disease Epidemiology: From Aetiology to Public Health Y1 - 2005/06/30/ M2 - 2nd PB - Oxford University Press CY - Oxford, UK SN - 0-1985-6806-1 SP - 152 EP - 173 N2 - - ER - TY - CHAP T1 - Malaria A1 - Pasvol G ED - Eddlestone m, Davidson R, Wilkinson R, Pierini S T2 - Oxford handbook of tropical Medicine Y1 - 2005/// M2 - 2nd Edition PB - Oxford University Press SN - 0 19 852509 5 SP - 9 EP - 37 N2 - - ER - TY - CHAP T1 - Presentation, diagnosis and differential diagnosis A1 - Stephenson P A1 - Partridge M ED - Dr John Haughney T2 - A primary care guide to COPD Y1 - 2005/// PB - Magister Consulting Ltd CY - Dartford, Kent SN - 1 873839 61 8 SP - 1 EP - 11 N2 - - ER - TY - CHAP T1 - Recombination hotspots as a point process. A1 - De Iorio M A1 - de Silva E A1 - Stumpf MPH T2 - Philosophical Transactions of the Royal Society B: Genetic Variation and Human Health Y1 - 2005/// N2 - - ER - TY - CHAP T1 - Source detection in an outbreak of legionnaire's disease A1 - Martinez-Beneito MA A1 - Abellan JJ A1 - Lopez-Quilez A A1 - Vanaclocha H A1 - Zurriaga O A1 - Jorques G A1 - Fenollar J ED - Baddeley A; Gregori P; Mateu J,Stoica R; Stoyan D T2 - Case studies in spatial point process models Y1 - 2005/// PB - Springer SN - 0-387-28311-0 SP - 169 EP - 182 N2 - - ER - TY - CHAP T1 - Parasites of wild brown rats (Rattus norvegicus) in the urban environment. A1 - Webster, .J.P. ED - Macdonald, D.W., Randall, D. & Hurst, C. T2 - Wildlife Conservation: Research and Development. Y1 - 2005/// PB - Oxford University Press SN - 0954637623 SP - 144 EP - 145 N2 - - ER - TY - CHAP T1 - Estrogen deprivation and hormone replacement therapy: effects on glucose and insulin metabolism and the metabolic syndrome A1 - Godsland, IF ED - Lauritzen C, Studd J T2 - Current Management of the Menopause Y1 - 2005/// VL - 1st PB - Dunitz CY - London SN - 1-84184-232-X N2 - - ER - TY - CHAP T1 - Self management education in COPD A1 - Partridge M ED - Dr John Haughney T2 - A primary care guide to COPD Y1 - 2005/// PB - Magister Consulting Ltd CY - Dartford, Kent SN - 1 873839 61 8 SP - 96 EP - 106 N2 - - ER - TY - CHAP T1 - Molecular variations in the core promoter, precore and core regions of hepatitis B virus, and their clinical significance. A1 - Karayiannis P A1 - Carman WF A1 - Thomas HC ED - Thomas HC; Lemon S; Zuckerman AJ T2 - Viral Hepatitis Y1 - 2005/// PB - Blackwell Publishing SN - 1-4051-30059 SP - 242 EP - 262 N2 - - ER - TY - CHAP T1 - Onchocerciasis A1 - Bradley JE A1 - Whitworth J A1 - Basáñez MG ED - D. Wakelin, F. Cox, D. Despommier & S Gillespie T2 - Topley and Wilson's Microbiology and Microbial Infections 10th ed. Y1 - 2005/// M2 - Parasitology PB - Edward Arnold Publishers Ltd. N2 - - ER - TY - CHAP T1 - Detection and Quantitation of HIV-1-Specific T Lymphocytes in HIV-1 Infected Individuals and Vaccine Recipients A1 - Nesrina Imami A1 - Antonio Pires ED - Liberman, A. P. T2 - Progress in AIDS Research Y1 - 2005/// PB - Nova Science Publishers CY - New York SN - 1-59454-181-7 SP - 109 EP - 137 N2 - - UR - http://www.novapublishers.com ER - TY - CHAP T1 - Molecular epidemiology A1 - P Vineis, G Matullo, M Berwick ED - W Ahrens, I Pigeot T2 - Handbook of epidemiology Y1 - 2005/// PB - Sringer CY - Berlin N2 - - ER - TY - CHAP T1 - Tuberculosis in British Wildlife A1 - Mathews, F. A1 - Webster, J.P. ED - Macdonald, D.W., Randall, D. & Hurst, C. T2 - Wildlife Conservation: Research and Development. Y1 - 2005/// PB - Oxford University Press. SP - 150 EP - 151 N2 - - ER - TY - CHAP T1 - Screening for type 2 diabetes A1 - Johnston, DG A1 - Alberti, KGMM A1 - Godsland, IF A1 - Pierce, M A1 - Shepperd, S ED - Marmot M, Elliott P T2 - Coronary Heart Disease Epidemiology: from aetiology to public health Y1 - 2005/// VL - 2nd PB - Oxford University Press CY - Oxford SN - 0-19-852573-7 N2 - - ER - TY - CHAP T1 - “Intracellular Models of M.tuberculosis Infection” A1 - Chan, John A1 - Silver, Richard A1 - Kampmann, Beate A1 - Wallis, Robert ED - Stuart Cole et al, T2 - “ Tuberculosis” Y1 - 2005/// PB - ASM Press, Washington (2005) N2 - - ER - TY - CHAP T1 - Hepatitis B surface antigen (HBsAg) variants. A1 - Carman WF A1 - Jazayeri M A1 - Basune A A1 - Thomas HC A1 - Karayiannis P ED - Thomas HC; Lemon S; Zuckerman AJ T2 - Viral Hepatitis Y1 - 2005/// PB - Blackwell Publishing SN - 1-4051-30059 SP - 225 EP - 241 N2 - - ER - TY - CHAP T1 - Domiciliary oxygen A1 - Partridge M ED - Dr John Haughney T2 - A primary care guide to COPD Y1 - 2005/// PB - Magister Consulting Ltd CY - Dartford, Kent SN - 1 873839 61 8 SP - 124 EP - 134 N2 - - ER - TY - CHAP T1 - Screening for Type 2 diabetes A1 - Johnston DG A1 - Alberti KGMM A1 - Godsland IF A1 - Pierce M A1 - Shepperd S ED - Marmot M, Elliott P T2 - Coronary Heart Disease Epidemiology Y1 - 2005/// VL - 2nd Edition PB - OUP CY - Oxford SP - 714 EP - 750 N2 - - ER - TY - CHAP T1 - Spirometry, an introduction A1 - Stephenson P A1 - Partridge M ED - Dr John Haughney T2 - A primary care guide to COPD Y1 - 2005/// PB - Magister Consulting Ltd CY - Dartford, Kent SN - 1 873839 61 8 SP - 25 EP - 35 N2 - - ER - TY - CHAP T1 - The mysterious "mind games" that parasites play: rats with fatal attraction to cats. A1 - Berdoy, M. A1 - Webster. J.P. ED - Macdonald, D.W., Randall, D. & Hurst, C. T2 - Wildlife Conservation: Research and Development. Y1 - 2005/// PB - Oxford University Pres SN - 09546376 2 3 SP - 145 EP - 147 N2 - - ER - TY - CHAP T1 - How to manage renal disease in pregnancy A1 - Lightstone L ED - Jayne Franklyn T2 - Horizons in Medicine 16 Updates on major clinical advances Y1 - 2004/08// PB - Royal College of Physicians of London CY - London SN - 1 86016 233 9 SP - 261 EP - 270 N2 - - ER - TY - CHAP T1 - Mobile Phone Positioning Systems and the Accessibility of Health Services. A1 - Löytönen, M A1 - Sabel, C E ED - R. Maheswaran and M. Craglia T2 - GIS in Public Health Practice Y1 - 2004/// PB - CRC Press CY - Boca Raton, USA SP - 277 EP - 285 N2 - - ER - TY - CHAP T1 - Using GIS for environmental exposure assessment: experiences from the Small Area Health Statistics Unit. A1 - de Hoogh K A1 - Briggs DJ A1 - Cockings S A1 - Bottle A ED - Maheswaran R; Craglia M T2 - GIS in public health practice - opportunities and pitfalls Y1 - 2004/// PB - Taylor and Francis CY - London SP - 109 EP - 124 N2 - - ER - TY - CHAP T1 - Malaria A1 - Pasvol G ED - Cohen, J and Powderly, WG T2 - Infectious Diseases Y1 - 2004/// PB - Mosby CY - London SP - 1579 EP - 1591 N2 - - ER - TY - CHAP T1 - Confusion and coma A1 - Pasvol G ED - Cohen, J and Powderly, WG T2 - Infectious Diseases Y1 - 2004/// PB - Mosby CY - London SP - 1459 EP - 1465 N2 - - ER - TY - CHAP T1 - Sex work in context A1 - Ward H A1 - Day S ED - Day S, Ward H T2 - Sex work, mobility and health in Europe Y1 - 2004/// PB - Kegan Paul CY - London SN - 0-7103-0942-2 SP - 15 EP - 33 N2 - - ER - TY - CHAP T1 - Refugee children in the UK A1 - Hodes M ED - M Malek & C Joughin T2 - Mental Health Services for Minority Ethnic Children Y1 - 2004/// PB - Jessica Kingsley CY - London SN - 1-84310-236-6 SP - 152 EP - 168 N2 - - ER - TY - CHAP T1 - La prise en charge des traitements contre le VIH/SIDA. L’esperience bresilienne. A1 - Bastos FI A1 - Petersen M A1 - Kerrigan D A1 - Boily MC ED - Levy, J; Pierret, J & Trottier, G T2 - Les Antirétroviraux: Expériences et Défis, Y1 - 2004/// PB - Les Presses de l’Université du Québec SP - 195 EP - 236 N2 - - ER - TY - CHAP T1 - Approaching health through the prism A1 - Day S A1 - Ward H ED - Day S and Ward H T2 - Sex work, mobility and health in Europe Y1 - 2004/// PB - Kegan Paul CY - London SN - 0-7103-0942-2 SP - 161 EP - 178 N2 - - ER - TY - CHAP T1 - Clustering of Disease. A1 - Sabel, C.E. ED - R. Maheswaran and M. Craglia T2 - GIS in Public Health Practice. Y1 - 2004/// PB - CRC Press CY - Boca Raton, USA SP - 51 EP - 67 N2 - - ER - TY - CHAP T1 - Extrapyramidal symptoms A1 - Dursun S A1 - Haddad PM A1 - Barnes TRE ED - P Haddad, S Dursun, B Deakin T2 - Adverse syndromes and psychiatric drugs Y1 - 2004/// PB - Oxford University Press CY - Oxford SN - 0-19-852748-9 SP - 1 EP - 20 N2 - - ER - TY - CHAP T1 - Introduction: Containing women: A1 - Ward H A1 - Day S ED - Day S, Ward H T2 - Sex work, mobility and health in Europe Y1 - 2004/// PB - Kegan Paul CY - London SN - 0-7103-0942-2 SP - 3 EP - 14 N2 - - ER - TY - CHAP T1 - Multilocus sequence typing: strain characterization, population biology, and patterns of evolutionary descent. A1 - Hanage WP A1 - Feil EJ A1 - Brueggemann AB A1 - Spratt BG ED - [new] T2 - Molecular Microbiology: Diagnostic Principles and Practice. Y1 - 2004/// N2 - - ER - TY - CHAP T1 - Asthma: Self management plans and patient education A1 - Barlow A A1 - Partridge MR ED - Scadding G and O'Connor B T2 - Key Advances in the Clinical Management of Asthma 2 Y1 - 2004/// PB - The Royal Society of Medicine Press Ltd CY - London SN - 1-8531-5561-6 SP - 35 EP - 40 N2 - - ER - TY - CHAP T1 - Policies towards the sex industry in A1 - Visser J A1 - Randers-Pehrson A ED - Day S and Ward H T2 - Sex work, mobility and health in Europe Y1 - 2004/// PB - Kegan Paul CY - London SN - 0-7103-0942-2 SP - 241 EP - 260 N2 - - ER - TY - CHAP T1 - Scientific evaluation of community-based Parkinson’s disease nurse specialists on patient outcomes and healthcare costs. Chapter in: The Effective Management of Parkinson’s disease A1 - Hurwitz B A1 - Jarman B A1 - Cook A A1 - Bajekal M ED - Findlay L, Hurwitz B, Miles A T2 - The Effective Management of Parkinson’s disease. Y1 - 2004/// PB - Aesculapius Medical Press CY - London N2 - - ER - TY - CHAP T1 - Asthma: Clinical features, Diagnosis and Treatment A1 - Partridge MR ED - Albert RK, Spiro SG and Jett JR T2 - Clinical Respiratory Medicine Y1 - 2004/// PB - Mosby CY - Philadelphia SN - 0-323-02497-1 SP - 889 N2 - - ER - TY - CHAP T1 - History of bias A1 - P Vineis ED - A Morabia T2 - History of epidemiology methods and concepts Y1 - 2004/// PB - Birkhauser CY - Basel N2 - - ER - TY - CHAP T1 - Parainfluenza viruses A1 - Psarras S A1 - Papadopoulos NG A1 - Johnston SL ED - Zuckerman, Banatvala, Griffiths, Pattison and Schoub T2 - Principles and Practice of Clinical Virology Fifth Edition Y1 - 2004/// PB - John Wiley & Son CY - UK SP - 299 EP - 321 N2 - - ER - TY - CHAP T1 - Scientific evaluation of community-based Parkinson's disease nurse specialists on patient outcomes and healthcare costs A1 - Hurwitz B A1 - Jarman B A1 - Cook A A1 - Bajekal M ED - Findlay L, Hurwitz B, Miles A T2 - The Effective Management of Parkinson's Disease Y1 - 2004/// PB - Aesculapius Medical Press N2 - - ER - TY - CHAP T1 - Co-ordination of Care A1 - Bosch Wvd A1 - Freeman GK ED - Jones RH, Grol R T2 - Oxford Textbook of General Practice Y1 - 2004/// VL - 1st PB - Oxford University Press CY - Oxford N2 - - ER - TY - CHAP T1 - Novel Vaccines Against Tuberculosis A1 - Wilkinson RJ ED - Myron M. Levine, James B. Kaper, Rino Rappuoli, Margaret Liu, and Michael F. Good T2 - New Generation Vaccines Y1 - 2004/// VL - 3 PB - Marcel Dekker CY - New York SP - 519 EP - 535 N2 - - ER - TY - CHAP T1 - Definition, epidemiology, diagnosis and management of anemia of malaria A1 - Pasvol G A1 - Abdalla SH ED - Abdalla SH and Pasvol G T2 - Malaria A hematological perspective Y1 - 2004/// PB - Imperial College Press SN - 1-86094-357-8 N2 - - ER - TY - CHAP T1 - High blood pressure A1 - Lawes CMM A1 - Vander Hoorn S A1 - Law MR A1 - Rodgers A. ED - Ezzati M; Lopez AD; Rodgers A; Murray CJL T2 - Comparative quantification of health risks. Global and Regional Burden to Disease Attributable to Selected Major Risk Factors Y1 - 2004/// PB - World Health Organization CY - Switzerland SN - 92-4-158031-3 SP - 281 EP - 390 N2 - - ER - TY - CHAP T1 - Challenges to psychiatry: antipsychiatry, the user movement and stigma. A1 - Moncrieff J A1 - Byrne P ED - P. Wright, J. Stern, M. Phelan T2 - Core Psychiatry Y1 - 2004/// SN - 0-7020-2718-9 SP - 1 EP - 18 N2 - - ER - TY - CHAP T1 - Approaching health through the prism A1 - Day S A1 - Ward H ED - Day S and Ward H T2 - Sex work, mobility and health in Europe Y1 - 2004/// PB - Kegan Paul CY - London SN - 0-7103-0942-2 SP - 139 EP - 160 N2 - - ER - TY - CHAP T1 - Undertaking an HIA. 1. Planning A1 - Mindell J A1 - Joffe M A1 - Ison E ED - Kemm J, Parry J, Palmer S. T2 - Health impact assessment Y1 - 2004/// PB - OUP CY - Oxford N2 - - ER - TY - CHAP T1 - Causality in epidemiology A1 - P Vineis ED - A Morabia T2 - History of epidemiology methods and concepts Y1 - 2004/// PB - Birkhauser CY - Basel N2 - - ER - TY - CHAP T1 - Health and environment information systems A1 - Aylin P A1 - Cockings S ED - Maheswaran M, Craglia M T2 - GIS in Public Health Practice Y1 - 2004/// PB - CRC Press CY - London N2 - - ER - TY - CHAP T1 - Pathogenesis of anemai of malaria A1 - Abdalla SH A1 - Pasvol G ED - Abdalla SH and Pasvol G T2 - Malaria A hematological perspective Y1 - 2004/// PB - Imperial College Press SN - 1-86094-357-8 N2 - - ER - TY - CHAP T1 - Changing behaviour: promoting sexual health A1 - Ward H ED - Jones R, Britten N, Culpepper L, Gass DA, Grol R, Mant D, Silagy C T2 - Oxford Textbook of Primary Medical Care Y1 - 2004/// PB - Oxford University Press CY - Oxford SN - 0-19-263219-1 SP - 397 EP - 402 N2 - - ER - TY - CHAP T1 - The Seattle 'sexual mixing', 'sexual networks' and 'sexual partnership types' studies A1 - Aral SO A1 - Hughes J A1 - Gorbach P A1 - Stoner B A1 - Manhart L A1 - Garnett G A1 - Foxman B A1 - Golden M A1 - Holmes KK ED - M Morris T2 - Network Epidemiology: A handbook for survey design and data collection Y1 - 2004/// PB - Oxford University Press CY - Oxford SN - 0-19-926901-7 SP - 139 EP - 171 N2 - - ER - TY - CHAP T1 - “ Acute Respiratory Infections” A1 - Kampmann, Beate ED - Eddleston M, Pierini S, Davidson RN and Wikinson RJ (eds) T2 - Oxford Handbook of Tropical Medicine Y1 - 2004/// VL - 2nd edition. CY - Oxford N2 - - ER - TY - CHAP T1 - Movement disorders in unmedicated schizophrenia A1 - Barbenel DM A1 - Barnes TRE ED - KP Sethi T2 - Drug-Induced Movement Disorders Y1 - 2004/// PB - Marcel Dekker CY - New York SP - 15 EP - 36 N2 - - ER - TY - CHAP T1 - Rhinoviruses A1 - Papadopoulos NG A1 - Johnston SL ED - Zuckerman, Banatvala, Griffiths, Pattison and Schoub T2 - Principles and Practice of Clinical Virology Fifth Edition Y1 - 2004/// PB - John Wiley & Son CY - UK N2 - - ER - TY - CHAP T1 - The utility of self-propagating hepatitis C virus RNAs in the stidy of molecular biology and of antiviral agents A1 - Karayiannis P ED - Hadziyannis S T2 - Hepatitis B and C 2004 Y1 - 2004/// SP - 43 EP - 55 N2 - - ER - TY - CHAP T1 - Difficult Adolescent Consultations: Reflections of a child & adolescent psychiatrist A1 - Kramer T ED - Donovan C; Suckling H T2 - Difficult Adolescent Consultations Y1 - 2004/// PB - Radcliff N2 - - ER - TY - CHAP T1 - Therapeutic intervention to prevent coronary heart disease and stroke A1 - Sever P ED - Weber,Jonanthan T2 - Horizons in Medicine 15 Y1 - 2003/// PB - Royal College of Physicians of London CY - London SN - 1 86016 196 0 SP - 263 EP - 272 N2 - - ER - TY - CHAP T1 - Malignant disease of the vulva and vagina A1 - Dina R A1 - Soutter P A1 - Thomas H ED - RW Shaw, WP Soutter, SL Stanton T2 - Gynaecology Y1 - 2003/// M2 - 3rd Edition PB - Churchill Livingstone CY - Edinburgh SP - 615 EP - 630 N2 - - ER - TY - CHAP T1 - Detection of Respiratory Viruses A1 - Taylor P A1 - Johnston SL ED - Gibson GJ; Geddes DM; Costabel U; Sterk PJ; Corrin B T2 - Respiratory Medicine Third Edition Y1 - 2003/// PB - Elsevier Science Limited CY - London SP - 385 EP - 390 N2 - - ER - TY - CHAP T1 - Macronutrients, fiber, cholesterol, and dietary patterns A1 - Appel LJ A1 - Elliott P ED - Whelton PK; He J; Louis GT T2 - Lifestyle modification for the prevention and treatment of hypertension Y1 - 2003/// PB - Marcel Dekker CY - New York SN - 0-8247-4118-8 SP - 243 EP - 273 N2 - - ER - TY - CHAP T1 - IL-4 Knock-out mice A1 - Kropf P A1 - Muller I ED - Fantuzzi G T2 - Cytokine Knockouts, 2nd Edition Y1 - 2003/// PB - Humana Press CY - Totowa, New Jersey, USA SP - 187 EP - 202 N2 - - ER - TY - CHAP T1 - Environmental Impacts, Exposure Assessment and Health Effects related to Arsenic Emissions from a Coal-Fired Power Plant in Central Slovakia; the EXPASCAN Study. A1 - Thornton I A1 - Nieuwenhuijsen MJ A1 - et al ED - Chappell WR, Abernathy CO, Calderon RL and Thomas DJ. T2 - Arsenic exposure and health effects V Y1 - 2003/// PB - Elsevier, San Diego N2 - - ER - TY - CHAP T1 - Benign tumours of the ovary. A1 - Soutter P A1 - Girling J A1 - Haidopoulos D ED - RW Shaw, WP Soutter, SL Stanton T2 - Gynaecology Y1 - 2003/// M2 - 3rd Edition PB - Churchill Livingstone CY - Edinburgh SP - 665 EP - 676 N2 - - ER - TY - CHAP T1 - Scales to measure behavioural and emotional adjustment in children and their families A1 - Gledhill J A1 - Garralda ME ED - D Skuse T2 - Child Psychology and Psychiatry: An Introduction Y1 - 2003/// PB - The Medicine Publishing Company CY - Oxon SP - 39 EP - 48 N2 - - ER - TY - CHAP T1 - Biological monitoring A1 - Droz P ED - Nieuwenhuijsen MJ T2 - Exposure assessment in Occupational and Environmental Epidemiology Y1 - 2003/// PB - Oxford University Press CY - Oxford N2 - - ER - TY - CHAP T1 - Molecular mechanisms of respiratory virus-induced inflammation A1 - Papi A A1 - Caramori G A1 - Bellettato CM A1 - Adcock I A1 - Johnston SL ED - Papadopoulos NG; Johnston SL T2 - Respiratory infections in allergy and asthma Y1 - 2003/// PB - Marcell Dekker CY - New York SP - 199 EP - 228 N2 - - ER - TY - CHAP T1 - Treatment of the Common Cold: prospects and implications for the treatment of asthma exacerbations A1 - Creer DD A1 - Gelder CM A1 - Johnston SL ED - Papadopoulos NG, Johnston SL; T2 - Respiratory infections in allergy and asthma Y1 - 2003/// PB - Marcell Dekker CY - New York SP - 675 EP - 710 N2 - - ER - TY - CHAP T1 - Tuberculosis A1 - Friedland JS ED - Cohen J & Powderly W T2 - Infectious Diseases Y1 - 2003/// PB - Mosby CY - London, UK SP - 401 EP - 418 N2 - - ER - TY - CHAP T1 - Asthma: communication and education A1 - Partridge MR ED - Gibson GJ, Geddes DM, Costabel U, Sterk PJ, Corrin B T2 - Respiratory Medicine Y1 - 2003/// M2 - 3rd PB - Saunders SN - 0-7020-2613-1 SP - 1357 EP - 1367 N2 - - ER - TY - CHAP T1 - Adjustment and psychopathology amongst Afro-Caribbean children and adolescents in the U.K. A1 - Kramer T A1 - Hodes M ED - D. Ndegwa & D. Olajide T2 - Main Issues in Mental Health and Race Y1 - 2003/// PB - Ashgate CY - Aldershot, England SP - 175 EP - 200 N2 - - ER - TY - CHAP T1 - Viral Infections: Effects on nasal and lower airway functions A1 - Hussain I A1 - Johnston SL ED - Corren J; Togias A; Bousquet J T2 - Upper and Lower Respiratory Disease Y1 - 2003/// PB - Marcel Dekker, Inc CY - New York N2 - - ER - TY - CHAP T1 - Personal exposure monitoring A1 - Nieuwenhuijsen MJ ED - Nieuwenhuijsen MJ T2 - Exposure assessment in Occupational and Environmental Epidemiology Y1 - 2003/// PB - Oxford University Press CY - Oxford N2 - - ER - TY - CHAP T1 - Somatisation and somatoform disorders in childhood and adolescence A1 - Garralda ME ED - D Skuse T2 - Child Psychology and Psychiatry: An Introduction Y1 - 2003/// PB - The Medicine Publishing Company CY - Oxon SP - 129 EP - 132 N2 - - ER - TY - CHAP T1 - Hepatitis C virus: Protein translation, IRES function and DNA immunisation. A1 - Karayiannis P ED - S.J. Hadziyannis T2 - Hepatitis B and C Y1 - 2003/// PB - Paschalides CY - Athens SN - 960-399-139-2 SP - 277 EP - 288 N2 - - ER - TY - CHAP T1 - Questionnaires A1 - NIEUWENHUIJSEN MJ ED - NIEUWENHUIJSEN MJ T2 - Exposure assessment in Occupational and Environmental Epidemiology Y1 - 2003/// N2 - - ER - TY - CHAP T1 - Treatment of Respiratory Viruses A1 - Mallia P A1 - Johnston SL ED - Weber J T2 - Horizons in Medicine - Updates in Major Clinical Advances Y1 - 2003/// PB - Royal College of Physicians CY - London UK SP - 145 EP - 152 N2 - - ER - TY - CHAP T1 - Spatial models in epidemiological applications A1 - S Richardson ED - PJ Green, NL Hjort and S Richardson T2 - Highly Structured Stochastic Systems Y1 - 2003/// PB - Oxford University Press SP - 237 EP - 259 N2 - - ER - TY - CHAP T1 - Increasing adherence to therapy through modifying the doctor/patient interaction A1 - Partridge MR ED - Partridge MR and Miles A T2 - The effective management of asthma. UK Key advances in clinical practice Series Y1 - 2003/// PB - Aesculapius Medical Press CY - London SN - 1-9030-4426-X SP - 89 EP - 100 N2 - - ER - TY - CHAP T1 - Diagnosis and management of cervical intraepithelial neoplasia and early invasive lesions. A1 - Soutter WP ED - AB MacLean, A Singer, H Critchley T2 - Lower Genital Tract Neoplasia Y1 - 2003/// PB - RCOG Press CY - London SP - 231 EP - 238 N2 - - ER - TY - CHAP T1 - Chap 15.1.3.1 Biochemistry and cellular physiology of heart muscle A1 - Sugden PH A1 - Severs NJ A1 - MacLeod KT A1 - Poole-Wilson PA ED - Warrell DA, Cox TM, Firth JD and Benz EJ Jr T2 - Oxford Textbook of Medicine 4th Ed Y1 - 2003/// PB - Oxford University Press SP - 809 EP - 820 N2 - - ER - TY - CHAP T1 - Mortality and sudden death in schizophrenia A1 - Barnes TRE A1 - Kerwin R ED - J Camm. T2 - Cardiovascular Risk Associated with Schizophrenia and its Treatment Y1 - 2003/// PB - Galliard Healthcare Communications CY - London SN - 0-9544351-0-9 SP - 7 EP - 23 N2 - - ER - TY - CHAP T1 - Family work and family therapy in child mental health A1 - Goldberg D A1 - Hodes M ED - E Garralda & C Hyde T2 - Managing Children with Psychiatric Problems Y1 - 2003/// PB - BMJ Publishing Group Ltd CY - London SP - 111 EP - 123 N2 - - ER - TY - CHAP T1 - Mechanisms of allorecognition A1 - Dupont, P J A1 - Herbert, P E A1 - Warrens, A N ED - Lesavre, P Drueke, T Legendre, C Niaudet, P T2 - Actualites Nephrologiques Jean Hamburger: Hopital Necker Y1 - 2003/// PB - Flammarion Medicine-Sciences CY - Paris SN - 2-257-10815-9 N2 - - ER - TY - CHAP T1 - ANOVA DDP Models: A Review A1 - De Iorio M A1 - Müller P A1 - Rosner GL A1 - MacEachern SN ED - D. Denison, M. Hansen, C. Holmes, B. Yu T2 - Nonlinear estimation and classifications Y1 - 2003/// PB - Springer – Verlag N2 - - ER - TY - CHAP T1 - Salt and blood pressure A1 - Elliott P ED - Izzo JL; Black HR T2 - Hypertension primer. The essentials of high blood pressure Y1 - 2003/// M2 - 3rd PB - American Heart Association;Lippincott, Williams & Wilkins CY - Dallas Texas SN - 0-7817-4509-8 SP - 277 EP - 279 N2 - - ER - TY - CHAP T1 - Maligant disease of the uterus A1 - Quinn M A1 - Jones B A1 - Dina R A1 - Soutter P ED - RW Shaw, WP Soutter, SL Stanton T2 - Gynaecology Y1 - 2003/// M2 - 3rd Edition PB - Churchill Livingstone CY - Edinburgh SP - 631 EP - 652 N2 - - ER - TY - CHAP T1 - The epidemiology of HIV/AIDS: Contributions to infectious diseases epidemiology A1 - Ghani A A1 - Boily M-C ED - Ellison E, Parker M, Campbell C T2 - LEarning from HIV and AIDS Y1 - 2003/// PB - Cambridge University Press SP - 59 EP - 87 N2 - - ER - TY - CHAP T1 - The hapatitis B virus: Genotypes, genome organisation and replication A1 - Karayiannis P ED - S.J. Hadziyannis T2 - Hepatitis B and C Y1 - 2003/// PB - Paschalides CY - Athens SN - 960-399-139-2 SP - 20 EP - 34 N2 - - ER - TY - CHAP T1 - Carcinoma of the ovary and fallopian tube A1 - Dina R A1 - Rustin GJS A1 - Soutter P ED - RW Shaw, WP Soutter, SL Stanton T2 - Gynaecology Y1 - 2003/// M2 - 3rd Edition PB - Churchill Livingstone CY - Edinburgh SP - 677 EP - 698 N2 - - ER - TY - CHAP T1 - Towards a sustainable policy to control TB in cattle. A1 - Woodroffe R A1 - Bourne FJ A1 - Donnelly CA A1 - Cox DR A1 - Gettinby G A1 - McInerney JP A1 - Morrison WI ED - Tatersall F; Manley W; T2 - Conservation and Conflict: Mammals and Farming in Britain Y1 - 2003/// PB - Linnean Society CY - London SP - 142 EP - 151 N2 - - ER - TY - CHAP T1 - Introduction to exposure assessment A1 - NIEUWENHUIJSEN MJ ED - NIEUWENHUIJSEN MJ T2 - Exposure assessment in Occupational and Environmental Epidemiology. Y1 - 2003/// PB - Oxford University Press. Oxford N2 - - ER - TY - CHAP T1 - Mechanisms of allorecognition A1 - Dupont PJ A1 - Herbert PE A1 - Warrens AN ED - Lesavre P, Drueke T, Legendre C and Niaudet P T2 - Actualites Nephrologiques Jean Hamburger Y1 - 2003/// PB - Flammarion SN - 2-257-10815-9 SP - 285 EP - 298 N2 - - ER - TY - CHAP T1 - Principles and Purpose for Child Health Informatics A1 - Blair M ED - Rigby M T2 - Vision and Value in Health Information Y1 - 2003/// PB - Radcliffe N2 - - ER - TY - CHAP T1 - Anxiety Disorders in Chilren and Adolescents A1 - Fung G A1 - Garralda ME ED - D Skuse T2 - Child Psychology and Psychiatry: An Introduction Y1 - 2003/// PB - The Medicine Publishing Company CY - Oxon SP - 141 EP - 146 N2 - - ER - TY - CHAP T1 - Management of vaginal intraepithelial neoplasia and invasive vaginal cancer. A1 - Soutter WP ED - AB MacLean, A Singer, H Critchley T2 - Lower Genital Tract Neoplasia Y1 - 2003/// PB - RCOG Press CY - London SP - 319 EP - 325 N2 - - ER - TY - CHAP T1 - Patient Education and Delivery of Care A1 - Partridge MR ED - Chung F, Fabbri LM T2 - Asthma: A European Respiratory Monograph Y1 - 2003/// PB - European Respiratory Society SN - 1-9040-9726-X SP - 449 EP - 458 N2 - - ER - TY - CHAP T1 - Chlorination and birth outcomes A1 - Nieuwenhuijsen MJ ED - Nieuwenhuijsen MJ T2 - Exposure assessment in Occupational and Environmental Epidemiology Y1 - 2003/// PB - Oxford University Press CY - Oxford N2 - - ER - TY - CHAP T1 - The changing Role of surgical treatment A1 - Soutter P ED - S Ghaem-Maghami, K Orton, P Soutter T2 - Key Advances in the Clinical Management of Ovarian Cancer Y1 - 2003/// SP - 23 EP - 26 N2 - - ER - TY - CHAP T1 - The influence of HIV/AIDS on demography and demographic research A1 - Gregson S ED - Ellison G; Parker M; Campbell C T2 - Learning from HIV and AIDS Y1 - 2003/// PB - Cambridge University Press N2 - - ER - TY - CHAP T1 - Malaria. A1 - Maitland K A1 - Newton C ED - Robert E Rakel T2 - Conns Current Therapy Y1 - 2003/// PB - WB Saunders CY - Houston, TX SP - 96 EP - 104 N2 - - ER - TY - CHAP T1 - Premalignant disease of the genital tract. A1 - Soutter P A1 - Dina R ED - RW Shaw, WP Soutter, SL Stanton T2 - Gynaecology Y1 - 2003/// M2 - 3rd Edition PB - Churchill Livingstone CY - Edinburgh SP - 561 EP - 582 N2 - - ER - TY - CHAP T1 - Child Health Indicators of Life and Development- Report to the European Commission Health Monitoring Programme A1 - Blair M A1 - Kohler L A1 - Rigby M A1 - Mechtler R A1 - et al ED - Rigby MJ, Kohler L T2 - C Y1 - 2002/09// PB - EU N2 - - ER - TY - CHAP T1 - Thrombocytopenia in the newborn A1 - Roberts IAG A1 - Murray NA T2 - Platelets Y1 - 2002/// SN - 0-1249-3951-1 SP - 635 EP - 658 N2 - - ER - TY - CHAP T1 - Risk factors for dyskinesia in the elderly A1 - Barnes TRE T2 - Principles and Practice of Geriatric Psychiatry Y1 - 2002/// M2 - 2nd SN - 0-4719-8197-4 SP - 527 EP - 533 N2 - - ER - TY - CHAP T1 - Primary Health Care Psychiatry A1 - Garralda ME T2 - Child and Adolescent Psychiatry Y1 - 2002/// M2 - 4th SN - 0-6320-1228-5 SP - 1090 EP - 1100 N2 - - ER - TY - CHAP T1 - Modelling the impact of traffic-related air pollution on childhood respiratory illness A1 - Best NG A1 - Ickstadt K A1 - Wolpert RP A1 - Cockings S A1 - Elliott P A1 - Bottle A A1 - Bennett J A1 - Reed S ED - Gatsonis C; Kass RE; Carlin B; Carriquiry A; Gelman A; Verdinelli I; West M T2 - Lecture notes in statistics 162: case studies in bayesian statistics Y1 - 2002/// PB - Springer Verlag CY - New York SN - 0-3879-5169-5 SP - 183 EP - 259 N2 - - ER - TY - CHAP T1 - Anaemia in newborns, infants and children A1 - Roberts I A1 - Vassilou G T2 - Essential Paediatric Haematology Y1 - 2002/// SN - 9-0582-3179-8 SP - 65 EP - 91 N2 - - ER - TY - CHAP T1 - Should asthma be managed by the patient or doctor; is education important? A1 - Partridge MR ED - Holgate ST and Johnston L T2 - Asthma: critical debates Y1 - 2002/// PB - Blackwell Science CY - London SN - 0-6320-5721-1 SP - 355 EP - 365 N2 - - ER - TY - CHAP T1 - Education and self management A1 - Partridge MR ED - Barnes PJ,Drazen J, Rennard S and Thomson N T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// PB - Academic Press CY - London SN - 0-1207-9028-9 SP - 737 EP - 742 N2 - - ER - TY - CHAP T1 - Modelling journey-time exposures to traffic-related air pollution A1 - Briggs DJ A1 - Gulliver J ED - Pillmann W; Tochtermann K T2 - Environmental communications in the information society: proceedings of the 16th international confe Y1 - 2002/// PB - International Society for Environmental Protection SN - 3-9500-0367-3 SP - 151 EP - 160 N2 - - ER - TY - CHAP T1 - Recurrent miscarriage A1 - Clifford K A1 - Regan L T2 - Obstetrics & Gynaecology: clinical and basic science aspects Y1 - 2002/// SN - 1-8609-4276-8 SP - 64 EP - 69 N2 - - ER - TY - CHAP T1 - Social function, chronic strains and personality difficulties A1 - Tyrer P A1 - Karlsen S A1 - Crawford MJ T2 - Ethnic minority psychiatric illness rates in the community (EMPIRIC) - Quantitative report Y1 - 2002/// SN - 0-1132-2582-2 SP - 63 EP - 71 N2 - - UR - http://www.doh.gov.uk/public/empiric.pdf ER - TY - CHAP T1 - The epidemiology of lymphatic filariasis control A1 - Michael E T2 - The filariae Y1 - 2002/// SN - 1-4020-7038-1 SP - 59 EP - 74 N2 - - ER - TY - CHAP T1 - Coalescent theory and modelling A1 - Balding DJ ED - Pagel M T2 - Encyclopedia of evolution Y1 - 2002/// SN - 0-1951-4864-9 SP - 170 EP - 175 N2 - - ER - TY - CHAP T1 - The need for information: environmental health indicators. A1 - Corvalan C A1 - Briggs DJ A1 - Kjelstrom T ED - Corvalan C; Briggs DJ; Zielhuis G T2 - Decision-making in environmental health: from evidence to action. Y1 - 2002/// PB - SPON Routledge CY - London SP - 25 EP - 55 N2 - - ER - TY - CHAP T1 - Hypopituitarism in adults A1 - Johnston DG A1 - Al Mrayat M A1 - Kearney T T2 - Conn's current therapy Y1 - 2002/// SN - 0-7216-8744-X SP - 637 EP - 643 N2 - - ER - TY - CHAP T1 - Modelling the impact of traffic-related air pollution on childhood respiratory illness A1 - Best NG A1 - Ickstadt K A1 - Wolpert RP A1 - Cockings S A1 - Elliott P A1 - Bottle A A1 - Bennett J A1 - Reed S T2 - Lecture notes in statistics 162: case studies in bayesian statistics Y1 - 2002/// SN - 0-3879-5169-5 SP - 183 EP - 259 N2 - - ER - TY - CHAP T1 - The Leishmaniasis Model A1 - Kropf P A1 - Brunson K A1 - Muller I ED - Kaufmann SHE & Kabelitz D T2 - Immunology of Infection, part of Methods in Microbiology Series, 2nd Edition Y1 - 2002/// PB - Academic Press Ltd CY - London SP - 463 EP - 492 N2 - - ER - TY - CHAP T1 - Disease clustering A1 - Elliott P ED - El-Shaarawi A; Piegorsch WW T2 - Encyclopaedia of environmentrics Y1 - 2002/// PB - John Wiley and Sons Ltd CY - Chichester SN - 0-4718-9997-6 SP - 530 EP - 533 N2 - - ER - TY - CHAP T1 - Changes in metabolic, inflammatory and endothelial indices of cardiovascular risk A1 - Godsland I T2 - Textbook of men's health Y1 - 2002/// SN - 1-8421-4011-6 SP - 317 EP - 335 N2 - - ER - TY - CHAP T1 - The Renal Transplant Recipient A1 - Warrens AN ED - Glynne P, Allen A and Pusey C T2 - Acute Renal Failure in Practice Y1 - 2002/// PB - Imperial College Press SN - 1-86094-287-3 SP - 453 EP - 464 N2 - - ER - TY - CHAP T1 - A lifecourse approach to Diabetes A1 - Colhoun HM A1 - Chaturvedi N T2 - A lifecourse approach to women's health Y1 - 2002/// SN - 0-1926-3289-2 SP - 121 EP - 133 N2 - - ER - TY - CHAP T1 - A GIS-based route mapping tool for disabled access in urban environments A1 - Briggs DJ A1 - Beale L ED - Pillmann W; Tochtermann K T2 - Environmental communications in the information society: proceedings of the 16th international confe Y1 - 2002/// PB - International Society for Environmental Protection SN - 3-9500-0367-3 SP - 161 EP - 167 N2 - - ER - TY - CHAP T1 - Academic Training in London A1 - Freeman G, A1 - Fuller J A1 - Hilton S A1 - Smith F ED - Harrison J, van Zwanenberg T T2 - GP Tomorrow Y1 - 2002/// VL - 2nd PB - Radcliffe Medical Press CY - Abingdon SP - 117 EP - 125 N2 - - ER - TY - CHAP T1 - Preparing for environmental health emergencies: the role of GIS A1 - Briggs D J A1 - Beale L ED - Briggs DJ; Forer P; Jarup L; Stern R T2 - GIS for emergency preparedness and health risk reduction (NATO advanced research workshop:2001 Apr: Y1 - 2002/// PB - Kluwer Academic Publishers SN - 1-4020 0798-1 SP - 3 EP - 34 N2 - - ER - TY - CHAP T1 - Carcinoma of the ovary and fallopian tube A1 - Lambert HE A1 - Thomas H A1 - Soutter WP T2 - Treatment of Cancer Y1 - 2002/// M2 - 4th SN - 0-3407-5964-X SP - 707 EP - 726 N2 - - ER - TY - CHAP T1 - Triggers of Asthma and COPD - Infections A1 - Message SD A1 - Johnston SL ED - Barnes PJ; Drazen JM; Rennard S; Thomson NC T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// PB - Academic Press CY - London SN - 0-1207-9028-9 SP - 407 EP - 420 N2 - - ER - TY - CHAP T1 - The use of simulation models in exploring the influence of network structures on the epidemiology of sexually transmitted infections A1 - Garnett GP A1 - Ghani AC T2 - The network paradigm in research on drug abuse, HIV, and other blood-borne and sexually transmitted Y1 - 2002/// SP - 63 EP - 69 N2 - - ER - TY - CHAP T1 - Laser and focused ultrasound ablation of primary and secondary liver tumours A1 - Dick EA A1 - Taylor-Robinson SD A1 - Gedroyc WM T2 - Multi-treatment modalities of liver tumours Y1 - 2002/// SN - 0-3064-6746-1 SP - 197 EP - 210 N2 - - ER - TY - CHAP T1 - Immune intervention in tuberculosis A1 - Young DB A1 - Robertson BD T2 - Immunology of Infectious Diseases Y1 - 2002/// SN - 1-5558-1214-7 SP - 439 EP - 451 N2 - - ER - TY - CHAP T1 - Geographical distribution of the cardiovascular mortality in Comunidad Valenciana (Spain) A1 - Ferrándiz J A1 - Abellán JJ A1 - López A A1 - Sanmartín P A1 - Vanaclocha H A1 - Zurriaga O A1 - Martínez-Beneito MA A1 - Melchor I A1 - Calabuig J ED - Briggs D; Forer P; Jarup L; Stern R T2 - GIS for Emergency preparedness and health risk reduction Y1 - 2002/// PB - The Netherlands: Kluwer Academic Publishers SP - 267 EP - 282 N2 - - ER - TY - CHAP T1 - Diseases of the vulva A1 - Soutter WP T2 - Obstetrics & Gynaecology: Clinical and basic aspects Y1 - 2002/// SN - 1-8609-4276-8 SP - 288 EP - 293 N2 - - ER - TY - CHAP T1 - Diseases of the cervix A1 - Soutter WP T2 - Obstetrics & Gynaecology: Clinical and basic aspects Y1 - 2002/// SN - 1-8609-4276-8 SP - 294 EP - 303 N2 - - ER - TY - CHAP T1 - Vascular Tone A1 - Hughes AD ED - Hunt BJ, Poston L, Schachter M, Halliday AW. T2 - An Introduction to Vascular Biology: From Basic Science to Clinical Practice Y1 - 2002/// PB - Cambridge University Press SN - 0-521-79652-0 SP - 3 EP - 32 N2 - - ER - TY - CHAP T1 - Pituitary adenomas A1 - Kearney T A1 - Johnston DG T2 - Endocrinology: specialist handbook Y1 - 2002/// SN - 1-8418-4158-7 SP - 1 EP - 19 N2 - - ER - TY - CHAP T1 - Promoting continuity of care for people with severe mental illness whose needs span primary, secondary and social care A1 - Freeman G A1 - Crawford MJ A1 - Weaver T A1 - Low J A1 - de Jonge E T2 - Report for the National Co-ordinating Centre for NHS Service Delivery and Organisation R & D (NCCSDO Y1 - 2002/// N2 - - UR - http://www.sdo.lshtm.ac.uk/pdf/coc_mentalillness_freeman.pdf ER - TY - CHAP T1 - Carcinoma of the vulva A1 - Soutter WP A1 - Thomas H T2 - Oxford Textbook of Oncology (2 volume set) Y1 - 2002/// M2 - 2nd SN - 0-1926-2926-3 SP - 1897 EP - 1911 N2 - - ER - TY - CHAP T1 - The molecular biology of hepatitis B virus A1 - Karayiannis P ED - N.Tassopoulos T2 - Hepatitis B: 21st Century Y1 - 2002/// SN - 9-6086-8980-5 SP - 41 EP - 54 N2 - - ER - TY - CHAP T1 - Carcinoma of the vulva and vagina A1 - Soutter WP A1 - Lambert HE A1 - Thomas H T2 - Treatment of Cancer Y1 - 2002/// M2 - 4th SN - 0-3407-5964-X SP - 461 EP - 773 N2 - - ER - TY - CHAP T1 - What are the mechanisms of corticosteroids resistance in asthma? A1 - Barnes PJ T2 - Asthma: Critical debates Y1 - 2002/// SN - 0-6320-5721-1 SP - 241 EP - 254 N2 - - ER - TY - CHAP T1 - Preparing for environmental health emergencies: the role of GIS A1 - Briggs DJ A1 - Beale L T2 - GIS for emergency preparedness and health risk reduction (NATO advanced research workshop:2001 Apr: Y1 - 2002/// SN - 1-4020 0798-1 SP - 3 EP - 34 N2 - - ER - TY - CHAP T1 - Study of clustering and outbreaks A1 - Elliott P ED - Olsen J; Saracci R; Trichopoulos D T2 - Teaching epidemiology Y1 - 2001/// PB - Oxford University Press/International Epidemiological Association SN - 0-1985-0969-3 SP - 311 EP - 320 N2 - - ER - TY - CHAP T1 - Epidemiology and control of nematode infection and disease in humans A1 - Bundy DAP A1 - Guyatt HL A1 - Michael E ED - Lee D; T2 - Biology of Nematodes Y1 - 2001/// PB - Harwood Academic Publishers SP - 595 EP - 613 N2 - - ER - TY - CHAP T1 - Sporadic and recurrent miscarriage A1 - Regan L A1 - Clifford K Y1 - 2001/// SN - 0-4430-6365-6 SP - 117 EP - 128 N2 - - ER - TY - CHAP T1 - Training of primary care workers in child protection A1 - Blair M ED - Carter Y, Bannon M T2 - Child Protection in Primary Care Y1 - 2001/// PB - Radcliffe SN - 1-8577-5224-4 N2 - - ER - TY - CHAP T1 - Suicide and suicide attempts A1 - Crawford M Y1 - 2001/// SN - 1-8530-2934-3 SP - 259 EP - 262 N2 - - ER - TY - CHAP T1 - Infection and pregnancy loss A1 - Regan L A1 - Jivraj S Y1 - 2001/// SN - 1-9003-6444-1 SP - 291 EP - 304 N2 - - ER - TY - CHAP T1 - Propellants A1 - Partridge MR A1 - Woodcock ED - Bisgaard H, O'Callaghan C and Smaldone GC T2 - Lung Biology in Health and Disease Series No 162 Y1 - 2001/// PB - Marcel Dekker CY - New York SN - 0-8247-0541-6 SP - 371 EP - 388 N2 - - ER - TY - CHAP T1 - Risk management and litigation A1 - Soutter WP Y1 - 2001/// SN - 1-8531-5480-6 SP - 281 EP - 295 N2 - - ER - TY - CHAP T1 - Epidemiology and control of human helminthiases A1 - Bundy DAP A1 - Michael E Y1 - 2001/// SN - 1-5780-8164-5 SP - 179 EP - 223 N2 - - ER - TY - CHAP T1 - Angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor blockers (ARBs), and aldosterone antagonism A1 - Opie LH A1 - Yusuf S A1 - Poole-Wilson PA A1 - Pfeffer M Y1 - 2001/// M2 - 5th SN - 0-7216-8757-1 SP - 107 EP - 153 N2 - - ER - TY - CHAP T1 - Schistosome host-parasite population genetics in the Zimbabwean highveld. A1 - Davies CM A1 - Webster JP A1 - Munatsi A A1 - Kruger O A1 - Ndamba J A1 - Noble LR A1 - Woolhouse MEJ ED - Madsen, H., Appleton, C.C. & M. Chimbari T2 - Medical and Veterinary Malacology in Africa Y1 - 2001/// PB - DBL publications CY - Charlottlund SN - 87-981250-7-9 SP - 62 EP - 82 N2 - - ER - TY - CHAP T1 - Obstetrics, fetal and paediatric A1 - Roberts I A1 - McCloy M Y1 - 2001/// SN - 0-6320-5114-0 SP - 87 EP - 107 N2 - - ER - TY - CHAP T1 - Liver disease in pregnancy A1 - Williamson C A1 - Nelson-Piercy C Y1 - 2001/// M2 - 3rd SN - 1-8564-2193-7 SP - 129 EP - 138 N2 - - ER - TY - CHAP T1 - Anticipating the future: models and modelling of resistance spread A1 - Anderson RM Y1 - 2001/// SN - 1-8531-5479-2 SP - 103 EP - 110 N2 - - ER - TY - CHAP T1 - Magnetic resonance imaging of the cervix A1 - Soutter WP A1 - DeSouza N Y1 - 2001/// SN - 9-0582-3100-3 SP - 15 EP - 32 N2 - - ER - TY - CHAP T1 - Academic General Practice A1 - Freeman GK ED - Ward C, Eccles S T2 - So you want to be a Brain Surgeon? Y1 - 2001/// VL - 2nd PB - Oxford University Press CY - Oxford SP - 78 N2 - - ER - TY - CHAP T1 - Answers to questions 63,64,66,67,68,69,70, 71,72 A1 - Hardman S A1 - Cowie MR Y1 - 2001/// SN - 0-7279-1489-8 SP - 133 EP - 152 N2 - - ER - TY - CHAP T1 - Anemia A1 - Pasvol G A1 - Abdalla SH ED - Guerrant R, Walker DH and Weller PF T2 - Essentials of Tropical Infectious Disease Y1 - 2001/// PB - Churchill Livingstone International CY - New York SN - 0-4430-7909-9 SP - 93 EP - 98 N2 - - ER - TY - CHAP T1 - Advances in the diagnosis of respiratory virus infectons A1 - Chauhan AJ A1 - Johnston SL ED - Skoner DP T2 - Asthma and Respiratory Infections Y1 - 2001/// PB - Marcek Dekker SN - 0-8247-7710-7 SP - 221 EP - 243 N2 - - ER - TY - CHAP T1 - Pathophysiology of heart failiure A1 - Purcell IF A1 - Poole-Wilson PA Y1 - 2001/// SN - 0-7216-8144-1 SP - 345 EP - 364 N2 - - ER - TY - CHAP T1 - Rates of asthma exacerbations during viral respiratory infection A1 - Corne JM A1 - Johnston SL A1 - Beasley R Y1 - 2001/// SN - 0-8247-7710-7 N2 - - ER - TY - CHAP T1 - The application of mathematical models in infectious disease research A1 - Anderson RM Y1 - 2001/// SN - 1-8531-5479-2 SP - 31 EP - 46 N2 - - ER - TY - CHAP T1 - Parasite epidemiology A1 - Bundy DAP A1 - Michael E Y1 - 2001/// SN - 0-4719-7729-2 SP - 21 EP - 25 N2 - - ER - TY - CHAP T1 - Evidence for upper respiratory tract viruses as precipitants for asthma exacerbations A1 - Corne JM A1 - Johnston SL A1 - Beasley R ED - Skoner T2 - Asthma and Respiratory Infections Y1 - 2001/// PB - Marcel Dekker, Inc CY - New York SP - 45 EP - 62 N2 - - ER - TY - CHAP T1 - Cardiovascular disease A1 - Poole-Wilson PA Y1 - 2001/// SN - 1-8990-4091-9 SP - 22 EP - 31 N2 - - ER - TY - CHAP T1 - Medical disorders in pregnancy A1 - Nelson-Piercy C A1 - Williamson C Y1 - 2001/// M2 - 3rd SN - 0-4430-6365-6 SP - 275 EP - 297 N2 - - ER - TY - CHAP T1 - Mortality in heart failure; selected aspects of pathophysiology and the implications of recent trials A1 - Poole-Wilson PA Y1 - 2001/// SN - 0-6202-7326-7 SP - 69 EP - 86 N2 - - ER - TY - CHAP T1 - Diuretics A1 - Opie LH A1 - Kaplan NM A1 - Poole-Wilson PA Y1 - 2001/// M2 - 5th SN - 0-7216-8757-1 SP - 84 EP - 106 N2 - - ER - TY - CHAP T1 - Carcinoma of the ovary and fallopian tube A1 - Soutter WP ED - S Campbell, A Monga T2 - Gynaecology by Ten Teachers Y1 - 2000/// M2 - 17th Edition PB - Arnold CY - London SP - 155 EP - 166 N2 - - ER - TY - CHAP T1 - Bayesian approaches to disease mapping A1 - Wakefield JC A1 - Best NG A1 - Waller LA ED - Elliott P; Wakefield JC; Best NG; Briggs DJ T2 - Spatial Epidemiology: Methods and Applications Y1 - 2000/// PB - Oxford University Press SN - 0-19-851532-4 SP - 104 EP - 127 N2 - - UR - http://www.oup.co.uk/isbn/0-19-851532-4 ER - TY - CHAP T1 - Mechanisms of respiratory syncytial virus induced asthma A1 - Johnston SL ED - Rimmer JS; Katarelis CH T2 - Proceedings XVII International Congress of Allergology and Clinical Immunology Y1 - 2000/// PB - Hogrefe & Huber Pubs CY - Seattle SP - 101 EP - 102 N2 - - ER - TY - CHAP T1 - Assessment of exposure and health effects. A1 - Nurminan T A1 - Nurminan N A1 - Corvalan C A1 - Briggs DJ ED - Corvalan C; Briggs DJ; Zielhuis G T2 - Decision-making in environmental health: from evidence to action. Y1 - 2000/// PB - SPON Routledge CY - London SP - 77 EP - 102 N2 - - ER - TY - CHAP T1 - Benign tumours of the ovary A1 - Soutter WP ED - S Campbell, A Monga T2 - Gynaecology by Ten Teachers Y1 - 2000/// M2 - 17th Edition PB - Arnold CY - London SP - 131 EP - 142 N2 - - ER - TY - CHAP T1 - Ecological correlation: the SAVIAH study. A1 - Best N A1 - Ickstadt K A1 - Wolpert R A1 - Briggs DJ ED - Elliott P; Best N; Wakefield J; Briggs DJ T2 - Spatial epidemiology: methods and applications. Y1 - 2000/// PB - Oxford University Press CY - Oxford SP - 393 EP - 414 N2 - - ER - TY - CHAP T1 - Personal exposure monitoring in environmental epidemiology. A1 - NIEUWENHUIJSEN M.J. ED - Elliott P, Wakefield J, Best N and Briggs D T2 - Disease and exposure mapping. Y1 - 2000/// PB - University Press, Oxford N2 - - ER - TY - CHAP T1 - Children of mothers with eating disorders A1 - Reder P A1 - McClure M A1 - Jolley A T2 - Family Matters: Interfaces between Child and Adult Mental Health Y1 - 2000/// PB - Routledge, Taylor & Francis Group. CY - London & Philadelphia SN - 0-415-22218-4 SP - 107 EP - 121 N2 - - ER - TY - CHAP T1 - The HEADLAMP approach: a new model for environmental health decision-making. A1 - Briggs DJ A1 - Zielhuis G A1 - Corvalan C ED - Corvalan C; Briggs DJ; Zielhuis G T2 - Decision-making in environmental health: from evidence to action. Y1 - 2000/// PB - SPON Routledge CY - London SP - 205 EP - 222 N2 - - ER - TY - CHAP T1 - Exposure assessment. A1 - Briggs DJ ED - Elliott P; Best N; Wakefield J; Briggs DJ T2 - Spatial epidemiology:methods and applications Y1 - 2000/// PB - Oxford University Press CY - Oxford SP - 335 EP - 359 N2 - - ER - TY - CHAP T1 - Dispersion modelling. A1 - Colvile R A1 - Briggs DJ ED - Elliott P; Best N; Wakefield J; Briggs DJ T2 - Spatial epidemiology: methods and applications. Y1 - 2000/// PB - Oxford University Press CY - Oxford SP - 375 EP - 392 N2 - - ER - TY - CHAP T1 - Common colds and respiratory viruses A1 - Bates A1 - Johnston SL ED - Busse WW; Katarelis CH T2 - Asthma and rhinitis Y1 - 2000/// PB - Blackwell Science CY - London SP - 1481 EP - 1492 N2 - - ER - TY - CHAP T1 - Methods for building environmental health indicators. A1 - Briggs DJ ED - Corvalan C; Briggs DJ; Zielhuis G T2 - Decision-making in environmental health: from evidence to action. Y1 - 2000/// PB - SPON Routledge CY - London SP - 57 EP - 75 N2 - - ER - TY - CHAP T1 - Using GIS to link environment and health data. A1 - Briggs DJ A1 - Field K ED - Corvalan C; Briggs DJ; Zielhuis G T2 - Decision-making in environmental health: from evidence to action Y1 - 2000/// PB - SPON Routledge CY - London SP - 133 EP - 157 N2 - - ER - TY - CHAP T1 - Health and environment analysis: the HEADLAMP project. A1 - Corvalan C A1 - Kjelstrom T A1 - Zielhuis G A1 - Briggs DJ ED - Corvalan C; Briggs DJ; Zielhuis G T2 - Decision-making in environmental health: from evidence to action Y1 - 2000/// PB - SPON Routledge CY - London SP - 1 EP - 10 N2 - - ER - TY - CHAP T1 - Bayesian Graphical Models and Software for GLMs A1 - Best NG A1 - Thomas A ED - Dey DK; Ghosh SK; Mallick B T2 - Generalised Linear Models: A Bayesian Perspective Y1 - 2000/// PB - Marcel Dekker CY - New York N2 - - ER - TY - CHAP T1 - Combining models of health and exposure data: the SAVIAH study A1 - Best NG A1 - Ickstadt K A1 - Wolpert RL A1 - Briggs DJ ED - Elliott P; Wakefield JC; Best NG; Briggs DJ T2 - Spatial Epidemiology: Methods and Applications Y1 - 2000/// PB - Oxford University Press SN - 0-19-851532-4 SP - 393 EP - 414 N2 - - UR - http://www.oup.co.uk/isbn/0-19-851532-4 ER - TY - CHAP T1 - Malignant disese of the ovary A1 - Soutter WP ED - DK Edmonds T2 - Dewhurst's Textbook of Obstetrics and Gynaecology for Postgraduates Y1 - 1999/// PB - Blackwell Science CY - Oxford SP - 560 EP - 571 N2 - - ER - TY - CHAP T1 - Chlamydia pneumoniae infections in children A1 - Biscione GL A1 - Johnston SL ED - Allegra L; Blasi F T2 - Chlamydia pneumoniae the lung and heart Y1 - 1999/// PB - Springer-Verlag Italia CY - Milano SP - 197 EP - 203 N2 - - ER - TY - CHAP T1 - Bayesian Ecological Modelling A1 - Best N ED - Lawson A; Biggeri A; Boehning D; Lessafre E; Viel J; Bertollini R T2 - Disease Mapping and Risk Assesment for Public Health Y1 - 1999/// PB - John Wiley and Sons CY - Chichester SP - 193 EP - 201 N2 - - ER - TY - CHAP T1 - What’s the point? Assessing disease risk using data on residential mobility A1 - Gatrell AC A1 - Sabel CE A1 - Mitchell JD ED - Barnett V, Turkman KF and Stein A (eds) T2 - Statistics for the Environment 4: Health & the Environment Y1 - 1999/// PB - John Wiley CY - Chichester N2 - - ER - TY - CHAP T1 - Triggers of asthma: viruses A1 - Busse WW A1 - Johnston SL ED - Djukanovic R; Holgate ST T2 - An atlas of asthma Y1 - 1999/// PB - Parthenon Publishing Group CY - London SP - 63 EP - 68 N2 - - ER - TY - CHAP T1 - Bayesian models for spatially correlated disease and exposure data A1 - Best N A1 - Arnold R A1 - Thomas A A1 - Waller L A1 - Conlon E ED - Bernardo J; Berger J; Dawid AP; Smith AFM T2 - Bayesian Statistics 6 Y1 - 1999/// PB - Oxford University Press CY - Oxford SP - 131 EP - 156 N2 - - ER - TY - CHAP T1 - The acute exacerbation of asthma:pathogenesis A1 - Papadopoulos NG A1 - Johnston SL ED - Holgate ST: Boushey HA; Fabbri LM T2 - Difficult asthma Y1 - 1999/// PB - Martin Dunitz CY - London SP - 183 EP - 204 N2 - - ER - TY - CHAP T1 - Rhinoviruses A1 - Papadopoulos NG A1 - Johnston SL ED - Zuckerman; Banatvala; Pattison T2 - Principles and Practice of Clinical Virology Fourth Edition Y1 - 1999/// PB - John Wiley & Son CY - UK SP - 329 EP - 343 N2 - - ER - TY - CHAP T1 - Geographical patterns of disease A1 - Elliott P A1 - Best N ED - Armitage P; Colton T T2 - Encyclopaedia of Biostatistics Y1 - 1998/// PB - John Wiley and Sons SP - 1694 EP - 1702 N2 - - ER - TY - CHAP T1 - Renal failure A1 - Warrens, A N ED - Hornick, P Lumley, J Grace, P T2 - Case presentations for the MRCS and AFRCS Y1 - 1997/// M2 - 2 PB - Butterworth Heinemann CY - London SN - 0-7506-3258-5 SP - 4 EP - 9 N2 - - ER - TY - CHAP T1 - Renal failure A1 - Warrens, A N ED - Hornick, P Lumley, J Grace, P T2 - Case presentations for the MRCS and AFRCS Y1 - 1997/// M2 - 1 PB - Butterworth Heinemann CY - London SN - 0-7506-3257-7 SP - 6 EP - 10 N2 - - ER - TY - CHAP T1 - Adhesion molecules in xenotransplantation A1 - Simon, A R A1 - Warrens, A N ED - Steinhoff, G T2 - Adhesion molecules in organ transplantation Y1 - 1997/// PB - Springer Verlag N2 - - ER - TY - CHAP T1 - Allergy A1 - Frew AJ A1 - Bradding P A1 - Johnston SL A1 - Lackie P A1 - Semper A A1 - Shute A A1 - Walls AF A1 - Holgate ST ED - Tomlinson, Heagerty, Weetman T2 - Mechanisms of Disease Y1 - 1997/// PB - Cambridge University Press CY - UK SP - 129 EP - 159 N2 - - ER - TY - CONF T1 - Bayesian shrinkage priors for detecting multiple causal variants from genome-wide association studies A1 - Hoggart, C A1 - De Iorio, M A1 - Whittakker, J A1 - Balding, D U1 - 35th European Mathematical Genetics Meeting Y1 - 2007/07// Y2 - // VL - 71 SP - 557 EP - 557 N2 - - ER - TY - CONF T1 - The interplay between recombination and selection can confound their inference from population data - But suggests a novel genome-wide method for detecting selection A1 - O'Reilly, P A1 - Birney, E A1 - Balding, D U1 - 35th European Mathematical Genetics Meeting Y1 - 2007/07// Y2 - // VL - 71 SP - 551 EP - 552 N2 - - ER - TY - CONF T1 - Turbo Genomic Control A1 - Astle, W A1 - Holmes, C A1 - Balding, D U1 - 35th European Mathematical Genetics Meeting Y1 - 2007/07// Y2 - // VL - 71 SP - 553 EP - 554 N2 - - ER - TY - CONF T1 - CD4 cell counts of 800 cells/mm(3) or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm(3) or greater A1 - Gras, L A1 - Kesselring, AM A1 - Griffin, JT A1 - van Sighem, AI A1 - Fraser, C A1 - Ghani, AC A1 - Miedema, F A1 - Reiss, P A1 - Lange, JMA A1 - de Wolf, F A1 - ATHENA A1 - Natl Observational Cohort Study U1 - 13th Conference on Retroviruses and Opportunistic Infections Y1 - 2007/06/01/ Y2 - // VL - 45 SP - 183 EP - 192 N2 - - ER - TY - CONF T1 - Using transmission dynamics models to validate vaccine efficacy measures prior to conducting HIV vaccine efficacy trials A1 - Desai, K A1 - Boily, MC A1 - Misse, B A1 - Anderson, RM U1 - DIMACS Workshop on Data Mining and Epidemiology Y1 - 2006/// Y2 - // VL - 70 SP - 139 EP - 161 N2 - - ER - TY - CONF T1 - Central nervous system involvement in hepatitis C virus infection: what to measure? A1 - Forton, DM A1 - Allsop, J A1 - Thomas, HC A1 - Taylor-Robinson, SD U1 - 12th International Symposium on Hepatic Encephalopathy and Nitrogen Metabolism Y1 - 2006/// Y2 - // SP - 284 EP - 290 N2 - - ER - TY - CONF T1 - Modelling complexity in health and social sciences: Bayesian graphical models as a tool for combining multiple sources of information A1 - Best N A1 - Jackson C A1 - Richardson S U1 - 3rd ASC International Conference on Survey Research Methods Y1 - 2005/09// Y2 - // PB - ASC N2 - - UR - http://www.asc.org.uk ER - TY - CONF T1 - Assessment of exposure to nephrotoxic agents from industrial emissions A1 - Hodgson, S A1 - Nieuwenhuijsen, MJ A1 - Colvile, R U1 - ISEE AD - Johannesburg, South Africa Y1 - 2005/// Y2 - 2005/09// VL - 16 (5) PB - Epidemiology SP - S54 N2 - - ER - TY - CONF T1 - Molecular biology related to pre-eclampsia A1 - Williamson, C U1 - 15th Congress of Gynaecology, Obstetrics and Reproductive Medicine Y1 - 2005/// Y2 - // VL - 1279 SP - 282 EP - 289 N2 - - ER - TY - CONF T1 - Renal effects in a population with ambient exposure to mercury and solvents A1 - Hodgson, S A1 - Nieuwenhuijsen, MJ A1 - Jarup, L U1 - International Society for Environmental Epidemiology (ISEE) AD - Johannesburg, South Africa Y1 - 2005/// Y2 - 2005/09// VL - 16 (5) PB - Epidemiology SP - S54 EP - S55 N2 - - ER - TY - CONF T1 - Ethnic differences in obese and overweight children A1 - Saxena S U1 - Understanding coronary risk factors AD - Institute of Mechanical Engineers Y1 - 2004/10// Y2 - // PB - Economic and Social Data Service N2 - - UR - http://www.ccsr.ac.uk/esds/events/2004-10-29/summaries/summary.pdf ER - TY - CONF T1 - Explaining variations in routine data at PCT level A1 - Saxena S U1 - Using primary care information to improve the public’s health AD - Royal Society of Medicine Y1 - 2004/03// Y2 - // PB - JRSM N2 - - ER - TY - CONF T1 - Cardiac rehabilitation A1 - Cowie, MR U1 - Symposium on What About the Workers Y1 - 2004/// Y2 - // SP - 51 EP - 56 N2 - - ER - TY - CONF T1 - Identifying populations at risk from mercury exposure in Runcorn A1 - Hodgson, S A1 - Nieuwenhuijsen, MJ A1 - Colvile, R A1 - Jarup, L U1 - ISEE AD - New York, USA Y1 - 2004/// Y2 - 2004/08// VL - 15 (4) PB - Epidemiology SP - S144 N2 - - ER - TY - CONF T1 - Predicting the behaviour of the renal transplant waiting list in the Pais Valencia (Spain) using simulation modeling A1 - Abellan, JJ A1 - Armero, C A1 - Conesa, D A1 - Perez-Panades, J A1 - Martinez-Beneito, MA A1 - Zurriaga, O A1 - Garcia-Blasco, MJ A1 - Vanaclocha, H U1 - Winter Simulation Conference 2004 Y1 - 2004/// Y2 - // SP - 1969 EP - 1974 N2 - - ER - TY - CONF T1 - Surveying the AIDS related risk behaviours of university students (Italy) A1 - Carducci A A1 - Calamusa A A1 - Manfredi P A1 - Williams JR A1 - Romano F A1 - Verani M A1 - Privitera G U1 - XV International AIDS conference AD - Bangkok Y1 - 2004/// Y2 - 2004/// PB - Medimond Publishing Co CY - Bologna SP - 153 EP - 158 N2 - - ER - TY - CONF T1 - Influenza evolution and immune selection A1 - Ferguson, NM A1 - Bush, RM U1 - 5th International Conference on Options for the Control of Influenza Y1 - 2004/// Y2 - // VL - 1263 SP - 12 EP - 16 N2 - - ER - TY - CONF T1 - Reduced pallidal magnetisation transfer ratios are associated with fatigue in pre-cirrhotic patients with primary biliary cirrhosis A1 - Forton, DM A1 - Prince, M A1 - Allsop, J A1 - Patel, N A1 - Goldblatt, J A1 - Thomas, HC A1 - Bassendine, M A1 - Jones, DEJ A1 - Taylor-Robinson, SD U1 - 11th International Symposium on Hepatic Encephalopathy and Nitrogen Metabolism Y1 - 2003/// Y2 - // SP - 173 EP - 174 N2 - - ER - TY - CONF T1 - Toll-like receptor 4 contributes to the efficient control of infection with the protozoan parasite Leishmania major A1 - Kropf P A1 - Freudenberg M A1 - Modolell M A1 - Price H A1 - Herath S A1 - Antoniazi S A1 - Galanos C A1 - Smith I A1 - Muller I U1 - International Cytokine Society AD - Dublin, Ireland Y1 - 2003/// Y2 - 2003/09/20/ N2 - - ER - TY - CONF T1 - Preventing Renal Disease: The NKRF ABLE project A1 - Lightstone L U1 - Ethnicity and Renal Failure: disparity or diversity? AD - British Library Y1 - 2003/// Y2 - 2003/10// PB - SouthWest Thames Renal Research Institute CY - St Helier Hospital, Carshalton, Surrey N2 - - ER - TY - CONF T1 - Bone marrow macrophages from TLR4-deficient mice display an impaired capacity to control the replication of Leishmania major parasites A1 - Kropf P A1 - Freudenberg M A1 - Modolell M A1 - Price H A1 - Herath S A1 - Antoniazi S A1 - Galanos C A1 - Smith S A1 - Muller I U1 - 17th Meeting of the EMDS AD - Leicester, UK Y1 - 2003/// N2 - - ER - TY - CONF T1 - Microfilarial load is directly associated with excess mortality in human onchocerciasis A1 - Little MP A1 - Breitling LP A1 - Basáñez M-G A1 - Boatin B U1 - 52nd (Centenary) Meeting of the American Society of Tropical Medicine and Hygiene AD - Philadelphia, USA Y1 - 2003/// Y2 - 2003/// PB - American Journal of Tropical Medicine and Hygiene SP - 248 EP - 249 N2 - - UR - http://www.astmh.org/ ER - TY - CONF T1 - The effect of different Onchocerca-Simulium combinations on the outcome of ivermectin-based control infections A1 - Basáñez M-G A1 - Kennedy S A1 - Williams JR U1 - 52nd (Centenary) Meeting of the American Society of Tropical Medicine and Hygiene AD - Philadelphia, USA Y1 - 2003/// Y2 - 2003/// PB - The American Journal of Tropical Medicine and Hygiene SP - 275 EP - 276 N2 - - UR - http://www.ajtmh.org/ ER - TY - CONF T1 - The sensitivity of a mathematical model for the transmission dynamics and control of human onchocerciasis to vector-related parameters A1 - Kennedy S A1 - Basáñez M-G A1 - Williams JR U1 - 52nd (Centenary) Meeting of the American Society of Tropical Medicine and Hygiene AD - Philadelphia, USA Y1 - 2003/// Y2 - 2003/// PB - The American Journal of Tropical Medicine and Hygiene SP - 283 N2 - - UR - http://www.ajtmh.org/ ER - TY - CONF T1 - Risk of leukaemia and related malignancies following radiation exposure: estimates for the UK population (Technical Report) A1 - Little MP U1 - Report of an Advisory Group on Ionising Radiation Y1 - 2003/// Y2 - 2003/// PB - Docs NRPB SP - 1 EP - 119 N2 - - ER - TY - CONF T1 - The sensitivity of a mathematical model for the transmission dynamics and control of human onchocerciasis to vector-related parameters A1 - Kennedy S A1 - Basáñez M-G A1 - Williams JR U1 - 52nd (Centenary) Meeting of the American Society of Tropical Medicine and Hygiene AD - Philadelphia, USA Y1 - 2003/// Y2 - 2003/// PB - The American Journal of Tropical Medicine and Hygiene SP - 229 EP - 230 N2 - - UR - http://www.astmh.org/ ER - TY - CONF T1 - Population biology of multiple helminth infections A1 - Bottomley C A1 - Isham V A1 - Basáñez MG U1 - 52nd (Centenary) Meeting of the American Society of Tropical Medicine and Hygiene AD - Philadelphia, USA Y1 - 2003/// Y2 - 2003/// PB - The American Journal of Tropical Medicine and Hygiene SP - 283 N2 - - UR - http://www.astmh.org/ ER - TY - CONF T1 - Density-dependence in filarial worm transmission A1 - Churcher TS A1 - Basáñez M-G A1 - Ferguson NM U1 - 52nd (Centenary) Meeting of the American Society of Tropical Medicine and Hygiene AD - Philadelphia, USA Y1 - 2003/// Y2 - 2003/// PB - The American Journal of Tropical Medicine and Hygiene SP - 91 N2 - - UR - http://www.astmh.org/ ER - TY - CONF T1 - The effect of different Onchocerca-Simulium combinations on the outcome of ivermectin-based control infections A1 - Basáñez M-G A1 - Kennedy S A1 - Williams JR U1 - 52nd (Centenary) Meeting of the American Society of Tropical Medicine and Hygiene AD - Philadelphia, USA Y1 - 2003/// Y2 - 2003/// PB - The American Journal of Tropical Medicine and Hygiene SP - 275 EP - 276 N2 - - UR - http://www.astmh.org/ ER - TY - CONF T1 - 3D ultrasound-based CFD for carotid flow prediction: a reproducibility study A1 - Glor, FP A1 - Ariff, B A1 - Augst, AD A1 - Barratt, DC A1 - Hughes, AD A1 - Thom, SAM A1 - Verdonck, P A1 - Xu, XY U1 - 2nd MIT Conference on Computational Fluid and Solid Mechanics Y1 - 2003/// Y2 - // SP - 1701 EP - 1704 N2 - - ER - TY - CONF T1 - Herd immunity and the design of vaccination programs A1 - Anderson, RM U1 - Workshop on the Consequences of Viral Disease Eradication Y1 - 2002/// Y2 - // SP - 65 EP - 77 N2 - - ER - TY - CONF T1 - TGF-beta and mycobacterial infection A1 - Roe T A1 - Lukey P A1 - Muller I A1 - Young D U1 - 5th International Congress on the Pathogenesis of Mycobacterial infections AD - Stockholm, Sweden Y1 - 2002/// Y2 - 2002/06/27/ N2 - - ER - TY - CONF T1 - Excess risk of kidney disease in a population living near chemical installations A1 - Hodgson, S A1 - Hansell, A A1 - Shepperd, S A1 - Flute, T A1 - Staples, B A1 - Nieuwenhuijsen, MJ A1 - Jarup, L U1 - International Society for Exposure Assessment (ISEA)/ISEE conference AD - Vancouver, Canada Y1 - 2002/// Y2 - 2002/08// VL - 13(4) PB - Epidemiology SP - S181 N2 - - ER - TY - CONF T1 - Parents occupationally exposed to radiation prior to the conception of their children. A review of the evidence concerning the incidence of cancer in their children (Technical Report) A1 - Little MP U1 - Committee on Medical Aspects of Radiation in the Environment (COMARE) AD - Chilton Y1 - 2002/// Y2 - 2002/// PB - NRPB N2 - - ER - TY - CONF T1 - Preparing for environmental health emergencies: The role of GIS A1 - Briggs, D A1 - Beale, L U1 - NATO Advanced Research Workshop on GIS for Emergency Preparedness and Health Risk Reduction Y1 - 2002/// Y2 - // VL - 11 SP - 3 EP - 34 N2 - - ER - TY - CONF T1 - Cross-talk between CD8* and cells in experimental cutaneous leishmaniasis A1 - Herath S A1 - Kropf P A1 - Muller I U1 - Immunoparasitology Meeting AD - Woods Hole, MA, USA Y1 - 2002/// Y2 - 2002/04/26/ N2 - - ER - TY - CONF T1 - Geographical distribution of cardiovascular mortality in Comunidad Valenciana (Spain) A1 - Ferrandiz, J A1 - Abellan, JJ A1 - Lopez, A A1 - Sanmartin, P A1 - Vanaclocha, H A1 - Zurriaga, O A1 - Martinez-Beneito, MA A1 - Melchor, I A1 - Calabuig, J U1 - NATO Advanced Research Workshop on GIS for Emergency Preparedness and Health Risk Reduction Y1 - 2002/// Y2 - // VL - 11 SP - 267 EP - 282 N2 - - ER - TY - CONF T1 - Ageing alters the course of nonhealing Leishmania major infections in IL-4 deficient BALB/c mice A1 - Muller I A1 - Herath S A1 - Kropf P U1 - Immunoparasitology Meeting AD - Woods Hole, MA, USA Y1 - 2002/// Y2 - 2002/04/26/ N2 - - ER - TY - CONF T1 - Use of Bayesian statistics in parasitological surveys A1 - Basáñez M-G A1 - Marshall C A1 - Carabin H A1 - Escalona M A1 - Vivas-Martínez S A1 - Joseph L A1 - Gyorkos T U1 - 51st Annual Meeting of the American Society of Tropical Medicine and Hygiene AD - Denver, USA Y1 - 2002/// Y2 - 2002/// PB - American Journal of Tropical Medicine and Hygiene SP - 226 N2 - - UR - http://www.astmh.org/ ER - TY - CONF T1 - Signalling through the T1/ST2 molecule is not necessary for Th2 differentiation, but is important for the regulation of type 1 responses in nonhealing Lesmania major infection A1 - Kropf P A1 - Herath S A1 - Klemenz R A1 - Muller I U1 - British Society for Parasitology, Trypanosomiasis and Leishmaniasis seminar AD - Edinburgh, UK Y1 - 2002/// Y2 - 2002/09/08/ N2 - - ER - TY - CONF T1 - The effects of immunotherapy with cytokines and/or vaccines in HAART treated patients A1 - Gotch, F A1 - Hardy, G A1 - Imami, N A1 - Sullivan, A A1 - Nelson, M A1 - Burton, C A1 - Pido-Lopez, J A1 - Pires, A A1 - Moss, R U1 - 14th International AIDS Conference Y1 - 2002/// Y2 - // SP - 279 EP - 284 N2 - - ER - TY - CONF T1 - Organ-specific distribution and cytokine production of CD4* T 1/ST2+ T cells in Leishmania major infected mice A1 - Kropf P A1 - Herath S A1 - Bickle Q A1 - Tewari R A1 - Syed N A1 - Klemenz R A1 - Muller I U1 - Immunoparasitology Meeting AD - Woods Hole, MA, USA Y1 - 2002/// Y2 - 2002/04/26/ N2 - - ER - TY - CONF T1 - Measuring what we do - HoNOSCA: a measure for clinicians to rate symptoms and functional impairments in child and adolescent psychiatry patients A1 - Garralda ME U1 - 4th Conference on psychiatric research in the North Y1 - 2002/// Y2 - 2002/// N2 - - ER - TY - CONF T1 - Use of ultrasound contrast agents in hepatology A1 - Lim, AKP A1 - Harvey, CJ A1 - Taylor-Robinson, SD A1 - Blomley, MJK A1 - Cosgrove, DO U1 - Falk Symposium on Medical Imaging in Gastroenterology and Hepatology Y1 - 2002/// Y2 - // VL - 124 SP - 132 EP - 139 N2 - - ER - TY - CONF T1 - The use of transmission dynamics models of infectious diseases to improve HIV prevention trials and public health decisions A1 - Desai K A1 - Boily MC A1 - Williams JR A1 - Garnett G A1 - Masse BR U1 - International Society for Clinical Biostatisitics/Society for Clinical Trials AD - London Y1 - 2001/// Y2 - 2001/06// PB - Elsevier Science Inc. CY - New York N2 - - ER - TY - CONF T1 - A method of vessel tracking for vessel diameter measurement on retinal images A1 - Gao, XH A1 - Bharath, A A1 - Stanton, A A1 - Hughes, A A1 - Chapman, N A1 - Thom, S U1 - International Conference on Image Processing (ICIP 2001) Y1 - 2001/// Y2 - // SP - 881 EP - 884 N2 - - ER - TY - CONF T1 - Anticipating the future: models and modelling of resistance spread A1 - Anderson, RM U1 - Symposium on Antimicrobial Resistance Y1 - 2001/// Y2 - // VL - 247 SP - 103 EP - 110 N2 - - ER - TY - CONF T1 - The application of mathematical models in infectious disease research A1 - Anderson, RM U1 - Colloquium on Automation in Threat Reduction and Infectious Disease Research Y1 - 2001/// Y2 - // SP - 31 EP - 46 N2 - - ER - TY - CONF T1 - The transmission dynamics of scrapie: Analyses using mathematical models A1 - Hagenaars, TJ A1 - Ferguson, NM A1 - Donnelly, CA A1 - Anderson, RM U1 - Meeting of the Society-for-Veterinary-Epidemiology-and-Preventive-Medicine Y1 - 2001/// Y2 - // SP - 211 EP - 218 N2 - - ER - TY - CONF T1 - Co-convenor Joint meeting of RSTMH/Wellcome Trust/UK MRC/DFID A1 - Moore DA U1 - Working in the tropics - how to do it Y1 - 2000/// Y2 - 2000/05/09/ N2 - - ER - TY - CONF T1 - Risk of second cancer in therapeutically irradiated populations. Comparison with cancer risks in the Japanese atomic bomb survivors and in other exposed groups (Technical Report) A1 - Little MP U1 - Report of an Advisory Group on Ionising Radiation Y1 - 2000/// Y2 - 2000/// PB - Docs NRPB SP - 1 EP - 105 N2 - - ER - TY - CONF T1 - End stage heart failure - options for medical treatment and beyond A1 - Poole-Wilson, PA U1 - Workshop on Surgical Remodeling in Heart Failure - Alternative to Transplantation Y1 - 2000/// Y2 - // SP - 19 EP - 30 N2 - - ER - TY - CONF T1 - The convergence technique in numerical solutions of coupled fluid-wall problems A1 - Zhao, SZ A1 - Xu, XY A1 - Collins, MW A1 - Stanton, AV A1 - Hughes, AD A1 - Thom, SA U1 - Conference on Cardiovascular Flow Modelling and Measurement with Application to Clinical Medicine Y1 - 1999/// Y2 - // VL - 70 SP - 125 EP - 134 N2 - - ER - TY - CONF T1 - Towards retinal vessel paramaterisation A1 - Xiaohong,G.X. A1 - Bharath,A.A. A1 - Hughes,A.D. A1 - Stanton,A.V. A1 - Chapman,N. A1 - Thom,S.A. U1 - SPIE Conference on Medical Imaging Y1 - 1997/// N2 - - ER - TY - CONF T1 - Hormone replacement therapy in diabetes A1 - Stevenson, JC A1 - Godsland, IF U1 - 8th International Congress on the Menopause Y1 - 1997/// Y2 - // SP - 315 EP - 322 N2 - - ER - TY - JFULL T1 - Replicative Competence of the T131I, K141E, and G145R Surface Variants of Hepatitis B Virus. A1 - Jammeh, S A1 - Thomas, HC A1 - Karayiannis, P J1 - J Infect Dis Y1 - 2007/10/01/ VL - 196 SN - 0022-1899 SP - 1010 EP - 1013 N2 - Variants of hepatitis B surface antigen have been described in different clinical settings, but their replicative capacity in vitro has remained unexplored. Point mutations leading to sT131I, sK141E, and sG145R amino-acid substitutions were engineered by site-directed mutagenesis into an infectious plasmid clone of the virus. The mutated constructs were transfected into Huh7 cells, and their replication capacity was documented by LightCycler (Roche Diagnostics) measurements of virion-associated hepatitis B virus (HBV) DNA, intracellular relaxed circular double-stranded DNA, and pregenomic RNA. The sT131I and sG145R variants replicated with efficiency equal to that of the wild type, whereas the sK141E variant was replication impaired. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17763322&query_hl=1 ER - TY - JFULL T1 - Eroding the resistance of Duffy negativity to invasion by Plasmodium vivax? A1 - Pasvol, G J1 - Trans R Soc Trop Med Hyg Y1 - 2007/10// VL - 101 SN - 0035-9203 SP - 953 EP - 954 N2 - Individuals possessing red cells negative for the Duffy blood group antigen are said to possess absolute resistance to infection by the malarial parasite Plasmodium vivax. Now in this issue of Transactions, initial evidence is presented from the Brazilian Amazon to suggest that P. vivax is being transmitted amongst Duffy-negative individuals. This supports data from East Africa where the same phenomenon has been observed. Thus the emerging picture is that P. vivax in both South America and in Africa is now evolving pathways other than Duffy to enter red cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17658565&query_hl=1 ER - TY - JFULL T1 - Control of a highly pathogenic H5N1 avian influenza outbreak in the GB poultry flock. A1 - Truscott, J A1 - Garske, T A1 - Chis-Ster, I A1 - Guitian, J A1 - Pfeiffer, D A1 - Snow, L A1 - Wilesmith, J A1 - Ferguson, NM A1 - Ghani, AC J1 - Proc Biol Sci Y1 - 2007/09/22/ VL - 274 SN - 0962-8452 SP - 2287 EP - 2295 N2 - The identification of H5N1 in domestic poultry in Europe has increased the risk of infection reaching most industrialized poultry populations. Here, using detailed data on the poultry population in Great Britain (GB), we show that currently planned interventions based on movement restrictions can be expected to control the majority of outbreaks. The probability that controls fail to keep an outbreak small only rises to significant levels if most transmission occurs via mechanisms which are both untraceable and largely independent of the local density of premises. We show that a predictor of the need to intensify control efforts in GB is whether an outbreak exceeds 20 infected premises. In such a scenario neither localized reactive vaccination nor localized culling are likely to have a substantial impact. The most effective of these contingent interventions are large radius (10km) localized culling and national vaccination. However, the modest impact of these approaches must be balanced against their substantial inconvenience and cost. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17644506&query_hl=1 ER - TY - JFULL T1 - Control of neglected tropical diseases. A1 - Hotez, PJ A1 - Molyneux, DH A1 - Fenwick, A A1 - Kumaresan, J A1 - Sachs, SE A1 - Sachs, JD A1 - Savioli, L J1 - N Engl J Med Y1 - 2007/09/06/ VL - 357 SN - 1533-4406 SP - 1018 EP - 1027 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17804846&query_hl=1 ER - TY - JFULL T1 - Functional constraint and small insertions and deletions in the ENCODE regions of the human genome. A1 - Clark, TG A1 - Andrew, T A1 - Cooper, GM A1 - Marguiles, EH A1 - Mullikin, JC A1 - Balding, DJ J1 - Genome Biol Y1 - 2007/09/04/ VL - 8 SN - 1465-6914 SP - R180 EP - R180 N2 - ABSTRACT: BACKGROUND: We describe the distribution of indels in the 44 ENCODE regions (~1% of the human genome) to evaluate the potential contribution of small insertion and deletion polymorphisms (indels) to human genetic variation [1]. We relate indels to known genomic annotation features and measures of evolutionary constraint. RESULTS: Indel rates are observed to be reduced approximately twenty-fold in exonic regions, five-fold in sequence that exhibits high evolutionary constraint in mammals and up to two-fold in some classes of regulatory elements (e.g. Formaldehyde Assisted Isolation of Regulatory Elements or FAIRE and hypersensitive sites). In addition, some non-coding transcription (start sites and 3UTR) and other chromatin-mediated regulatory sites also appear to have reduced indel rates. Overall indel rates for these data are estimated to be smaller than single nucleotide polymorphism (SNP) rates by a factor of approximately two, with both rates measured as base pairs (bp) per 100kb to facilitate comparison. CONCLUSION: Indel rates show a broadly similar distribution across genomic features compared to SNP density rates, with a reduction in rates in coding transcription and evolutionary constrained sequence. However, unlike indels, SNP rates do not appear to be reduced in some non-coding functional sequences such as pseudo-exons, FAIRE and hypersensitive sites. We conclude that indel rates are greatly reduced in transcribed and evolutionary constrained DNA and discuss why indel (but not SNP) rates appear to be constrained at some regulatory sites. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17784950&query_hl=1 ER - TY - JFULL T1 - Change in Salt Intake Affects Blood Pressure of Chimpanzees. Implications for Human Populations. A1 - Elliott, P A1 - Walker, LL A1 - Little, MP A1 - Blair-West, JR A1 - Shade, RE A1 - Lee, DR A1 - Rouquet, P A1 - Leroy, E A1 - Jeunemaitre, X A1 - Ardaillou, R A1 - Paillard, F A1 - Meneton, P A1 - Denton, DA J1 - Circulation Y1 - 2007/09/04/ SN - 1524-4539 N2 - BACKGROUND: -Addition of up to 15.0 g/d salt to the diet of chimpanzees caused large rises in blood pressure, which reversed when the added salt was removed. Effects of more modest alterations to sodium intakes in chimpanzees, akin to current efforts to lower sodium intakes in the human population, are unknown. Methods and Results-Sodium intakes were altered among 17 chimpanzees in Franceville, Gabon, and 110 chimpanzees in Bastrop, Tex. In Gabon, chimpanzees had a biscuit diet of constant nutrient composition except that the sodium content was changed episodically over 3 years from 75 to 35 to 120 mmol/d. In Bastrop, animals were divided into 2 groups; 1 group continued on the standard diet of 250 mmol/d sodium for 2 years, and sodium intake was halved for the other group. Lower sodium intake was associated with lower systolic, diastolic, and mean arterial blood pressures in Gabon (2-tailed P<0.001, unadjusted and adjusted for age, sex, and baseline weight) and Bastrop (P<0.01, unadjusted; P=0.08 to 0.10, adjusted), with no threshold down to 35 mmol/d sodium. For systolic pressure, estimates were -12.7 mm Hg (95% confidence interval, -16.9 to -8.5, adjusted) per 100 mmol/d lower sodium in Gabon and -10.9 mm Hg (95% confidence interval, -18.9 to -2.9, unadjusted) and -5.7 mm Hg (95% confidence interval, -12.2 to 0.7, adjusted) for sodium intake lower by 122 mmol/d in Bastrop. Baseline systolic pressures higher by 10 mm Hg were associated with larger falls in systolic pressure by 4.3/2.9 mm Hg in Gabon/Bastrop per 100 mmol/d lower sodium. Conclusions-These findings from an essentially single-variable experiment in the species closest to Homo sapiens with high intakes of calcium and potassium support intensified public health efforts to lower sodium intake in the human population. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17785625&query_hl=1 ER - TY - JFULL T1 - Parasitological impact of two-year preventive chemotherapy on schistosomiasis and soil-transmitted helminthiasis in Uganda A1 - Zhang, Y A1 - Koukounari, A A1 - Kabateriene, N A1 - Flemming, F A1 - Kazibwe, F A1 - Tukahebwa, E A1 - Stothard, J.R. A1 - Webster, J.P. A1 - Fenwick, A J1 - BMC Medicine Y1 - 2007/09/03/ VL - 5 ER - TY - JFULL T1 - Src family tyrosine kinases mediate contraction of rat isolated tail arteries in response to a hyposmotic stimulus. A1 - Wijetunge, S A1 - Hughes, AD J1 - J Hypertens Y1 - 2007/09// VL - 25 SN - 0263-6352 SP - 1871 EP - 1878 N2 - OBJECTIVE: Hypotonic solutions cause vasoconstriction in rat tail arteries, due largely to activation of L-type calcium channels (CaV1.2). We studied possible roles of tyrosine kinases, particularly src family kinases (SFK) and extracellular signal-related kinases (ERK1/2), in this response. METHODS: Rat tail arteries were mounted on a myograph for measurement of isometric force. Arteries were bathed in isosmotic physiological saline solution (300 mOsm/l) containing 50 mmol/l mannitol and were stimulated by a hyposmotic solution containing 0 mmol/l mannitol (PSS-M). Activation of tyrosine kinases and ERK1/2 by hyposmotic solution was examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blotting on rat tail artery lysates with specific phospho-antibodies. RESULTS: Western blotting showed SFK src and yes present in rat tail artery. PSS-M increased tyrosine phosphorylation of several proteins, including SFK and ERK1/2. Genistein blocked phosphorylation of SFK and ERK1/2 by PSS-M. In isolated arteries PSS-M caused a contraction inhibited by the tyrosine kinase inhibitor, genistein, and three structurally different selective SFK inhibitors, herbimycin-A, PP1 and SU6656. Mitogen-activated protein kinase kinase inhibitor PD98059 or selective inhibitors of platelet-derived growth factor receptor (AG1296) and epidermal growth factor receptor (AG1478) had no effect on contraction induced by a hypotonic solution. CONCLUSIONS: Hyposmotic conditions activate SFK, src and yes, and contract rat tail artery by a SFK-dependent mechanism. ERK1/2 are activated by the hypotonic solution, but do not play a role in the contractile response. SFK modulation of CaV1.2 may be an important mechanism mediating vasoconstriction to mechanical stimuli in vascular smooth muscle. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17762651&query_hl=1 ER - TY - JFULL T1 - Does vitamin D supplementation in infancy reduce the risk of pre-eclampsia? A1 - Hyppönen, E A1 - Hartikainen, AL A1 - Sovio, U A1 - Järvelin, MR A1 - Pouta, A J1 - Eur J Clin Nutr Y1 - 2007/09// VL - 61 SN - 0954-3007 SP - 1136 EP - 1139 N2 - Vitamin D has been suggested to affect the balance between T helper (Th1) and (Th2) type cytokines by favouring Th2 domination. We investigated the association between infant vitamin D supplementation and later pre-eclampsia, a disorder suggested to be dominated by Th1 response. We used data on 2969 women born in the Northern Finland Birth Cohort 1966 of whom 68 (2.3%) had pre-eclampsia in their first pregnancy. Risk of pre-eclampsia was halved (OR 0.49, 95% confidence interval (CI) 0.26-0.92) in participants who had received vitamin D supplementation regularly during the first year of life and this association was not affected by adjustment for own birth order, birth weight, gestational age, social class in 1966 and hospitalizations or pregnancy-induced hypertension of their mothers. Together with earlier observations on a reduced risk of type 1 diabetes after vitamin D supplementation, these data suggest that vitamin D intake in infancy may affect long-term programming of the immune response pattern.European Journal of Clinical Nutrition (2007) 61, 1136-1139; doi:10.1038/sj.ejcn.1602625; published online 31 January 2007. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17268418&query_hl=1 ER - TY - JFULL T1 - Effect of host lactate on gonococci and meningococci: new concepts on the role of metabolites in pathogenicity. A1 - Smith, H A1 - Tang, CM A1 - Exley, RM J1 - Infect Immun Y1 - 2007/09// VL - 75 SN - 0019-9567 SP - 4190 EP - 4198 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17562766&query_hl=1 ER - TY - JFULL T1 - Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET. A1 - Metra, M A1 - Torp-Pedersen, C A1 - Cleland, JG A1 - Di Lenarda, A A1 - Komajda, M A1 - Remme, WJ A1 - Dei Cas, L A1 - Spark, P A1 - Swedberg, K A1 - Poole-Wilson, PA A1 - for the COMET investigators J1 - Eur J Heart Fail Y1 - 2007/09// VL - 9 SN - 1388-9842 SP - 901 EP - 909 N2 - BACKGROUND: It is unclear whether beta-blocker therapy should be reduced or withdrawn in patients who develop acute decompensated heart failure (HF). We studied the relationship between changes in beta-blocker dose and outcome in patients surviving a HF hospitalisation in COMET. METHODS: Patients hospitalised for HF were subdivided on the basis of the beta-blocker dose administered at the visit following hospitalisation, compared to that administered before. RESULTS: In COMET, 752/3029 patients (25%, 361 carvedilol and 391 metoprolol) had a non-fatal HF hospitalisation while on study treatment. Of these, 61 patients (8%) had beta-blocker treatment withdrawn, 162 (22%) had a dose reduction and 529 (70%) were maintained on the same dose. One-and two-year cumulative mortality rates were 28.7% and 44.6% for patients withdrawn from study medication, 37.4% and 51.4% for those with a reduced dosage (n.s.) and 19.1% and 32.5% for those maintained on the same dose (HR,1.59; 95%CI, 1.28-1.98; p<0.001, compared to the others). The result remained significant in a multivariable model: (HR, 1.30; 95%CI, 1.02-1.66; p=0.0318). No interaction with the beneficial effects of carvedilol, compared to metoprolol, on outcome was observed (p=0.8436). CONCLUSIONS: HF hospitalisations are associated with a high subsequent mortality. The risk of death is higher in patients who discontinue beta-blocker therapy or have their dose reduced. The increase in mortality is only partially explained by the worse prognostic profile of these patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17581778&query_hl=1 ER - TY - JFULL T1 - ADHD and comorbid disorders in relation to family environment and symptom severity. A1 - Hurtig, T A1 - Ebeling, H A1 - Taanila, A A1 - Miettunen, J A1 - Smalley, S A1 - McGough, J A1 - Loo, S A1 - Järvelin, MR A1 - Moilanen, I J1 - Eur Child Adolesc Psychiatry Y1 - 2007/09// VL - 16 SN - 1018-8827 SP - 362 EP - 369 N2 - BACKGROUND: To examine the comorbidity of ADHD in association with family environment and the severity of ADHD. METHOD: A screening for ADHD symptoms was conducted among adolescents in the Northern Finland 1986 Birth Cohort (N = 6622). A sample of those adolescents (n = 457), aged 16-18 years, with and without ADHD symptoms was assessed with a diagnostic interview (Kiddie-SADS-PL) and ADHD and comorbid disorders were studied in association with the family characteristics and the number of ADHD symptoms. RESULTS: Adolescents with ADHD had more commonly conduct disorder (P < 0.001), oppositional defiant disorder (P < 0.001), substance abuse (P < 0.001) and mild depression (P < 0.001) than adolescents without ADHD. Adolescents with ADHD and comorbid disorders had more ADHD symptoms (P < 0.001) than those with ADHD alone. Compared to adolescents with ADHD alone those with ADHD and comorbidity lived significantly more commonly in non-intact families, in low-income families, with mothers who were dissatisfied with life and with parents who showed little interest in their adolescents' activities. CONCLUSIONS: Adolescents who develop externalizing disorders comorbid to ADHD seem to suffer from a severe form of ADHD and live in family environments that may not provide sufficient support for optimal development of an adolescent with ADHD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17401612&query_hl=1 ER - TY - JFULL T1 - Why do patients decline to take part in a research project involving pulmonary rehabilitation? A1 - Taylor, R A1 - Dawson, S A1 - Roberts, N A1 - Sridhar, M A1 - Partridge, MR J1 - Respir Med Y1 - 2007/09// VL - 101 SN - 0954-6111 SP - 1942 EP - 1946 N2 - BACKGROUND: It is important that those taking part in research trials are as representative as possible of those with the disease being studied. In a study of those with chronic obstructive pulmonary disease involving pulmonary rehabilitation, 120 of 297 suitable patients responded that they did not wish to take part in the trial. We were keen to know why these patients declined to take part in the study. METHODS: A total of 120 patients who had responded that they did not wish to take part in the main trial were approached to ask if they would be willing to undertake a semi-structured face-to-face interview in their own home or by telephone. Those who were willing (n=39) underwent tape-recorded interviews and data analysis was performed using the framework method. RESULTS: This was a qualitative study which revealed that several themes influenced patients' willingness or otherwise to take part in a research project involving pulmonary rehabilitation. Travelling to the hospital and location of the rehabilitation, along with competing commitments, and a variable perception of the benefits to the patient were clearly major factors and some had previous negative experiences of either the hospital, healthcare or research. While there was an element of negativity or impaired understanding regarding the research itself, the other factors appeared to be of greater importance. CONCLUSION: Recruitment to pulmonary rehabilitation courses or recruitment to research involving pulmonary rehabilitation may be more successful if the location of the rehabilitation can be made as near to the patient's home as possible, and if the patient is given as much information as possible about what is involved. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17540553&query_hl=1 ER - TY - JFULL T1 - Sexual Dimorphism in Superantigen Shock Involves Elevated TNF-{alpha} and TNF-{alpha} induced Hepatic Apoptosis. A1 - Faulkner, L A1 - Altmann, DM A1 - Ellmerich, S A1 - Huhtaniemi, I A1 - Stamp, G A1 - Sriskandan, S J1 - Am J Respir Crit Care Med Y1 - 2007/09/01/ VL - 176 SN - 1073-449X SP - 473 EP - 482 N2 - Rationale: There is conflicting evidence regarding sex differences in the outcome from severe sepsis and toxic shock. Superantigen-mediated toxic shock affects a higher proportion of female patients. Objectives: The objective of the current study was to investigate sexual dimorphism in superantigen-associated sepsis and in superantigen-mediated shock and to identify the key mechanisms responsible for this sex difference. Methods: We measured mortality and serum cytokines after induction of sepsis with isogenic superantigen-positive and superantigen-negative Streptococcus pyogenes in HLA class II transgenics. During superantigen-mediated toxic shock, we measured mortality, T-cell responses, systemic tumor necrosis factor (TNF)-alpha and TNF receptors, TNF-alpha-induced hepatocyte apoptosis, and conditioning of these responses by tamoxifen treatment. Measurements and Main Results: In both superantigen-associated sepsis and in superantigen-mediated shock, serum TNF-alpha was increased in females compared with males. This was not attributable to a detectable difference in splenic TNF-alpha transcription; rather, serum soluble TNF receptors were higher in males. Pretreatment of females with the estrogen receptor modulator tamoxifen increased serum soluble TNF receptors, reduced the early serum TNF-alpha response, and improved mortality in females challenged with staphylococcal enterotoxin B. Lethal superantigen shock was characterized by hepatocyte apoptosis, and was reproduced by injection of TNF-alpha. Females had enhanced susceptibility to TNF-alpha-mediated lethality. TNF-alpha-induced hepatocyte apoptosis was greater in females, and was reduced by tamoxifen pretreatment. Conclusions: Sexual dimorphism in experimental superantigen toxic shock results from increased systemic TNF-alpha in females, coupled with an increased susceptibility to TNF-alpha-induced hepatocyte apoptosis. Both processes are abrogated by estrogen receptor modulators. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17575097&query_hl=1 ER - TY - JFULL T1 - Synergistic inhibition of HIV-1 infection by combinations of soluble polyanions with other potential microbicides. A1 - Gantlett, KE A1 - Weber, JN A1 - Sattentau, QJ J1 - Antiviral Res Y1 - 2007/09// VL - 75 SN - 0166-3542 SP - 188 EP - 197 N2 - Several polyanionic compounds with potential for use as topically applied microbicides to prevent HIV-1 sexual transmission, such as PRO 2000, are currently in phase III clinical efficacy trials. Microbicidal formulations may well comprise combinations of inhibitors to increase potency, reduce dose and minimize problems of HIV-1 resistance. We have therefore evaluated in vitro, the anti-HIV-1 activity of two leading polyanionic microbicides combined with other antiretroviral agents with microbicidal potential. Dextran sulfate (DS) and PRO 2000 were combined with the neutralizing antibody IgG1b12, the peptide-based fusion inhibitor T20, the CCR5 antagonist TAK779 and the cyanobacterial protein cyanovirin-N. Anti-HIV-1 activity was assessed in a single cycle replication assay using pseudoviruses carrying a luciferase reporter gene and the envelope glycoproteins from HIV-1 isolates JR-FL (R5) and HxB2 (X4), against both immortalized and primary CD4+ cell targets. The data were analyzed for synergy using Calcusyntrade mark software. Results indicate that PRO 2000 and DS can act synergistically with most inhibitors tested, although the degree of synergy depends on inhibitor concentration and combination. These data provide a rational basis for testing of microbicide combinations in vivo. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17408760&query_hl=1 ER - TY - JFULL T1 - Schistosoma haematobium infection and morbidity before and after large-scale administration of praziquantel in Burkina Faso. A1 - Koukounari, A A1 - Gabrielli, AF A1 - Toure, S A1 - Bosque-Oliva, E A1 - Zhang, Y A1 - Sellin, B A1 - Donnelly, CA A1 - Fenwick, A A1 - Webster, JP J1 - J Infect Dis Y1 - 2007/09/01/ VL - 196 SN - 0022-1899 SP - 659 EP - 669 N2 - BACKGROUND: In sub-Saharan Africa, 112 million people are infected with Schistosoma haematobium, with the most intense infections in children 5-15 years old. METHODS: We describe a longitudinal epidemiological study that evaluates the relationship between S. haematobium infection and associated morbidity in children before and after the large-scale administration of praziquantel for schistosomiasis and albendazole for soil-transmitted helminths. RESULTS: At baseline, higher intensities of S. haematobium infection were observed in children with anemia and/or severe microhematuria, but there was no apparent association between the risk of undernutrition and intensity of S. haematobium infection. Significant reductions in the prevalence and intensity of S. haematobium infection 1 year after treatment were, however, observed. Children who benefited the most from anthelmintic treatment in terms of increased hemoglobin concentrations were those who had anemia at baseline and those with highly positive microhematuria scores at baseline. CONCLUSIONS: This study suggests that even a single round of mass chemotherapy can have a substantial impact on S. haematobium infection and its associated morbidity in children. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17674306&query_hl=1 ER - TY - JFULL T1 - Ethnicity and quality of diabetes care in a health system with universal coverage: population-based cross-sectional survey in primary care. A1 - Gray, J A1 - Millett, C A1 - Saxena, S A1 - Netuveli, G A1 - Khunti, K A1 - Majeed, A J1 - J Gen Intern Med Y1 - 2007/09// VL - 22 SN - 1525-1497 SP - 1317 EP - 1320 N2 - BACKGROUND: The UK has a universal health care system that is free at the point of access. Over the past decade, the UK government has implemented an ambitious agenda of quality improvement initiatives in chronic disease management. OBJECTIVE: To assess the quality of diabetes care and intermediate clinical outcomes within a multiethnic population after a sustained period of investment in quality improvement. DESIGN: Population based cross-sectional survey, using electronic general practice records, carried out between November 2005 and January 2006. PATIENTS: Seven thousand six hundred five adults (>or=18 years) with diabetes registered with 32 primary care practices. MEASUREMENTS: Percentage achievement by ethnic group (black, south Asian, or white) of the quality indicators for diabetes in a new pay-for performance contract. RESULTS: There were only modest variations in recording of process measures of care between ethnic groups, with no significant differences in recent measurement of blood pressure, HbA1c, cholesterol, micro-albuminuria, creatinine, or retinopathy screening attendance. Blacks and south Asians were significantly less likely to meet all three national treatment targets for diabetes (HbA1c /= 20 years old, self-reported as US White, US Black, Mexican American, English White, English Black, Bangladeshi, Pakistani, Indian or Chinese the presence of diabetes, defined as self-report of doctor diagnosis or glycated haemoglobin (HbA(1c)) > 6.1%, was ascertained. Comparisons of proportions were made using chi(2)-tests. Receiver operating characteristic (ROC) curves were calculated for BMI, WC and WHR predicting diabetes. Results Other ethnic groups had a higher prevalence of diagnosed diabetes than English Whites. The crude prevalence of diabetes in English Whites of normal weight (BMI < 25 kg/m(2)) was 3.4%. Higher prevalences were seen in other ethnic groups (5.0-10.9%). Based on ROC curves, both WC and WHR had better discriminating ability for diabetes than BMI for both genders and some ethnic groups. Conclusions Ethnic differences exist in the crude prevalence of diabetes, even in those characterized as normal weight by BMI. Thus, clinicians need to exercise caution in interpreting diabetes risk associated with a normal BMI. The use of other anthropometric measures, such as WC or WHR, may improve risk determination across different ethnic groups. More research is needed to determine the thresholds for different anthropometric measures that improve diabetes risk determination. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17725630&query_hl=1 ER - TY - JFULL T1 - Positive replication and linkage disequilibrium mapping of the chromosome 21q22.1 malaria susceptibility locus. A1 - Khor, CC A1 - Vannberg, FO A1 - Chapman, SJ A1 - Walley, A A1 - Aucan, C A1 - Loke, H A1 - White, NJ A1 - Peto, T A1 - Khor, LK A1 - Kwiatkowski, D A1 - Day, N A1 - Scott, A A1 - Berkley, JA A1 - Marsh, K A1 - Peshu, N A1 - Maitland, K A1 - Williams, TN A1 - Hill, AV J1 - Genes Immun Y1 - 2007/08/16/ SN - 1466-4879 N2 - Four cytokine receptor genes are located on Chr21q22.11, encoding the alpha and beta subunits of the interferon-alpha receptor (IFNAR1 and IFNAR2), the beta subunit of the interleukin 10 receptor (IL10RB) and the second subunit of the interferon-gamma receptor (IFNGR2). We previously reported that two variants in IFNAR1 were associated with susceptibility to malaria in Gambians. We now present an extensive fine-scale mapping of the associated region utilizing 45 additional genetic markers obtained from public databases and by sequencing a 44 kb region in and around the IFNAR1 gene in 24 Gambian children (12 cases/12 controls). Within the IFNAR1 gene, a newly studied C --> G single-nucleotide polymorphism (IFNAR1 272354c-g) at position -576 relative to the transcription start was found to be more strongly associated with susceptibility to severe malaria. Association was observed in three populations: in Gambian (P=0.002), Kenyan (P=0.022) and Vietnamese (P=0.005) case-control studies. When all three studies were combined, using the Mantel-Haenszel test, the presence of IFNAR1 -576G was associated with a substantially elevated risk of severe malaria (N=2444, OR=1.38, 95% CI: 1.17-1.64; P=1.7 x 10(-4)). This study builds on previous work to further highlight the importance of the type-I interferon pathway in malaria susceptibility and illustrates the utility of typing SNPs within regions of high linkage disequilibrium in multiple populations to confirm initial positive associations.Genes and Immunity advance online publication, 16 August 2007; doi:10.1038/sj.gene.6364417. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17703179&query_hl=1 ER - TY - JFULL T1 - Geographic and demographic clustering of gonorrhoea in London. A1 - Risley, C A1 - Ward, H A1 - Choudhury, B A1 - Bishop, C A1 - Fenton, K A1 - Spratt, B A1 - Ison, CA A1 - Ghani, A J1 - Sex Transm Infect Y1 - 2007/08/16/ SN - 1368-4973 N2 - BACKGROUND: Gonorrhoea is an important cause of sexual ill-health and is concentrated in geographic areas and demographic groups. This study explores the distribution of gonorrhoea across London. METHODS: Epidemiological data on all gonorrhoea cases were collected from 13 major genitourinary clinics in London between 1st June and 30th November 2004. Samples were stored centrally and typed using NG-MAST. The postcode of each case's main residence was used to calculate incidence of gonorrhoea by borough using data from the UK 2001 census and a population survey on residence of men who have sex with men (MSM). RESULTS: In total 2891 cases were confirmed, 1822 of which had postcode data, resided in London and had their strain successfully typed. There was a very high incidence of gonorrhoea in MSM (1834 per 100,000 population) and heterosexuals of black ethnicity (392 per 100,000). The incidence amongst heterosexuals was highest in: City of London (390 per 100,000, 95% CI 213-566), Southwark (308 per 100,000, 95% CI 280-336), Hackney (284 per 100,000, 95% CI 254-313) and Lambeth (216 per 100,000, 95% CI 194-239) and was not associated with measures of social deprivation (correlation coefficient=0.0008, p=0.97) but was strongly associated with black ethnicity (correlation coefficient=0.48, p=0.01). Forty-five percent of cases had one of the 21 major strains; eight of these strains were significantly clustered geographically and persisted for a shorter duration than those that were not clustered. Patients travelled a mean of 7.7 km from their home to the clinic. CONCLUSIONS: High gonorrhoea incidence in London is observed in MSM and heterosexuals of black ethnicity. Endemic strains in both MSM and heterosexuals are diagnosed at multiple clinics. Interventions, including partner notification, must therefore operate between clinics. UR - http://tinyurl.com/ysvgw2 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17702771&query_hl=1 ER - TY - JFULL T1 - Is air travel safe for those with lung disease? A1 - Coker, RK A1 - Shiner, RJ A1 - Partridge, MR J1 - Eur Respir J Y1 - 2007/08/09/ SN - 0903-1936 N2 - Airlines commonly report respiratory in-flight emergencies; flight outcomes have not been examined prospectively in large numbers of respiratory patients. We conducted a prospective observational study of flight outcomes in this group.UK respiratory specialists were invited to recruit patients planning air travel. Centres undertook their usual pre-flight assessment. Within two weeks of return, patients completed a questionnaire documenting symptoms, in-flight oxygen use, and unscheduled healthcare use.Six hundred and sixteen patients were recruited; 500 (81%) returned questionnaires. The commonest diagnoses were airway (54%) and diffuse parenchymal lung disease (23%). Twelve patients died, seven before flying and five within one month. Pre-flight assessment included oximetry (96%), spirometry (95%), hypoxic challenge (45%) and walk test (10%). Eleven percent did not fly. In those who flew, unscheduled respiratory healthcare use rose from 9% in the four weeks beforehand to 19% in the four weeks after travel. However, when compared with self-reported data during the preceding year, medical consultations rose by just 2%.In patients flying after careful respiratory specialist assessment, commercial air travel appears generally safe. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17690127&query_hl=1 ER - TY - JFULL T1 - Trends in hospital admissions, in-hospital case fatality and population mortality from congenital heart disease in England, 1994 to 2004. A1 - Billett, J A1 - Majeed, A A1 - Gatzoulis, MA A1 - Cowie, M J1 - Heart Y1 - 2007/08/07/ SN - 1468-201X N2 - Objective To ascertain time trends in rates of hospital admission, operations, in- hospital case fatality and general mortality for congenital heart disease (CHD) in England and Wales. Design Retrospective analysis of Hospital Episodes Statistics for England (April 1995-March 2004) and mortality statistics for England and Wales (1994-2003). Population All NHS patients admitted with a primary diagnosis of CHD to hospitals in England, and all deaths in England and Wales with an underlying cause of CHD. Main outcome measures Age standardised hospital admission rates, case fatality rates and death rates from congenital heart disease. Results Between 1995/96 and 2003/04 the age standardised hospital admission rate for CHD increased from 30.7 per 100,000 (95% CI 29.9-31.4) to 35.5 per 100,000 (95% CI 34.7-36.4) in males and from 28.2 per 100,000 (95% CI 27.4-28.9) to 32.8 per 100,000 (95% CI 32.0-33.6) in females. Between 1997/98 and 2003/04 in-hospital case fatality rates fell from 2.10% (95% CI 1.97-2.22) to 0.83% (95% CI 0.74-0.92). Population mortality fell steadily over the decade 1994 to 2003 in men and women, with the largest proportionate decrease in the 1-4 year age group. Conclusion Admission rates for CHD have increased over the past decade, particularly amongst patients in older age groups. There has also been a significant decrease in both in-hospital case fatality rates and in general population mortality rates. These trends are consistent with improvements in the quality of care for these patients, improvements in survival and the predicted expansion in the number of adults living with CHD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17646196&query_hl=1 ER - TY - JFULL T1 - Comorbidity, health care utilisation and process of care measures in patients with congenital heart disease in the UK: cross-sectional population-based study with case control analysis. A1 - Billett, J A1 - Cowie, MR A1 - Gatzoulis, MA A1 - Vonder Muhll, IF A1 - Majeed, A J1 - Heart Y1 - 2007/08/07/ SN - 1468-201X N2 - Background Relatively little is known about the prevalence of comorbidities, patterns of health care utilisation and primary care recording of clinical indicators in patients with congenital heart disease. Methods We conducted a population-based case control study using data from general practices across the UK contributing data to the QRESEARCH primary care database. The subjects were 9952 cases of congenital heart disease and 29837 matched controls. Outcome measures were: Prevalence (%) of selected comorbidities; adjusted odds ratios (OR) for risk of comorbidities, health care utilisation and clinical indicator recording. Results The overall crude prevalence of congenital heart disease was 3.05 per 1000 patients (95% CI 2.90 to 3.11). Prevalence of key comorbidities in congenital heart disease patients ranged from 2.4% (95% CI 2.1 to 2.7) for epilepsy to 9.3% (95% CI 8.8 to 9.9) for hypertension. After adjusting for smoking and deprivation, cases were significantly more likely than controls to have each of the cardiovascular comorbidities e.g. adjusted odds ratio for atrial fibrillation 7.6 (6.1 to 9.3), and also had an increased risk of diabetes, epilepsy and renal disease. Patients with congenital heart disease were heavier users of primary care than controls. congenital heart disease patients were also more likely than controls to have lifestyle and risk factor measurements recorded in primary care e.g. adjusted odds ratio for BMI recording in cases versus controls 1.23 (95% CI 1.16 to 1.31), although overall levels of recording were low. Conclusions There is a significant burden of comorbidity associated with congenital heart disease, and levels of primary care utilisation and referral to secondary care are high in this patient population. The predicted future expansion in the numbers of adults with congenital heart disease owing to improvements in survival will have implications for primary and secondary care, and not just tertiary centres offering specialist care. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17646191&query_hl=1 ER - TY - JFULL T1 - Ethnic inequalities in the management and outcome of diabetes in three English Primary Care Trusts. A1 - Soljak, M A1 - Majeed, A A1 - Eliahoo, J A1 - Dornhorst, A J1 - Int J Equity Health Y1 - 2007/08/02/ VL - 6 SN - 1475-9276 SP - 8 EP - 8 N2 - ABSTRACT: BACKGROUND: Although the prevalence of diabetes is three to five times higher in UK South Asians than Whites, there are no reports of the extent of ethnicity recording in routine general practice, and few population-based published studies of the effect of South Asian ethnicity on diabetes care and outcomes. We aimed to determine the effect of ethnicity and healthcare factors in an English population. METHODS: Data was obtained in 2002 on all 21,343 diabetic patients registered in 99% of all computerised general practitioner (GP) practices in three NW London Primary Care Trusts (PCTs), covering a total registered population of 720,000. Previously practices had been provided with training, data entry support and feedback. Treatment and outcome measures included drug treatment and blood pressure (BP), total cholesterol and haemoglobin A1c (HbA1c) levels. RESULTS: Seventy per cent of diabetic patients had a valid ethnicity code. In the relatively older White population, we expected a smaller proportion with a normal BP, but BP differences between the groups were small, suggesting poorer control in non-White ethnic groups. There were also significant differences between ethnic groups in the proportions of insulin-treated patients, with a smaller proportion of South Asians- 4.7% compared to 7.1% of Whites- receiving insulin, although the proportion with a satisfactory HbA1c was smaller- 25.6% compared to 37.9%. CONCLUSIONS: Recording the ethnicity of existing primary care patients is feasible, beginning with patients with established diseases such as diabetes. We have shown that the lower proportion of South Asian patients with good diabetes control, and who are receiving insulin, is at least partly due to poorer standards of care in South Asians, although biological factors could also contribute. This study highlights the need to capture ethnicity data in clinical trials and in routine care, to specifically investigate the reasons for these ethnic differences, and to consider more intensive management of diabetes and education about the disease in South Asian patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17678547&query_hl=1 ER - TY - JFULL T1 - Effects of travel mode on exposures to particulate air pollution. A1 - Briggs, DJ A1 - de Hoogh, K A1 - Morris, C A1 - Gulliver, J J1 - Environ Int Y1 - 2007/08/02/ SN - 0160-4120 N2 - Monitoring was carried out of particulate concentrations whilst simultaneously walking and driving 48 routes in London, UK. Monitoring was undertaken during May and June 2005. Route lengths ranged from 601 to 1351 m, and most routes were travelled in both directions. Individual journey times ranged from 1.5 to 15 min by car (average 3.7 min) and 7.3 to 30 min (average 12.8 min) whilst walking; car trips were therefore repeated up to 5 times for each single walking trip and the results averaged for the route. Car trips were made with windows closed and the ventilation system on a moderate setting. Results show that mean exposures while walking are greatly in excess of those while driving, by a factor 4.7 for the coarse particle mass (PM10-PM2.5), 2.2 for the fine particle mass (PM2.5-PM1), 1.9 for the very fine particle mass (t, M1V, W80R, M173T) in ICP. W80R was not present in Caucasians and M1V was detected uniquely in 1 British case. M173T and -1g>t occur both in Caucasian cases and controls, and we found a significant association of M173T with ICP (OR, 3.2; 95% confidence interval, 1.1-11.2; P = .02) when the allele frequencies of both Caucasian cohorts were analyzed together. We demonstrate functional defects in either translation efficiency or activity for 3 of the 4 variants (-1g>t, M1V, M173T). CONCLUSIONS: This is the first report of functional variants in FXR. We propose that these variants may predispose to ICP, and because FXR has a central role in regulating bile and lipid homeostasis they may be associated with other cholestatic and dyslipidemic disorders. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17681172&query_hl=1 ER - TY - JFULL T1 - How much do delayed healthcare seeking, delayed care provision, and diversion from primary care contribute to the transmission of STIs? A1 - Mercer, CH A1 - Sutcliffe, L A1 - Johnson, AM A1 - White, PJ A1 - Brook, G A1 - Ross, JD A1 - Dhar, J A1 - Horner, P A1 - Keane, F A1 - Jungmann, E A1 - Sweeney, J A1 - Kinghorn, G A1 - Garnett, GG A1 - Stephenson, JM A1 - Cassell, JA J1 - Sex Transm Infect Y1 - 2007/08// VL - 83 SN - 1368-4973 SP - 400 EP - 405 N2 - OBJECTIVES: To quantify the contribution of patient delay, provider delay, and diversion between services to delayed access to genitourinary medicine (GUM) clinics. To describe the factors associated with delay, and their contribution to STI transmission. METHODS: Cross-sectional survey of 3184 consecutive new patients attending four GUM clinics purposively selected from across England to represent different types of population. Patients completed a short written questionnaire that collected data on sociodemographics, access, and health-seeking behaviour. Questionnaires were then linked to routinely collected individual-level demographic and diagnostic data. RESULTS: Patient delay is a median of 7 days, and does not vary by demographic or social characteristics, or by clinic. However, attendance at a walk-in appointment was associated with a marked reduction in patient delay and provider delay. Among symptomatics, 44.8% of men and 58.0% of women continued to have sex while awaiting treatment, with 7.0% reporting sex with >1 partner; 4.2% of symptomatic patients reported sex without using condoms with new partner(s) since their symptoms had begun. Approximately 25% of all patients had already sought or received care in general practice, and these patients experienced greater provider delay. CONCLUSIONS: Walk-in services are associated with a reduction in patient and provider delay, and should be available to all populations. Patients attending primary care require clear care pathways when referred on to GUM clinics. Health promotion should encourage symptomatic patients to seek care quickly, and to avoid sexual contact before treatment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17475683&query_hl=1 ER - TY - JFULL T1 - Food omega-3 fatty acid intake of individuals (total, linolenic acid, long-chain) and their blood pressure: INTERMAP study. A1 - Ueshima, H A1 - Stamler, J A1 - Elliott, P A1 - Chan, Q A1 - Brown, IJ A1 - Carnethon, MR A1 - Daviglus, ML A1 - He, K A1 - Moag-Stahlberg, A A1 - Rodriguez, BL A1 - Steffen, LM A1 - Van Horn, L A1 - Yarnell, J A1 - Zhou, B A1 - INTERMAP Research Group J1 - Hypertension Y1 - 2007/08// VL - 50 SN - 1524-4563 SP - 313 EP - 319 N2 - Findings from short-term randomized trials indicate that dietary supplements of omega-3 polyunsaturated fatty acids (PFA) lower blood pressure of hypertensive persons, but effect size in nonhypertensive individuals is small and nonsignificant. Data are lacking on food omega-3 PFA and blood pressure in general populations. The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) is an international cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population-based samples in China, Japan, United Kingdom, and United States. We report associations of food omega-3 PFA intake (total, linolenic acid, long-chain) of individuals with blood pressure. Systolic and diastolic blood pressure were measured 8 times at 4 visits. With several models to control for possible confounders (dietary, other), linear regression analyses showed inverse relationship of total omega-3 PFA from food (percent kilocalories, from four 24-hour dietary recalls) to systolic and diastolic blood pressures. With adjustment for 17 variables, estimated systolic blood pressure/diastolic blood pressure differences with 2 standard deviation higher (0.67% kcal) omega-3 PFA were -0.55/-0.57 mm Hg (Z-score -1.33, -2.00); for 2238 persons without medical or dietary intervention, -1.01/-0.98 mm Hg (Z -1.63, -2.25); for 2038 nonhypertensive persons from this sub-cohort, -0.91/-0.92 mm Hg (Z -1.80, -2.38). For linolenic acid (largely from vegetable foods), blood pressure differences were similar, eg, for the 2238 "nonintervened" individuals, -0.97/-0.87 mm Hg (Z -1.52, -1.95); blood pressure differences were -0.32/-0.45 mm Hg for long-chain omega-3 PFA (largely from fish). In summary, food omega-3 PFA intake related inversely to blood pressure, including in nonhypertensive persons, with small estimated effect size. Food omega-3 PFA may contribute to prevention and control of adverse blood pressure levels. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17548718&query_hl=1 ER - TY - JFULL T1 - Effects of metoprolol and carvedilol on pre-existing and new onset diabetes in patients with chronic heart failure: data from the Carvedilol Or Metoprolol European Trial (COMET). A1 - Torp-Pedersen, C A1 - Metra, M A1 - Charlesworth, A A1 - Spark, P A1 - Lukas, MA A1 - Poole-Wilson, PA A1 - Swedberg, K A1 - Cleland, JG A1 - Di Lenarda, A A1 - Remme, WJ A1 - Scherhag, A A1 - COMET investigators J1 - Heart Y1 - 2007/08// VL - 93 SN - 1468-201X SP - 968 EP - 973 N2 - BACKGROUND: Beta blocker treatment may worsen glucose metabolism. OBJECTIVE: To study the development of new onset diabetes in a large cohort of patients with heart failure treated with either metoprolol or carvedilol. DESIGN: Prospective and retrospective analysis of a controlled clinical trial. SETTING: Multinational multicentre study. PATIENTS: 3029 patients with chronic heart failure. INTERVENTIONS: Randomly assigned treatment with carvedilol (n = 1511, target dose 50 mg daily) or metoprolol tartrate (n = 1518, target dose 100 mg daily). RESULTS: Diabetic events (diabetic coma, peripheral gangrene, diabetic foot, decreased glucose tolerance or hyperglycaemia) and new onset diabetes (clinical diagnosis, repeated high random glucose level or glucose lowering drugs) were assessed in 2298 patients without diabetes at baseline. Diabetic events occurred in 122/1151 (10.6%) patients in the carvedilol group and 149/1147 (13.0%) patients in the metoprolol group (hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.61 to 0.99; p = 0.039). New onset diabetes was diagnosed in 119/1151 (10.3%) v 145/1147 (12.6%) cases in the carvedilol and metoprolol treatment groups (HR = 0.78, CI 0.61 to 0.997; p = 0.048), respectively. Patients with diabetes at baseline had an increased mortality compared with non-diabetic subjects (45.3% v 33.9%; HR = 1.45, CI 1.28 to 1.65). Both diabetic and non-diabetic subjects at baseline had a similar reduction in mortality with carvedilol compared with metoprolol (RR = 0.85; CI 0.69 to 1.06 and RR = 0.82; CI 0.71 to 0.94, respectively). CONCLUSION: A high prevalence and incidence of diabetes is found in patients with heart failure over a course of 5 years. New onset diabetes is more likely to occur during treatment with metoprolol than during treatment with carvedilol. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17237130&query_hl=1 ER - TY - JFULL T1 - Use of albumin creatinine ratio and urine albumin concentration as a screening test for albuminuria in an Indo-Asian population. A1 - Jafar, TH A1 - Chaturvedi, N A1 - Hatcher, J A1 - Levey, AS J1 - Nephrol Dial Transplant Y1 - 2007/08// VL - 22 SN - 0931-0509 SP - 2194 EP - 2200 N2 - BACKGROUND: Albuminuria (>30 mg/day) based on 24 h urine albumin excretion is one of the criteria for chronic kidney disease (CKD) and a predictor of cardiovascular disease (CVD). Differences in urine albumin concentration and creatinine excretion rates between Indo-Asians and other populations may require different threshold values for detection of albuminuria. We compared the use of spot urine albumin concentration and urine albumin to creatinine excretion ratio for detection of albuminuria in this population. METHODS: A total of 577 subjects aged >/=40 years, 54% of whom were women, were recruited from the general population in Karachi, Pakistan. Albumin concentration (mg/l) and albumin to creatinine ratio (mg/g of creatinine) were determined in a spot morning urine sample, and albuminuria (30 mg/day or greater) measured in a 24 h urine collected on the subsequent day. RESULTS: The median (25-75 percentile) of urine albumin excretion was 4.8 (3.6-10.3) mg/day: 5.4 (3.7-12.5) mg/day in men and 4.5 (3.8-8.9) mg/day in women. The overall prevalence (95% CI) of albuminuria was 11.8% (7.2-12.0%): 14.8% in men and 9.2% in women (P = 0.04). The areas under the receiver operator characteristic (ROC) curves for urine albumin concentration were 0.86 (0.82-0.90) and 0.88 (0.84-0.92), respectively, in women and men. The areas under the ROC curves for albumin to creatinine ratio were 0.86 (0.82-0.89) and 0.90 (0.86-0.93), respectively, in women and men. For urine albumin concentration, the sensitivity and specificity were 37 and 97%, respectively, in women and 69 and 94%, respectively, in men at the conventionally recommended value of 2 mg/dl. The discriminator value of urine albumin concentration identified in the analysis was 0.5 mg/dl in women (sensitivity of 87% and specificity of 75%) and 1.7 mg/dl in men (sensitivity of 74% and specificity of 93%). For the albumin to creatinine ratio, the sensitivity and specificity were 46 and 95%, respectively, in women and 60 and 97%, respectively, in men at cut-off value of 30 mg/g. CONCLUSION: Both urine albumin concentration and albumin to creatinine ratio are acceptable tests for population screening for albuminuria in Indo-Asians. While sensitivities may be suboptimal, particularly in women, lowering the existing thresholds would compromise specificity. Those who screen positive need evaluation and management of CKD and prevention of CVD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17405790&query_hl=1 ER - TY - JFULL T1 - Behaviour change in generalised HIV epidemics: impact of reducing cross-generational sex and delaying age at sexual debut. A1 - Hallett, TB A1 - Gregson, S A1 - Lewis, JJ A1 - Lopman, BA A1 - Garnett, GP J1 - Sex Transm Infect Y1 - 2007/08// VL - 83 Suppl 1 SN - 1368-4973 SP - i50 EP - i54 N2 - BACKGROUND: Sexual behavioural change is essential to prevent HIV infections in Africa and statistical analysis of risk factors at the individual-level may be used to design interventions. The importance of reducing cross-generational sex (young women having sex with older men) and delaying age at first sex on the spread of HIV at the population-level has been presumed but not scientifically investigated and quantified. METHODS: A mathematical model of heterosexual spread of HIV was developed to predict the population-level impact of reducing cross-generational sex and delaying sexual debut. RESULTS: The impact of behaviour change on the spread of HIV is sensitive to the structure and reaction of the sexual network. Reducing cross-generational sex could have little impact on the risk of infection unless it is accompanied by a reduction in the number of risky sexual contacts. Even peer-to-peer sexual mixing can support high endemic levels of HIV. The benefit of delaying sexual debut is comparatively small and is reduced if males continue to prefer young partners or if young women spend more time unmarried. In Manicaland, Zimbabwe, if older men were to use condoms as frequently as young men, the reduction in risk of infection could exceed that generated by a two-year delay in first sex. CONCLUSIONS: At the individual-level avoiding sex with older partners and delaying sexual debut can decrease the risk of infection but at the population-level these interventions may do little to limit the spread of HIV without wider-ranging behavioural changes throughout the sexual network. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17314125&query_hl=1 ER - TY - JFULL T1 - Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. A1 - Stewart, EA A1 - Gostout, B A1 - Rabinovici, J A1 - Kim, HS A1 - Regan, L A1 - Tempany, CM J1 - Obstet Gynecol Y1 - 2007/08// VL - 110 SN - 0029-7844 SP - 279 EP - 287 N2 - OBJECTIVE: To assess several measures of the long-term outcome of magnetic resonance-guided focused ultrasound surgery for symptomatic uterine leiomyomata. METHODS: Data on 359 women completing 24-month follow-up in all clinical trials of magnetic resonance-guided focused ultrasound surgery for uterine leiomyomata were analyzed. Quality of life outcomes, measured by the symptom severity score of the Uterine Fibroid Symptoms Quality Of Life Questionnaire were assessed for 24 months after treatment. Clinical endpoints, including uterine shrinkage, the need for additional leiomyoma treatment, and the time to additional leiomyoma treatment, were all assessed. The nonperfused volume ratio after treatment, calculated from the gadolinium-enhanced magnetic resonance imaging after treatment and the best measure of tissue necrosis after treatment, was used to assess outcome based on completeness of leiomyoma ablation. RESULTS: Women undergoing magnetic resonance-guided focused ultrasound surgery for symptomatic uterine leiomyomata have durable symptom relief, as measured by the symptom severity score at 24 months, with significantly greater improvement with more complete ablation (P<.001). Survival analysis demonstrates a significant reduction in the percentage of women undergoing additional leiomyoma treatment (P=.001) in women in the high nonperfused volume group. The mean shrinkage and mean residual nonperfused volume ratio are both significantly above zero at 6 months in the high nonperfused volume group (P<.001). The incidence of adverse events is low. However, for women with minimal treatment, the risk of additional procedures is high. CONCLUSION: Magnetic resonance-guided focused ultrasound surgery is an effective treatment for uterine leiomyomata and results in sustained symptomatic relief. LEVEL OF EVIDENCE: III. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17666601&query_hl=1 ER - TY - JFULL T1 - Astrocyte-leucocyte interactions and the mechanisms regulating matrix degradation in CNS tuberculosis. A1 - Green, JA A1 - Friedland, JS J1 - Biochem Soc Trans Y1 - 2007/08// VL - 35 SN - 0300-5127 SP - 686 EP - 688 N2 - The CNS (central nervous system) has a unique pattern of immune response to infection. TB (tuberculosis) of the CNS is devastating with widespread tissue destruction. In TB, astrocyte-leucocyte interactions are key in regulating MMP (matrix metalloproteinase) activity and are regulated by complex signalling pathways. A synergistic interaction between interferon gamma and monocyte-derived mediators drives high-level astrocyte MMP-9 secretion; this and other networking effects are inhibited by steroids. Better understanding of regulatory mechanisms may identify potential switch points that could be future therapeutic targets. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635122&query_hl=1 ER - TY - JFULL T1 - Use of blood alcohol concentration in resuscitation room patients. A1 - Csipke, E A1 - Touquet, R A1 - Patel, T A1 - Franklin, J A1 - Brown, A A1 - Holloway, P A1 - Batrick, N A1 - Crawford, MJ J1 - Emerg Med J Y1 - 2007/08// VL - 24 SN - 1472-0213 SP - 535 EP - 538 N2 - OBJECTIVE: To clarify the use of blood alcohol concentration (BAC) in the emergency department resuscitation room, by comparing it with a subsequent alcohol questionnaire and by surveying patients' attitudes to BAC testing. DESIGN: Observational study. PARTICIPANTS: 273 resuscitation room patients at St Mary's Hospital, Paddington between August 2005 and February 2006. MAIN OUTCOME MEASURES: BAC comparison to questionnaire results, and attitudes to BAC testing. RESULTS: The level of agreement between positive screening by questionnaire and a BAC of >80 mg/100 ml was low (kappa = 0.29, 95% confidence interval 0.12 to 0.46) because each test measures different aspects of drinking. Patients accepted the use of BAC tests in detecting alcohol use, though a small minority reported concerns over confidentiality. CONCLUSION: Use of BAC testing complements later questionnaire screening to identify alcohol misuse in patients initially brought to the emergency department resuscitation room, providing results are fed back to the patient. Potential ethical, judicial and insurance concerns should not prevent the use of BAC when judged to be in the patient's best interest. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17652671&query_hl=1 ER - TY - JFULL T1 - Clinical course of isolated stable angina due to coronary heart disease. A1 - Poole-Wilson, PA A1 - Vokó, Z A1 - Kirwan, BA A1 - de Brouwer, S A1 - Dunselman, PH A1 - Lubsen, J A1 - for the ACTION investigators J1 - Eur Heart J Y1 - 2007/08// VL - 28 SN - 0195-668X SP - 1928 EP - 1935 N2 - Aims To describe the clinical course of patients with stable angina due to coronary heart disease without a history of cardiovascular (CV) events or revascularization (isolated angina). Methods and results Of 7665 patients in a trial comparing long-acting nifedipine with placebo, 2170 (28%) had isolated angina. During a mean follow-up of 4.9 years, 147 of these died (1.4/100 patient-years), while 761 (8.7/100 patient-years) either died, or had a cardiac event or procedure. The first event was death in 82, myocardial infarction or heart failure in 112, coronary revascularization in 171, and chest pain requiring hospitalization in 396. Six hundred and twelve patients (6.8/100 patient-years) underwent coronary angiography (CAG), followed by revascularization in 371. Sixty-eight of 262 deaths or major cardiac events were preceded by chest pain requiring hospitalization or revascularization. Event-rates after CAG were higher than before. The stroke rate was 0.7/100 patient-years (75 patients). Conclusion Patients with stable isolated angina have low rates of death and major cardiac events, but relatively high rates of chest pain requiring hospitalization despite contemporary management. Since the majority of deaths and major CV clinical events are not preceded by clear warning symptoms, the main clinical implication is that measures to prevent such events must target all patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17562665&query_hl=1 ER - TY - JFULL T1 - Prevention strategies for sexually transmitted infections: importance of sexual network structure and epidemic phase. A1 - Ward, H J1 - Sex Transm Infect Y1 - 2007/08// VL - 83 Suppl 1 SN - 1368-4973 SP - i43 EP - i49 N2 - This article explores the relationship between sexual network structure and epidemic phase in sexually transmitted disease epidemiology, and discusses how this may be used to inform prevention strategies at the population level. There are relatively few empirical studies of sexual networks, and even fewer that track the evolution of networks over time. Most studies focus on networks in the context of disease transmission and will miss the network structure in the wider population. Results from disease-related studies in the early epidemic phase show densely connected networks with multiple short loops. In later hyperendemic phases, networks appear more loosely connected with a dominance of long branching structures. The latter structure has also been described from non-diseased populations. These structures evolve over time, both of the epidemic curve and as a cohort ages and undergoes demographic change. Population strategies for prevention should vary depending on network structure and epidemic phase. In early and late epidemic phases, interventions focusing on high-risk populations--that is, dense areas of a sexual network--will have a large population effect. In contrast, for established endemic diseases a smaller change (of behaviour or interruption of transmission through screening) in a larger proportion of the population could have the largest population impact. Further empirical work on the way network structures relate to epidemic phase, and how this changes with age and social development will help to inform intervention strategies at the population level. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17389716&query_hl=1 ER - TY - JFULL T1 - Analysis of complex flow and the relationship between blood pressure, wall shear stress, and intima-media thickness in the human carotid artery. A1 - Augst, AD A1 - Ariff, B A1 - McG Thom, SA A1 - Xu, XY A1 - Hughes, AD J1 - Am J Physiol Heart Circ Physiol Y1 - 2007/08// VL - 293 SN - 0363-6135 SP - H1031 EP - H1037 N2 - BACKGROUND: Previous clinical studies have observed relationships between increased intima-media thickness (IMT) in the carotid artery, elevated blood pressure, and low wall shear stress (WSS) calculated from the Poiseuille equation. This study used numerical methods to more accurately determine WSS in the carotid artery and to investigate possible determinants of increased IMT. METHODS: IMT [common carotid artery (CCA) and bulb], CCA flow velocity, brachial systolic (SBP) and diastolic blood pressure (DBP), and carotid systolic pressure (cSBP) were measured in 14 healthy subjects (aged 44 +/- 16 yr). Flow patterns in the carotid bifurcation were determined by computational fluid dynamics (CFD) based on three-dimensional ultrasound geometry. Instantaneous and time-averaged wall shear stress (WSS(av)), oscillatory shear index (OSI), and wall shear stress angle gradients (WSSAG) were calculated. RESULTS: IMT was positively related to SBP, DBP, cSBP, and WSSAG and inversely related to WSS(av) in the CCA. In the bulb, IMT was positively related to SBP and cSBP but was not significantly related to WSS(av) or WSSAG. IMT was unrelated to OSI in both the CCA and the bulb. CONCLUSION: Increased carotid artery IMT in healthy subjects with no evidence of focal plaques is primarily a response to elevated pressure. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17449549&query_hl=1 ER - TY - JFULL T1 - Predictive value of local and core laboratory echocardiographic assessment of cardiac function in patients with chronic stable angina: The ACTION study. A1 - Dart, AM A1 - Otterstad, JE A1 - Kirwan, BA A1 - Parker, JD A1 - de Brouwer, S A1 - Poole-Wilson, PA A1 - Lubsen, J A1 - ACTION investigators J1 - Eur J Echocardiogr Y1 - 2007/08// VL - 8 SN - 1525-2167 SP - 275 EP - 283 N2 - AIMS: To evaluate the relationship between echocardiographic cardiac function and outcome in patients with stable symptomatic angina. METHODS: Baseline echo left ventricular ejection fraction and volume data measured in a central laboratory was available for 7016 patients (92% of the total) participating in the ACTION trial (A Coronary disease Trial Investigating Outcome with Nifedipine GITS). Ejection fraction was also measured by investigators. Evaluation of the different echocardiographic variables was based on adjusted hazard ratios comparing the unfavourable limit of the 90% range of the variable concerned to the favourable limit. RESULTS: The centrally measured ejection fraction was the most powerful predictor of all-cause death (adjusted hazard ratio=2.5), myocardial infarction, any stroke or transient ischaemic attack and overt heart failure (adjusted hazard ratio=4.5). The addition of either end systolic volume or end diastolic volume to ejection fraction did not materially affect the power of prediction. Compared to the central ejection fraction measurement, the investigator-measured ejection fraction was a less powerful predictor for all outcomes considered. CONCLUSION: Routine echocardiography carefully analysed by standardised methods provides useful prognostic information in patients with stable angina, including for total mortality. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17416207&query_hl=1 ER - TY - JFULL T1 - Gaze strategies during planning in first-episode psychosis. A1 - Huddy, VC A1 - Hodgson, TL A1 - Kapasi, M A1 - Mutsatsa, SH A1 - Harrison, I A1 - Barnes, TR A1 - Joyce, EM J1 - J Abnorm Psychol Y1 - 2007/08// VL - 116 SN - 0021-843X SP - 589 EP - 598 N2 - Eye movements were measured during the performance of a computerized Tower of London task to specify the source of planning abnormalities in patients with 1st-episode schizophrenia or schizoaffective disorder. Subjects viewed 2 arrays of colored balls in the upper and lower parts of the screen. They were asked to plan the shortest sequence of moves required to rearrange the balls in the lower screen to match the upper arrangement. Compared with healthy controls, patients made more planning errors, and decision times were longer. However, the patients showed the same gaze biases as controls prior to making a response, indicating that they understood the requirements of the task, approached the task in a strategic manner by identifying the nature of the problem, and used appropriate fixation strategies to plan and elaborate solutions. The patients showed increased duration of long-gaze periods toward both parts of the screen. This suggests that the patients had difficulty in encoding the essential features of the stimulus array. This finding is compatible with slowing of working memory consolidation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17696714&query_hl=1 ER - TY - JFULL T1 - Detailed analysis of variation at and around mitochondrial position 16189 in a large Finnish cohort reveals no significant associations with early growth or metabolic phenotypes at age 31 years. A1 - Das, S A1 - Bennett, AJ A1 - Sovio, U A1 - Ruokonen, A A1 - Martikainen, H A1 - Pouta, A A1 - Hartikainen, AL A1 - Franks, S A1 - Elliott, P A1 - Poulton, J A1 - Järvelin, MR A1 - McCarthy, MI J1 - J Clin Endocrinol Metab Y1 - 2007/08// VL - 92 SN - 0021-972X SP - 3219 EP - 3223 N2 - CONTEXT: Mitochondrial dysfunction is increasingly implicated in pathogenesis of adult metabolic disease. Rare mitochondrial (mt) DNA mutations impair glucose homeostasis, but the contribution of common variants is unclear. In small studies, variation within the OriB origin of replication (at mt16189 in particular) has been associated with both early growth and adult metabolic phenotypes and may contribute to life-course relationships between the two. OBJECTIVE: The aim was to study a large well-characterized cohort to determine whether previously reported small-scale associations between OriB sequence variation and early growth and adult metabolic phenotypes are robust. DESIGN/SETTING/PARTICIPANTS: This was a genetic association study of 5470 individuals from the population-based Northern Finland Birth Cohort of 1966, followed prospectively from pregnancy to age 31 yr. MAIN OUTCOME MEASURES: We measured indices of early growth (including birth weight, placental weight, and ponderal index) and adult metabolic homeostasis (including body mass index, fasting glucose and insulin, indices of insulin action and secretion) and their relationship to variation in the OriB region. RESULTS: Previously reported associations could not be confirmed. There were no significant (P < 0.01, uncorrected) associations between OriB sequence variation and measures of early growth including birth weight (P = 0.52, comparing individuals with mt16189T to those with a homopolymeric C-tract) and placental weight (P = 0.49). There were no significant associations with adult metabolic phenotypes including fasting glucose (P = 0.07), fasting insulin (P = 0.42), and homeostatic model assessment-derived measures of insulin sensitivity or secretion (P = 0.45 and P = 0.56, respectively). CONCLUSION: Despite substantial power to detect previously reported effects, mtDNA variations around OriB are not major contributors to variation in early growth and metabolic phenotypes during early adulthood. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17535991&query_hl=1 ER - TY - JFULL T1 - Long-term follow-up of the hepatitis C HENCORE cohort: response to therapy and occurrence of liver-related complications. A1 - Pradat, P A1 - Tillmann, HL A1 - Sauleda, S A1 - Braconier, JH A1 - Saracco, G A1 - Thursz, M A1 - Goldin, R A1 - Winkler, R A1 - Alberti, A A1 - Esteban, JI A1 - Hadziyannis, S A1 - Rizzetto, M A1 - Thomas, H A1 - Manns, MP A1 - Trepo, C A1 - HENCORE Group J1 - J Viral Hepat Y1 - 2007/08// VL - 14 SN - 1352-0504 SP - 556 EP - 563 N2 - The aims of the study were to verify the long-term effect of time on viral clearance in hepatitis C virus (HCV) patients and to find out factors possibly associated with disease progression. A total of 1641 patients recruited from eight European centres in 1996-1997 were re-analysed 5-7 years after inclusion. The occurrence of decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation was analysed in relation to different host and viral factors. Ninety-three per cent of the HCV patients who had cleared the virus (spontaneously or after antiviral therapy) remained HCV-RNA-negative during follow up and may be considered as 'cured'. Among patients who were sustained responders at inclusion, 2.3% developed liver complications during follow up, and 31% of non-responders did. Advanced age at infection and presence of the human leucocyte antigen (HLA) DRB1*1201-3 allele were possibly associated with a higher rate of progression to decompensated cirrhosis or HCC. Decompensated cirrhosis might be further associated with male gender, non-response to previous therapy, and lack of HLA DRB1*1301 allele, whereas HCC seems to be associated with the presence of the HLA DQ02 allele. Long-term follow up of HCV patients indicates that virological response persists over time and is associated with a very low incidence of liver complications. Advanced age at inclusion, advanced age at infection, viral genotype 1, non-response to previous therapy and possibly some specific HLA alleles are factors independently associated with a faster rate of progression towards liver complications. The large proportion of patients lost to follow up stresses the need for a strengthened and optimized management of HCV patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17650289&query_hl=1 ER - TY - JFULL T1 - Long-term associations of outdoor air pollution with mortality in Great Britain. A1 - Elliott, P A1 - Shaddick, G A1 - Wakefield, JC A1 - de Hoogh, C A1 - Briggs, DJ J1 - Thorax Y1 - 2007/07/31/ SN - 0040-6376 N2 - BACKGROUND: Recent studies have indicated long-term effects on mortality of particulate and sulphur dioxide (SO2) pollution, but uncertainties remain over size of any effects, potential latency and generalisability. METHODS: Small-area study across electoral wards in Great Britain of mean annual black smoke (BS) and SO2 concentrations (from 1966) and subsequent all cause and cause-specific mortality. Use of random effect models within a Bayesian framework, adjusted for social deprivation and urban/rural classification. Different latencies and changes in associations over time were assessed. RESULTS: We found significant associations of BS and SO2 concentrations with mortality. Effects were stronger for respiratory illness than other causes of mortality, for the most recent exposure periods (shorter latency times) and most recent mortality period (lower pollutant concentrations). In pooled analysis across four sequential four-year mortality periods (1982-98), adjusted excess relative risk for respiratory mortality was 3.6% (95% CI 2.6-4.5%) per 10 microg/m(3) BS, and 13.2% (11.5-14.9 %) per 10 ppb SO2, and in the most recent period (1994-98) it was 19.3% (5.1-35.7%) and 21.7% (2.9-38.5%) respectively. CONCLUSIONS: Our findings add to the evidence that air pollution has long-term effects on mortality, and point to continuing public health risks even at the relatively lower levels of BS and SO2 that now occur. They thus have importance for policies on public health protection through regulation and control of air pollution. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17666438&query_hl=1 ER - TY - JFULL T1 - Rate of change and instability in body mass index, insulin resistance and lipid metabolism as predictors of atherosclerotic vascular disease. A1 - Christen, A A1 - Efstathiadou, Z A1 - Laspa, E A1 - Johnston, DG A1 - Godsland, IF J1 - J Clin Endocrinol Metab Y1 - 2007/07/31/ SN - 0021-972X N2 - Context: By definition, levels of metabolic risk factors predict atherosclerotic vascular disease (AVD), but the effects of long-term adverse change and instability remain under-researched. Objective: To quantify long-term rates of change and instability in risk factors and relate these measures to clinical AVD outcomes. Design: Prospective cohort study with unmatched and age- and follow-up-matched control analyses. Setting: Teaching hospital day ward. Participants: Four-hundred and sixty-five predominantly healthy white males in an occupational cohort, who had undergone repeated metabolic risk factor measurements (mean observation period 11.6 years, range 2-28), 62 of whom developed clinical AVD. Main outcome measures: Rate of change and instability in metabolic risk factor levels were quantified in each individual by linear regression with time and evaluated as predictors of AVD and coronary and cerebrovascular disease separately. Results: As expected, baseline and/or mean follow-up measures of established risk-factors relating to blood pressure, lipid metabolism and sub-clinical inflammation were significant predictors. Predictors independent of baseline and mean follow-up levels, confirmed in matched and unmatched analyses, were: i) AVD: instability in weight (cases vs controls:2.9% vs +2.5%); ii) coronary heart disease: instability in body mass index (3.0% vs +2.3%), a decline (-0.041 vs -0.011 per decade) and instability (19.1% v 14.6%) in the HDL / non-HDL cholesterol ratio, declining ESR and increasing uric acid; iii) cerebrovascular disease: a decline in insulin sensitivity (-0.394 vs 0.324 per decade). Conclusions: Within an individual, long-term change in metabolic risk factors, as well as their absolute levels, can be important in AVD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17666474&query_hl=1 ER - TY - JFULL T1 - A patient with suspected miscarriage is found to have hypertension, renal failure, and thrombocytopenia: case outcome. A1 - Laing, CM A1 - Roberts, R A1 - Lightstone, L A1 - Graham, A A1 - Cook, TH A1 - Summers, S A1 - Pusey, CD J1 - BMJ Y1 - 2007/07/28/ VL - 335 SN - 1468-5833 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17656546&query_hl=1 ER - TY - JFULL T1 - Lay educators in asthma self management: Reflections on their training and experiences. A1 - Brown, C A1 - Hennings, J A1 - Caress, AL A1 - Partridge, MR J1 - Patient Educ Couns Y1 - 2007/07/25/ SN - 0738-3991 N2 - OBJECTIVE: To capture the experiences and feelings of lay educators in an asthma self-management programme to aid understanding of optimal methods of recruitment, training and retention, and to enhance their value within the programme. METHODS: A multi site randomised controlled equivalence trial of asthma educators and primary care practice based nurses during which the educators were asked to keep a diary of their experience. A qualitative thematic analysis of these diaries was undertaken. RESULTS: Eight lay educators supplied diaries. From these diaries emerged personal reasons for involvement in the programme, constructive comments on the training programme, a need for preparation for the realities of clinical practice and significant ongoing support and training. CONCLUSION: Lay educators are a potential resource for giving self-management education to patients with long-term conditions such as asthma. However, there are some considerations that need to be taken into account regarding contracts, retention and continual support. PRACTICE IMPLICATIONS: Lay educators need a flexible but comprehensive training programme, contracts, on site mentoring and support. They seem most contented when welcomed by health professionals and treated as part of the team. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17662568&query_hl=1 ER - TY - JFULL T1 - Prediction of mode of death in heart failure: the Seattle Heart Failure Model. A1 - Mozaffarian, D A1 - Anker, SD A1 - Anand, I A1 - Linker, DT A1 - Sullivan, MD A1 - Cleland, JG A1 - Carson, PE A1 - Maggioni, AP A1 - Mann, DL A1 - Pitt, B A1 - Poole-Wilson, PA A1 - Levy, WC J1 - Circulation Y1 - 2007/07/24/ VL - 116 SN - 1524-4539 SP - 392 EP - 398 N2 - BACKGROUND: Prognosis and mode of death in heart failure patients are highly variable in that some patients die suddenly (often from ventricular arrhythmia) and others die of progressive failure of cardiac function (pump failure). Prediction of mode of death may facilitate decisions about specific medications or devices. METHODS AND RESULTS: We used the Seattle Heart Failure Model (SHFM), a validated prediction model for total mortality in heart failure, to assess the mode of death in 10,538 ambulatory patients with New York Heart Association class II to IV heart failure and predominantly systolic dysfunction enrolled in 6 randomized trials or registries. During 16,735 person-years of follow-up, 2014 deaths occurred, which included 1014 sudden deaths and 684 pump-failure deaths. Compared with a SHFM score of 0, patients with a score of 1 had a 50% higher risk of sudden death, patients with a score of 2 had a nearly 3-fold higher risk, and patients with a score of 3 or 4 had a nearly 7-fold higher risk (P<0.001 for all comparisons; 1-year area under the receiver operating curve, 0.68). Stratification of risk of pump-failure death was even more pronounced, with a 4-fold higher risk with a score of 1, a 15-fold higher risk with a score of 2, a 38-fold higher risk with a score of 3, and an 88-fold higher risk with a score of 4 (P<0.001 for all comparisons; 1-year area under the receiver operating curve, 0.85). The proportion of deaths caused by sudden death versus pump-failure death decreased from a ratio of 7:1 with a SHFM score of 0 to a ratio of 1:2 with a SHFM score of 4 (P trend <0.001). CONCLUSIONS: The SHFM score provides information about the likely mode of death among ambulatory heart failure patients. Investigation is warranted to determine whether such information might predict responses to or cost-effectiveness of specific medications or devices in heart failure patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17620506&query_hl=1 ER - TY - JFULL T1 - Motion-compensated MR valve imaging with COMB tag tracking and super-resolution enhancement. A1 - Dowsey, AW A1 - Keegan, J A1 - Lerotic, M A1 - Thom, S A1 - Firmin, D A1 - Yang, GZ J1 - Med Image Anal Y1 - 2007/07/24/ SN - 1361-8415 N2 - Understanding the morphology and function of heart valves is important to the study of underlying causes of heart failure. Existing techniques such as those based on echocardiography are limited by the relatively low signal-to-noise ratio (SNR), attenuation artefacts, and restricted access. The alternative of cardiovascular MR imaging offers versatility and accuracy in 3D localisation, but is hampered by large movements of the valves throughout the cardiac cycle. This paper presents a motion-compensated adaptive imaging approach for MR valve imaging. To illustrate its clinical potential, 3D motion of the aortic valve plane is first captured through a single breath-hold COMB tag pre-scan and then tracked in real-time with an automatic method based on multi-resolution image registration. Motion-compensated coverage of the aortic valve is then acquired prospectively, thus allowing its clear 3D reconstruction and visualisation. To provide isotropic voxel coverage of the imaging volume, retrospective projection onto convex sets (POCS) super-resolution enhancement is applied to the slice-select direction. In vivo results demonstrate the effectiveness of the proposed motion-compensation and super-resolution schemes for depicting the structure of the valve leaflets throughout the cardiac cycle. The proposed method fundamentally changes the way MR imaging is performed by transforming it from a spatially to materially localised imaging method. This also has important implications for quantifying blood flow and myocardial perfusion, as well as tracking anatomy and function of the heart. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17804277&query_hl=1 ER - TY - JFULL T1 - Falling into TRAPS - receptor misfolding in the TNF receptor 1-associated periodic fever syndrome. A1 - Kimberley, FC A1 - Lobito, AA A1 - Siegel, RM A1 - Screaton, GR J1 - Arthritis Res Ther Y1 - 2007/07/23/ VL - 9 SN - 1478-6362 SP - 217 EP - 217 N2 - ABSTRACT: TNF receptor-associated periodic syndrome (TRAPS) is a dominantly inherited disease caused by missense mutations in the TNF receptor 1 (TNFR1) gene. Patients suffer from periodic bouts of severe abdominal pain, localised inflammation, migratory rashes, and fever. More than 40 individual mutations have been identified, all of which occur in the extracellular domain of TNFR1. In the present review we discuss new findings describing aberrant trafficking and function of TNFR1 harbouring TRAPS mutations, challenging the hypothesis that TRAPS pathology is driven by defective receptor shedding, and we suggest that TNFR1 might acquire novel functions in the endoplasmic reticulum, distinct from its role as a cell surface receptor. We also describe the clinical manifestations of TRAPS, current treatment regimens, and the widening array of patient mutations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17666110&query_hl=1 ER - TY - JFULL T1 - The potential cost-effectiveness of prophylactic human papillomavirus vaccines in Canada. A1 - Brisson, M A1 - Van de Velde, N A1 - De Wals, P A1 - Boily, MC J1 - Vaccine Y1 - 2007/07/20/ VL - 25 SN - 0264-410X SP - 5399 EP - 5408 N2 - AIM: Clinical trials have shown prophylactic human papillomavirus (HPV) vaccines to be effective against infection and disease. We examined whether HPV vaccination has the potential to be cost-effective. METHODS: A cohort model of the natural history of HPV was developed, which fits simultaneously Canadian age and type-specific data for infection, cervical intraepithelial neoplasia, cervical cancer (CC) and genital warts (GW). Quality-Adjusted Life-Years (QALYs) lost and costs were estimated using data from the literature. RESULTS: Vaccinating 12-year-old girls (efficacy=95%, no waning, cost/course=CAN$ 400) against HPV-16/18 and HPV-6/11/16/18 is estimated to cost the health provider CAN$ 31,000 (80%CrI: 15,000-55,000) and CAN$ 21,000 (80%CrI: 11,000-33,000) per QALY-gained, respectively. Results were most sensitive to age at vaccination, duration of vaccine protection, vaccine cost and QALY-lost due to GW, and were least sensitive to the medical costs. CONCLUSION: Vaccinating adolescent girls against HPV is likely to be cost-effective. The main benefit of vaccination will be in reducing CC mortality. However, unless screening is modified, the treatment costs saved through vaccination will be insignificant compared to the cost of HPV immunization. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17561316&query_hl=1 ER - TY - JFULL T1 - Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC). A1 - Ferrari, P A1 - Jenab, M A1 - Norat, T A1 - Moskal, A A1 - Slimani, N A1 - Olsen, A A1 - Tjønneland, A A1 - Overvad, K A1 - Jensen, MK A1 - Boutron-Ruault, MC A1 - Clavel-Chapelon, F A1 - Morois, S A1 - Rohrmann, S A1 - Linseisen, J A1 - Boeing, H A1 - Bergmann, M A1 - Kontopoulou, D A1 - Trichopoulou, A A1 - Kassapa, C A1 - Masala, G A1 - Krogh, V A1 - Vineis, P A1 - Panico, S A1 - Tumino, R A1 - Gils, CH A1 - Peeters, P A1 - Bueno-de-Mesquita, HB A1 - Ocké, MC A1 - Skeie, G A1 - Lund, E A1 - Agudo, A A1 - Ardanaz, E A1 - López, DC A1 - Sanchez, MJ A1 - Quirós, JR A1 - Amiano, P A1 - Berglund, G A1 - Manjer, J A1 - Palmqvist, R A1 - Guelpen, BV A1 - Allen, N A1 - Key, T A1 - Bingham, S A1 - Mazuir, M A1 - Boffetta, P A1 - Kaaks, R A1 - Riboli, E J1 - Int J Cancer Y1 - 2007/07/19/ SN - 0020-7136 N2 - Alcohol consumption may be associated with risk of colorectal cancer (CRC), but the epidemiological evidence for an association with specific anatomical subsites, types of alcoholic beverages and current vs. lifetime alcohol intake is inconsistent. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 478,732 study subjects free of cancer at enrolment between 1992 and 2000 were followed up for an average of 6.2 years, during which 1,833 CRC cases were observed. Detailed information on consumption of alcoholic beverages at baseline (all cases) and during lifetime (1,447 CRC cases, 69% of the cohort) was collected from questionnaires. Cox proportional hazard models were used to examine the alcohol-CRC association. After adjustment for potential confounding factors, lifetime alcohol intake was significantly positively associated to CRC risk (hazard ratio, HR = 1.08, 95%CI = 1.04-1.12 for 15 g/day increase), with higher cancer risks observed in the rectum (HR = 1.12, 95%CI = 1.06-1.18) than distal colon (HR = 1.08, 95%CI = 1.01-1.16), and proximal colon (HR = 1.02, 95%CI = 0.92-1.12). Similar results were observed for baseline alcohol intake. When assessed by alcoholic beverages at baseline, the CRC risk for beer (HR = 1.38, 95%CI = 1.08-1.77 for 20-39.9 vs. 0.1-2.9 g/day) was higher than wine (HR = 1.21, 95%CI = 1.02-1.44), although the two risk estimates were not significantly different from each other. Higher HRs for baseline alcohol were observed for low levels of folate intake (1.13, 95%CI = 1.06-1.20 for 15 g/day increase) compared to high folate intake (1.03, 95%CI = 0.98-1.09). In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day. (c) 2007 Wiley-Liss, Inc. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17640039&query_hl=1 ER - TY - JFULL T1 - Are cancer risks associated with exposures to ionising radiation from internal emitters greater than those in the Japanese A-bomb survivors? A1 - Little, MP A1 - Hall, P A1 - Charles, MW J1 - Radiat Environ Biophys Y1 - 2007/07/17/ SN - 0301-634X N2 - After ingestion or inhalation of radionuclides, internal organs of the human body will be exposed to ionising radiation. Current risk estimates of radiation-associated cancer from internal emitters are largely based on extrapolation of risk from high-dose externally exposed groups. Concerns have been expressed that extrapolated risk estimates from internal emitters are greatly underestimated, by factors of ten or more, thus implying a severe underestimation of the true risks. Therefore, data on cancer mortality and incidence in a number of groups who received exposure predominantly from internal emitters are examined and excess relative risks per Sv are compared with comparable (age at exposure, time since exposure, gender) matched subsets of the Japanese atomic bomb survivor cohort. Risks are examined separately for low LET and high LET internal emitters. There are eight studies informative for the effects of internal low LET radiation exposure and 12 studies informative for the effects of internal high LET radiation. For 11 of the 20 cancer endpoints (subgroups of particular study cohorts) examined in the low LET internal emitter studies, the best estimate of the excess relative risk is greater than the corresponding estimate in the Japanese atomic bomb survivors and for the other nine it is less. For four of these 20 studies, the relative risk is significantly (2-sided P < 0.05) different from that in the Japanese atomic bomb survivors, in three cases greater than the atomic bomb survivor relative risk and in one case less. Considering only those six low LET studies/endpoints with 100 or more deaths or cases, for four out of six studies/endpoints the internal emitter risk is greater than that in the Japanese atomic bomb survivors. For seven of the 24 cancer endpoints examined in the high LET internal emitter studies the best estimate of the ERR in the internal emitter study is greater than the corresponding estimate in the Japanese atomic bomb survivors and for the other 17 it is less. For six studies, the relative risk is significantly (2-sided P < 0.05) different from that in the Japanese atomic bomb survivors, in one case greater than the atomic bomb survivor relative risk and in five cases less. Considering only those eight high LET studies/endpoints with 100 or more deaths or cases, for five out of eight studies/endpoints the internal emitter risk is greater than that in the Japanese atomic bomb survivors. These results suggest that excess relative risks in the internal emitter studies do not appreciably differ from those in the Japanese atomic bomb survivors. However, there are substantial uncertainties in estimates of risks in the internal emitter studies, particularly in relation to lung cancer associated with radon daughter (alpha particle) exposure, so a measure of caution should be exercised in these conclusions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17639450&query_hl=1 ER - TY - JFULL T1 - Physical activity and risk of endometrial cancer: The European prospective investigation into cancer and nutrition A1 - Friedenreich, C A1 - Cust, A A1 - Lahmann, PH A1 - Steindorf, K A1 - Boutron-Ruault, MC A1 - Clavel-Chapelon, F A1 - Mesrine, S A1 - Linseisen, J A1 - Rohrmann, S A1 - Pischon, T A1 - Schulz, M A1 - Tjonneland, A A1 - Johnsen, NF A1 - Overvad, K A1 - Mendez, M A1 - Arguelles, MV A1 - Garcia, CM A1 - Larranaga, N A1 - Chirlaque, MD A1 - Ardanaz, E A1 - Bingham, S A1 - Khaw, KT A1 - Allen, N A1 - Key, T A1 - Trichopoulou, A A1 - Dilis, V A1 - Trichopoulos, D A1 - Pala, V A1 - Palli, D A1 - Tumino, R A1 - Panico, S A1 - Vineis, P A1 - Bueno-de-Mesquita, HB A1 - Peeters, PHM A1 - Monninkhof, E A1 - Berglund, G A1 - Manjer, J A1 - Slimani, N A1 - Ferrari, P A1 - Kaaks, R A1 - Riboli, E J1 - INT J CANCER Y1 - 2007/07/15/ VL - 121 SN - 0020-7136 SP - 347 EP - 355 N2 - The etiologic role of physical activity in endometrial cancer risk remains unclear given the few epidemiologic studies that have been conducted. To investigate this relation more fully, an analysis was,undertaken in the European prospective investigation into cancer and nutrition (EPIC). During an average 6.6 years of follow-up, 689 incident endometrial cancer cases were identified from an analytic cohort within EPIC of 253,023 women. Cox proportional hazards models were used to estimate the associations between type of activity (total, occupational, household, recreational) and endometrial cancer risk. For total activity, women in the highest compared with the lowest quartile of activity had a risk of 0.88 (95% confidence interval (95% CI = 0.61-1.27). No clear associations between each type of activity and endometrial cancer risk were found for the total study population combined. Associations were more evident in the stratified results, with premenopausal women who were active versus inactive experiencing a risk of 0.66 (95% CI = 0.38-1.14) overall. Among premenopausal women, for household and recreational activities the risk estimates in the highest as compared with the lowest quartiles were, respectively, 0.48 (95% CI = 0.23-0.99) and 0.78 (95% CI = 0.44-1.39). No effect modification by body mass index, hormone replacement therapy, oral contraceptive use or energy intake was found. This study provides no evidence of a protective effect of increased physical activity in endometrial cancer risk in all women but some support for a benefit among premenopausal women. The relative risk reductions are most apparent for household activities. (C) 2007 Wiley-Liss, Inc. ER - TY - JFULL T1 - Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition A1 - Jenab, M A1 - Riboli, E A1 - Cleveland, RJ A1 - Norat, T A1 - Rinaldi, S A1 - Nieters, A A1 - Biessy, C A1 - Tjonneland, A A1 - Olsen, A A1 - Overvad, K A1 - Gronbaek, H A1 - Clavel-Chapelon, F A1 - Boutron-Ruault, MC A1 - Linseisen, J A1 - Boeing, H A1 - Pischon, T A1 - Trichopoulos, D A1 - Oikonomou, E A1 - Trichopoulou, A A1 - Panico, S A1 - Vineis, P A1 - Berrino, F A1 - Tumino, R A1 - Masala, G A1 - Peters, PH A1 - van Gils, CH A1 - Bueno-de-Mesquita, HB A1 - Ocke, MC A1 - Lund, E A1 - Mendez, MA A1 - Tormo, MJ A1 - Barricarte, A A1 - Martinez-Garcia, C A1 - Dorronsoro, M A1 - Quiros, JR A1 - Hallmans, G A1 - Palmqvist, R A1 - Berglund, G A1 - Manjer, J A1 - Key, T A1 - Allen, NE A1 - Bingham, S A1 - Khaw, KT A1 - Cust, A A1 - Kaaks, R J1 - INT J CANCER Y1 - 2007/07/15/ VL - 121 SN - 0020-7136 SP - 368 EP - 376 N2 - Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C-peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) -1 and -2 with colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C-peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR = 1.56, 95% CI = 1.16-2.09, p(trend) < 0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR = 1.37, 95% CI = 1.00-1.88, p(trend) = 0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR 1.67, 95% CI = 1.14-2.46, p(trend) < 0.01) than in the rectum (OR 1.42, 95% CI = 0.90-2.25, p(trend) = 0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP-1 or -2. This large prospective study confirms that hyperinsulinemia, as determined by C-peptide levels, is associated with an increased colorectal cancer risk. (C) 2007 Wiley-Liss, Inc. ER - TY - JFULL T1 - CTLs target Th cells that acquire bystander MHC class I-peptide complex from APCs. A1 - Cox, JH A1 - McMichael, AJ A1 - Screaton, GR A1 - Xu, XN J1 - J Immunol Y1 - 2007/07/15/ VL - 179 SN - 0022-1767 SP - 830 EP - 836 N2 - CTLs can acquire MHC class I-peptide complexes from their target cells, whereas CD4(+) T cells obtain MHC class II-peptide complexes from APCs in a TCR-specific manner. As a consequence, Ag-specific CTL can kill each other (fratricide) or CD4(+) T cells become APCs themselves. The purpose of the acquisition is not fully understood and may be either inhibition or prolongation of an immunological response. In this study, we demonstrate that human CD4(+) Th cells are able to capture membrane fragments from APC during the process of immunological synapse formation. The fragments contain not only MHC class II-peptide complexes but also MHC class I-peptide complexes, rendering these cells susceptible to CTL killing in an Ag-specific manner. The control of CD4(+) Th cells by Ag-specific CTL, therefore, maybe another mechanism to regulate CD4(+) T cell expansion in normal immune responses or cause immunopathology during the course of viral infections such as HIV. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17617573&query_hl=1 ER - TY - JFULL T1 - A single dose of vitamin D enhances immunity to mycobacteria. A1 - Martineau, AR A1 - Wilkinson, RJ A1 - Wilkinson, KA A1 - Newton, SM A1 - Kampmann, B A1 - Hall, BM A1 - Packe, GE A1 - Davidson, RN A1 - Eldridge, SM A1 - Maunsell, ZJ A1 - Rainbow, SJ A1 - Berry, JL A1 - Griffiths, CJ J1 - Am J Respir Crit Care Med Y1 - 2007/07/15/ VL - 176 SN - 1073-449X SP - 208 EP - 213 N2 - RATIONALE: Vitamin D was used to treat tuberculosis (TB) in the preantibiotic era. Prospective studies to evaluate the effect of vitamin D supplementation on antimycobacterial immunity have not previously been performed. OBJECTIVES: To determine the effect of vitamin D supplementation on antimycobacterial immunity and vitamin D status. METHODS: A double-blind randomized controlled trial was conducted in 192 healthy adult TB contacts in London, United Kingdom. Participants were randomized to receive a single oral dose of 2.5 mg vitamin D or placebo and followed up at 6 weeks. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was assessed with a functional whole blood assay (BCG-lux assay), which measures the ability of whole blood to restrict luminescence, and thus growth, of recombinant reporter mycobacteria in vitro; the readout is expressed as a luminescence ratio (luminescence postinfection/baseline luminescence). IFN-gamma responses to the Mycobacterium tuberculosis antigens early secretory antigenic target-6 and culture filtrate protein 10 were determined with a second whole blood assay. Vitamin D supplementation significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro compared with placebo (mean luminescence ratio at follow-up, 0.57, vs. 0.71, respectively; 95% confidence interval for difference, 0.01-0.25; p=0.03) but did not affect antigen-stimulated IFN-gamma secretion. CONCLUSIONS: A single oral dose of 2.5 mg vitamin D significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro without affecting antigen-stimulated IFN-gamma responses. Clinical trials should be performed to determine whether vitamin D supplementation prevents reactivation of latent TB infection. Clinical trial registered with www.clinicaltrials.gov (NCT 00157066). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17463418&query_hl=1 ER - TY - JFULL T1 - Protective efficacy of a monovalent oral type 1 poliovirus vaccine - Authors' reply. A1 - Grassly, NC A1 - Wenger, J A1 - Bahl, S A1 - Sutter, RW A1 - Aylward, RB J1 - Lancet Y1 - 2007/07/14/ VL - 370 SN - 1474-547X SP - 129 EP - 130 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17630026&query_hl=1 ER - TY - JFULL T1 - Influence of Pulsatile Flow on LDL Transport in the Arterial Wall. A1 - Sun, N A1 - Wood, NB A1 - Hughes, AD A1 - Thom, SA A1 - Xu, XY J1 - Ann Biomed Eng Y1 - 2007/07/14/ SN - 0090-6964 N2 - The accumulation of low-density lipoprotein (LDL) is one of the important factors in atherogenesis. Two different time scales may influence LDL transport in vivo: (1) LDL transport is coupled to blood flow with a pulse cycle of around 1 s in humans; (2) LDL transport within the arterial wall is mediated by transmural flow in the order of 10(-8) m/s. Most existing models have assumed steady flow conditions and overlooked the interactions between physical phenomena with different time scales. The objective of this study was to investigate the influence of pulsatile flow on LDL transport and examine the validity of steady flow assumption. The effect of pulsatile flow on transmural transport was incorporated by using a lumen-free cyclic (LFC) and a lumen-free time-averaged (LFTA) procedures. It is found that the steady flow simulation predicted a focal distribution in the post-stenotic region, differing from the diffuse distribution pattern produced by the pulsatile flow simulation. The LFTA procedure, in which time-averaged shear-dependent transport properties calculated from instantaneous wall shear stress (WSS) were used, predicted a similar distribution pattern to the LFC simulations. We conclude that the steady flow assumption is inadequate and instantaneous hemodynamic conditions have important influence on LDL transmural transport in arterial geometries with disturbed and complicated flow patterns. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17629792&query_hl=1 ER - TY - JFULL T1 - Antihypertensive-associated incident diabetes: controversy persists. A1 - Gupta, AK A1 - Poulter, NR J1 - Arch Intern Med Y1 - 2007/07/09/ VL - 167 SN - 0003-9926 SP - 1433; author reply 1434 EP - 1435; author reply 1434 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17620540&query_hl=1 ER - TY - JFULL T1 - A patient with suspected miscarriage is found to have hypertension, renal failure, and thrombocytopenia: case progression. A1 - Laing, CM A1 - Roberts, R A1 - Lightstone, L A1 - Graham, A A1 - Cook, TH A1 - Summers, S A1 - Pusey, CD J1 - BMJ Y1 - 2007/07/07/ VL - 335 SN - 1468-5833 SP - 44 N2 - L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17615226&query_hl=1 ER - TY - JFULL T1 - Salt intake and hypertension in Chile: the need for health interventions A1 - Garcia-Larsen, V. A1 - Zarate, V. A1 - Jimenez de la Jara, J. J1 - BMJ Y1 - 2007/07/04/ UR - http://www.bmj.com/cgi/eletters?lookup=by_date&days=5&ck=nck#171023 ER - TY - JFULL T1 - Variation in estimated recombination rates across human populations. A1 - Graffelman, J A1 - Balding, DJ A1 - Gonzalez-Neira, A A1 - Bertranpetit, J J1 - Hum Genet Y1 - 2007/07/03/ SN - 0340-6717 N2 - Recently it has been reported that recombination hotspots appear to be highly variable between humans and chimpanzees, and there is evidence for between-person variability in hotspots, and evolutionary transience. To understand the nature of variation in human recombination rates, it is important to describe patterns of variability across populations. Direct measurement of recombination rates remains infeasible on a large scale, and population-genetic approaches can be imprecise, and are affected by demographic history. Reports to date have suggested broad similarity in recombination rates at large genomic scales and across human populations. Here, we examine recombination rate estimates at a finer population and genomic scale: 28 worldwide populations and 107 SNPs in a 1 Mb stretch of chromosome 22q. We employ analysis of variance of recombination rate estimates, corrected for differences in effective population size using genome-wide microsatellite mutation rate estimates. We find substantial variation in fine-scale rates between populations, but reduced variation within continental groups. All effects examined (SNP-pair, region, population and interactions) were highly significant. Adjustment for effective population size made little difference to the conclusions. Observed hotspots tended to be conserved across populations, albeit at varying intensities. This holds particularly for populations from the same region, and also to a considerable degree across geographical regions. However, some hotspots appear to be population-specific. Several results from studies on the population history of humans are in accordance with our analysis. Our results suggest that between-population variation in DNA sequences may underly recombination rate variation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17609980&query_hl=1 ER - TY - JFULL T1 - Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II) A1 - Kogevinas, M A1 - Zock, JP A1 - Jarvis, D A1 - Kromhout, H A1 - Lillienberg, L A1 - Plana, E A1 - Radon, K A1 - Toren, K A1 - Alliksoo, A A1 - Benke, G A1 - Blanc, PD A1 - Dahlman-Hoglund, A A1 - D'Errico, A A1 - Hery, M A1 - Kennedy, S A1 - Kunzli, N A1 - Leynaert, B A1 - Mirabelli, MC A1 - Muniozguren, N A1 - Norback, D A1 - Olivieri, M A1 - Payo, F A1 - Villani, S A1 - van Sprundel, M A1 - Urrutia, I A1 - Wieslander, G A1 - Sunyer, J A1 - Anto, JM J1 - LANCET Y1 - 2007/07// VL - 370 SN - 0140-6736 SP - 336 EP - 341 N2 - Background The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents.Methods We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study Centre.Findings A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4,1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2,1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year.Interpretation Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely. ER - TY - JFULL T1 - Sickle cell disease as a paradigm of immigration hematology: new challenges for hematologists in Europe. A1 - Roberts, I A1 - de Montalembert, M J1 - Haematologica Y1 - 2007/07// VL - 92 SN - 1592-8721 SP - 865 EP - 871 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17606434&query_hl=1 ER - TY - JFULL T1 - Chronic sphenoid sinusitis revisited: comparison of multidetector axial sections, multiplanar reconstructions, and virtual sinoscopy with endoscopic sinus surgery. A1 - Wankhar, B A1 - Bapuraj, JR A1 - Gupta, AK A1 - Khandelwal, N A1 - Saxena, AK A1 - Batchala, PP A1 - Gandhi, D J1 - Arch Otolaryngol Head Neck Surg Y1 - 2007/07// VL - 133 SN - 0886-4470 SP - 710 EP - 716 N2 - OBJECTIVES: To assess the role of multidetector computed tomography (CT) and CT virtual sinoscopy in the evaluation of chronic sphenoid sinusitis and to compare the imaging findings with functional endoscopic sinus surgery. DESIGN: Prospective study. SETTING: Tertiary care teaching hospital. PATIENTS: Thirty patients with chronic sphenoid sinusitis referred for preoperative CT. INTERVENTIONS: Thin-section helical axial CT was performed using a multidetector CT scanner with multiplanar reformation (MPR) and volume-rendered or virtual sinoscopy images. Sixty sinuses were divided into quadrants for analysis. Extrasinus extension was labeled as the "fifth quadrant." MAIN OUTCOME MEASURES: Imaging findings were compared with those of functional endoscopic sinus surgery, and accuracy of the imaging modality was determined. RESULTS: Multidetector CT (axial CT and MPR) was found to be 100% sensitive, specific, and accurate in the evaluation of extent of sinusitis, status of the sinus septum, integrity of the optic nerve canal in relation to the sinus, and type of sinus pneumatization. Axial CT and MPR images showed sensitivity of 98% and specificity of 92% compared with functional endoscopic sinus surgery in evaluating the ostia. Regarding carotid canal integrity, axial CT and MPRs were 100% sensitive and 98% specific. Virtual sinoscopy showed sensitivity and specificity of 67% and 92%, respectively, for the 22 ostia that could be visualized and evaluated using this modality. CONCLUSIONS: Axial multidetector CT with secondary MPRs provide the necessary preoperative information regarding extent of disease and sphenoid sinus anatomy. Virtual sinoscopy is a navigational aid, an adjunct to endoscopy, and an educational tool for surgeons-in-training. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17638786&query_hl=1 ER - TY - JFULL T1 - Enhanced ex vivo stimulation of Mycobacterium tuberculosis-specific T cells in human immunodeficiency virus-infected persons via antigen delivery by the Bordetella pertussis adenylate cyclase vector. A1 - Connell, TG A1 - Shey, MS A1 - Seldon, R A1 - Rangaka, MX A1 - van Cutsem, G A1 - Simsova, M A1 - Marcekova, Z A1 - Sebo, P A1 - Curtis, N A1 - Diwakar, L A1 - Meintjes, GA A1 - Leclerc, C A1 - Wilkinson, RJ A1 - Wilkinson, KA J1 - Clin Vaccine Immunol Y1 - 2007/07// VL - 14 SN - 1556-6811 SP - 847 EP - 854 N2 - The genetically detoxified Bordetella pertussis adenylate cyclase is a promising delivery system for immunodominant tuberculosis antigens in gamma interferon release assays. This system has not been evaluated in human immunodeficiency virus (HIV)-infected persons in high tuberculosis prevalence areas. A whole-blood gamma interferon release assay with Mycobacterium tuberculosis antigens (early-secreted antigenic target 6, culture filtrate protein 10, alpha-crystallin 2, and TB10.3) delivered by adenylate cyclase in addition to native tuberculosis antigens (without adenylate cyclase delivery) was evaluated in 119 adults in Khayelitsha Township, Cape Town, South Africa. Results were compared to tuberculin skin test results of 41 HIV-positive and 42 HIV-negative asymptomatic persons, in addition to 36 HIV-positive persons with recently diagnosed smear- or culture-positive pulmonary tuberculosis. Delivery of tuberculosis antigens by adenylate cyclase decreased by 10-fold the amount of antigen required to restimulate T cells. Furthermore, the responses of HIV-positive persons with a low response to native tuberculosis antigens were enhanced when these antigens were delivered by adenylate cyclase. When gamma interferon responses to the tuberculosis antigens (with or without delivery by adenylate cyclase) were combined, a significantly higher number of patients were scored positive than by tuberculin skin testing. Ex vivo responses to tuberculosis antigens delivered by adenylate cyclase are maintained in the context of HIV infection. Our findings suggest that the majority of those in this population are infected with tuberculosis, which is of significant public health importance. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17522328&query_hl=1 ER - TY - JFULL T1 - The missing care bundle: antibiotic prescribing in hospitals. A1 - Cooke, FJ A1 - Holmes, AH J1 - Int J Antimicrob Agents Y1 - 2007/07// VL - 30 SN - 0924-8579 SP - 25 EP - 29 N2 - The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes. In short, care bundles aim to ensure that all patients consistently receive the best care or treatment, all of the time. This approach has been successfully applied to the management of various conditions, particularly in the critical care setting. The Institute for Healthcare Improvement's '100K lives campaign' consisted of six care bundles, three of which have addressed preventing hospital-acquired infection. The UK Department of Health's delivery programme to reduce healthcare-associated infections (HCAIs), including methicillin-resistant Staphylococcus aureus (MRSA), includes six 'high-impact interventions', which are care bundles to reduce HCAIs. However, we suggest that one key intervention is missing, and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile, to tackle antibiotic resistance and to improve patient care. The missing intervention addresses the process of antibiotic prescribing. We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics, both for treatment and prophylaxis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17499482&query_hl=1 ER - TY - JFULL T1 - Indian Asian men have less peripheral arterial disease than European men for equivalent levels of coronary disease. A1 - Chaturvedi, N A1 - Coady, E A1 - Mayet, J A1 - Wright, AR A1 - Shore, AC A1 - Byrd, S A1 - McG Thom, SA A1 - Kooner, JS A1 - Schalkwijk, CG A1 - Hughes, AD J1 - Atherosclerosis Y1 - 2007/07// VL - 193 SN - 0021-9150 SP - 204 EP - 212 N2 - OBJECTIVES: Indian Asians have high rates of heart disease and stroke, but risks of peripheral arterial disease appear to be low. This paradox, and reasons for it, have not been explored. We compared ethnic differences in peripheral arterial disease for a given level of coronary disease. METHODS: We studied 83 European and 84 Indian Asian men with a range of coronary disease. Extent of coronary atheroma was quantified by coronary artery calcification score on multislice CT. Femoral intima-media thickness (IMT) was measured by ultrasound. RESULTS: Femoral IMT was 1.58, 2.06, 2.12, and 2.69 mm in Europeans, and 0.61, 1.41, 1.81 and 2.29 in Indian Asians by increasing categories of coronary atheroma (p=0.003 for ethnic difference, adjusted for age and lumen diameter). Adjustment for smoking and systolic blood pressure, the only risk factors adversely distributed in Europeans, only partly accounted for this ethnic difference (p=0.05). Other risk factors, including lipids, obesity, insulin and glycaemic status, more adversely distributed in Indian Asians, could not account for ethnic differences. Prevalence of abnormal ankle brachial index and lower limb atherosclerotic plaque was also greater in Europeans. CONCLUSIONS: For a given level of coronary disease, Indian Asians have less lower limb atherosclerosis than Europeans, unexplained by established risk factors. Further study of these populations would help tease out relative contributions of risk factors to atherosclerosis in different vessel beds. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16860806&query_hl=1 ER - TY - JFULL T1 - Drug effects on the mechanical properties of large arteries in humans A1 - Hope, SA A1 - Hughes, AD J1 - CLIN EXP PHARMACOL P Y1 - 2007/07// VL - 34 SN - 0305-1870 SP - 688 EP - 693 N2 - 1. Arteries become stiffer with increasing age and various disease states. A complete description of arterial mechanical properties in vivo is not possible, although a number of methods have been used.2. Detailed discussion in the present review is limited to pulse wave velocity and estimates of central waveform morphology derived by the application of a generalized arterial transfer function.3. Many drugs affect these parameters, either increasing or decreasing apparent stiffness. However, the extent to which changes reflect changes in blood pressure rather than more fundamental vessel wall properties remains unclear. Similarly, it is as yet unknown whether determining the need for, or assessing the effectiveness of, drug treatment by the assessment of arterial mechanical properties will offer any advantage and the usefulness of these techniques as routine clinical tools remains to be established. ER - TY - JFULL T1 - Disentangling HLA associations: Multivariate association study using Bayesian logistic regression A1 - Vignal, C A1 - Bansal, A A1 - Balding, D J1 - GENET EPIDEMIOL Y1 - 2007/07// VL - 31 SN - 0741-0395 SP - 502 EP - 502 ER - TY - JFULL T1 - Role of MRI in investigating the effects of elastic compression stockings on the deformation of the superficial and deep veins in the lower leg. A1 - Downie, SP A1 - Firmin, DN A1 - Wood, NB A1 - Thom, SA A1 - Hughes, AD A1 - Wolfe, JN A1 - Xu, XY J1 - J Magn Reson Imaging Y1 - 2007/07// VL - 26 SN - 1053-1807 SP - 80 EP - 85 N2 - PURPOSE: To evaluate the potential of MRI to investigate the mechanical effects of compression stockings on the veins of the lower limb. MATERIALS AND METHODS: The right calves of eight healthy volunteers were imaged in the prone position, with and without the presence of a compression stocking. Cross-sectional areas of all peroneal and posterior tibial veins, both saphenous veins, and any sufficiently large superficial veins were segmented in all subjects at mid-calf level in both cases. Variation in cross-sectional area along the axis of the great saphenous vein and a peroneal vein was also examined in three subjects. RESULTS: The mean cross-sectional area reduction was found to be greater in the deep veins (64%) than in the superficial veins (39%). Deep-vein cross-sections were generally elliptical, while superficial veins were approximately circular. Significant axial fluctuations were found in the cross-sectional areas. CONCLUSION: MRI offers a precise source of data on the mechanical effects of lower-limb compression. Ultrasound (US) may be more cost-effective, but the data acquired are less comprehensive. Future biomechanical studies of lower-limb compression should make use of MRI. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17659543&query_hl=1 ER - TY - JFULL T1 - The interplay between recombination and selection can confound their inference from population data - But suggests a novel genome-wide method for detecting selection A1 - O'Reilly, P A1 - Birney, E A1 - Balding, D J1 - ANN HUM GENET Y1 - 2007/07// VL - 71 SN - 0003-4800 SP - 551 EP - 552 ER - TY - JFULL T1 - Bayesian shrinkage priors for detecting multiple causal variants from genome-wide association studies A1 - Hoggart, C A1 - De Iorio, M A1 - Whittakker, J A1 - Balding, D J1 - ANN HUM GENET Y1 - 2007/07// VL - 71 SN - 0003-4800 SP - 557 EP - 557 ER - TY - JFULL T1 - Reduced systolic wave generation and increased peripheral wave reflection in chronic heart failure. A1 - Curtis, SL A1 - Zambanini, A A1 - Mayet, J A1 - McG Thom, SA A1 - Foale, R A1 - Parker, KH A1 - Hughes, AD J1 - Am J Physiol Heart Circ Physiol Y1 - 2007/07// VL - 293 SN - 0363-6135 SP - H557 EP - H562 N2 - In human heart failure the role of wave generation by the ventricle and wave reflection by the vasculature is contentious. The aim of this study was to compare wave generation and reflection in normal subjects with patients with stable compensated heart failure. Twenty-nine normal subjects and 67 patients with heart failure (New York Heart Association class II or III) were studied by noninvasive techniques applied to the common carotid artery. Data were analyzed by wave intensity analysis to determine the nature and direction of waves during the cardiac cycle. The energy carried by an early systolic forward compression wave (S wave) generated by the left ventricle and responsible for acceleration of flow in systole was significantly reduced in subjects with heart failure (P < 0.001), and the timing of the peak of this wave was delayed. In contrast, reflection of this wave was increased in subjects with heart failure (P < 0.001), but the timing of reflections with respect to the S wave was unchanged. The energy of an expansion wave generated by the heart in protodiastole was unaffected by heart failure. The carotid artery wave speed and the augmentation index did not significantly differ between subjects with heart failure compared with normal individuals. The ability of the left ventricle to generate a forward compression wave is markedly impaired in heart failure. Increased wave reflection serves to maintain systolic blood pressure but also places an additional load on cardiac function in heart failure. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17400718&query_hl=1 ER - TY - JFULL T1 - Modified Overt Aggression Scale (MOAS) for people with intellectual disability and aggressive challenging behaviour: A reliability study A1 - Oliver, PC A1 - Crawford, MJ A1 - Rao, B A1 - Reece, B A1 - Tyrer, P J1 - J APPL RES INTELLECT Y1 - 2007/07// VL - 20 SP - 368 EP - 372 N2 - Background Reliable measures of aggressive challenging behaviour are required if interventions aimed at reducing this behaviour among people with intellectual disability (ID) are to be formally evaluated. The present authors examined the reliability of the Modified Overt Aggression Scale (MOAS), an instrument not yet formally tested in those with ID, in a sample of people who participated in a randomized trial of neuroleptic medication for aggressive challenging behaviour.Method Sixty interviews using the MOAS were carried out by two interviewers 2-5 days apart with 23 carers of 14 people who had shown aggressive challenging behaviour. Level of agreement between these two ratings was examined for four subscales of aggression and for total MOAS score.Results The level of agreement between the raters was high for verbal aggression (intraclass correlation coefficient, ICC = 0.90), physical aggression against others (ICC = 0.90) and for total MOAS score (ICC = 0.93). Levels of agreement on the other two subscales were lower but still in the good/moderate range.Conclusion The MOAS provides a reliable measure of verbal and physical aggression among people with ID who reside in community settings and is suitable for use in studies evaluating the effectiveness of interventions aimed at reducing aggressive challenging behaviour in this group. ER - TY - JFULL T1 - Patients who have dilated cardiomyopathy must have a trial of bridge to recovery: the case against that proposition. A1 - Poole-Wilson, PA J1 - Heart Fail Clin Y1 - 2007/07// VL - 3 SN - 1551-7136 SP - 317 EP - 319 N2 - The idea that patients who have dilated cardiomyopathy (presumably a large heart with near-normal coronary arteries) must have a trial of bridge to recovery is risible. Many such patients should be managed so that they go directly to transplantation and others may be better treated with drug therapy. Some may be more suited to destination therapy. What is needed in this field is more precise terminology, clearer statements of clinical intent at the time of device insertion, improved characterization of patients, more accurate clinical assessment, and above all more information from randomized clinical trials. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17723939&query_hl=1 ER - TY - JFULL T1 - Male fertility-related disorders: cause for concern or a stalking horse? A1 - Toledano, MB A1 - Nelson, PD J1 - Arch Dis Child Y1 - 2007/07// VL - 92 SN - 1468-2044 SP - 565 EP - 567 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17588967&query_hl=1 ER - TY - JFULL T1 - Prevalence and nature of side effects during clozapine maintenance treatment and the relationship with clozapine dose and plasma concentration. A1 - Yusufi, B A1 - Mukherjee, S A1 - Flanagan, R A1 - Paton, C A1 - Dunn, G A1 - Page, E A1 - Barnes, TR J1 - Int Clin Psychopharmacol Y1 - 2007/07// VL - 22 SN - 0268-1315 SP - 238 EP - 243 N2 - Clozapine is associated with non-neurological side effects that can be subjectively unpleasant and/or clinically serious. We sought to: (i) assess the nature and prevalence of side effects experienced by patients receiving maintenance treatment with clozapine and (ii) explore the relationship between clozapine plasma concentration and side effect burden. Patients were receiving clozapine maintenance treatment. Open questioning followed by systematic enquiry using the Antipsychotic Non-neurological Side Effects Rating Scale were used to assess side effects. Trough plasma clozapine and norclozapine concentrations were measured. One hundred and three patients participated. On open questioning, 61 patients reported a total of 117 side effects, whereas systematic enquiry identified an additional 649 side effects, with each patient reporting at least one. Clozapine plasma concentrations were significantly but weakly correlated with total Antipsychotic Non-neurological Side Effects Rating Scale score (Pearson correlation=0.29, P<0.004). Patients with a plasma clozapine concentration >0.25 mg/l were significantly more likely to have moderate/severe side effects than patients with lower plasma concentrations (63/76 vs. 12/23, chi=9.07, d.f.=1, P<0.01). The side-effect burden associated with maintenance clozapine treatment is high and the true extent can only be ascertained by systematic inquiry. The use of target plasma concentrations below those used for acute treatment should be explored as a strategy for minimizing side effects. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17519648&query_hl=1 ER - TY - JFULL T1 - Innate immunity in the pathogenesis of virus-induced asthma exacerbations. A1 - Johnston, SL J1 - Proc Am Thorac Soc Y1 - 2007/07// VL - 4 SN - 1546-3222 SP - 267 EP - 270 N2 - The major asthma morbidity, mortality, and health care costs are a result of acute exacerbations. However, exacerbations are only partially responsive to current therapies and new approaches to treatment are needed. The great majority of acute asthma exacerbations are associated with respiratory viral infections and, of viruses implicated, approximately 60% are human rhinoviruses (RVs). The mechanisms of RV-induced asthma exacerbations are poorly understood. We have previously shown that adults with asthma have increased susceptibility to naturally occurring RV infections. Our recent studies have investigated mechanisms of innate host defense against RV infection. First, primary bronchial epithelial cells from subjects with asthma were shown to replicate RV in vitro to several logs, whereas those of normal control subjects were resistant to infection. This resistance was a result of rapid induction of apoptosis and of interferon (IFN)-beta in the normal cells, whereas these responses were deficient in asthmatic cells. These studies were recently extended to a novel family of three related proteins, the IFN-lambdas 1-3, production of which was also deficient in vitro and related to asthma exacerbation severity in vivo. These studies identify novel mechanisms for the increased susceptibility of subjects with asthma to RV infection. Further studies are now required to investigate whether administration of IFN-beta or IFN-lambda may be beneficial in the treatment of asthma exacerbations, to determine whether similar deficiencies are observed in children and in subjects with nonatopic asthma, and to investigate the mechanisms of deficient IFN production in asthma to help identify better therapeutic strategies for asthma exacerbations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17607011&query_hl=1 ER - TY - JFULL T1 - Resource utilization implications of treatment were able to be assessed from appropriately reported clinical trial data. A1 - Poole-Wilson, PA A1 - Kirwan, BA A1 - Vokó, Z A1 - de Brouwer, S A1 - Dunselman, PH A1 - van Dalen, FJ A1 - Lubsen, J A1 - ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) investigators J1 - J Clin Epidemiol Y1 - 2007/07// VL - 60 SN - 0895-4356 SP - 727 EP - 733 N2 - BACKGROUND AND OBJECTIVE: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data. METHODS: Data from a trial comparing long-acting nifedipine gastrointestinal therapeutic system to placebo in 7,665 patients with stable angina pectoris was analyzed. RESULTS: Relative to placebo, nifedipine significantly increased mean cardiovascular (CV) event-free survival by 41 days but had no effect on mean survival. Per 100 years of follow-up, 78.1 patient-years of double-blind nifedipine administration reduced use of another calcium antagonist, an angiotensin converting enzyme inhibitor, an angiotensin receptor blocker, a diuretic and a cardiac glycoside by 1.54, 3.73, 2.63, 2.23, and 0.64 years, respectively, whereas 0.21 less hospitalization for overt heart failure, 0.47 less hospitalization for any stroke or transient ischemic attack, 0.8 less coronary angiogram, 0.38 less coronary bypass procedure, and 0.13 additional orthopedic procedure was required. Combining resource utilization with cost data for one particular hospital showed that one additional year of CV event-free survival costs an average additional euro 3,036 in the setting considered. CONCLUSION: Appropriately tabulated clinical trial data allows clinicians to judge the resource utilization implications and economic effect of treatment decisions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17573989&query_hl=1 ER - TY - JFULL T1 - Impacts of widespread badger culling on cattle tuberculosis: concluding analyses from a large-scale field trial. A1 - Donnelly, CA A1 - Wei, G A1 - Johnston, WT A1 - Cox, DR A1 - Woodroffe, R A1 - Bourne, FJ A1 - Cheeseman, CL A1 - Clifton-Hadley, RS A1 - Gettinby, G A1 - Gilks, P A1 - Jenkins, HE A1 - Le Fevre, AM A1 - McInerney, JP A1 - Morrison, WI J1 - Int J Infect Dis Y1 - 2007/07// VL - 11 SN - 1201-9712 SP - 300 EP - 308 N2 - BACKGROUND: Bovine tuberculosis (TB) has re-emerged as a major problem for British cattle farmers. Failure to control the infection has been linked to transmission from European badgers; badger culling has therefore formed a component of British TB control policy since 1973. OBJECTIVES AND DESIGN: To investigate the impact of repeated widespread badger culling on cattle TB, the Randomised Badger Culling Trial compared TB incidence in cattle herds in and around ten culling areas (each 100 km2) with those in and around ten matched unculled areas. RESULTS: Overall, cattle TB incidence was 23.2% lower (95% confidence interval (CI) 12.4-32.7% lower) inside culled areas, but 24.5% (95% CI 0.6% lower-56.0% higher) higher on land 0.9), but were less reliable at resolutions below ca. 500 m. Impending enhancements in the available land cover and light emissions data are expected to improve the capability of this modelling approach in the future. (c) 2007 Elsevier Inc. All rights reserved. ER - TY - JFULL T1 - A high-performance liquid chromatography and nuclear magnetic resonance spectroscopy-based analysis of commercially available praziquantel tablets. A1 - Li, J A1 - Wang, Y A1 - Fenwick, A A1 - Clayton, TA A1 - Lau, YY A1 - Legido-Quigley, C A1 - Lindon, JC A1 - Utzinger, J A1 - Holmes, E J1 - J Pharm Biomed Anal Y1 - 2007/06/23/ SN - 0731-7085 N2 - The amount of active ingredient in 20 commercially sourced batches of praziquantel (PZQ) tablets was determined using a high-performance liquid chromatography-ultraviolet (HPLC-UV) assay in conjunction with an anthentic, lot of PZQ powder. The general composition of each batch of tablets was also examined by means of (1)H nuclear magnetic resonance (NMR) spectroscopy and the NMR data were subjected to pattern recognition analysis by means of principal component analysis. The HPLC-UV results showed that each batch of PZQ tablets contained approximately the required amount of PZQ (600mg per tablet). The NMR analysis showed a high degree of compositional variation between manufacturers, which caused by variation in excipients, along with some batch-to-batch variation in the tablets from a single manufacturer. Additionally, the PZQ tablets from one manufacturer were found to have an extra component (methyl-4-hydroxybenzoate) that was not detected in the other preparations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17659859&query_hl=1 ER - TY - JFULL T1 - Slower CD4 cell decline following cessation of a 3 month course of HAART in primary HIV infection: findings from an observational cohort. A1 - Fidler, S A1 - Fox, J A1 - Touloumi, G A1 - Pantazis, N A1 - Porter, K A1 - Babiker, A A1 - Weber, J J1 - AIDS Y1 - 2007/06/19/ VL - 21 SN - 0269-9370 SP - 1283 EP - 1291 N2 - OBJECTIVE: To investigate the effect of a short course of HAART during primary HIV infection (PHI) on rate of CD4 cell and viral load change. METHODS: Data following HAART cessation from 89 individuals (seroconverting 1999-2003) who chose to take a 3 month course of HAART at PHI were compared with 179 untreated controls in CASCADE, using linear and nonlinear random effects models. Participants were non-randomized but frequency matched for age, sex, risk factor, year of seroconversion and presentation within the first 6 months of seroconversion. Time to CD4 cell count < 350 cells/microl and initiation of clinically indicated antiretroviral therapy (ART) were also compared as competing risks. RESULTS: The rate of CD4 cell decline following therapy cessation appeared significantly slower among treated participants than untreated controls: losses of 51 cells/microl [95% confidence interval (CI), 32-69] and 77 cells/microl (95% CI, 65-89), respectively, 3 years after seroconversion (P = 0.011). Based on extrapolated data, viral loads also differed significantly at this point (4.09 and 4.53 copies/ml, respectively). At 2 years, there was no significant difference in mean viral load levels: 4.31 copies/ml (95% CI, 4.14-4.48) and 4.47 copies/ml (95% CI, 4.28-4.66), respectively. CASCADE seroconverters were more likely to reach CD4 cell count < 350 cells/microl or initiate clinically indicated ART (hazard ratio, 1.45; 95% CI, 1.02-2.05; P = 0.039). CONCLUSION: A short course of ART at PHI may delay CD4 cell decline. Confirmation of this requires a randomized clinical trial powered to address definitively the role of ART intervention in PHI (currently underway through SPARTAC). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17545704&query_hl=1 ER - TY - JFULL T1 - Expression of PD-L1, a marker of disease status, is not reduced by HAART in aviraemic patients. A1 - Rosignoli, G A1 - Cranage, A A1 - Burton, C A1 - Nelson, M A1 - Steel, A A1 - Gazzard, B A1 - Gotch, F A1 - Imami, N J1 - AIDS Y1 - 2007/06/19/ VL - 21 SN - 0269-9370 SP - 1379 EP - 1381 N2 - Anergy and defective immune responses are characteristic of chronic HIV-1 infection. The programmed death 1 (PD-1)/PD-1 ligand (PD-L1) pathway appears to be involved in downregulating T-cell functionality. We found raised levels of PD-L1 in aviraemic chronically infected HIV-1-positive patients, which may contribute to incomplete immune reconstitution after treatment with HAART. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17545722&query_hl=1 ER - TY - JFULL T1 - Diagnostic scope of and exposure to primary care physicians in Australia, New Zealand, and the United States: cross sectional analysis of results from three national surveys. A1 - Bindman, AB A1 - Forrest, CB A1 - Britt, H A1 - Crampton, P A1 - Majeed, A J1 - BMJ Y1 - 2007/06/16/ VL - 334 SN - 1468-5833 SP - 1261 EP - 1261 N2 - OBJECTIVES: To compare mix of patients, scope of practice, and duration of visit in primary care physicians in Australia, New Zealand, and the United States. DESIGN: Comparison of three comparable cross sectional surveys performed in 2001-2. Physicians completed a questionnaire on patients' demographics, diagnoses, and duration of visit. SETTING: Primary care practice. PARTICIPANTS: 79,790 office visits in Australia, 10,064 in New Zealand, and 25,838 in the US. MAIN OUTCOME MEASURES: Diagnostic codes were mapped to the Johns Hopkins expanded diagnostic clusters. Scope of practice was defined as the number of expanded diagnostic clusters accounting for 75% of all managed problems related to morbidity. Exposure to primary care was calculated from duration of visits recorded by the physician, and reports on rates of visits to primary care for each country. RESULTS: In each country, primary care physicians managed an average of 1.4 morbidity related problems per visit. In the US, 46 expanded diagnostic clusters accounted for 75% of problems managed compared with 52 in Australia, and 57 in New Zealand. Correlations in the frequencies of managed health problems between countries were high (0.87-0.97 for pairwise comparisons). Though primary care visits were longer in the US than in New Zealand and Australia, the per capita annual exposure to primary care physicians in the US (29.7 minutes) was about half of that in New Zealand (55.5 minutes) and about a third of that in Australia (83.4 minutes) because of higher rates of visits to primary care in these countries. CONCLUSIONS: Despite differences in the supply and financing of primary care across countries, many aspects of the clinical practice of primary care physicians are remarkably similar in Australia, New Zealand, and the US. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17504790&query_hl=1 ER - TY - JFULL T1 - ABAM, a model for bioaccumulation of POPs in birds: validation for adult herring gulls and their eggs in Lake Ontario. A1 - Norstrom, RJ A1 - Clark, TP A1 - Enright, M A1 - Leung, B A1 - Drouillard, KG A1 - Macdonald, CR J1 - Environ Sci Technol Y1 - 2007/06/15/ VL - 41 SN - 0013-936X SP - 4339 EP - 4347 N2 - An Avian BioAccumulation Model (ABAM) of persistent organic pollutant (POP) uptake and elimination in adult life-stage of birds was validated by simulation of concentrations of DDE, dieldrin, mirex, and HCB in herring gull eggs in Lake Ontario for the years 1985, 1990, and 1992. These chemicals represented a range of whole-body half-lives of 82-265 days in the gull. Dietary intake of POPs by a female gull was simulated by a dynamic bioenergetics model which included dependence on temperature, photoperiod, egg production, and feeding chicks. Concentrations in the two main prey fish of the gull in Lake Ontario were used for POP exposure. Clearance from the female was based on a two compartment toxicokinetic model. Egg concentrations were estimated from egg/whole body female concentration ratios. Simulated concentrations were compared to measured concentrations in gull eggs from 4 different colonies in the northern part of Lake Ontario. Simulations using a diet of 81% fish and 19% uncontaminated food resulted in the best fit with least variance among predicted and measured data. The mean ratio of predicted to measured concentrations in eggs was 1.0 +/- 0.27 among chemicals, years, and colonies for this exposure scenario. This result was in excellent agreement with field assessments of herring gull diet composition in Lake Ontario of 80-82% fish. The ability to perform accurate a priorisimulations for the range of test conditions employed in the validation constituted a rigorous test of the soundness of the model's structure and parameterization. With species-specific adjustments, ABAM can be regarded as a general model for lipophilic POPs bioaccumulation in birds. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17626434&query_hl=1 ER - TY - JFULL T1 - Loss of discrete memory B cell subsets is associated with impaired immunization responses in HIV-1 infection and may be a risk factor for invasive pneumococcal disease. A1 - Hart, M A1 - Steel, A A1 - Clark, SA A1 - Moyle, G A1 - Nelson, M A1 - Henderson, DC A1 - Wilson, R A1 - Gotch, F A1 - Gazzard, B A1 - Kelleher, P J1 - J Immunol Y1 - 2007/06/15/ VL - 178 SN - 0022-1767 SP - 8212 EP - 8220 N2 - Invasive pneumococcal infection is an important cause of morbidity and mortality in HIV-1-infected individuals. B cells play an important role in maintaining serologic memory after infection. IgM memory B cells are significantly reduced in HIV-1-infected patients and their frequency is similar to that observed in other patient groups (splenectomized individuals and patients with primary Ab deficiency) who are also known to have an increased risk of invasive pneumococcal infection. Antiretroviral therapy does not restore marginal zone B cell percentages. Immunization with the 23-valent polysaccharide pneumococcal vaccine shows that HIV-1-infected patients have impaired total IgM and IgG pneumococcal vaccines compared with healthy controls. Loss of switched memory B cells was associated with impaired tetanus toxoid IgG vaccine responses. Results of this study demonstrate that defects in B cell memory subsets are associated with impaired humoral immune responses in HIV-1 patients who are receiving antiretroviral therapy and may be a contributory factor to the increased risk of invasive pneumococcal infection observed in HIV-1 infection. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17548660&query_hl=1 ER - TY - JFULL T1 - Clinical, immunological, and epidemiological importance of antituberculosis T cell responses in HIV-infected Africans A1 - Rangaka, MX A1 - Diwakar, L A1 - Seldon, R A1 - van Cutsem, G A1 - Meintjes, GA A1 - Morroni, C A1 - Mouton, P A1 - Shey, MS A1 - Maartens, G A1 - Wilkinson, KA A1 - Wilkinson, RJ J1 - CLIN INFECT DIS Y1 - 2007/06/15/ VL - 44 SN - 1058-4838 SP - 1639 EP - 1646 N2 - Background. Human immunodeficiency virus (HIV)-associated tuberculosis is a major cause of mortality in Africa. The assay of T cell interferon-gamma released in response to antigens of greater specificity than purified protein derivative is a useful improvement over the Mantoux tuberculin skin test, but few studies have evaluated interferon gamma secretion in HIV-infected individuals.Methods. Mycobacterium tuberculosis antigen-specific interferon-gamma secretion was assessed by whole blood assay and enzyme-linked immunospot, which were compared with the Mantoux tuberculin skin test in HIV-infected and HIV-uninfected individuals without active tuberculosis and HIV-infected patients with pulmonary tuberculosis in Khayelitsha, South Africa.Results. The skin test and whole blood assay responses to purified protein derivative in HIV-positive subjects were decreased, compared with responses in HIV-negative subjects (P < .001). By contrast, the responses to M. tuberculosis antigens (early secreted antigenic target 6, culture filtrate protein 10, TB10.3, and alpha-crystallin 2) were less affected, indicating a high prevalence of latent tuberculosis (similar to 80%) in both HIV-negative and HIV-positive subject groups. Whole blood assay responses did not differ between the HIV-positive subjects without tuberculosis and HIV-positive subjects with tuberculosis, but the enzyme-linked immunospot method response to early secreted antigenic target 6 and culture filtrate protein 10 was higher in the group of HIV-infected subjects with tuberculosis (P <= .04), although this group had lower CD4(+) cell counts. A ratio of the combined enzyme-linked immunospot method response divided by the CD4(+) cell count of 11.0 had 88% sensitivity and 80% specificity for active pulmonary tuberculosis in HIV-infected individuals.Conclusions. Interferon-gamma release appears to be less impaired than skin testing by HIV coinfection. The novel potential to relate the enzyme-linked immunospot method and CD4(+) cell count to assist diagnosis of active tuberculosis in patients with HIV infection is important and deserves further evaluation. ER - TY - JFULL T1 - Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European prospective investigation into cancer and nutrition A1 - Cust, AE A1 - Allen, NE A1 - Rinaldi, S A1 - Dossus, L A1 - Friedenreich, C A1 - Olsen, A A1 - Tjonneland, A A1 - Overvad, K A1 - Clavel-Chapelon, F A1 - Boutron-Ruault, MC A1 - Linseisen, J A1 - Chang-Claude, J A1 - Boeing, H A1 - Schulz, M A1 - Benetou, V A1 - Trichopoulou, A A1 - Trichopoulos, D A1 - Palli, D A1 - Berrino, F A1 - Tumino, R A1 - Mattiello, A A1 - Vineis, P A1 - Quiros, JR A1 - Agudo, A A1 - Sanchez, MJ A1 - Larranaga, N A1 - Navarro, C A1 - Ardanaz, E A1 - Bueno-De-Mesquita, HB A1 - Peeters, PHM A1 - van Gils, CH A1 - Bingham, S A1 - Khaw, KT A1 - Key, T A1 - Slimani, N A1 - Riboli, E A1 - Kaaks, R J1 - INT J CANCER Y1 - 2007/06/15/ VL - 120 SN - 0020-7136 SP - 2656 EP - 2664 N2 - We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, to examine the associations between prediagnostic serum concentrations of C-peptide, insulin-like growth factor binding protein (IGFBP)-l and IGFBP-2, and endometrial cancer risk. Among pre- and postmenopausal women, who were not currently using exogenous hormones, 286 women developed incident endometrial cancer during an average 5.1 years follow-up. Using risk set sampling, 555 matched control subjects were selected. In conditional logistic regression models adjusted for matching factors only, endometrial cancer risk increased with increasing serum levels of C-peptide (relative risks (RR) for the top vs. bottom quartile = 2.13 [95% confidence interval (CI) 1.33-3.41], p(trend) = 0.001, and decreasing serum levels of IGFBP-2 (RR for the lop vs. bottom quartile = 0.56 [95% CI 0.35-0.90], p(trend) = 0.03, but was not significantly associated with IGFBP-1 levels (RR for the top vs. bottom quartile = 0.76 [95% CI 0.47-1.21], p(trend) = 0.25). In BMI-adjusted models, only the C-peptide association remained marginally statistically significant (RR for the top vs. bottom quartile = 1.56 [95% CI 0.94-2.571, p(trend) = 0.05 for C-peptide; 0.84 [95% CI 0.50-1.40], p(trend) = 0.74 for IGFBP-2; and 1.08 [95% CI 0.65-1.781, p(trend) = 0.86 for IGFBP-1 levels). These associations were stronger among nonfasting women (<= 6 hr since last meal; 63% of subjects) but were not evident among fasting women, although the interactions were not statistically significant. The C-peptide-risk association was substantially attenuated after adjustment for free estradiol in postmenopausal women (RR for the top vs. bottom quartile = 1.28 [95 % CI 0.67-2.45], p(trend) = 0.42. Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer. (c) 2007 Wiley-Liss, Inc. ER - TY - JFULL T1 - Synergistic Up-regulation of Epithelial Cell Matrix Metalloproteinase-9 Secretion in Tuberculosis. A1 - Elkington, PT A1 - Green, JA A1 - Emerson, JE A1 - Lopez-Pascua, LD A1 - Boyle, JJ A1 - O'kane, CM A1 - Friedland, JS J1 - Am J Respir Cell Mol Biol Y1 - 2007/06/15/ SN - 1044-1549 N2 - Mycobacterium tuberculosis (MTb) kills approximately 2 million people each year. MTb must drive host tissue destruction to disseminate and also to cause pulmonary cavitation. Matrix metalloproteinase-9 (MMP-9, gelatinase B) is implicated in this Tb-related immunopathology. We demonstrate that conditioned media from MTb-infected monocytes (CoMTb) but not direct infection with MTb up-regulates MMP-9 gene expression and secretion from primary human bronchial epithelial cells (NHBE). MMP-9 secretion was increased 8.7-fold by CoMTb (p<0.05) as assayed by gelatin zymography. A549 and 16HBE14o epithelial cell MMP secretion was significantly less than primary NHBE secretion. MMP-9 secretion was decreased 53.2% by inhibition of the p38 MAPK by SB203580 (p<0.01) and 48.3% by inhibition of ERK with PD98059 (p<0.05). MMP-9 secretion was prostaglandin-independent. TNF-alpha was necessary but not sufficient for MMP-9 up-regulation by the monocyte-epithelial cell network. Soluble factors derived from Tb culture synergized with TNF-alpha to increase MMP-9 secretion by NHBE 6-fold (p<0.01 compared to either stimulus alone). Together these data reveal a new mechanism by which host- and pathogen-derived factors act together in MTb infection to drive MAPK-dependent MMP-9 secretion from respiratory epithelial cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17575075&query_hl=1 ER - TY - JFULL T1 - Kenneth Anthony ("Tony") Kalanyi Kebba - Obituary A1 - Gotch, F J1 - BRIT MED J Y1 - 2007/06/09/ VL - 334 SN - 0959-8146 SP - 1227 EP - 1227 ER - TY - JFULL T1 - RESOLVE-ing sepsis in children - not yet! A1 - Nadel, S J1 - Crit Care Y1 - 2007/06/08/ VL - 11 SN - 1466-609X SP - 138 EP - 138 N2 - ABSTRACT: The Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective study of drotrecogin alfa activated versus placebo was the largest study of adjunctive therapy ever performed in children with severe sepsis. Despite this, the study failed to show any significant differences in outcome between the treatment and placebo groups. The results raise questions about how we should perform meaningful clinical trials in relatively rare conditions such as paediatric sepsis, where the easily measurable endpoints (such as death) are infrequent. A radical rethink of the design of such studies is urgently needed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17561989&query_hl=1 ER - TY - JFULL T1 - Impact of a pay-for-performance incentive on support for smoking cessation and on smoking prevalence among people with diabetes. A1 - Millett, C A1 - Gray, J A1 - Saxena, S A1 - Netuveli, G A1 - Majeed, A J1 - CMAJ Y1 - 2007/06/05/ VL - 176 SN - 1488-2329 SP - 1705 EP - 1710 N2 - BACKGROUND: Many people with diabetes continue to smoke despite being at high risk of cardiovascular disease. We examined the impact of a pay-for-performance incentive in the United Kingdom introduced in 2004 as part of the new general practitioner contract to improve support for smoking cessation and to reduce the prevalence of smoking among people with chronic diseases such as diabetes. METHODS: We performed a population-based longitudinal study of the recorded delivery of cessation advice and the prevalence of smoking using electronic records of patients with diabetes obtained from participating general practices. The survey was carried out in an ethnically diverse part of southwest London before (June-October 2003) and after (November 2005-January 2006) the introduction of a pay-for-performance incentive. RESULTS: Significantly more patients with diabetes had their smoking status ever recorded in 2005 than in 2003 (98.8% v. 90.0%, p <0.001). The proportion of patients with documented smoking cessation advice also increased significantly over this period, from 48.0% to 83.5% (p < 0.001). The prevalence of smoking decreased significantly from 20.0% to 16.2% (p < 0.001). The reduction over the study period was lower among women (adjusted odds ratio 0.71, 95% confidence interval 0.53-0.95) but was not significantly different in the most and least affluent groups. In 2005, smoking rates continued to differ significantly with age (10.6%-25.1%), sex (women, 11.5%; men, 20.6%) and ethnic background (4.9%-24.9%). INTERPRETATION: The introduction of a pay-for-performance incentive in the United Kingdom increased the provision of support for smoking cessation and was associated with a reduction in smoking prevalence among patients with diabetes in primary health care settings. Health care planners in other countries may wish to consider introducing similar incentive schemes for primary care physicians. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17548383&query_hl=1 ER - TY - JFULL T1 - Quantifying HIV-1 transmission due to contaminated injections A1 - White, RG A1 - Cooper, BS A1 - Kedhar, A A1 - Orroth, KK A1 - Biraro, S A1 - Baggaley, RF A1 - Whitworth, J A1 - Korenromp, EL A1 - Ghani, A A1 - Boily, MC A1 - Hayes, RJ J1 - P NATL ACAD SCI USA Y1 - 2007/06/05/ VL - 104 SN - 0027-8424 SP - 9794 EP - 9799 N2 - Assessments of the importance of different routes of HIV-1 (HIV) transmission are vital for prioritization of control efforts. Lack of consistent direct data and large uncertainty in the risk of HIV transmission from HIV-contaminated injections has made quantifying the proportion of transmission caused by contaminated injections in sub-Saharan Africa difficult and unavoidably subjective. Depending on the risk assumed, estimates have ranged from 2.5% to 30% or more. We present a method based on an age-structured transmission model that allows the relative contribution of HIV-contaminated injections, and other routes of HIV transmission, to be robustly estimated, both fully quantifying and substantially reducing the associated uncertainty. To do this, we adopt a Bayesian perspective, and show how prior beliefs regarding the safety of injections and the proportion of HIV incidence due to contaminated injections should, in many cases, be substantially modified in light of age-stratified incidence and injection data, resulting in improved (posterior) estimates. Applying the method to data from rural southwest Uganda, we show that the highest estimates of the proportion of incidence due to injections are reduced from 15.5% (95% credible interval) (0.7%,44.9%)to 5.2% (0.5%,17.0%) if random mixing is assumed, and from 14.6% (0.7%, 42.5%) to 11.8% (1.2%, 32.5%) under assortative mixing. Lower, and more widely accepted, estimates remain largely unchanged, between 1% and 3% (0.1-6.3%). Although important uncertainty remains, our analysis shows that in rural Uganda, contaminated injections are unlikely to account for a large proportion of HIV incidence. This result is likely to be generalizable to many other populations in sub-Saharan Africa. ER - TY - JFULL T1 - Type 2 diabetes TCF7L2 risk genotypes alter birth weight: A study of 24,053 individuals A1 - Freathy, RM A1 - Weedon, MN A1 - Bennett, A A1 - Hypponen, E A1 - Relton, CL A1 - Knight, B A1 - Shields, B A1 - Parnell, KS A1 - Groves, CJ A1 - Ring, SM A1 - Pembrey, ME A1 - Ben-Shlomo, Y A1 - Strachan, DP A1 - Power, C A1 - Jarvelin, MR A1 - McCarthy, MI A1 - Smith, GD A1 - Hattersley, AT A1 - Frayling, TM J1 - AM J HUM GENET Y1 - 2007/06// VL - 80 SN - 0002-9297 SP - 1150 EP - 1161 N2 - The role of genes in normal birth-weight variation is poorly understood, and it has been suggested that the genetic component of fetal growth is small. Type 2 diabetes genes may influence birth weight through maternal genotype, by increasing maternal glycemia in pregnancy, or through fetal genotype, by altering fetal insulin secretion. We aimed to assess the role of the recently described type 2 diabetes gene TCF7L2 in birth weight. We genotyped the polymorphism rs7903146 in 15,709 individuals whose birth weight was available from six studies and in 8,344 mothers from three studies. Each fetal copy of the predisposing allele was associated with an 18-g (95% confidence interval [CI] 7-29 g) increase in birth weight (P = .001) and each maternal copy with a 30-g (95% CI 15-45 g) increase in offspring birth weight (P = 2.8 x 10(-5)). Stratification by fetal genotype suggested that the association was driven by maternal genotype (31-g [ 95% CI 9-48 g] increase per allele; corrected P = .003). Analysis of diabetes- related traits in 10,314 nondiabetic individuals suggested the most likely mechanism is that the risk allele reduces maternal insulin secretion ( disposition index reduced by similar to 0.15 standard deviation; P =1 x 10(-4)), which results in increased maternal glycemia in pregnancy and hence increased offspring birth weight. We combined information with the other common variant known to alter fetal growth, the - 30G -> A polymorphism of glucokinase (rs1799884). The 4% of offspring born to mothers carrying three or four risk alleles were 119 g (95% CI 62-172 g) heavier than were the 32% born to mothers with none (for overall trend, P = 2 x 10(-7)), comparable to the impact of maternal smoking during pregnancy. In conclusion, we have identified the first type 2 diabetes - susceptibility allele to be reproducibly associated with birth weight. Common gene variants can substantially influence normal birth-weight variation. ER - TY - JFULL T1 - A unifying explanation of the arterial pulse waveform in humans and the implications for central blood pressure augmentation A1 - Davies, J A1 - Hadjiloizou, N A1 - Manisty, C A1 - Whinnett, Z A1 - Foale, R A1 - Malik, I A1 - Hughes, A A1 - Parker, K A1 - Darrel, D A1 - Mayet, J J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A79 EP - A80 ER - TY - JFULL T1 - Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors. A1 - Deforche, K A1 - Camacho, R A1 - Grossman, Z A1 - Silander, T A1 - Soares, MA A1 - Moreau, Y A1 - Shafer, RW A1 - Van Laethem, K A1 - Carvalho, AP A1 - Wynhoven, B A1 - Cane, P A1 - Snoeck, J A1 - Clarke, J A1 - Sirivichayakul, S A1 - Ariyoshi, K A1 - Holguin, A A1 - Rudich, H A1 - Rodrigues, R A1 - Bouzas, MB A1 - Cahn, P A1 - Brigido, LF A1 - Soriano, V A1 - Sugiura, W A1 - Phanuphak, P A1 - Morris, L A1 - Weber, J A1 - Pillay, D A1 - Tanuri, A A1 - Harrigan, PR A1 - Shapiro, JM A1 - Katzenstein, DA A1 - Kantor, R A1 - Vandamme, AM J1 - Infect Genet Evol Y1 - 2007/06// VL - 7 SN - 1567-1348 SP - 382 EP - 390 N2 - Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17127103&query_hl=1 ER - TY - JFULL T1 - Factors affecting adherence to asthma treatment in an international cohort of young and middle-aged adults A1 - Corsico, AG A1 - Cazzoletti, L A1 - de Marco, R A1 - Janson, C A1 - Jarvis, D A1 - Zoia, MC A1 - Bugiani, M A1 - Accordini, S A1 - Villani, S A1 - Marinoni, A A1 - Gislason, D A1 - Gulsvik, A A1 - Pin, I A1 - Vermeire, P A1 - Cerveri, I J1 - RESP MED Y1 - 2007/06// VL - 101 SN - 0954-6111 SP - 1363 EP - 1367 N2 - Background: A major reason of the poor control of asthma is that patients fail to adhere to their treatment. The aim of the study was to identify factors affecting changes in asthma treatment adherence in an international cohort.Methods: A follow-up study was carried out by means of a structured clinical interview in 971 subjects with asthma from 12 countries who participated in both the European Community Respiratory Health Survey: ECRHS-I (1990-94) and ECRHS-II (1998-2002). Subjects were considered adherent if they reported they normally took all the prescribed drugs. A logistic model was used to study the adjusted effect of the determinants.Results: The net change in adherence to anti-asthmatic treatment per 10 years of follow-up was -2% (95% Cl: -9.5, 5.5), 7.5% (-2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the 428 non-adherent subjects in ECRHS-I, having regular consultations with health care professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08-10.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.11-3.75). No effect of gender, age, duration of the disease, smoking habit and educational level was observed. Conclusions: Our findings highlight the key role of doctors and nurses in educating and regularly reviewing the patients and support the efforts for an improvement of clinical Communication. (c) 2006 Elsevier Ltd. AU rights reserved. ER - TY - JFULL T1 - Optimal consultations for those with respiratory illness A1 - Roberts, NR A1 - Partridge, MR J1 - Breathe Y1 - 2007/06// IS - 4 VL - 3 PB - European Respiratory Society SP - 331 EP - 337 ER - TY - JFULL T1 - Ethnic disparities in diabetes management and pay-for-performance in the UK: the Wandsworth Prospective Diabetes Study. A1 - Millett, C A1 - Gray, J A1 - Saxena, S A1 - Netuveli, G A1 - Khunti, K A1 - Majeed, A J1 - PLoS Med Y1 - 2007/06// VL - 4 SN - 1549-1676 SP - e191 EP - e191 N2 - BACKGROUND: Pay-for-performance rewards health-care providers by paying them more if they succeed in meeting performance targets. A new contract for general practitioners in the United Kingdom represents the most radical shift towards pay-for-performance seen in any health-care system. The contract provides an important opportunity to address disparities in chronic disease management between ethnic and socioeconomic groups. We examined disparities in management of people with diabetes and intermediate clinical outcomes within a multiethnic population in primary care before and after the introduction of the new contract in April 2004. METHODS AND FINDINGS: We conducted a population-based longitudinal survey, using electronic general practice records, in an ethnically diverse part of southwest London. Outcome measures were prescribing levels and achievement of national treatment targets (HbA1c < or = 7.0%; blood pressure [BP] < 140/80 mm Hg; total cholesterol < or = 5 mmol/l or 193 mg/dl). The proportion of patients reaching treatment targets for HbA1c, BP, and total cholesterol increased significantly after the implementation of the new contract. The extents of these increases were broadly uniform across ethnic groups, with the exception of the black Caribbean patient group, which had a significantly lower improvement in HbA1c (adjusted odds ratio [AOR] 0.75, 95% confidence interval [CI] 0.57-0.97) and BP control (AOR 0.65, 95% CI 0.53-0.81) relative to the white British patient group. Variations in prescribing and achievement of treatment targets between ethnic groups present in 2003 were not attenuated in 2005. CONCLUSIONS: Pay-for-performance incentives have not addressed disparities in the management and control of diabetes between ethnic groups. Quality improvement initiatives must place greater emphasis on minority communities to avoid continued disparities in mortality from cardiovascular disease and the other major complications of diabetes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17564486&query_hl=1 ER - TY - JFULL T1 - Second-order analysis of inhomogeneous spatial point processes using case-control data. A1 - Diggle, PJ A1 - Gómez-Rubio, V A1 - Brown, PE A1 - Chetwynd, AG A1 - Gooding, S J1 - Biometrics Y1 - 2007/06// VL - 63 SN - 0006-341X SP - 550 EP - 557 N2 - Methods for the statistical analysis of stationary spatial point process data are now well established, methods for nonstationary processes less so. One of many sources of nonstationary point process data is a case-control study in environmental epidemiology. In that context, the data consist of a realization of each of two spatial point processes representing the locations, within a specified geographical region, of individual cases of a disease and of controls drawn at random from the population at risk. In this article, we extend work by Baddeley, Møller, and Waagepetersen (2000, Statistica Neerlandica54, 329-350) concerning estimation of the second-order properties of a nonstationary spatial point process. First, we show how case-control data can be used to overcome the problems encountered when using the same data to estimate both a spatially varying intensity and second-order properties. Second, we propose a semiparametric method for adjusting the estimate of intensity so as to take account of explanatory variables attached to the cases and controls. Our primary focus is estimation, but we also propose a new test for spatial clustering that we show to be competitive with existing tests. We describe an application to an ecological study in which juvenile and surviving adult trees assume the roles of controls and cases. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17688507&query_hl=1 ER - TY - JFULL T1 - Relationship between E23K (an established type II diabetes-susceptibility variant within KCNJ11), polycystic ovary syndrome and androgen levels. A1 - Barber, TM A1 - Bennett, AJ A1 - Gloyn, AL A1 - Groves, CJ A1 - Sovio, U A1 - Ruokonen, A A1 - Martikainen, H A1 - Pouta, A A1 - Taponen, S A1 - Weedon, MN A1 - Hartikainen, AL A1 - Wass, JA A1 - Järvelin, MR A1 - Zeggini, E A1 - Franks, S A1 - McCarthy, MI J1 - Eur J Hum Genet Y1 - 2007/06// VL - 15 SN - 1018-4813 SP - 679 EP - 684 N2 - Polycystic ovary syndrome (PCOS) is strongly associated with hyperinsulinaemia and type II diabetes (T2D). Sequence variation within KCNJ11 (encoding Kir6.2, the beta-cell inwardly rectifying potassium channel) is implicated in the pathogenesis of neonatal diabetes, hyperinsulinaemia of infancy and multifactorial T2D. Comprehensive tagging studies have demonstrated that the KCNJ11 E23K variant (or ABCC8 A1369S in LD>0.9) is responsible for the known association between KCNJ11 and T2D. Given the phenotypic overlap between PCOS and T2D, we investigated whether E23K is involved in susceptibility to PCOS and related traits. Case-control analyses for the KCNJ11 E23K variant were performed in (a) 374 PCOS cases and 2574 controls of UK British/Irish origin, and (b) 550 women with PCOS symptoms and 1114 controls from a Finnish birth cohort. The relationship between E23K genotype and androgen levels (a key intermediate phenotype relevant to PCOS) in 1380 samples was studied. The UK case-control analysis revealed no association between E23K genotypes and PCOS status (P=0.49; Cochran-Armitage test), and no significant relationship between E23K genotype and androgen measures in the samples for which these phenotypes were available (P=0.19). Similarly, the Finnish case-control analysis showed no association between E23K genotypes and PCOS status (P=0.75; Cochran-Armitage test), and no significant relationship between E23K genotype and androgen measures in the samples for which these phenotypes were available (Finnish controls, P=0.25; Finnish cases, P=0.08). In conclusion, these data (involving >4600 subjects) provide no evidence that common variants of the KCNJ11 E23K polymorphism have a major influence on PCOS susceptibility, though modest effect sizes (OR<1.25) cannot be excluded. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17342155&query_hl=1 ER - TY - JFULL T1 - Predictors of progression of coronary artery calcium in type 2 diabetes: The predict study A1 - Elkeles, RS A1 - Rubens, M A1 - Godsland, IF A1 - Nugara, F A1 - Richmond, W A1 - Flather, MD J1 - ATHEROSCLEROSIS SUPP Y1 - 2007/06// VL - 8 SN - 1567-5688 SP - 8 EP - 8 ER - TY - JFULL T1 - Diabetes prevalence, process of care and outcomes in relation to practice size, caseload and deprivation: national cross-sectional study in primary care. A1 - Millett, C A1 - Car, J A1 - Eldred, D A1 - Khunti, K A1 - Mainous, AG A1 - Majeed, A J1 - J R Soc Med Y1 - 2007/06// VL - 100 SN - 0141-0768 SP - 275 EP - 283 N2 - OBJECTIVE: To examine the association between practice list size, deprivation and the quality of care of patients with diabetes. DESIGN: Population-based cross-sectional study using Quality and Outcomes Framework data. SETTING: England and Scotland. PARTICIPANTS: 55,522,778 patients and 8970 general practices with 1,852,762 people with diabetes. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Seventeen process and surrogate outcome measures of diabetes care. RESULTS: The prevalence of diabetes was 3.3%. Prevalence differed with practice list size and deprivation: smaller and more deprived practices had a higher mean prevalence than larger and more affluent practices (3.8% versus 2.8%). Practices with large patient list sizes had the highest quality of care scores, even after stratifying for deprivation. However, with the exception of retinal screening, peripheral pulses and neuropathy testing, differences in achievement between small and large practices were modest (<5%). Small practices performed nearly as well as the largest practices in achievement of intermediate outcome targets for HbA1c, blood pressure and cholesterol (smallest versus largest practices: 57.4% versus 58.7%; 70.7% versus 70.7%; and 69.5% versus 72.7%, respectively). Deprivation had a negative effect on the achieved scores and this was more pronounced for smaller practices. CONCLUSION: Our study provides some evidence of a volume-outcome association in the management of diabetes in primary care; this appears most pronounced in deprived areas. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17541098&query_hl=1 ER - TY - JFULL T1 - CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater. A1 - Gras, L A1 - Kesselring, AM A1 - Griffin, JT A1 - van Sighem, AI A1 - Fraser, C A1 - Ghani, AC A1 - Miedema, F A1 - Reiss, P A1 - Lange, JM A1 - de Wolf, F A1 - ATHENA, Netherlands National Observational Cohort Study J1 - J Acquir Immune Defic Syndr Y1 - 2007/06/01/ VL - 45 SN - 1525-4135 SP - 183 EP - 192 N2 - OBJECTIVE: CD4 cell count changes in therapy-naive patients were investigated during 7 years of highly active antiretroviral therapy (HAART) in an observational cohort. METHODS: Three endpoints were studied: (1) time to >or=800 CD4 cells/mm in 5299 therapy-naive patients starting HAART, (2) CD4 cell count changes during 7 years of uninterrupted HAART in a subset of 544 patients, and (3) reaching a plateau in CD4 cell restoration after 5 years of HAART in 366 virologically suppressed patients. RESULTS: Among patients with <50, 50 to 200, 200 to 350, 350 to 500, and >or=500 CD4 cells/mm at baseline, respectively, 20%, 26%, 46%, 73%, and 87% reached >or=800 CD4 cells/mm within 7 years of starting HAART. Periods with HIV RNA levels >500 copies/mL and age >or=50 years were associated with lesser increases in CD4 cell counts between 6 months and 7 years. Having reached >or=800 CD4 cells/mm at 5 years, age >or=50 years, and >or=1 HIV RNA measurement >1000 copies/mL between 5 and 7 years were associated with a plateau in CD4 cell restoration. CONCLUSIONS: Restoration to CD4 cell counts >or=800 cells/mm is feasible within 7 years of HAART in most HIV-infected patients starting with >or=350 cells/mm and achieving sufficient suppression of viral replication. Particularly in patients >or=50 years of age, it may be beneficial to start earlier than current guidelines recommend. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17414934&query_hl=1 ER - TY - JFULL T1 - Asthma: 1987-2007. What have we achieved and what are the persisting challenges? A1 - Partridge, MR J1 - Prim Care Respir J Y1 - 2007/06// VL - 16 SN - 1471-4418 SP - 145 EP - 148 N2 - Despite an increasing prevalence of asthma, enormous advances have been made in our understanding and management of asthma over the last 20 years. Work begun two or three decades ago demonstrated the inflammatory nature of asthma, emphasised the need for regular treatment, and introduced the goal of maintaining normal lung function. More recent work demonstrated the benefits of adding a long-acting inhaled beta-agonist to low-dose inhaled steroids as an alternative to escalating the steroid dosage. More recently still, studies and regulatory approval have led to the possibility of the same inhaler being used for maintenance therapy and for relief. However, these new ways of using old medicines, along with some new medicines such as omalizumab, should not detract us from looking beyond the prescription. The challenges facing us now are to determine why the prevalence of asthma has increased so dramatically, and in the absence of a cure how we can best help increasing numbers of people with asthma benefit from the treatment which is available. This will involve a much more aggressive implementation of advice regarding self-management education and a restructuring of health services to provide a service that is cognisant of the fact that, like us, patients are increasingly busy - and if they are to benefit from regular review, that review needs to be offered at a convenient time and by convenient methods. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17530142&query_hl=1 ER - TY - JFULL T1 - Evidence for boosting Mycobacterium tuberculosis-specific IFN-gamma responses at 6 weeks following tuberculin skin testing A1 - Naseer, A A1 - Naqvi, S A1 - Kampmann, B J1 - EUR RESPIR J Y1 - 2007/06// VL - 29 SN - 0903-1936 SP - 1282 EP - 1283 ER - TY - JFULL T1 - Assessment of exposure to mercury from industrial emissions: comparing "distance as a proxy" and dispersion modelling approaches. A1 - Hodgson, S A1 - Nieuwenhuijsen, MJ A1 - Colvile, R A1 - Jarup, L J1 - Occup Environ Med Y1 - 2007/06// VL - 64 SN - 1470-7926 SP - 380 EP - 388 N2 - BACKGROUND: The Runcorn area, north-west England, contains many pollution sources, the health effects of which have been under discussion for over 100 years. Preliminary investigations revealed an excess risk of mortality from kidney disease in people living nearest to several point sources of pollution, using distance as a proxy for exposure. Ongoing epidemiological investigations into the effect of ambient mercury exposure on dose and renal effect required a more refined assessment of exposure. METHODS: Atmospheric dispersion modelling was used to assess mercury dispersion from three mercury-emitting sources (including a large chlor alkali plant), based on knowledge of emissions, local meteorology and topography. RESULTS: The model was sensitive to various input parameters, with different dispersion patterns and ground-level concentrations, and therefore different exposed populations identified when different input parameters were defined. The different approaches to exposure assessment also had an impact on the epidemiological findings. The model output correlated well with weekly monitoring data collected in the local area, although the model underestimated concentrations in close proximity to the chlor alkali plant. The model identified that one point source did not contribute significantly to ground-level mercury concentrations, so that inclusion of this source when using the "distance as a proxy" approach led to significant exposure misclassification. CONCLUSIONS: The model output indicates that assessment of ambient exposure should give consideration to the magnitude of emissions, point source characteristics, local meteorology and topography to ensure that the most appropriate exposure classification is reached. Even if dispersion modelling cannot be undertaken, these data can be used to inform and improve the distance as a proxy approach, and improve the interpretability of the epidemiological findings. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17182645&query_hl=1 ER - TY - JFULL T1 - IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. A1 - Martineau, AR A1 - Wilkinson, KA A1 - Newton, SM A1 - Floto, RA A1 - Norman, AW A1 - Skolimowska, K A1 - Davidson, RN A1 - Sørensen, OE A1 - Kampmann, B A1 - Griffiths, CJ A1 - Wilkinson, RJ J1 - J Immunol Y1 - 2007/06/01/ VL - 178 SN - 0022-1767 SP - 7190 EP - 7198 N2 - Vitamin D deficiency is associated with susceptibility to tuberculosis, and its biologically active metabolite, 1alpha,25 dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)), has pleiotropic immune effects. The mechanisms by which 1alpha,25(OH)(2)D(3) protects against tuberculosis are incompletely understood. 1alpha,25(OH)(2)D(3) reduced the growth of mycobacteria in infected human PBMC cultures in a dose-dependent fashion. Coculture with agonists or antagonists of the membrane or nuclear vitamin D receptors indicated that these effects were primarily mediated by the nuclear vitamin D receptors. 1alpha,25(OH)(2)D(3) reduced transcription and secretion of protective IFN-gamma, IL-12p40, and TNF in infected PBMC and macrophages, indicating that 1alpha,25(OH)(2)D(3) does not mediate protection via these cytokines. Although NOS2A was up-regulated by 1alpha,25(OH)(2)D(3), inhibition of NO formation marginally affected the suppressive effect of 1alpha,25(OH)(2)D(3) on bacillus Calmette Guérin in infected cells. By contrast, 1alpha,25(OH)(2)D(3) strongly up-regulated the cathelicidin hCAP-18 gene, and some hCAP-18 polypeptide colocalized with CD14 in 1alpha,25(OH)(2)D(3) stimulated PBMC, although no detectable LL-37 peptide was found in supernatants from similar 1alpha,25(OH)(2)D(3)-stimulated PBMC cultures. A total of 200 mug/ml of the active peptide LL-37, in turn, reduced the growth of Mycobacterium tuberculosis in culture by 75.7%. These findings suggest that vitamin D contributes to protection against TB by "nonclassical" mechanisms that include the induction of antimicrobial peptides. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17513768&query_hl=1 ER - TY - JFULL T1 - Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model. A1 - Sun, N A1 - Wood, NB A1 - Hughes, AD A1 - Thom, SA A1 - Yun Xu, X J1 - Am J Physiol Heart Circ Physiol Y1 - 2007/06// VL - 292 SN - 0363-6135 SP - H3148 EP - H3157 N2 - The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17277019&query_hl=1 ER - TY - JFULL T1 - Millennium development goals: an unbalanced approach to global health. A1 - Poole-Wilson, PA J1 - Nat Clin Pract Cardiovasc Med Y1 - 2007/06// VL - 4 SN - 1743-4300 SP - 289 EP - 289 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17522717&query_hl=1 ER - TY - JFULL T1 - Prospective study of sputum induction, gastric washing, and bronchoalveolar lavage for the diagnosis of pulmonary tuberculosis in patients who are unable to expectorate. A1 - Brown, M A1 - Varia, H A1 - Bassett, P A1 - Davidson, RN A1 - Wall, R A1 - Pasvol, G J1 - Clin Infect Dis Y1 - 2007/06/01/ VL - 44 SN - 1537-6591 SP - 1415 EP - 1420 N2 - BACKGROUND: Many adults with pulmonary tuberculosis are unable to expectorate. Gastric washing, sputum induction using nebulized hypertonic saline, and bronchoscopy with bronchoalveolar lavage have all been used to obtain specimens for diagnosis, but to our knowledge, the timing and volume of induced sputum have not been well studied, and these 3 methods have not been compared. METHODS: The study recruited consecutive adult inpatients with chest radiography findings suggestive of tuberculosis who were unable to expectorate. Subjects provided 3 induced sputum samples for culture on day 1 and additional samples on days 2 and 3. In addition, gastric washing specimens were collected on days 1, 2, and 3. A proportion of subjects with negative smear results underwent bronchoalveolar lavage. RESULTS: The study recruited 140 subjects. Among 107 subjects who provided 3 gastric washing specimens and at least 3 induced sputum specimens, 43% had cultures positive for Mycobacterium tuberculosis. Use of 3 induced sputum samples detected more cases than did use of 3 gastric washings (39% vs. 30%; P=.03). Among 79 subjects with culture results for all 5 induced sputum specimens, there was no difference in yield between samples obtained by induced sputum induction performed in a single day or that performed over 3 days (34% vs. 37%; P=.63). There was no association between sputum volume and positive culture results. No additional cases were diagnosed in the 21 patients who underwent bronchoscopy. CONCLUSIONS: Use of 3 induced sputum samples was more sensitive than use of 3 gastric washings for diagnosis of tuberculosis in patients who could not expectorate spontaneously. Use of bronchoscopy with bronchoalveolar lavage did not increase diagnostic sensitivity. Samples could be collected in 1 day, allowing for faster diagnosis, faster initiation of treatment, and shorter hospital stay. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17479935&query_hl=1 ER - TY - JFULL T1 - National trends in the use and costs of anti-obesity medications in England 1998-2005. A1 - Srishanmuganathan, J A1 - Patel, H A1 - Car, J A1 - Majeed, A J1 - J Public Health (Oxf) Y1 - 2007/06// VL - 29 SN - 1741-3842 SP - 199 EP - 202 N2 - BACKGROUND: To report the trends in the use and costs of anti-obesity medications in England from 1998 to 2005. METHODS: We analysed data on all community anti-obesity drug prescriptions in England collated by the prescription cost analysis system. RESULTS: Between 1998 and 2005, Orlistat prescriptions rose 36-fold from 17,880 to 646,700 and total cost increased by over 35-fold. Sibutramine prescriptions rose from 2001 to 2005 from 53,393 to 227,000, a 4-fold increase. Although prescriptions of Orlistat and Sibutramine have increased substantially since they were first introduced, the rate of growth decreased substantially in recent years until 2005, when a significant increase in the number and cost of prescriptions for orlistat occurred yet again. CONCLUSIONS: We found a large increase in the use and costs of anti-obesity prescriptions, consistent with the increased awareness of obesity amongst health care professionals and the public. Despite this large increase, there are still no head-to-head studies at a national level that directly compare all anti-obesity medication in use in the UK. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17494061&query_hl=1 ER - TY - JFULL T1 - Differences in the magnitude rather than the timing of wave reflection can explain the ASCOT results A1 - Manisty, C A1 - Davies, J A1 - Whinnett, Z A1 - Francis, D A1 - Zambanini, A A1 - Zambanini, A A1 - Curtis, S A1 - Thom, S A1 - Hughes, A A1 - Mayet, J J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A80 EP - A80 ER - TY - JFULL T1 - TLR9 polymorphisms determine murine lymphocyte responses to Helicobacter: results from a genome-wide scan. A1 - Anderson, AE A1 - Worku, ML A1 - Khamri, W A1 - Bamford, KB A1 - Walker, MM A1 - Thursz, MR J1 - Eur J Immunol Y1 - 2007/06// VL - 37 SN - 0014-2980 SP - 1548 EP - 1561 N2 - Immune responses to microorganisms in the gastrointestinal tract must be carefully controlled to avoid disease. Helicobacter are Gram-negative bacteria which cause persistent infection and, in a minority of hosts, peptic ulceration or gastric cancer. Lymphocyte responses are important determinants of the outcome of infection. Therefore, it is important to identify the genetic determinants of lymphocyte responses to this mucosal pathogen. Using a (C57BL/6xBALB/c) F2 mouse model of Helicobacter infection, we mapped a region of linkage for lymphoproliferation to chromosome 9. Analysis of candidate genes in this region revealed variation of DNA sequence and gene expression in the TLR9 gene between C57BL/6 and BALB/c mouse strains. Reporter assays demonstrated higher levels of TLR9 transcriptional activity and increased NF-kappaB activation associated with the C57BL/6 TLR9 promoter and coding sequences. The importance of TLR9 in the control of lymphocyte responses was confirmed by demonstrating that lymphoproliferation and IFN-gamma secretion was diminished in the TLR9-/- mouse. Furthermore, neutrophil infiltration of the gastric epithelium is reduced in the absence of TLR9. Regulation of TLR9 expression and signalling therefore appears to play an important role in the control of lymphocyte responses to Helicobacter and potentially other luminal microorganisms. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17474149&query_hl=1 ER - TY - JFULL T1 - Misleading meta-analysis: a need to look beyond the headlines. A1 - Chaturvedi, N A1 - Bilous, R A1 - Hardy, R A1 - Remuzzi, G A1 - Ruggenenti, P A1 - Viberti, GC J1 - Diabet Med Y1 - 2007/06// VL - 24 SN - 0742-3071 SP - 587 EP - 591 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17490423&query_hl=1 ER - TY - JFULL T1 - Health, livelihoods, and nutrition in low-income rural systems. A1 - Joffe, M J1 - Food Nutr Bull Y1 - 2007/06// VL - 28 SN - 0379-5721 SP - S227 EP - S236 N2 - BACKGROUND: Absolute poverty remains a major challenge: the proportion of the world population living with hunger, food insecurity, and undernutrition has fallen, but the absolute number remains stubbornly large. An even larger number of people have enough to eat but suffer from severe micronutrient deficiencies. OBJECTIVES: To provide a conceptual framework showing the interdependence of hunger and poverty with ill health among the rural poor. METHODS: Review of the relevant health, nutrition, agriculture, and economics literature and organization of the findings into a systems framework. RESULTS: Economic growth is not a sufficient answer to rural poverty. The predicament of poor households can be represented in terms of a self-reinforcing cycle involving nutrition, health, and productivity. The degree of poverty limits the quantity and quality of food intake. Macro- and micronutrient deficiencies interfere with child growth and development and impair immune function, resulting in a predisposition to infectious diseases. Health status strongly influences the quantity and quality of labor and achieved educational status. The high risk of child mortality prevents households from going through the demographic transition to smaller families and better-educated children. The death of a working adult may be catastrophic for the household. This self-reinforcing cycle means that the beneficial effects of an intervention are propagated around the cycle, potentiating its impact. Each main element--nutrition, health, and productivity--also has numerous other determinants and can be influenced by interventions. Interventions that increase the carrying capacity of the household's environment are likely to be more sustainable than "technical fixes," such as lifesaving medical treatment. CONCLUSIONS: The self-reinforcing cycle is likely to be self-perpetuating without outside intervention. For any rural area where poverty reduction is planned, the key bottlenecks need to be identified. This can be done by using a causal diagram, as described in this paper. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17658069&query_hl=1 ER - TY - JFULL T1 - A high density genome-wide association study identifies novel susceptibility genes for type 2 diabetes mellitus and reveals new mechanisms for glucose intolerance A1 - Sladek, R A1 - Rocheleau, G A1 - Rung, J A1 - Dina, C A1 - Shen, LS A1 - Serre, D A1 - Boutin, P A1 - Prentki, M A1 - Posner, BI A1 - Balding, DJ A1 - Meyre, D A1 - Polychronakos, C A1 - Froguel, P J1 - DIABETES Y1 - 2007/06// VL - 56 SN - 0012-1797 SP - A94 EP - A94 ER - TY - JFULL T1 - Evaluation of molecular typing methods in characterizing a European collection of epidemic methicillin-resistant Staphylococcus aureus strains: the HARMONY collection. A1 - Cookson, BD A1 - Robinson, DA A1 - Monk, AB A1 - Murchan, S A1 - Deplano, A A1 - de Ryck, R A1 - Struelens, MJ A1 - Scheel, C A1 - Fussing, V A1 - Salmenlinna, S A1 - Vuopio-Varkila, J A1 - Cuny, C A1 - Witte, W A1 - Tassios, PT A1 - Legakis, NJ A1 - van Leeuwen, W A1 - van Belkum, A A1 - Vindel, A A1 - Garaizar, J A1 - Haeggman, S A1 - Olsson-Liljequist, B A1 - Ransjo, U A1 - Muller-Premru, M A1 - Hryniewicz, W A1 - Rossney, A A1 - O'Connell, B A1 - Short, BD A1 - Thomas, J A1 - O'Hanlon, S A1 - Enright, MC J1 - J Clin Microbiol Y1 - 2007/06// VL - 45 SN - 0095-1137 SP - 1830 EP - 1837 N2 - We analyzed a representative sample of methicillin-resistant Staphylococcus aureus (MRSA) from 11 European countries (referred to as the HARMONY collection) using three molecular typing methods used within the HARMONY group to examine their usefulness for large, multicenter MRSA surveillance networks that use these different laboratory methodologies. MRSA isolates were collected based on their prevalence in each center and their genetic diversity, assessed by pulsed-field gel electrophoresis (PFGE). PFGE groupings (< or = 3 bands difference between patterns) were compared to those made by sequencing of the variable repeats in the protein A gene spa and clonal designations based on multilocus sequence typing (MLST), combined with PCR analysis of the staphylococcal chromosome cassette containing the mec genes involved in methicillin resistance (SCCmec). A high level of discrimination was achieved using each of the three methodologies, with discriminatory indices between 89.5% and 91.9% with overlapping 95% confidence intervals. There was also a high level of concordance of groupings made using each method. MLST/SCCmec typing distinguished 10 groups containing at least two isolates, and these correspond to the majority of nosocomial MRSA clones described in the literature. PFGE and spa typing resolved 34 and 31 subtypes, respectively, within these 10 MRSA clones, with each subtype differing only slightly from the most common pattern using each method. The HARMONY group has found that the methods used in this study differ in their availability and affordability to European centers involved in MRSA surveillance. Here, we demonstrate that the integration of such technologies is achievable, although common protocols (such as we have developed for PFGE) may also be important, as is the use of centralized Internet sites to facilitate data analysis. PFGE and spa-typing data from analysis of MRSA isolates from the many centers that have access to the relevant equipment can be compared to reference patterns/sequences, and clonal designations can be made. In the majority of cases, these will correspond to those made by the (more expensive) method of choice-MLST/SCCmec typing-and these alternative methods can therefore be used as frontline typing systems for multicenter surveillance of MRSA. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17428929&query_hl=1 ER - TY - JFULL T1 - Enhanced systemic no bioavailability by growth-hormone mediated IGF-1 increase improves number and function of endothelial progenitor cells in aged individuals A1 - Thum, T A1 - Hoeber, S A1 - Froese, S A1 - Klink, I A1 - Stichtenoth, DO A1 - Galuppo, P A1 - Jakob, M A1 - Tsikas, D A1 - Anker, SD A1 - Poole-Wilson, PA A1 - Ertl, G A1 - Bauersachs, J J1 - ATHEROSCLEROSIS SUPP Y1 - 2007/06// VL - 8 SN - 1567-5688 SP - 215 EP - 215 ER - TY - JFULL T1 - The Clinical Assessment of Retinal Microvascular Structure and Therapeutic Implications. A1 - Hughes, AD J1 - Curr Treat Options Cardiovasc Med Y1 - 2007/06// VL - 9 SN - 1092-8464 SP - 236 EP - 241 N2 - Examination of the retinal microvasculature is widely used to assess diabetic eye disease and as an indicator of target organ damage in hypertension. The diagnostic value of grading of hypertensive retinopathy is dubious; however, many recent studies have demonstrated that hypertensive retinopathy is associated with a range of risk factors for cardiovascular disease and may predict cardiovascular events independently of blood pressure. Developments in digital imaging and computer-assisted analysis have facilitated the quantitative assessment of microvascular changes in cardiovascular disease. These approaches may be useful for assessing cardiovascular risk and targeting therapeutic intervention. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17601388&query_hl=1 ER - TY - JFULL T1 - Matched-related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research A1 - Panepinto, JA A1 - Walters, MC A1 - Carreras, J A1 - Marsh, J A1 - Bredeson, CN A1 - Gale, RP A1 - Hale, GA A1 - Horan, J A1 - Hows, JM A1 - Klein, JP A1 - Pasquini, R A1 - Roberts, I A1 - Sullivan, K A1 - Eapen, M A1 - Ferster, A A1 - Non Malignant Marrow Disorders J1 - BRIT J HAEMATOL Y1 - 2007/06// VL - 137 SN - 0007-1048 SP - 479 EP - 485 N2 - We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received > 10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide-containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy. ER - TY - JFULL T1 - Influenza pandemic vaccines: spread them thin? A1 - Fraser, C J1 - PLoS Med Y1 - 2007/06// VL - 4 SN - 1549-1676 SP - e228 EP - e228 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17579513&query_hl=1 ER - TY - JFULL T1 - Differential effects of SERCA2a transfection on ventricular arrhythmia susceptibility in the normal rat heart A1 - Lyon, AR A1 - Poole-Wilson, PA A1 - Peters, NS A1 - Harding, SE J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S20 EP - S20 ER - TY - JFULL T1 - Emergence of 19A as virulent and multidrug resistant Pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine. A1 - Pelton, SI A1 - Huot, H A1 - Finkelstein, JA A1 - Bishop, CJ A1 - Hsu, KK A1 - Kellenberg, J A1 - Huang, SS A1 - Goldstein, R A1 - Hanage, WP J1 - Pediatr Infect Dis J Y1 - 2007/06// VL - 26 SN - 0891-3668 SP - 468 EP - 472 N2 - BACKGROUND: The long-term effects of selective pressure from conjugate pneumococcal vaccine on the serotype distribution and antimicrobial resistance of carriage and invasive isolates of Streptococcus pneumoniae are unknown. Early changes demonstrate a reduction in vaccine serotypes and an increase in nonvaccine serotypes (NVT) among both carriage and invasive isolates. Ongoing surveillance is necessary to identify emerging invasive serotypes and antimicrobial susceptibilities. METHODS: Enhanced surveillance of invasive pneumococcal disease in Massachusetts began in October 2001 and remains ongoing. Isolates from children less than 5 are sent to the Massachusetts Department of Public Health and subsequently to the Maxwell Finland laboratory for serotyping and determination of antimicrobial susceptibility. Annual incidence rates for vaccine serotype and NVT disease are calculated using 2000 census data. RESULTS: NVT caused 72%-91% of invasive pneumococcal disease annually in children less than 5 years of age between 2002 and 2005. Serotype 19A has emerged as the most frequent cause of IPD in Massachusetts. A multidrug-resistant clone (ceftriaxone, amoxicillin, azithromycin and trimethoprim-sulfamethoxazole) (MLST 320) was first identified in Massachusetts in 2005. CONCLUSIONS: Three years after the introduction of pneumococcal conjugate vaccine for universal administration to children less than 2 in Massachusetts, a significant increase in invasive disease due to serotype 19A was observed. Although MLST 199 remains the most frequent sequence type among invasive isolates (of 19A), a multidrug-resistant sequence type, not previously identified in Massachusetts, has become an important cause of invasive disease. Further surveillance of the changing ecology of S. pneumoniae is necessary as a 4-year time period is not sufficient to fully evaluate the impact of PCV of pneumococcal infections. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17529860&query_hl=1 ER - TY - JFULL T1 - Atopy, wheeze and bronchial responsiveness in young Chilean adults. Do dietary antioxidants matter? A1 - García-Larsen, V A1 - Chinn, S A1 - Arts, IC A1 - Amigo, H A1 - Rona, RJ J1 - Allergy Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 714 EP - 715 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17508981&query_hl=1 ER - TY - JFULL T1 - Mechanical and cold hypersensitivity in nerve-injured C57BL/6J mice is not associated with fear-avoidance- and depression-related behaviour. A1 - Hasnie, FS A1 - Wallace, VC A1 - Hefner, K A1 - Holmes, A A1 - Rice, AS J1 - Br J Anaesth Y1 - 2007/06// VL - 98 SN - 0007-0912 SP - 816 EP - 822 N2 - BACKGROUND: Neuropathic pain is associated with significant co-morbidity, including anxiety and depression, which impact considerably on the overall patient experience. However, pain co-morbidity symptoms are rarely assessed in animal models of neuropathic pain. To improve the clinical validity of a widely used rodent model of traumatic peripheral neuropathy, we have investigated fear-avoidance- and depression-related behaviours in nerve-injured and sham-operated mice over a 4 week period. METHODS: Male C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) or sham surgery and were assessed on days 7, 14, and 28 after operation. Withdrawal thresholds to punctate mechanical and cooling stimuli were measured. Mice were tested on the novel open-field and elevated plus-maze tests for fear-avoidance behaviour, and on the tail suspension test for depression-related behaviour. RESULTS: Hypersensitivity to punctate mechanical and cool stimuli was evident up to day 28 after PSNL. However, there was no change in fear-avoidance- or depression-related behaviours regardless of interval after-surgery. CONCLUSION: These data demonstrate that pain behaviour in nerve-injured C57BL/6J mice was not associated with alterations in emotion-related behaviours. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17478455&query_hl=1 ER - TY - JFULL T1 - Can organisational change reduce hospital acquired infections? A1 - Holmes, AH J1 - J Hosp Infect Y1 - 2007/06// VL - 65 Suppl 2 SN - 0195-6701 SP - 191 EP - 192 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17540269&query_hl=1 ER - TY - JFULL T1 - An annual, prospective, international study of outpatients with cardiovascular disease or risk factors: design and methods of the CardioMonitor registry. A1 - Steinberg, BA A1 - Ballantyne, CM A1 - Bhatt, DL A1 - Montalescot, G A1 - Mehta, S A1 - O'Hagan, P A1 - Poole-Wilson, PA A1 - Cannon, CP J1 - Crit Pathw Cardiol Y1 - 2007/06// VL - 6 SN - 1535-2811 SP - 72 EP - 75 N2 - OBJECTIVE: To assess penetration and patterns of treatments in outpatients with cardiovascular disease (CVD) or risk factors. STUDY: An international, observational survey of physicians treating outpatients with CVD or risk factors. DESIGN AND SETTING: A unique, diversified group of physicians caring for patients with CVD or risk factors is sampled annually in countries around the world. Participating physicians register up to 15 patients with CVD or risk factors, recording demographics, medical history, clinical data, diagnoses, and medications. The registry has run annually, with different cohorts of physicians and patients each year. RESULTS: Over 9 years, the CardioMonitor registry has included participation by 18,145 physicians, registering 264,570 patients from 16 countries. Of these, 100,495 (38%) patients had cardiac disease, 26,720 (10%) had cerebrovascular disease, and 21,231 (8%) had peripheral arterial disease (not exclusive diagnoses). The remainder, 139,234 (52.6%) patients did not have clinically significant vascular disease, but had risk factors, including hypertension, diabetes, or dyslipidemia. CONCLUSION: This registry of outpatients with cardiovascular risk factors or disease with detailed medication use recorded offers new insights into trends in current practice of medicine for this large group of patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17667869&query_hl=1 ER - TY - JFULL T1 - The safety of amiodarone in patients with heart failure. A1 - Torp-Pedersen, C A1 - Metra, M A1 - Spark, P A1 - Lukas, MA A1 - Moullet, C A1 - Scherhag, A A1 - Komajda, M A1 - Cleland, JG A1 - Remme, W A1 - Di Lenarda, A A1 - Swedberg, K A1 - Poole-Wilson, PA A1 - COMET Investigators J1 - J Card Fail Y1 - 2007/06// VL - 13 SN - 1532-8414 SP - 340 EP - 345 N2 - BACKGROUND: Uncertainty persists about the safety and efficacy of amiodarone for the management of heart failure. METHODS AND RESULTS: We randomized 3029 patients with chronic heart failure to receive carvedilol or metoprolol and followed patients for a median of 58 months. One hundred fifty-five of 1466 patients in New York Heart Association (NYHA) Class II and 209 of 1563 in Class III or IV received amiodarone at baseline. Persistence with amiodarone treatment was high and 66% received amiodarone after 4 years. During follow-up, 38.7% and 58.9% of patients receiving amiodarone in NYHA Classes II and III + IV died versus 26.2% and 43.3% not receiving amiodarone (P < .001). This difference was maintained in multivariable analysis (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-1.7, P < .001). The difference was explained by an increased risk of death due to circulatory failure (HR 2.4, CI 1.9-3.1, P < .001) in patients receiving amiodarone. Sudden death was not different (HR 1.07, CI 0.8-1.4, P = .7). The increased risk was similar across NYHA classes with HR of 1.60 (CI 1.2-2.1, P < .001) in NYHA Class II versus 1.58 (CI 1.3-1.9, P < .001) in Classes III + IV. CONCLUSIONS: Treatment with amiodarone was associated with an increased risk of death from circulatory failure independent of functional class. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17602979&query_hl=1 ER - TY - JFULL T1 - Trachoma: transmission, infection, and control. A1 - Gambhir, M A1 - Basáñez, MG A1 - Turner, F A1 - Kumaresan, J A1 - Grassly, NC J1 - Lancet Infect Dis Y1 - 2007/06// VL - 7 SN - 1473-3099 SP - 420 EP - 427 N2 - Mass antibiotic treatment and facial cleanliness are central to WHO's strategy for the elimination of blindness caused by trachoma. Recent studies have highlighted the heterogeneous response of communities to mass treatment and the complex relation between infection with Chlamydia trachomatis and clinical disease. It is important to be able to explain these findings to predict and maximise the effect of treatment on active trachoma disease and blindness in the community. Here we review the immunobiology of trachoma and provide a simple conceptual model of disease pathogenesis. We show how incorporating this model into a mathematical framework leads to an explanation of the observed community distribution of infection, bacterial load, and disease with age. The predictions of the model and empirical data show some differences that underscore the importance of individual heterogeneity in response to infection. The implications of disease transmission and pathogenesis for trachoma control programmes are discussed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17521595&query_hl=1 ER - TY - JFULL T1 - Risk factors for renal injury in patients with meningomyelocele. A1 - Arora, G A1 - Narasimhan, KL A1 - Saxena, AK A1 - Kaur, B A1 - Mittal, BR J1 - Indian Pediatr Y1 - 2007/06// VL - 44 SN - 0019-6061 SP - 417 EP - 420 N2 - PATIENTS AND METHODS: Thirty operated patients of myelodysplasia were clinically evaluated for the age at presentation, the extent of lesion and neurological deficit. Urological assessment was done with urine cultures, serum creatinine, radiological (ultrasound of kidney, ureters and bladder, voiding cystourethrogram) and urodynamic (water cystometry) parameters. An objective scoring for bladder (Galloway, et al.) was applied. Dimercapto-succinic acid (DMSA) scan was done in all the patients for evidence of renal scars. The results of above investigations were correlated with presence or absence of renal scars (renal injury) on DMSA scan. None of the patients had received any prior bladder care. RESULTS: Twenty one patients had no renal scars and 9 patients had evidence of renal scarring. Patients with renal scars were older at presentation, they had greater degree of hydroureteronephrosis (P < or = 0.001) and vesicoureteric reflux (P < or = 0.005). The incidence of high leak pressures (>25 cm of water, P < or = 0.05), unacceptable bladder volumes (maximum cystometric capacity < 60% for age, P < or = 0.005) and high risk Galloway's score (> 5, P < or = 0.05) was high in patients with associated renal scarring as compared to their nonscarred counterparts. Three of these patients had serum creatinine >1 mg/dl (P < or = 0.005). The incidence of urinary complaints and positive urine cultures was also higher in these patients (NS). CONCLUSION: Increasing age, evidence of hydroureteronephrosis and vesicoureteric reflux, high leak pressures, low bladder volume and high combined Galloway score (>5) define a high risk bladder in our population and predispose to renal injury in patients of myelodysplasia. Early referral for bladder risk assessment and management of all myelodysplasia patients is recommended. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17620693&query_hl=1 ER - TY - JFULL T1 - RSV-infected airway epithelial cells cause biphasic up-regulation of CCR1 expression on human monocytes. A1 - Morrison, PT A1 - Thomas, LH A1 - Sharland, M A1 - Friedland, JS J1 - J Leukoc Biol Y1 - 2007/06// VL - 81 SN - 0741-5400 SP - 1487 EP - 1495 N2 - Respiratory syncytial virus (RSV) infection can cause extensive airway inflammation, which is orchestrated by chemokines and their receptors. RSV-infected epithelial cells secrete many cytokines and chemokines, but little is known about regulation of chemokine receptors on target cells. We investigated the effects of conditioned media (CM) from RSV-infected epithelial cells on monocyte CCR1, CCR2, and CCR5 expression. RSV-CM but not control-CM stimulated a biphasic increase in cell-surface CCR1, and levels peaked at 36 h and 96 h poststimulation. Similar CCR1 up-regulation occurred on monocyte-derived macrophages. Cytochlasin D and colchicine blocked both peaks of expression, demonstrating requirement of a functional cytoskeleton. Intracellular staining revealed little internal sequestration of CCR1 protein, and CCR1 up-regulation was inhibited by actinomycin D and cycloheximide, indicating that both waves of RSV-CM-induced surface CCR1 expression were dependent on de novo transcription and protein synthesis. Cytokine-neutralizing experiments showed that the effects of RSV-CM were decreased by blocking TNF-alpha (percent inhibition=51+/-2.3% at 36 h peak and 42+/-7.7% at 96 h peak) and to a lesser extent, IL-1 (percent inhibition=32+/-7.2% at 36 h and 23+/-2.9% at 96 h). In summary, RSV-CM causes a biphasic up-regulation of surface CCR1 on monocytes, which is dependent on an intact cytoskeleton, requires new gene transcription and protein synthesis, and is mediated in part by the proinflammatory cytokines TNF-alpha and IL-1. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17389578&query_hl=1 ER - TY - JFULL T1 - Fishing injury resulting in Mycobacterium fortuitum palmar abscess. A1 - Patel, B A1 - Nanchalal, J A1 - Friedland, JS J1 - Eur J Clin Microbiol Infect Dis Y1 - 2007/06// VL - 26 SN - 0934-9723 SP - 427 EP - 429 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17458567&query_hl=1 ER - TY - JFULL T1 - Chemokines and their receptors in respiratory disease: a therapeutic target for respiratory syncytial virus infection. A1 - Thomas, LH A1 - Friedland, JS A1 - Sharland, M J1 - Expert Rev Anti Infect Ther Y1 - 2007/06// VL - 5 SN - 1744-8336 SP - 415 EP - 425 N2 - Cell recruitment is a multistep process orchestrated by chemokines and their receptors. The chemokine/receptor system is central to many inflammatory diseases, making it a key target for therapeutic intervention. Despite complexity and redundancy within the system, effective antagonists are in development and undergoing clinical trials, for example, maraviroc, for use in HIV treatment. Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants, with global annual infection estimated at 64 million people. Current treatment is purely supportive, with no effective vaccine available. RSV pathology is partly due to excessive airway inflammation. Evidence is growing for a key role for chemokine receptors. Receptor blockade may therefore provide a feasible therapeutic option to inhibit RSV-induced inflammation and thereby reduce disease severity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17547506&query_hl=1 ER - TY - JFULL T1 - Age-dependent impairment of endothelial progenitor cells is corrected by growth hormone-mediated increase of insulin-like growth factor-1 A1 - Thum, T A1 - Hoeber, S A1 - Klink, I A1 - Stichtenoth, DO A1 - Tsilkas, D A1 - Anker, SD A1 - Poole-Wilson, PA A1 - Borlak, J A1 - Erti, G A1 - Bauersachs, J J1 - ARTERIOSCL THROM VAS Y1 - 2007/06// VL - 27 SN - 1079-5642 SP - E137 EP - E137 ER - TY - JFULL T1 - Response to letter regarding article, "anabolic deficiency in men with chronic heart failure: Prevalence and detrimental impact on survival" A1 - Jankowska, EA A1 - Biel, B A1 - Majda, J A1 - Banasiak, W A1 - Ponikowski, P A1 - Lopuszanska, M A1 - Szklarska, A A1 - Anker, SD A1 - Poole-Wilson, PA A1 - Medras, M J1 - CIRCULATION Y1 - 2007/05/29/ VL - 115 SN - 0009-7322 SP - E549 EP - E549 ER - TY - JFULL T1 - Naturalistic follow-up of co-morbid substance use in schizophrenia: the West London first-episode study. A1 - Harrison, I A1 - Joyce, EM A1 - Mutsatsa, SH A1 - Hutton, SB A1 - Huddy, V A1 - Kapasi, M A1 - Barnes, TR J1 - Psychol Med Y1 - 2007/05/29/ SN - 0033-2917 SP - 1 EP - 10 N2 - Background. The impact of co-morbid substance use in first-episode schizophrenia has not been fully explored.Method. This naturalistic follow-up of a cohort of 152 people with first-episode schizophrenia examined substance use and clinical outcome in terms of symptoms and social and neuropsychological function.Results. Data were collected on 85 (56%) of the patient cohort after a median period of 14 months. Over the follow-up period, the proportion of smokers rose from 60% at baseline to 64%. While 30% reported lifetime problem drinking of alcohol at baseline, only 15% had problem drinking at follow-up. Furthermore, while at baseline 63% reported lifetime cannabis use and 32% were currently using the drug, by the follow-up assessment the latter figure had fallen to 18.5%. At follow-up, persistent substance users had significantly more severe positive and depressive symptoms and greater overall severity of illness. A report of no lifetime substance use at baseline was associated with greater improvement in spatial working memory (SWM) at follow-up.Conclusions. Past substance use may impede recovery of SWM performance in people with schizophrenia in the year or so following first presentation to psychiatric services. The prevalence of substance use other than tobacco tends to diminish over this period, in the absence of specific interventions. Persistent substance use in first-episode schizophrenia is associated with more severe positive and depressive symptoms but not negative symptoms, and should be a target for specific treatment intervention. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17532864&query_hl=1 ER - TY - JFULL T1 - Natural Ventilation for Prevention of Airborne Contagion: Authors' Reply. A1 - Escombe, AR A1 - Moore, DA A1 - Friedland, JS A1 - Evans, CA A1 - Gilman, RH J1 - PLoS Med Y1 - 2007/05/29/ VL - 4 SN - 1549-1676 SP - e195 N2 - L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17535109&query_hl=1 ER - TY - JFULL T1 - Protective efficacy of a monovalent oral type 1 poliovirus vaccine: a case-control study (vol 369, pg 1356, 2007) A1 - Grassly, NC A1 - Wenger, J A1 - Durrani, S J1 - LANCET Y1 - 2007/05/26/ VL - 369 SN - 0140-6736 SP - 1790 EP - 1790 ER - TY - JFULL T1 - Corticosteroids and beta2 agonists differentially regulate rhinovirus-induced interleukin-6 via distinct Cis-acting elements. A1 - Edwards, MR A1 - Haas, J A1 - Panettieri, RA A1 - Johnson, M A1 - Johnston, SL J1 - J Biol Chem Y1 - 2007/05/25/ VL - 282 SN - 0021-9258 SP - 15366 EP - 15375 N2 - Interleukin-6 (IL-6) is a proinflammatory cytokine up-regulated by rhinovirus infection during acute exacerbations of asthma and chronic obstructive pulmonary disease. The role of IL-6 during exacerbations is unclear; however, it is believed IL-6 could contribute to airway and systemic inflammation. In this study we investigate the effects of common asthma treatments fluticasone propionate and beta(2) agonists salmeterol and salbutamol on IL-6 production in BEAS-2B and primary bronchial epithelial cells. Salmeterol and salbutamol enhanced rhinovirus- and IL-1beta-induced IL-6 production; however, fluticasone treatment caused a reduction of IL-6 protein and mRNA. Combined activity of salmeterol and fluticasone at equimolar concentrations had no effect on rhinovirus or IL-1beta induction of IL-6. The induction of IL-6 by salmeterol was dependent upon the beta(2) receptor and could also be induced by cAMP or cAMP-elevating agents forskolin and rolipram. Using transfection of IL-6 promoter reporter constructs, dominant negative mutants, and electromobility shift assays, it was found that NF-kappaB was the only transcription factor required for rhinovirus induction of IL-6 gene expression. Salmeterol caused an augmentation of rhinovirus-induced promoter activation via a mechanism dependent upon the c/EBP and/or CRE (cyclic AMP response element) cis-acting sites. The suppressive effect of FP was dependent upon distinct glucocorticoid response element sequences proximal to the transcriptional start site within the IL-6 promoter. The data demonstrate that beta(2) agonists can augment IL-6 expression by other stimuli in an additive manner via cyclic AMP and that the negative effect of steroids is mediated by glucocorticoid response elements within the IL-6 promoter. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17395587&query_hl=1 ER - TY - JFULL T1 - Searching for novel biomarkers of centrally and peripehrally-acting neurotoxicants, using surface-enhanced laser desorption/ionisation-time-of-flight mass spectrometry (SELDI-TOF MS). A1 - Fang, M A1 - Boobis, AR A1 - Edwards, RJ J1 - Food Chem Toxicol Y1 - 2007/05/24/ SN - 0278-6915 N2 - The neurotoxicity of chemicals to humans is difficult to monitor as there are no suitable methods of detecting early neuronal dysfunction. Here, a proof of principle study was designed to assess the potential of identifying protein biomarkers in accessible biofluids for this purpose. Groups of rats were treated with a range of doses of the model neurotoxicants, acrylamide (0, 2, 10, 50mg/kg) and methylmercury (0, 0.2, 1, 5mg/kg) for up to 3 weeks and samples of serum, urine, and cerebral spinal fluid analysed by surface-enhanced laser desorption/ionisation-time-of-flight mass spectrometry. There was no neuropathology up to the highest dose tested. Protein profiles were obtained from all samples and changes in the levels of many proteins were detected in both serum and urine, although not cerebral spinal fluid. In serum, the combination of three protein ion levels with m/z values of 4968, 9402 and 12,948 was able to correctly classify the treatment groups thus: 88% control, 100% acrylamide, 92% methylmercury. In urine, three protein ions with m/z values of 4944, 12,966 and 21,992 classified correctly the groups: 67% control, 94% acrylamide, 97% methylmercury. Similar classifications using other serum and urinary protein ions were also possible. This indicates the potential of serum and urine protein biomarkers for the assessment of sub-clinical neurotoxicity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17602814&query_hl=1 ER - TY - JFULL T1 - Burden, features, and outcome of neurological involvement in acute falciparum malaria in Kenyan children. A1 - Idro, R A1 - Ndiritu, M A1 - Ogutu, B A1 - Mithwani, S A1 - Maitland, K A1 - Berkley, J A1 - Crawley, J A1 - Fegan, G A1 - Bauni, E A1 - Peshu, N A1 - Marsh, K A1 - Neville, B A1 - Newton, C J1 - JAMA Y1 - 2007/05/23/ VL - 297 SN - 1538-3598 SP - 2232 EP - 2240 N2 - CONTEXT: Plasmodium falciparum appears to have a particular propensity to involve the brain but the burden, risk factors, and full extent of neurological involvement have not been systematically described. OBJECTIVES: To determine the incidence and describe the clinical phenotypes and outcomes of neurological involvement in African children with acute falciparum malaria. DESIGN, SETTING, AND PATIENTS: A review of records of all children younger than 14 years admitted to a Kenyan district hospital with malaria from January 1992 through December 2004. Neurological involvement was defined as convulsive seizures, agitation, prostration, or impaired consciousness or coma. MAIN OUTCOME MEASURES: The incidence, pattern, and outcome of neurological involvement. RESULTS: Of 58,239 children admitted, 19,560 (33.6%) had malaria as the primary clinical diagnosis. Neurological involvement was observed in 9313 children (47.6%) and manifested as seizures (6563/17,517 [37.5%]), agitation (316/11,193 [2.8%]), prostration (3223/15,643 [20.6%]), and impaired consciousness or coma (2129/16,080 [13.2%]). In children younger than 5 years, the mean annual incidence of admissions with malaria was 2694 per 100,000 persons and the incidence of malaria with neurological involvement was 1156 per 100,000 persons. However, readmissions may have led to a 10% overestimate in incidence. Children with neurological involvement were older (median, 26 [interquartile range {IQR}, 15-41] vs 21 [IQR, 10-40] months; P<.001), had a shorter duration of illness (median, 2 [IQR, 1-3] vs 3 [IQR, 2-3] days; P<.001), and a higher geometric mean parasite density (42.0 [95% confidence interval {CI}, 40.0-44.1] vs 30.4 [95% CI, 29.0-31.8] x 10(3)/microL; P<.001). Factors independently associated with neurological involvement included past history of seizures (adjusted odds ratio [AOR], 3.50; 95% CI, 2.78-4.42), fever lasting 2 days or less (AOR, 2.02; 95% CI, 1.64-2.49), delayed capillary refill time (AOR, 3.66; 95% CI, 2.40-5.56), metabolic acidosis (AOR, 1.55; 95% CI, 1.29-1.87), and hypoglycemia (AOR, 2.11; 95% CI, 1.31-3.37). Mortality was higher in patients with neurological involvement (4.4% [95% CI, 4.2%-5.1%] vs 1.3% [95% CI, 1.1%-1.5%]; P<.001). At discharge, 159 (2.2%) of 7281 patients had neurological deficits. CONCLUSIONS: Neurological involvement is common in children in Kenya with acute falciparum malaria, and is associated with metabolic derangements, impaired perfusion, parasitemia, and increased mortality and neurological sequelae. This study suggests that falciparum malaria exposes many African children to brain insults. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17519413&query_hl=1 ER - TY - JFULL T1 - Modeling the long-term antibody response of a human papillomavirus (HPV) virus-like particle (VLP) type 16 prophylactic vaccine. A1 - Fraser, C A1 - Tomassini, JE A1 - Xi, L A1 - Golm, G A1 - Watson, M A1 - Giuliano, AR A1 - Barr, E A1 - Ault, KA J1 - Vaccine Y1 - 2007/05/22/ VL - 25 SN - 0264-410X SP - 4324 EP - 4333 N2 - The duration over which antibody responses persist following HPV vaccination is unknown. To estimate the longevity of responses induced by HPV-16 vaccination, two models were fitted to serum anti-HPV-16 levels measured during a 48-month study period. The first was a conventional model of antibody decay and the second was a modified model that accounts for long-lived immune memory. Using the antibody decay model, it was estimated that following administration of a three-dose regimen of HPV-16 vaccine in women aged 16-23 years, anti-HPV-16 levels will remain above those induced naturally by HPV-16 infection for 12 years, and above detectable levels for 32 years in 50% of vaccinees. With the modified model, which fitted the data better (p<0.001), it was estimated that near life-long persistence of anti-HPV-16 following vaccination is expected at titer levels above those associated with reduction of natural HPV-16 infection in 76% of these subjects, and above detectable levels in 99% of these subjects. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17445955&query_hl=1 ER - TY - JFULL T1 - Antiphase oscillations of endothelium and smooth muscle [Ca(2+)](i) in vasomotion of rat mesenteric small arteries. A1 - Rahman, A A1 - Hughes, A A1 - Matchkov, V A1 - Nilsson, H A1 - Aalkjær, C J1 - Cell Calcium Y1 - 2007/05/22/ SN - 0143-4160 N2 - The mechanisms leading to vasomotion in the presence of noradrenaline and inhibitors of the sarcoplasmic/endoplasmic reticulum calcium ATPase were investigated in isolated rat mesenteric small arteries. Isobaric diameter and isometric force were measured together with membrane potential in endothelial cells and smooth muscle cells (SMC). Calcium in the endothelial cells and SMC was imaged with confocal microscopy. In the presence of noradrenaline and cyclopiazonic acid, ryanodine-insensitive oscillations in tone were produced. The frequency was about 1min(-1) and amplitude about 70% of the maximal tone. The amplitude was reduced by indomethacin and increased with L-NAME. Vasomotion was inhibited by nifedipine and by 40mM potassium. The frequency was increased and amplitude decreased by removal of the endothelium and by application of charybdotoxin and apamin. The vasomotion was associated with in-phase oscillations of membrane potential in endothelial cells and SMC and oscillations of [Ca(2+)](i) that were in near anti-phase. We suggest a working model for the generation of oscillation based on a membrane oscillator where ion channels in both endothelial cells and SMC interact via a current running between the two cell types through myoendothelial gap junctions, which sets up a near anti-phase oscillation of [Ca(2+)](i) in the two cell types. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17524481&query_hl=1 ER - TY - JFULL T1 - Use of administrative data or clinical databases as predictors of risk of death in hospital: comparison of models. A1 - Aylin, P A1 - Bottle, A A1 - Majeed, A J1 - BMJ Y1 - 2007/05/19/ VL - 334 SN - 1468-5833 SP - 1044 EP - 1044 N2 - OBJECTIVE: To compare risk prediction models for death in hospital based on an administrative database with published results based on data derived from three national clinical databases: the national cardiac surgical database, the national vascular database and the colorectal cancer study. DESIGN: Analysis of inpatient hospital episode statistics. Predictive model developed using multiple logistic regression. SETTING: NHS hospital trusts in England. PATIENTS: All patients admitted to an NHS hospital within England for isolated coronary artery bypass graft (CABG), repair of abdominal aortic aneurysm, and colorectal excision for cancer from 1996-7 to 2003-4. MAIN OUTCOME MEASURES: Deaths in hospital. Performance of models assessed with receiver operating characteristic (ROC) curve scores measuring discrimination (<0.7=poor, 0.7-0.8=reasonable, >0.8=good) and both Hosmer-Lemeshow statistics and standardised residuals measuring goodness of fit. RESULTS: During the study period 152 523 cases of isolated CABG with 3247 deaths in hospital (2.1%), 12 781 repairs of ruptured abdominal aortic aneurysm (5987 deaths, 46.8%), 31 705 repairs of unruptured abdominal aortic aneurysm (3246 deaths, 10.2%), and 144,370 colorectal resections for cancer (10,424 deaths, 7.2%) were recorded. The power of the complex predictive model was comparable with that of models based on clinical datasets with ROC curve scores of 0.77 (v 0.78 from clinical database) for isolated CABG, 0.66 (v 0.65) and 0.74 (v 0.70) for repairs of ruptured and unruptured abdominal aortic aneurysm, respectively, and 0.80 (v 0.78) for colorectal excision for cancer. Calibration plots generally showed good agreement between observed and predicted mortality. CONCLUSIONS: Routinely collected administrative data can be used to predict risk with similar discrimination to clinical databases. The creative use of such data to adjust for case mix would be useful for monitoring healthcare performance and could usefully complement clinical databases. Further work on other procedures and diagnoses could result in a suite of models for performance adjusted for case mix for a range of specialties and procedures. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17452389&query_hl=1 ER - TY - JFULL T1 - The detection of airborne transmission of tuberculosis from HIV-infected patients, using an in vivo air sampling model. A1 - Escombe, AR A1 - Oeser, C A1 - Gilman, RH A1 - Navincopa, M A1 - Ticona, E A1 - Martínez, C A1 - Caviedes, L A1 - Sheen, P A1 - Gonzalez, A A1 - Noakes, C A1 - Moore, DA A1 - Friedland, JS A1 - Evans, CA J1 - Clin Infect Dis Y1 - 2007/05/15/ VL - 44 SN - 1537-6591 SP - 1349 EP - 1357 N2 - BACKGROUND: Nosocomial transmission of tuberculosis remains an important public health problem. We created an in vivo air sampling model to study airborne transmission of tuberculosis from patients coinfected with human immunodeficiency virus (HIV) and to evaluate environmental control measures. METHODS: An animal facility was built above a mechanically ventilated HIV-tuberculosis ward in Lima, Peru. A mean of 92 guinea pigs were continuously exposed to all ward exhaust air for 16 months. Animals had tuberculin skin tests performed at monthly intervals, and those with positive reactions were removed for autopsy and culture for tuberculosis. RESULTS: Over 505 consecutive days, there were 118 ward admissions by 97 patients with pulmonary tuberculosis, with a median duration of hospitalization of 11 days. All patients were infected with HIV and constituted a heterogeneous group with both new and existing diagnoses of tuberculosis. There was a wide variation in monthly rates of guinea pigs developing positive tuberculin test results (0%-53%). Of 292 animals exposed to ward air, 159 developed positive tuberculin skin test results, of which 129 had laboratory confirmation of tuberculosis. The HIV-positive patients with pulmonary tuberculosis produced a mean of 8.2 infectious quanta per hour, compared with 1.25 for HIV-negative patients with tuberculosis in similar studies from the 1950s. The mean monthly patient infectiousness varied greatly, from production of 0-44 infectious quanta per hour, as did the theoretical risk for a health care worker to acquire tuberculosis by breathing ward air. CONCLUSIONS: HIV-positive patients with tuberculosis varied greatly in their infectiousness, and some were highly infectious. Use of environmental control strategies for nosocomial tuberculosis is therefore a priority, especially in areas with a high prevalence of both tuberculosis and HIV infection. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17443474&query_hl=1 ER - TY - JFULL T1 - A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. A1 - Frayling, TM A1 - Timpson, NJ A1 - Weedon, MN A1 - Zeggini, E A1 - Freathy, RM A1 - Lindgren, CM A1 - Perry, JR A1 - Elliott, KS A1 - Lango, H A1 - Rayner, NW A1 - Shields, B A1 - Harries, LW A1 - Barrett, JC A1 - Ellard, S A1 - Groves, CJ A1 - Knight, B A1 - Patch, AM A1 - Ness, AR A1 - Ebrahim, S A1 - Lawlor, DA A1 - Ring, SM A1 - Ben-Shlomo, Y A1 - Jarvelin, MR A1 - Sovio, U A1 - Bennett, AJ A1 - Melzer, D A1 - Ferrucci, L A1 - Loos, RJ A1 - Barroso, I A1 - Wareham, NJ A1 - Karpe, F A1 - Owen, KR A1 - Cardon, LR A1 - Walker, M A1 - Hitman, GA A1 - Palmer, CN A1 - Doney, AS A1 - Morris, AD A1 - Smith, GD A1 - Hattersley, AT A1 - McCarthy, MI J1 - Science Y1 - 2007/05/11/ VL - 316 SN - 1095-9203 SP - 889 EP - 894 N2 - Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17434869&query_hl=1 ER - TY - JFULL T1 - A UK Audit of Screening for the Metabolic Side Effects of Antipsychotics in Community Patients. A1 - Barnes, TR A1 - Paton, C A1 - Cavanagh, MR A1 - Hancock, E A1 - Taylor, DM J1 - Schizophr Bull Y1 - 2007/05/04/ SN - 0586-7614 N2 - Reviews of the association between psychotic disorder, the metabolic syndrome, diabetes, and antipsychotic drugs conclude that there is a need for active, routine physical health screening of patients' prescribed antipsychotic drugs. From published guidelines, we derived the audit standard that all such patients should, as a minimum, have their blood pressure, body mass index (BMI) (or other measure of obesity such as waist circumference), blood glucose (or HbA(1c)), and plasma lipids measured at least once a year. We conducted an audit of the clinical records of 1966 eligible patients under the care of 48 multidisciplinary, assertive outreach clinical teams in 21 mental health services across the United Kingdom. This revealed a recorded measurement within the previous year for blood pressure in 26% of the patients, obesity in 17%, blood glucose (or HbA(1c)) in 28% and plasma lipids in 22%, with all 4 measures documented in 11%. In the total national sample, 6% had a documented diagnosis of diabetes, 6% hypertension, and 6% dyslipidemia. Extrapolating from the prevalence of these disorders in similar populations suggests that for every patient with a known diagnosis of diabetes, another had not been recognized, for every known case of hypertension, 4 had been missed, and for every known case of dyslipidemia, 7 had been missed. The responses of the clinical teams to a questionnaire yielded information on obstacles to screening in routine practice, revealing uncertainty about whose responsibility this was, a lack of confidence about the interpretation of abnormal screening results, and limited access to basic equipment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17483101&query_hl=1 ER - TY - JFULL T1 - Proteome characterization of a human urothelial cell line resistant to the bladder carcinogen 4-aminobiphenyl A1 - Pastorelli, R A1 - Saletta, F A1 - Carpi, D A1 - Campagna, R A1 - Dell'Osta, C A1 - Schiarea, S A1 - Vineis, P A1 - Airoldi, L A1 - Matullo, G J1 - PROTEOME SCI Y1 - 2007/05/03/ VL - 5 N2 - Background: The aromatic amine 4-aminobiphenyl (4-ABP) is an environmental and occupational contaminant known to be a major etiological agent of human bladder cancer. 4-ABP metabolites are able to form DNA adducts that may induce mutations and initiate bladder carcinogenesis. Cells exposed to 4-ABP may develop resistance to the carcinogen. The aim of the present study was to detect and identify proteins whose expression is altered in the bladder carcinoma RT112 sub-lines selected for acquired resistance to 4-ABP, in order to disentangle the mechanisms.Results: Differential proteome analysis of cell lysates showed an overall perturbation in cell metabolism and energy pathways in the 4-ABP-resistant human urothelial clones, with over-expression of membrane trafficking proteins such as annexin 2. The resistant clones had altered expression of many proteins linked directly (i.e. lamin A/C, programmed cell death 6 interacting protein) or indirectly (i.e. 94 kDa glucose-regulated protein, fatty acid-binding protein) to decreased apoptosis, suggesting that resistance to 4-ABP might be associated with low apoptotic activity.Conclusion: Our data provide evidence that deregulation of apoptosis and membrane trafficking proteins might be strongly implicated in the selection of carcinogen resistant cells. Some of these proteins might have potential as biomarkers of resistance and cancer risk. ER - TY - JFULL T1 - Characterization of androgen-regulated expression of CYP3A5 in human prostate A1 - Moilanen, AM A1 - Hakkola, J A1 - Vaarala, MH A1 - Kauppila, S A1 - Hirvikoski, P A1 - Vuoristo, JT A1 - Edwards, RJ A1 - Paavonen, TK J1 - CARCINOGENESIS Y1 - 2007/05// VL - 28 SN - 0143-3334 SP - 916 EP - 921 N2 - Testosterone is needed for the growth and development of the prostate. Androgen deprivation therapy is used for the treatment of prostate cancer. CYP3A5 is a human drug-metabolizing cytochrome P450 enzyme that metabolizes testosterone to the inactive 6 beta-hydroxylated metabolite. We identified CYP3A5 as a novel androgen-regulated gene in human prostate by GeneChip analysis of human prostate tissues obtained from patients 3 days after therapeutic castration and from control patients. We further showed androgen induction of CYP3A5 messenger RNA (mRNA) in LNCaP prostate cancer cell line. Immunoblotting studies revealed CYP3A5 protein expression in all prostate samples studied. Immunohistochemistry and in situ hybridization was used for localization of CYP3A5 expression in prostate tissue. CYP3A5 was detected both in luminal and in basal epithelial cells of human prostate. Androgen response element was identified in the CYP3A5 proximal promoter and in electrophoretic mobility shift assay androgen receptor was found to bind this element. Androgen induction was abolished by mutation of the response element. We suggest that CYP3A5 is a part of an autoregulatory feedback loop controlling prostate cell exposure to androgens. ER - TY - JFULL T1 - Unusual features of the cell cycle in mycobacteria: polar-restricted growth and the snapping-model of cell division. A1 - Thanky, NR A1 - Young, DB A1 - Robertson, BD J1 - Tuberculosis (Edinb) Y1 - 2007/05// VL - 87 SN - 1472-9792 SP - 231 EP - 236 N2 - Cell division patterns in mycobacteria have been examined in order to further our understanding of how these important organisms grow in the apparent absence of key systems required for the growth of rod-shaped bacteria. Analysis of the distribution of cell lengths in the population during different phases of growth showed that the modal cell length decreases during later phases of growth, declining from 3.5 to 2.5 microm for Mycobacterium bovis BCG cells sampled in log phase and stationary phase, respectively. The population also became more homogeneous, as indicated by the proportion of cells in the most common class increasing from 15% to 28%. Similar patterns were observed for Mycobacterium smegmatis and Mycobacterium tuberculosis. Consistent with other actinomycetes, and in contrast to most rod-shaped bacteria, the deposition of newly synthesised peptidoglycan in mycobacteria is restricted to the poles of the cell, as evidenced by staining with fluorescently labelled vancomycin. A "V-form" of bacteria was observed in cultures at all stages of growth, but the proportion decreased in older cultures. The V-shape appears to be a result of the uneven splitting of the exterior cell envelope at the new septum; this exposes the new peptidoglycan which is illustrated by spots of fluorescent vancomycin staining associated with the exterior side of the "V", and supports the 'snapping division model'. The restriction of growth to the poles of the cell differs from the pattern observed in other rod-shaped bacteria, in which the cell poles are inert and lateral growth occurs by deposition of peptidoglycan along the body of the cylinder. The mechanisms that maintain the shape of mycobacteria and that identify the mid-point for cell division remain to be determined. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17287144&query_hl=1 ER - TY - JFULL T1 - Monitoring peripheral blood regulatory T cells on clinically defined groups of kidney transplant recipients. A1 - Sagoo, P A1 - Sawitzki, B A1 - Hernandez-Fuentes, M A1 - Perucha, E A1 - Craciun, L A1 - Brouard, S A1 - Chaprnan, S A1 - Bradeau, C A1 - Peters, B A1 - Roberts, I A1 - Janssen, U A1 - Soulillou, JP A1 - Warrens, AN A1 - Wood, K A1 - Goldman, M A1 - Volk, HD A1 - Lechler, RI J1 - AM J TRANSPLANT Y1 - 2007/05// VL - 7 SN - 1600-6135 SP - 340 EP - 340 ER - TY - JFULL T1 - Impact of the population at risk of diabetes on projections of diabetes burden in the United States: an epidemic on the way. A1 - Mainous, AG A1 - Baker, R A1 - Koopman, RJ A1 - Saxena, S A1 - Diaz, VA A1 - Everett, CJ A1 - Majeed, A J1 - Diabetologia Y1 - 2007/05// VL - 50 SN - 0012-186X SP - 934 EP - 940 N2 - AIMS/HYPOTHESIS: The aim of this study was to make projections of the future diabetes burden for the adult US population based in part on the prevalence of individuals at high risk of developing diabetes. MATERIALS AND METHODS: Models were created from data in the nationally representative National Health and Nutrition Examination Survey (NHANES) II mortality survey (1976-1992), the NHANES III (1988-1994) and the NHANES 1999-2002. Population models for adults (>20 years of age) from NHANES III data were fitted to known diabetes prevalence in the NHANES 1999-2002 before making future projections. We used a multivariable diabetes risk score to estimate the likelihood of diabetes incidence in 10 years. Estimates of future diabetes (diagnosed and undiagnosed) prevalence in 2011, 2021, and 2031 were made under several assumptions. RESULTS: Based on the multivariable diabetes risk score, the number of adults at high risk of diabetes was 38.4 million in 1991 and 49.9 million in 2001. The total diabetes burden is anticipated to be 11.5% (25.4 million) in 2011, 13.5% (32.6 million) in 2021, and 14.5% (37.7 million) in 2031. Among individuals aged 30 to 39 years old who are not currently targeted for screening according to age, the prevalence of diabetes is expected to rise from 3.7% in 2001 to 5.2% in 2031. By 2031, 20.2% of adult Hispanic individuals are expected to have diabetes. CONCLUSIONS/INTERPRETATION: The prevalence of diabetes is projected to rise to substantially greater levels than previously estimated. Diabetes prevalence within the Hispanic community is projected to be potentially overwhelming. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17119914&query_hl=1 ER - TY - JFULL T1 - Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. A1 - Penders, J A1 - Thijs, C A1 - van den Brandt, PA A1 - Kummeling, I A1 - Snijders, B A1 - Stelma, F A1 - Adams, H A1 - van Ree, R A1 - Stobberingh, EE J1 - Gut Y1 - 2007/05// VL - 56 SN - 0017-5749 SP - 661 EP - 667 N2 - BACKGROUND AND AIMS: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. METHODS: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. RESULTS: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR(adj) = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p(for trend) = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR(adj) = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR(adj) = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR(adj) = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR(adj) = 1.73; 95% CI 1.08 to 2.78). CONCLUSION: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17047098&query_hl=1 ER - TY - JFULL T1 - Biomarkers of tolerance in kidney transplants. A1 - Hernandez-Fuentes, MP A1 - Sawitzki, B A1 - Sagoo, P A1 - Craciun, L A1 - Brouard, S A1 - Perucha, E A1 - Chapman, S A1 - Bradeau, C A1 - Peters, B A1 - Roberts, I A1 - Sergeant, R A1 - Janssen, U A1 - Warrens, A A1 - Wood, K A1 - Soulillou, JP A1 - Goldman, M A1 - Volk, HD A1 - Lechler, RI J1 - AM J TRANSPLANT Y1 - 2007/05// VL - 7 SN - 1600-6135 SP - 337 EP - 337 ER - TY - JFULL T1 - Poorer health and nutritional outcomes in orphans and vulnerable young children not explained by greater exposure to extreme poverty in Zimbabwe. A1 - Watts, H A1 - Gregson, S A1 - Saito, S A1 - Lopman, B A1 - Beasley, M A1 - Monasch, R J1 - Trop Med Int Health Y1 - 2007/05// VL - 12 SN - 1360-2276 SP - 584 EP - 593 N2 - OBJECTIVE: To describe patterns of association between different groups of young orphans and vulnerable children (OVC) and their nutritional and health outcomes; and to develop a theoretical framework to analyse the determinants of child malnutrition and ill-health, and identify the different mechanisms which contribute to these outcomes in such children. METHODS: We developed and tested a theoretical framework to explain why orphans and vulnerable children experience more ill-health and malnutrition based on statistical analysis of data on 31 672 children aged 0-17 years (6753 aged under 5 years) selected from the Zimbabwe OVC Baseline Survey 2004. RESULTS: 28% of children aged 0-4 years at last birthday were either orphans or vulnerable children. They were more likely than non-vulnerable children to have suffered recently from diarrhoeal illness (age- and sex-adjusted odds ratio, AOR, 1.27; 95% CI 1.09-1.48) and acute respiratory infection (1.27; 1.01-1.59) and to be stunted (1.24; 1.09-1.41) and underweight (1.18; 1.02-1.36). After further adjustment for exposure to extreme poverty, OVC remained at greater risk of diarrhoeal disease (AOR 1.25; 1.07-1.46) and chronic malnutrition (1.21; 1.07-1.38). In 0-17-year-olds, OVC with acute respiratory infection were more likely not to have received any treatment even after adjusting for poverty (AOR 1.29; 95% CI 1.16-1.43). CONCLUSION: Differences in exposure to extreme poverty among young children by OVC status were relatively small and did not explain the greater malnutrition and ill-health seen in OVC. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17445126&query_hl=1 ER - TY - JFULL T1 - Interactions between Neisseria meningitidis and the complement system. A1 - Schneider, MC A1 - Exley, RM A1 - Ram, S A1 - Sim, RB A1 - Tang, CM J1 - Trends Microbiol Y1 - 2007/05// VL - 15 SN - 0966-842X SP - 233 EP - 240 N2 - Meningococcal infection remains a worldwide health problem, and understanding the mechanisms by which Neisseria meningitidis evades host innate and acquired immunity is crucial. The complement system is vital for protecting individuals against N. meningitidis. However, this pathogen has evolved several mechanisms to avoid killing by human complement. Bacterial structures such as polysaccharide capsule and those which mimic or bind host molecules function to prevent complement-mediated lysis and phagocytosis. This review provides an update on the recent findings on the diverse mechanisms by which N. meningitidis avoids complement-mediated killing, and how polymorphisms in genes encoding human complement proteins affect susceptibility to this important human pathogen. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17398100&query_hl=1 ER - TY - JFULL T1 - Neutrophils as antigen-presenting cells: Bridging innate and adaptive immunity. A1 - Ambrose, LR A1 - Smith, LM A1 - Little, MAP A1 - Dupont, PJ A1 - Warrens, AN J1 - AM J TRANSPLANT Y1 - 2007/05// VL - 7 SN - 1600-6135 SP - 412 EP - 412 ER - TY - JFULL T1 - The effect of Toxoplasma gondii on animal behavior: playing cat and mouse. A1 - Webster, JP J1 - Schizophr Bull Y1 - 2007/05// VL - 33 SN - 0586-7614 SP - 752 EP - 756 N2 - A convincing body of evidence now exists to indicate that the ubiquitous protozoan Toxoplasma gondii can cause permanent behavioral changes in its host, even as a consequence of adult-acquired latent infection. Such behavioral alterations appear to be the product of strong selective pressures for the parasite to enhance transmission from its intermediate host reservoir, primarily rodent, to its feline definitive host, wherein sexual reproduction can occur and the life cycle completed. This article reviews evidence of behavioral alterations in animal hosts and considers what these may elucidate about the potential mechanisms involved and what implications such alterations could have on animal and human health. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17218613&query_hl=1 ER - TY - JFULL T1 - Variations in plasma phytoestrogen concentrations in European adults. A1 - Peeters, PH A1 - Slimani, N A1 - van der Schouw, YT A1 - Grace, PB A1 - Navarro, C A1 - Tjonneland, A A1 - Olsen, A A1 - Clavel-Chapelon, F A1 - Touillaud, M A1 - Boutron-Ruault, MC A1 - Jenab, M A1 - Kaaks, R A1 - Linseisen, J A1 - Trichopoulou, A A1 - Trichopoulos, D A1 - Dilis, V A1 - Boeing, H A1 - Weikert, C A1 - Overvad, K A1 - Pala, V A1 - Palli, D A1 - Panico, S A1 - Tumino, R A1 - Vineis, P A1 - Bueno-de-Mesquita, HB A1 - van Gils, CH A1 - Skeie, G A1 - Jakszyn, P A1 - Hallmans, G A1 - Berglund, G A1 - Key, TJ A1 - Travis, R A1 - Riboli, E A1 - Bingham, SA J1 - J Nutr Y1 - 2007/05// VL - 137 SN - 0022-3166 SP - 1294 EP - 1300 N2 - Dietary phytoestrogens may play a role in chronic disease occurrence. The aim of our study was to assess the variability of plasma concentrations in European populations. We included 15 geographical regions in 9 European countries (Denmark, France, Germany, Greece, Italy, Spain, Sweden, The Netherlands, and UK) and a 16th region, Oxford, UK, where participants were recruited from among vegans and vegetarians. All subjects were participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma concentrations of 3 isoflavones (daidzein, genistein, and glycitein), 2 metabolites of daidzein [O-desmethylangolensin (O-DMA) and equol] and 2 mammalian lignans (enterodiol and enterolactone) were measured in 1414 participants. We computed geometric means for each region and used multivariate regression analysis to assess the influence of region, adjusted for gender, age, BMI, alcohol intake, smoking status, and laboratory batch. Many subjects had concentrations below the detection limit [0.1 microg/L (0.4 nmol/L)] for glycitein (80%), O-DMA (73%) and equol (62%). Excluding subjects from Oxford, UK, the highest concentrations of isoflavones were in subjects from the Netherlands and Cambridge, UK [2-6 microg/L (7-24 nmol/L); P < 0.05], whereas concentrations for lignans were highest in Denmark [8 microg/L (27 nmol/L); P < 0.05]. Isoflavones varied 8- to 13-fold, whereas lignans varied 4-fold. In the vegetarian/vegan cohort of Oxford, concentrations of isoflavones were 5-50 times higher than in nonvegetarian regions. Region was the most important determinant of plasma concentrations for all 7 phytoestrogens. Despite the fact that plasma concentrations of phytoestrogens in Europe were low compared with Asian populations, they varied substantially among subjects from the 16 different regions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17449595&query_hl=1 ER - TY - JFULL T1 - Anthropometric factors and risk of endometrial cancer: the European prospective investigation into cancer and nutrition A1 - Friedenreich, C A1 - Cust, A A1 - Lahmann, PH A1 - Steindorf, K A1 - Boutron-Ruault, MC A1 - Clavel-Chapelon, F A1 - Mesrine, S A1 - Linseisen, J A1 - Rohrmann, S A1 - Boeing, H A1 - Pischon, T A1 - Tjonneland, A A1 - Halkjaer, J A1 - Overvad, K A1 - Mendez, M A1 - Redondo, ML A1 - Garcia, CM A1 - Larranaga, N A1 - Tormo, MJ A1 - Gurrea, AB A1 - Bingham, S A1 - Khaw, KT A1 - Allen, N A1 - Key, T A1 - Trichopoulou, A A1 - Vasilopoulou, E A1 - Trichopoulos, D A1 - Pala, V A1 - Palli, D A1 - Tumino, R A1 - Mattiello, A A1 - Vineis, P A1 - Bueno-de-Mesquita, HB A1 - Peeters, PHM A1 - Berglund, G A1 - Manjer, J A1 - Lundin, E A1 - Lukanova, A A1 - Slimani, N A1 - Jenab, M A1 - Kaaks, R A1 - Riboli, E J1 - CANCER CAUSE CONTROL Y1 - 2007/05// VL - 18 SN - 0957-5243 SP - 399 EP - 413 N2 - Objective To examine the association between anthropometry and endometrial cancer, particularly by menopausal status and exogenous hormone use subgroups.Methods Among 223,008 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, there were 567 incident endometrial cancer cases during 6.4 years of follow-up. The analysis was performed with Cox proportional hazards modeling.Results Weight, body mass index (BMI), waist and hip circumferences and waist-hip ratio (WHR) were strongly associated with increased risk of endometrial cancer. The relative risk (RR) for obese (BMI 30- < 40 kg/m(2)) compared to normal weight (BMI < 25) women was 1.78, 95% CI = 1.41-2.26, and for morbidly obese women (BMI >= 40) was 3.02, 95% CI = 1.66-5.52. The RR for women with a waist circumference of >= 88 cm vs. < 80 cm was 1.76, 95% CI = 1.42-2.19. Adult weight gain of >= 20 kg compared with stable weight (+/- 3 kg) increased risk independent of body weight at age 20 (RR = 1.75, 95% CI = 1.11-2.77). These associations were generally stronger for postmenopausal than premenopausal women, and oral contraceptives never-users than ever-users, and much stronger among never-users of hormone replacement therapy compared to ever-users. Conclusion Obesity, abdominal adiposity, and adult weight gain were strongly associated with endometrial cancer risk. These associations were particularly evident among never-users of hormone replacement therapy. ER - TY - JFULL T1 - Early growth and adult respiratory function in men and women followed from the fetal period to adulthood. A1 - Canoy, D A1 - Pekkanen, J A1 - Elliott, P A1 - Pouta, A A1 - Laitinen, J A1 - Hartikainen, AL A1 - Zitting, P A1 - Patel, S A1 - Little, MP A1 - Järvelin, MR J1 - Thorax Y1 - 2007/05// VL - 62 SN - 0040-6376 SP - 396 EP - 402 N2 - BACKGROUND: While some studies suggest that poor fetal growth rate, as indicated by lower birth weight, is associated with poor respiratory function in childhood, findings among adults remain inconsistent. A study was undertaken to determine the association between early growth and adult respiratory function. METHODS: A longitudinal birth cohort study was performed of 5390 men and women born full term and prospectively followed from the fetal period to adulthood. Weight at birth and infancy were recorded, and forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were assessed by standard spirometry at age 31 years. RESULTS: Adult FEV(1) and FVC increased linearly with higher birth weight in both men and women with no apparent threshold. After adjustment for sex, adult height and other potential confounders operating through the life course, every 500 g higher birth weight was associated with a higher FEV(1) of 53.1 ml (95% CI 38.4 to 67.7) and higher FVC of 52.5 ml (95% CI 35.5 to 69.4). These positive associations persisted across categories of smoking, physical activity and body mass index, with the lowest respiratory function noted among those with lower birth weight who were smokers, led a sedentary lifestyle or were overweight. Weight gain in infancy was also positively associated with adult lung function. CONCLUSION: Birth weight is continuously and independently associated with adult respiratory function. It is plausible that poor growth in early life may restrict normal lung growth and development, which could have long-term consequences on lung function later in life. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17105780&query_hl=1 ER - TY - JFULL T1 - Mechanisms of action of TRAIL in inhibiting immune response to alogeneic tissue. A1 - Kumar, R A1 - Herbert, PE A1 - Warrens, AN J1 - AM J TRANSPLANT Y1 - 2007/05// VL - 7 SN - 1600-6135 SP - 148 EP - 148 ER - TY - JFULL T1 - Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC) A1 - Tjonneland, A A1 - Christensen, J A1 - Olsen, A A1 - Stripp, C A1 - Thomsen, BL A1 - Overvad, K A1 - Peeters, PHM A1 - van Gils, CH A1 - Bueno-de-Mesquita, HB A1 - Ocke, MC A1 - Thiebaut, A A1 - Fournier, AS A1 - Clavel-Chapelon, F A1 - Berrino, F A1 - Palli, D A1 - Tumino, R A1 - Panico, S A1 - Vineis, P A1 - Agudo, A A1 - Ardanaz, E A1 - Martinez-Garcia, C A1 - Amiano, P A1 - Navarro, C A1 - Quiros, JR A1 - Key, TJ A1 - Reeves, G A1 - Khaw, KT A1 - Bingham, S A1 - Trichopoulou, A A1 - Trichopoulos, D A1 - Naska, A A1 - Nagel, G A1 - Chang-Claude, J A1 - Boeing, H A1 - Lahmann, PH A1 - Manjer, J A1 - Wirfalt, E A1 - Hallmans, G A1 - Johansson, I A1 - Lund, E A1 - Skeie, G A1 - Hjartaker, A A1 - Ferrari, P A1 - Slimani, N A1 - Kaaks, R A1 - Riboli, E J1 - CANCER CAUSE CONTROL Y1 - 2007/05// VL - 18 SN - 0957-5243 SP - 361 EP - 373 N2 - Objective Most epidemiologic studies have suggested an increased risk of breast cancer with increasing alcohol intake. Using data from 274,688 women participating in the European Prospective Investigation into Cancer and Nutrition study (EPIC), we investigated the relation between alcohol intake and the risk of breast cancer.Methods Incidence rate ratios (IRRs) based on Cox proportional hazard models were calculated using reported intake of alcohol, recent (at baseline) and lifetime exposure. We adjusted for known risk factors and stratified according to study center as well as potentially modifying host factors.Results During 6.4 years of follow up, 4,285 invasive cases of breast cancer within the age group 35-75 years were identified. For all countries together the IRR per 10 g/day higher recent alcohol intake (continuous) was 1.03 (95% confidence interval (CI): 1.01-1.05). When adjusted, no association was seen between lifetime alcohol intake and risk of breast cancer. No difference in risk was shown between users and non-users of HRT, and there was no significant interaction between alcohol intake and BMI, HRT or dietary folate.Conclusion This large European study supports previous findings that recent alcohol intake increases the risk of breast cancer. ER - TY - JFULL T1 - Intervention following deliberate self-harm: enough evidence to act? A1 - Crawford, MJ A1 - Kumar, P J1 - Evid Based Ment Health Y1 - 2007/05// VL - 10 SN - 1362-0347 SP - 37 EP - 39 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17459970&query_hl=1 ER - TY - JFULL T1 - The role of antibiotics in asthma A1 - Blasi, F A1 - Johnston, SL J1 - INT J ANTIMICROB AG Y1 - 2007/05// VL - 29 SN - 0924-8579 SP - 485 EP - 493 N2 - There is increasing evidence that atypical respiratory pathogens such as Chlamydophila pneumoniae and Mycoplasma pneumoniae may contribute to the pathogenesis of both stable asthma and asthma exacerbations. It is postulated that these organisms may contribute to inflammation in the airways possibly by activating inflammatory mechanisms in the respiratory tract.The macrolide class of antibiotics may have a part to play in the management of asthma by exerting anti-inflammatory effects on the chronically inflamed airways in addition to their anti-infective action. The ketolide antibiotics may also have similar properties.This paper discusses the role of these antibiotics in the management of asthma. (C) 2006 Elsevier B.V and the International Society of Chemotherapy. All rights reserved. ER - TY - JFULL T1 - The relation of adult bronchial responsiveness to serious childhood respiratory illness in the ECRHS. A1 - Chinn, S A1 - Janson, C A1 - Svanes, C A1 - Dharmage, S A1 - Jarvis, D J1 - Respir Med Y1 - 2007/05// VL - 101 SN - 0954-6111 SP - 983 EP - 988 N2 - BACKGROUND: Respiratory symptoms in adulthood have been found to be associated with childhood respiratory infection, but few studies have analyzed adult bronchial responsiveness (BHR) with adequate adjustment for known risk factors. OBJECTIVE: To estimate the relation of BHR with serious childhood respiratory infections in a large population study. METHODS: The European Community Respiratory Health Survey (ECRHS) was a cross-sectional population-based survey in 34 centers. Data on serious respiratory infections before the age of 5 years and possible confounders were obtained from a questionnaire administered in the clinic. Blood samples were taken for measurement of total immunoglobulin E (IgE) and specific IgE to four common allergens, and spirometry and bronchial challenge with methacholine were performed. A continuous measure of BHR was analyzed by multiple regression, in 11,282 participants, in relation to serious respiratory infection and other potential risk factors, adjusted for center and major determinants of adult BHR. RESULTS: Those reporting a serious childhood respiratory infection had greater BHR, by an amount corresponding to approximately 0.23 doubling doses (95% confidence interval 0.02-0.44) of the amount of methacholine causing a 20% fall (PD(20)) in forced expiratory volume in 1s (FEV(1)). All childhood factors explained less than 0.3% of variation in BHR in addition to over 20% by factors measured in adulthood. The relation of BHR to BMI was confined to smokers. CONCLUSIONS: We found an effect of serious childhood respiratory infection on adult BHR, but this was small in comparison to relations of BHR to IgE-sensitization and airway caliber. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17049442&query_hl=1 ER - TY - JFULL T1 - Mechanisms of virus-induced asthma exacerbations: state-of-the-art. A GA(2)LEN and InterAirways document A1 - Papadopoulos, NG A1 - Xepapadaki, P A1 - Mallia, P A1 - Brusselle, G A1 - Watelet, JB A1 - Xatzipsalti, M A1 - Foteinos, G A1 - van Drunen, CM A1 - Fokkens, WJ A1 - D'Ambrosio, C A1 - Bonini, S A1 - Bossios, A A1 - Lotvall, J A1 - van Cauwenberge, P A1 - Holgate, ST A1 - Canonica, GW A1 - Szczeklik, A A1 - Rohde, G A1 - Kimpen, J A1 - Pitkaranta, A A1 - Makela, M A1 - Chanez, P A1 - Ring, J A1 - Johnston, SL J1 - ALLERGY Y1 - 2007/05// VL - 62 SN - 0105-4538 SP - 457 EP - 470 N2 - Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research. ER - TY - JFULL T1 - Socioeconomic status, asthma and chronic bronchitis in a large community-based study A1 - Ellison-Loschmann, L A1 - Sunyer, J A1 - Plana, E A1 - Pearce, N A1 - Zock, JP A1 - Jarvis, D A1 - Janson, C A1 - Anto, JM A1 - Kogevinas, M A1 - European Community Resp Hlth Surve J1 - EUR RESPIR J Y1 - 2007/05// VL - 29 SN - 0903-1936 SP - 897 EP - 905 N2 - The present study investigated the relationship between socioeconomic status, using measures of occupational class and education level, and the prevalence and incidence of asthma (with and without atopy) and chronic bronchitis using data from the European Community Respiratory Health Survey (ECRHS).Asthma and chronic bronchitis were studied prospectively within the ECRHS (n=9,023). Incidence analyses comprised subjects with no history of asthma or bronchitis at baseline. Asthma symptoms were also assessed as a continuous score.Bronchitis risk was associated with low educational level (prevalence odds ratio (POR) 1.9; 95% confidence interval (CI) 1.4-2.8) and occupational class (1.8; 1.2-2.7). Incident bronchitis also increased with low educational level (risk ratio (RR) 2.8; 95%CI 1.5-5.4). Prevalent and incident asthma with no atopy were associated with low educational level. Subjects in the low occupational class (incident risk ratio (IRR) 1.4; 95%CI 1.2-1.7) and education group (IRR 1.3; 95% CI 1.1-1.6) had higher mean asthma scores than those in higher socioeconomic groups.Lower educational level was associated with increased risk of prevalent and incident chronic bronchitis and asthma with no atopy. Lower socioeconomic groups tended to have a higher prevalence and incidence of asthma, particularly higher mean asthma scores. Adjustment for variables associated with asthma and bronchitis explained little of the observed health differences by socioeconomic status. ER - TY - JFULL T1 - Modification of dendritic cells for the induction of tolerance. A1 - Khan, AH A1 - Harper, JE A1 - Beutelspacher, SC A1 - Lombardi, G A1 - McClure, MO A1 - George, AJT J1 - AM J TRANSPLANT Y1 - 2007/05// VL - 7 SN - 1600-6135 SP - 487 EP - 487 ER - TY - JFULL T1 - Proteolysis of the endothelial cell protein C receptor by neutrophil proteinase 3. A1 - Villegas-Mendez, A A1 - Montes, R A1 - Ambrose, LR A1 - Warrens, AN A1 - Laffan, M A1 - Lane, DA J1 - J Thromb Haemost Y1 - 2007/05// VL - 5 SN - 1538-7933 SP - 980 EP - 988 N2 - BACKGROUND: The endothelial cell protein C receptor (EPCR) presents protein C to the thrombin:thrombomodulin complex on the endothelium of large vessels, and enhances the generation of activated protein C (APC) and activation of protease-activated receptor-1. A previous report has demonstrated binding of soluble (s) EPCR to activated neutrophils via surface proteinase 3 (PR3). METHODS: We now report further characterization of this interaction. Activated neutrophils and purified PR3 both decrease endothelial cell (EC) surface EPCR, suggestive of its proteolysis. RESULTS: When added to purified recombinant sEPCR, PR3 produced multiple cleavages, with early products including 20 kDa N-terminal and C-terminal (after Lys(176)) fragments. The binding of active site blocked PR3 to sEPCR was studied by surface plasmon resonance. Estimates of the K(D) of 18.5-102 nM were obtained with heterogeneous binding, suggestive of more than a single interaction site. CONCLUSIONS: This work demonstrates PR3 binding to and proteolysis of EPCR and suggests a mechanism by which anticoagulant and cell protective pathways can be down-regulated during inflammation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17459006&query_hl=1 ER - TY - JFULL T1 - Humidity control as a strategy for lattice optimization applied to crystals of HLA-A*1101 complexed with variant peptides from dengue virus. A1 - Chotiyarnwong, P A1 - Stewart-Jones, GB A1 - Tarry, MJ A1 - Dejnirattisai, W A1 - Siebold, C A1 - Koch, M A1 - Stuart, DI A1 - Harlos, K A1 - Malasit, P A1 - Screaton, G A1 - Mongkolsapaya, J A1 - Jones, EY J1 - Acta Crystallogr Sect F Struct Biol Cryst Commun Y1 - 2007/05/01/ VL - 63 SN - 1744-3091 SP - 386 EP - 392 N2 - T-cell recognition of the antigenic peptides presented by MHC class I molecules normally triggers protective immune responses, but can result in immune enhancement of disease. Cross-reactive T-cell responses may underlie immunopathology in dengue haemorrhagic fever. To analyze these effects at the molecular level, the functional MHC class I molecule HLA-A*1101 was crystallized bound to six naturally occurring peptide variants from the dengue virus NS3 protein. The crystals contained high levels of solvent and required optimization of the cryoprotectant and dehydration protocols for each complex to yield well ordered diffraction, a process that was facilitated by the use of a free-mounting system. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17565177&query_hl=1 ER - TY - JFULL T1 - Extremely low-frequency magnetic fields and fertility in welders - Reply A1 - Jensen, TK A1 - Joffe, M A1 - Bonde, JP J1 - OCCUP MED-OXFORD Y1 - 2007/05// VL - 57 SN - 0962-7480 SP - 225 EP - 226 ER - TY - JFULL T1 - Number of allergens to be tested to assess allergenic sensitization in epidemiologic studies: results of the European Community Respiratory Health Survey I. A1 - Bousquet, PJ A1 - Hooper, R A1 - Kogevinas, M A1 - Jarvis, D A1 - Burney, P J1 - Clin Exp Allergy Y1 - 2007/05// VL - 37 SN - 0954-7894 SP - 780 EP - 787 N2 - BACKGROUND: Many clinical and epidemiological studies have measured the prevalence of IgE sensitization using skin tests and/or serum-specific IgE. Most of them have been done in only one country using a battery of selected allergens relevant to that country. In multi-centre studies, the number of tested allergens is often limited by the cost. It is therefore difficult to compare prevalence of sensitized subjects between studies. OBJECTIVE: To define the number and the type of allergen that should be tested in order to characterize a person as sensitized. METHOD: Subjects were selected from the European Community Respiratory Health Survey I. All subjects underwent skin prick tests to nine of the most common allergens. In addition, two local allergens were tested in some centres. RESULT: Using nine allergens, 35.6% of the 11 355 subjects were sensitized. The prevalence of sensitization increased with the number of tested allergens. Seven allergens enabled the identification of almost all sensitized subjects, adding another one inducing, in most countries, an increase of prevalence under 0.5%. Adding one local allergen to the battery of tests increased the overall estimated prevalence by only 1%. This increase was not seen in Ireland and was less marked in the United Kingdom (0.3%) but was greater in France (2.6%), Australia (2.5%) and Belgium (1.9%). CONCLUSION: Seven selected allergens (Dermatophagoides pteronyssinus, cat, grass, birch, olive pollen, Alternaria and Cladosporium) allow the identification of almost all sensitized subjects in epidemiologic studies. Inclusion of local allergen should be considered in a standard panel for international studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17456226&query_hl=1 ER - TY - JFULL T1 - Identification of tolerant patients based on a combinational analysis of foxp3 and aMannosidase transcription. A1 - Sawitzki, BS A1 - Hernandez-Fuentes, M A1 - Sagoo, P A1 - Perucha, E A1 - Lemoine, A A1 - Brouard, S A1 - Chapman, S A1 - Peters, B A1 - Roberts, I A1 - Janssen, U A1 - Soulillou, JP A1 - Warrens, A A1 - Wood, K A1 - Goldman, M A1 - Lechler, R A1 - Volk, HD J1 - AM J TRANSPLANT Y1 - 2007/05// VL - 7 SN - 1600-6135 SP - 488 EP - 488 ER - TY - JFULL T1 - C-terminal antibodies (CTAbs): a simple and broadly applicable approach for the rapid generation of protein-specific antibodies with predefined specificity. A1 - Edwards, RJ A1 - Wrigley, A A1 - Bai, Z A1 - Bateman, M A1 - Russell, H A1 - Murray, S A1 - Lu, H A1 - Taylor, GW A1 - Boobis, AR A1 - Sriskandan, S J1 - Proteomics Y1 - 2007/05// VL - 7 SN - 1615-9853 SP - 1364 EP - 1372 N2 - Recent advances in proteomic techniques have resulted in an ever-increasing need to produce antibodies. Here, to address this problem, a technically simple approach of targeting the extreme C-termini of proteins with antibodies (CTAbs) was investigated in proteins secreted by the human pathogen Streptococcus pyogenes. Target proteins were identified by a conventional proteomic approach and CTAbs produced against synthetic five amino acid peptides representing the C-terminus of each target protein. In every case where protein secretion was demonstrated (n = 20), CTAbs were successfully produced and bound specifically to the target protein (100% success rate). The apparent specificity was consistent with the structural heterogeneity of the C-termini of S. pyogenes proteins. The global specificity of CTAb binding was defined using a combinatorial library of synthetic peptides representing structural variants of the original synthetic immunogen. This is a systematic and comprehensive approach for the development of antibodies with defined specificity that can be used in a range of applications. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17407178&query_hl=1 ER - TY - JFULL T1 - The burden of diabetes and its complications: trends and implications for intervention. A1 - Chaturvedi, N J1 - Diabetes Res Clin Pract Y1 - 2007/05// VL - 76 Suppl 1 SN - 0168-8227 SP - S3 EP - S12 N2 - Much of the burden of diabetes is due to the development of vascular complications, including cardiovascular diseases, retinopathy and nephropathy. Improvements in patient management to promote tight control of glycaemia have helped to reduce the prevalence of microvascular complications, but cardiovascular diseases continue to be the leading cause of death in patients with type 2 diabetes. Globally, the number of people with diabetes is predicted to almost double over the next 30 years, with much of this increase occurring in developing countries. The growing prevalence of obesity is the major factor driving the increasing prevalence of type 2 diabetes, and the increase in obesity in adolescents is of particular concern. Consequently, the overall number of people with the vascular complications of diabetes is also predicted to increase. Prevention of diabetes is the best strategy for reducing the risk of complications, and screening of high-risk individuals is already being promoted in some countries. Lifestyle changes, focusing on diet, exercise and weight loss are effective in preventing diabetes in such people. However, more information is required about the long-term sustainability of these changes, and programmes also need to be adapted to meet the needs of developing countries. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17343954&query_hl=1 ER - TY - JFULL T1 - Physical activity and bronchial hyperresponsiveness: European Community Respiratory Health Survey II. A1 - Shaaban, R A1 - Leynaert, B A1 - Soussan, D A1 - Antó, JM A1 - Chinn, S A1 - de Marco, R A1 - Garcia-Aymerich, J A1 - Heinrich, J A1 - Janson, C A1 - Jarvis, D A1 - Sunyer, J A1 - Svanes, C A1 - Wjst, M A1 - Burney, PG A1 - Neukirch, F A1 - Zureik, M J1 - Thorax Y1 - 2007/05// VL - 62 SN - 0040-6376 SP - 403 EP - 410 N2 - BACKGROUND: Identification of the risk factors for bronchial hyperresponsiveness (BHR) would increase the understanding of the causes of asthma. The relationship between physical activity and BHR in men and women aged 28.0-56.5 years randomly selected from 24 centres in 11 countries participating in the European Community Respiratory Health Survey II was investigated. METHODS: 5158 subjects answered questionnaires about physical activity and performed BHR tests. Participants were asked about the frequency and duration of usual weekly exercise resulting in breathlessness or sweating. BHR was defined as a decrease in forced expiratory volume in 1 s of at least 20% of its post-saline value for a maximum methacholine dose of 2 mg. RESULTS: Both frequency and duration of physical activity were inversely related to BHR. The prevalence of BHR in subjects exercising or=4 times a week was 14.5%, 11.6% and 10.9%, respectively (p<0.001). The corresponding odds ratios were 1.00, 0.78 (95% CI 0.62 to 0.99) and 0.69 (95% CI 0.50 to 0.94) after controlling for potential confounding factors. The frequency of BHR in subjects exercising <1 h, 1-3 h and >or=4 h a week was 15.9%, 10.9% and 10.7%, respectively (p<0.001). The corresponding adjusted odds ratios were 1.00, 0.70 (95% CI 0.57 to 0.87) and 0.67 (95% CI 0.50 to 0.90). Physical activity was associated with BHR in all studied subgroups. CONCLUSIONS: These results suggest that BHR is strongly and independently associated with decreased physical activity. Further studies are needed to determine the mechanisms underlying this association. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17121869&query_hl=1 ER - TY - JFULL T1 - The effect of public health measures on the 1918 influenza pandemic in US cities A1 - Bootsma, MCJ A1 - Ferguson, NM J1 - P NATL ACAD SCI USA Y1 - 2007/05/01/ VL - 104 SN - 0027-8424 SP - 7588 EP - 7593 N2 - During the 1918 influenza pandemic, the U.S., unlike Europe, put considerable effort into public health interventions. There was also more geographic variation in the autumn wave of the pandemic in the U.S. compared with Europe, with some cities seeing only a single large peak in mortality and others seeing double-peaked epidemics. Here we examine whether differences in the public health measures adopted by different cities can explain the variation in epidemic patterns and overall mortality observed. We show that city-specific per-capita excess mortality in 1918 was significantly correlated with 1917 per-capita mortality, indicating some intrinsic variation in overall mortality, perhaps related to sociodemographic factors. In the subset of 23 cities for which we had partial data on the timing of interventions, an even stronger correlation was found between excess mortality and how early in the epidemic interventions were introduced. We then fitted an epidemic model to weekly mortality in 16 cities with nearly complete intervention-timing data and estimated the impact of interventions. The model reproduced the observed epidemic patterns well. in line with theoretical arguments, we found the time-limited interventions used reduced total mortality only moderately (perhaps 10-30%), and that the impact was often very limited because of interventions being introduced too late and lifted too early. San Francisco, St. Louis, Milwaukee, and Kansas City had the most effective interventions, reducing transmission rates by up to 30-50%. Our analysis also suggests that individuals reactively reduced their contact rates in response to high levels of mortality during the pandemic. ER - TY - JFULL T1 - Is it possible totissue type a kidney donor who is no longer available? A1 - Srikantha, M A1 - Sergeant, R A1 - Hernandez-Fuentes, M A1 - Lechler, RI A1 - Warrens, AN J1 - AM J TRANSPLANT Y1 - 2007/05// VL - 7 SN - 1600-6135 SP - 268 EP - 268 ER - TY - JFULL T1 - Relation between chemokine receptor use, disease stage, and HIV-1 subtypes A and D: results from a rural Ugandan cohort. A1 - Kaleebu, P A1 - Nankya, IL A1 - Yirrell, DL A1 - Shafer, LA A1 - Kyosiimire-Lugemwa, J A1 - Lule, DB A1 - Morgan, D A1 - Beddows, S A1 - Weber, J A1 - Whitworth, JA J1 - J Acquir Immune Defic Syndr Y1 - 2007/05/01/ VL - 45 SN - 1525-4135 SP - 28 EP - 33 N2 - OBJECTIVES: To determine whether there are differences in coreceptor use in subjects infected with HIV-1 envelope subtypes A and D that could explain the differences in progression rates between these subtypes in a rural Ugandan cohort. METHODS: HIV-1 was subtyped in env by V3 sequencing or heteroduplex mobility assay. Coreceptor use was determined by the ability of the isolates to replicate in U87 CD4 cells expressing different coreceptors. The Fisher exact test was used to examine the relation between coreceptor use and subtype, clinical stage, and V3 charge. The Kruskall-Wallis nonparametric test was used to examine the association between median CD4 cell counts, coreceptor use, and subtype. Logistic regression was used to examine predicted coreceptor use at different CD4 groupings. RESULTS: Isolates from 66 participants were analyzed. Thirty-one were infected with subtype A, and 35 were infected with subtype D. Although this work was based on a small sample size, we found statistically significant differences. The probability of having an X4 virus was higher in subtype D infections than in subtype A infections among those with a non-AIDS clinical status (Fisher exact test, P = 0.040). Logistic regression analysis, in which we predicted X4 use by subtype and stratified by CD4 group, confirmed these findings among those with a CD4 count >200 cells/microL (likelihood ratio test, P = 0.003). R5 viruses were associated with higher median CD4 cell counts than X4 or X4/R5 (Kruskall-Wallis test, P = 0.0045). A V3 charge of +5 and greater was highly associated with X4 virus (Fisher exact test, P = 0.006). CONCLUSIONS: These subtype differences in coreceptor use may partially explain the faster progression rates we have previously reported in individuals infected with subtype D compared with subtype A. Our observations may have implications for the future use of coreceptor inhibitors in this population. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17310935&query_hl=1 ER - TY - JFULL T1 - Invasive group A streptococcal infection in injecting drug users and non-drug users in a single UK city. A1 - Curtis, SJ A1 - Tanna, A A1 - Russell, HH A1 - Efstratiou, A A1 - Paul, J A1 - Cubbon, M A1 - Sriskandan, S J1 - J Infect Y1 - 2007/05// VL - 54 SN - 0163-4453 SP - 422 EP - 426 N2 - OBJECTIVES: Injecting drug users (IDU) represent an increasing proportion of patients with invasive group A streptococcal (GAS) disease. Our aims were to characterise the clinical presentation and strains causing GAS bacteremia in IDU from a single UK city (Brighton and Hove), and to compare this patient group with non-drug users (non-DU) with GAS bacteremia. METHODS: Consecutive GAS blood culture isolates from twenty-two IDU and twenty-two non-DU presenting to the city hospital were studied. Clinical features, strain emm typing and superantigen toxin genotyping were investigated. RESULTS: GAS invasive disease presented differently in IDU compared to non-DU with a predominance of injection site abscesses and lower mortality in IDU. GAS strains from IDU were predominantly emm82 and emm83 types, which are uncommon in the UK and emm82 strains appeared clonal. The non-DU GAS strains demonstrated a broader range of emm types including most frequently emm1 and emm89. There was no major difference in superantigen gene profile between the isolate groups. CONCLUSION: The distinct presentation of invasive GAS disease in IDU compared with non-DU was associated with distinct emm types, a predominance of abscesses, and low mortality, although the small numbers preclude definitive conclusions. Further study is required to establish if these findings reflect strain differences or epidemiological differences in colonisation patterns and injecting practice. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17116332&query_hl=1 ER - TY - JFULL T1 - Non-parametric estimation of the case fatality ratio with competing risks data: An application to Severe Acute Respiratory Syndrome (SARS) A1 - Jewell, NP A1 - Lei, XD A1 - Ghani, AC A1 - Donnelly, CA A1 - Leung, GM A1 - Ho, LM A1 - Cowling, BJ A1 - Hedley, AJ J1 - STAT MED Y1 - 2007/04/30/ VL - 26 SN - 0277-6715 SP - 1982 EP - 1998 N2 - For diseases with some level of associated mortality, the case fatality ratio measures the proportion of diseased individuals who die from the disease. In principle, it is straightforward to estimate this quantity from individual follow-up data that provides times from onset to death or recovery. In particular, in a competing risks context, the case fatality ratio is defined by the limiting value of the sub-distribution function, F, (t) = Pr(T <= t and J = 1), associated with death, as t -> infinity, where T denotes the time from onset to death (J = 1) or recovery (J = 2). When censoring is present, however, estimation of F-1(infinity) is complicated by the possibility of little information regarding the right tail of F-1, requiring use of estimators of F-1 (t*) or F-1 (t*)/(F-1 (t*) + F-2(t*)) where t* is large, with F-2(t) = Pr(T <= t and J = 2) being the analogous sub-distribution function associated with recovery. With right censored data, the variability of such estimators increases as t* increases, suggesting the possibility of using estimators at lower values of t* where bias may be increased but overall mean squared error be smaller. These issues are investigated here for non-parametric estimators of F-1 and F-2. The ideas are illustrated on case fatality data for individuals infected with Severe Acute Respiratory Syndrome (SARS) in Hong Kong in 2003. Copyright (c) 2006 John Wiley & Sons, Ltd. ER - TY - JFULL T1 - Voluntary counselling and testing: uptake, impact on sexual behaviour, and HIV incidence in a rural Zimbabwean cohort. A1 - Sherr, L A1 - Lopman, B A1 - Kakowa, M A1 - Dube, S A1 - Chawira, G A1 - Nyamukapa, C A1 - Oberzaucher, N A1 - Cremin, I A1 - Gregson, S J1 - AIDS Y1 - 2007/04/23/ VL - 21 SN - 0269-9370 SP - 851 EP - 860 N2 - OBJECTIVES: To examine the determinants of uptake of voluntary counselling and testing (VCT) services, to assess changes in sexual risk behaviour following VCT, and to compare HIV incidence amongst testers and non-testers. METHODS: Prospective population-based cohort study of adult men and women in the Manicaland province of eastern Zimbabwe. Demographic, socioeconomic, sexual behaviour and VCT utilization data were collected at baseline (1998-2000) and follow-up (3 years later). HIV status was determined by HIV-1 antibody detection. In addition to services provided by the government and non-governmental organizations, a mobile VCT clinic was available at study sites. RESULTS: Lifetime uptake of VCT increased from under 6% to 11% at follow-up. Age, increasing education and knowledge of HIV were associated with VCT uptake. Women who took a test were more likely to be HIV positive and to have greater HIV knowledge and fewer total lifetime partners. After controlling for demographic characteristics, sexual behaviour was not independently associated with VCT uptake. Women who tested positive reported increased consistent condom use in their regular partnerships. However, individuals who tested negative were more likely to adopt more risky behaviours in terms of numbers of partnerships in the last month, the last year and in concurrent partnerships. HIV incidence during follow-up did not differ between testers and non-testers. CONCLUSION: Motivation for VCT uptake was driven by knowledge and education rather than sexual risk. Increased sexual risk following receipt of a negative result may be a serious unintended consequence of VCT. It should be minimized with appropriate pre- and post-test counselling. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17415040&query_hl=1 ER - TY - JFULL T1 - Protective efficacy of a monovalent oral type 1 poliovirus vaccine: a case-control study. A1 - Grassly, NC A1 - Wenger, J A1 - Durrani, S A1 - Bahl, S A1 - Deshpande, JM A1 - Sutter, RW A1 - Heymann, DL A1 - Aylward, RB J1 - Lancet Y1 - 2007/04/21/ VL - 369 SN - 1474-547X SP - 1356 EP - 1362 N2 - BACKGROUND: A high-potency monovalent oral type 1 poliovirus vaccine (mOPV1) was developed in 2005 to tackle persistent poliovirus transmission in the last remaining infected countries. Our aim was to assess the efficacy of this vaccine in India. METHODS: We estimated the efficacy of mOPV1 used in supplementary immunisation activities from 2076 matched case-control pairs of confirmed cases of poliomyelitis caused by type 1 wild poliovirus and cases of non-polio acute flaccid paralysis in India. The effect of the introduction of mOPV1 on population immunity was calculated on the basis of estimates of vaccination coverage from data for non-polio acute flaccid paralysis. FINDINGS: In areas of persistent poliovirus transmission in Uttar Pradesh, the protective efficacy of mOPV1 was estimated to be 30% (95% CI 19-41) per dose against type 1 paralytic disease, compared with 11% (7-14) for the trivalent oral vaccine. 76-82% of children aged 0-23 months were estimated to be protected by vaccination against type 1 poliovirus at the end of 2006, compared with 59% at the end of 2004, before the introduction of mOPV1. INTERPRETATION: Under conditions where the efficacy of live-attenuated oral poliovirus vaccines is compromised by a high prevalence of diarrhoea and other infections, a dose of high-potency mOPV1 is almost three times more effective against type 1 poliomyelitis disease than is trivalent vaccine. Achieving high coverage with this new vaccine in areas of persistent poliovirus transmission should substantially improve the probability of rapidly eliminating transmission of the disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17448821&query_hl=1 ER - TY - JFULL T1 - Necrotizing fasciitis in captive juvenile Crocodylus porosus caused by Streptococcus agalactiae: an outbreak and review of the animal and human literature. A1 - Bishop, EJ A1 - Shilton, C A1 - Benedict, S A1 - Kong, F A1 - Gilbert, GL A1 - Gal, D A1 - Godoy, D A1 - Spratt, BG A1 - Currie, BJ J1 - Epidemiol Infect Y1 - 2007/04/20/ SN - 0950-2688 SP - 1 EP - 8 N2 - We observed an outbreak of necrotizing fasciitis associated with Streptococcus agalactiae infection in a group of juvenile saltwater crocodiles (Crocodylus porosus). We undertook screening of crocodiles and the environment to clarify the source of the outbreak and evaluated the isolates cultured from post-mortem specimens with molecular methods to assess clonality and the presence of known group B streptococcal virulence determinants. The isolates were indistinguishable by pulsed-field gel electrophoresis. They were a typical serotype Ia strain with the Calpha-like protein gene, epsilon (or alp1), the mobile genetic elements IS381 ISSag1 and ISSag2, and belonged to multi-locus sequence type (ST) 23. All of these characteristics suggest they were probably of human origin. We review the medical and veterinary literature relating to S. agalactiae necrotizing fasciitis, epidemiology and virulence determinants. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17445318&query_hl=1 ER - TY - JFULL T1 - Diagnostic criteria and adjudication process both determine published event-rates: The ACTION trial experience. A1 - Kirwan, BA A1 - Lubsen, J A1 - Brouwer, SD A1 - Danchin, N A1 - Battler, A A1 - Bayes de Luna, A A1 - Dunselman, PH A1 - Glasser, S A1 - Koudstaal, PJ A1 - Sutton, G A1 - van Dalen, FJ A1 - Poole-Wilson, PA A1 - on behalf of the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) investigators J1 - Contemp Clin Trials Y1 - 2007/04/19/ SN - 1551-7144 N2 - OBJECTIVE: Few trials report event-adjudication procedures in detail. Using data from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study, we compared the impact on event-rates of an adjudication strategy based on systematic screening of all reported serious adverse events (SAEs) with a strategy based on investigator diagnoses. The final diagnosis was always made by a critical events committee (CEC) using standard criteria. METHODS: ACTION randomized 7665 patients with stable angina to either nifedipine or placebo. Pre-specified events included acute or procedural myocardial infarction (MI), refractory angina, heart failure and debilitating stroke. Clinically related SAEs including in-hospital procedures were combined into episodes independent from the investigator diagnoses entered on SAE reports. All fatal episodes and those episodes suggestive of pre-specified events were adjudicated by the CEC. RESULTS: During follow-up, 17,081 episodes were reported in 5312 patients. The SAE descriptions ruled out the occurrence of a pre-specified event in 28%. The remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory angina, 275 of heart failure and 190 of debilitating stroke were diagnosed (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397 patients) that were fatal or for which the investigator had reported any of the diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure and 14 of debilitating stroke would have been missed (total=228). CONCLUSION: Both the diagnostic criteria used and the adjudication process determine event-rates and conclusions about treatment effects in clinical trials. Published trial reports should always state if event-adjudication was independent of the diagnoses of investigators, and if all events of interest were adjudicated or only the first one. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17509947&query_hl=1 ER - TY - JFULL T1 - Re: Cellular telephone use and cancer risk: update of a nationwide Danish cohort study. A1 - Ahlbom, A A1 - Feychting, M A1 - Cardis, E A1 - Elliott, P J1 - J Natl Cancer Inst Y1 - 2007/04/18/ VL - 99 SN - 1460-2105 SP - 655; author reply 655 EP - 656; author reply 656 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17440169&query_hl=1 ER - TY - JFULL T1 - Evidence guiding the treatment of children with mycobacterial diseases - Editorial commentary A1 - Nicol, MP A1 - Wilkinson, RJ J1 - CLIN INFECT DIS Y1 - 2007/04/15/ VL - 44 SN - 1058-4838 SP - 1065 EP - 1066 ER - TY - JFULL T1 - Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) A1 - Wang, SS A1 - Slager, SL A1 - Brennan, P A1 - Holly, EA A1 - De Sanjose, S A1 - Bernstein, L A1 - Boffetta, P A1 - Cerhan, JR A1 - Maynadie, M A1 - Spinelli, JJ A1 - Chiu, BCH A1 - Cocco, PL A1 - Mensah, F A1 - Zhang, YW A1 - Nieters, A A1 - Dal Maso, L A1 - Bracci, PM A1 - Costantini, AS A1 - Vineis, P A1 - Severson, RK A1 - Roman, E A1 - Cozen, W A1 - Weisenburger, D A1 - Davis, S A1 - Franceschi, S A1 - La Vecchia, C A1 - Foretova, L A1 - Becker, N A1 - Staines, A A1 - Vornanen, M A1 - Zheng, TZ A1 - Hartge, P J1 - BLOOD Y1 - 2007/04/15/ VL - 109 SN - 0006-4971 SP - 3479 EP - 3488 N2 - A role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% Cl = 1.1-2.3), and leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology. ER - TY - JFULL T1 - Response to the letter to the editor. A1 - Briggs, D A1 - Krzyzanowski, M A1 - Vineis, P J1 - Int J Cancer Y1 - 2007/04/15/ VL - 120 SN - 0020-7136 SP - 1827 N2 - L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17230519&query_hl=1 ER - TY - JFULL T1 - Gender differences in the relationship between leptin, insulin resistance and the autonomic nervous system. A1 - Flanagan, DE A1 - Vaile, JC A1 - Petley, GW A1 - Phillips, DI A1 - Godsland, IF A1 - Owens, P A1 - Moore, VM A1 - Cockington, RA A1 - Robinson, JS J1 - Regul Pept Y1 - 2007/04/05/ VL - 140 SN - 0167-0115 SP - 37 EP - 42 N2 - OBJECTIVES: Leptin, an important hormonal regulator of body weight, has been shown to stimulate the sympathetic nervous system (SNS) in vitro although the physiological relevance remains unclear. Increased SNS activity has been implicated in the pathogenesis of insulin resistance and an increased cardiovascular risk. We have therefore investigated the relationship between leptin, insulin resistance and cardiac autonomic activity in healthy young adults. 130 healthy men and women age 20.9 years were studied. Insulin sensitivity was assessed using the IVGTT and minimal model with simultaneous measures of leptin. Cardiac autonomic activity was assessed using spectral analysis of heart rate variability. RESULTS: Women showed significantly higher fasting leptin, heart rate and cardiac sympathetic activity, and lower insulin sensitivity. Men showed inverse correlations between insulin resistance and heart rate, and between insulin resistance and cardiac sympatho-vagal ratio. Women, in contrast, showed no SNS relationship with insulin resistance, but rather an inverse correlation between leptin and the sympatho-vagal ratio, suggesting that leptin in women is associated with SNS activity. The correlation remained significant after adjustment for BMI and waist-to-hip ratio (beta=-0.33 and p=0.008). CONCLUSION: Insulin resistance and SNS activity appear to be linked, although the relationship showed marked gender differences, and the direction of causality was unclear from this cross-sectional study. Leptin appears to exert a greater effect on the SNS in women, possibly because of their greater fat mass. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17187873&query_hl=1 ER - TY - JFULL T1 - Recent HIV-1 infection in a high-risk Ugandan cohort: implications for Phase IIB test-of-concept HIV vaccine trials. A1 - Kebba, A A1 - Imami, N A1 - Bugembe-Lule, D A1 - Senkaali, D A1 - Kaleebu, P A1 - Grosskurth, H A1 - Gotch, F J1 - Pharmacogenomics Y1 - 2007/04// VL - 8 SN - 1462-2416 SP - 409 EP - 414 N2 - Assessment of vaccine efficacy on end points used in Phase IIB test-of-concept trials will require taking into consideration the effect of variables correlated with the end points and distribution of the variables within subgroups of the trial population. Here we report that evaluation of sexual activity in vaccinees and longitudinal collection of plasma viral load data from putative transmitters prior to transmission will contribute to the plausible assessment of efficacy against acquisition of infection. Data also suggest that efficacy on post-infection end points may depend on whether transmission pairs are matched or mismatched for HLA class I alleles. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17391079&query_hl=1 ER - TY - JFULL T1 - Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen) poisoning. A1 - Morgan, OW A1 - Griffiths, C A1 - Majeed, A J1 - PLoS Med Y1 - 2007/04// VL - 4 SN - 1549-1676 SP - e105 EP - e105 N2 - BACKGROUND: Paracetamol (acetaminophen) poisoning is the leading cause of acute liver failure in Great Britain and the United States. Successful interventions to reduced harm from paracetamol poisoning are needed. To achieve this, the government of the United Kingdom introduced legislation in 1998 limiting the pack size of paracetamol sold in shops. Several studies have reported recent decreases in fatal poisonings involving paracetamol. We use interrupted time-series analysis to evaluate whether the recent fall in the number of paracetamol deaths is different to trends in fatal poisoning involving aspirin, paracetamol compounds, antidepressants, or nondrug poisoning suicide. METHODS AND FINDINGS: We calculated directly age-standardised mortality rates for paracetamol poisoning in England and Wales from 1993 to 2004. We used an ordinary least-squares regression model divided into pre- and postintervention segments at 1999. The model included a term for autocorrelation within the time series. We tested for changes in the level and slope between the pre- and postintervention segments. To assess whether observed changes in the time series were unique to paracetamol, we compared against poisoning deaths involving compound paracetamol (not covered by the regulations), aspirin, antidepressants, and nonpoisoning suicide deaths. We did this comparison by calculating a ratio of each comparison series with paracetamol and applying a segmented regression model to the ratios. No change in the ratio level or slope indicated no difference compared to the control series. There were about 2,200 deaths involving paracetamol. The age-standardised mortality rate rose from 8.1 per million in 1993 to 8.8 per million in 1997, subsequently falling to about 5.3 per million in 2004. After the regulations were introduced, deaths dropped by 2.69 per million (p = 0.003). Trends in the age-standardised mortality rate for paracetamol compounds, aspirin, and antidepressants were broadly similar to paracetamol, increasing until 1997 and then declining. Nondrug poisoning suicide also declined during the study period, but was highest in 1993. The segmented regression models showed that the age-standardised mortality rate for compound paracetamol dropped less after the regulations (p = 0.012) but declined more rapidly afterward (p = 0.031). However, age-standardised rates for aspirin and antidepressants fell in a similar way to paracetamol after the regulations. Nondrug poisoning suicide declined at a similar rate to paracetamol after the regulations were introduced. CONCLUSIONS: Introduction of regulations to limit availability of paracetamol coincided with a decrease in paracetamol-poisoning mortality. However, fatal poisoning involving aspirin, antidepressants, and to a lesser degree, paracetamol compounds, also showed similar trends. This raises the question whether the decline in paracetamol deaths was due to the regulations or was part of a wider trend in decreasing drug-poisoning mortality. We found little evidence to support the hypothesis that the 1998 regulations limiting pack size resulted in a greater reduction in poisoning deaths involving paracetamol than occurred for other drugs or nondrug poisoning suicide. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17407385&query_hl=1 ER - TY - JFULL T1 - Early metabolic defects following gestational diabetes in three ethnic groups of anti-GAD antibodies negative women with normal fasting glucose. A1 - Kousta, E A1 - Lawrence, NJ A1 - Godsland, IF A1 - Penny, A A1 - Anyaoku, V A1 - Millauer, BA A1 - Robinson, S A1 - Johnston, DG A1 - McCarthy, MI J1 - Hormones (Athens) Y1 - 2007/04// VL - 6 SN - 1109-3099 SP - 138 EP - 147 N2 - OBJECTIVE: To characterise early metabolic abnormalities and the impact of ethnicity following gestational diabetes mellitus (GDM). DESIGN: Women with a history of GDM belonging to three different ethnic groups were evaluated. Using the insulin-modified, frequently-sampled intravenous glucose tolerance test (FSIVGTT) and HOMA we studied 34 European, 16 South Asian and 10 Afro-Caribbean women with normal fasting glucose following GDM and 44 European, 16 South Asian and 19 Afro-Caribbean controls to assess insulin action and secretion. RESULTS: European post-GDM women had lower insulin sensitivity by FSIVGTT [0.6 (0.1-5.1) vs 1.5 (0.8-2.8) x10(-4).min(-1).pmol(-1).l(-1), p=0.010, adjusted for BMI p=0.054] and by HOMA [72(22-235) vs 153(55-421)%, p=0.004, adjusted for BMI p=0.006], and reduced -cell function [lower disposition index 0.05(0.01-0.40) vs 0.11(0.05-0.25)min(-1), p=0.017] compared with controls. South Asian post-GDM women had decreased -cell function [lower HOMA (%B) (73 (37-147) vs 124 (59-262) %, p=0.048 and acute insulin response to glucose (463 (131-1639) vs 1039 (393-2748) pmol/l h, p=0.052] than controls. Afro-Caribbean post-GDM women had lower glucose disappearance rate [1.3(0.6-2.8) vs 2.6 (1.8-3.8) 10(-2)/min, p=0.003] than controls, suggesting subtle glucose intolerance. CONCLUSIONS: Women with a history of GDM of three different ethnic groups, even in the presence of normal fasting glucose, display a range of metabolic abnormalities, including -cell dysfunction with variable insulin resistance. These derangements may be influenced by ethnicity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17704045&query_hl=1 ER - TY - JFULL T1 - Development and application of an ethically and epidemiologically advantageous assay for the multi-locus microsatellite analysis of Schistosoma mansoni. A1 - Gower, CM A1 - Shrivastava, J A1 - Lamberton, PH A1 - Rollinson, D A1 - Webster, BL A1 - Emery, A A1 - Kabatereine, NB A1 - Webster, JP J1 - Parasitology Y1 - 2007/04// VL - 134 SN - 0031-1820 SP - 523 EP - 536 N2 - Non-availability of adult worms from living hosts remains a key problem in population genetic studies of schistosomes. Indirect sampling involving passage through laboratory animals presents significant ethical and practical drawbacks, and may result in sampling biases such as bottlenecking processes and/or host-induced selection pressures. The novel techniques reported here for sampling, storage and multi-locus microsatellite analysis of larval Schistosoma mansoni, allowing genotyping of up to 7 microsatellite loci from a single larva, circumvent these problems. The utility of these assays and the potential problems of laboratory passage, were evaluated using 7 S. mansoni population isolates collected from school-children in the Hoima district of Uganda, by comparing the associated field-collected miracidia with adult worms and miracidia obtained from a single generation in laboratory mice. Analyses of laboratory-passaged material erroneously indicated the presence of geographical structuring in the population, emphasizing the dangers of indirect sampling for population genetic studies. Bottlenecking and/or other sampling effects were demonstrated by reduced variability of adult worms compared to their parent field-collected larval samples. Patterns of heterozygote deficiency were apparent in the field-collected samples, which were not evident in laboratory-derived samples, potentially indicative of heterozygote advantage in establishment within laboratory hosts. Genetic distance between life-cycle stages in the majority of isolates revealed that adult worms and laboratory-passaged miracidia clustered together whilst segregating from field miracidia, thereby further highlighting the utility of this assay. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17096873&query_hl=1 ER - TY - JFULL T1 - Helicobacter infection in the surfactant protein D-deficient mouse. A1 - Khamri, W A1 - Worku, ML A1 - Anderson, AE A1 - Walker, MM A1 - Hawgood, S A1 - Reid, KB A1 - Clark, HW A1 - Thursz, MR J1 - Helicobacter Y1 - 2007/04// VL - 12 SN - 1083-4389 SP - 112 EP - 123 N2 - BACKGROUND: Surfactant protein D (SP-D), a component of innate immunity, is expressed in the gastric mucosa and is up-regulated in the presence of Helicobacter infection. SP-D binds to Helicobacter in vitro, suggesting the involvement of SP-D in Helicobacter-induced immune responses. The aim of this study was to determine the role of SP-D in gastric epithelial defense in vivo. METHODS: Specific pathogen-free SP-D-deficient mice (SP-D(-/-)) and C57BL/6 wild-type controls were challenged by gavage with different doses of Helicobacter felis, a mouse-adapted Helicobacter strain. Mice were assessed for colonization rates and density of infection. Inflammatory responses were measured by neutrophil counting and T-cell responses by proliferation assays on spleen cells stimulated with H. felis sonicate. The in vitro effect of SP-D on Helicobacter uptake by monocyte-derived dendritic cells was assessed by confocal microscopy and FACS analyses. RESULTS: SP-D(-/-) mice were more susceptible to low-dose infectious challenge than C57BL/6 controls (p = .02). The density of colonization was higher in the SP-D(-/-) infected mice. Neutrophil infiltrates were lower in the SP-D(-/-) mice, particularly in the acid-secreting regions of the stomach. T-cell proliferative responses to Helicobacter antigen were reduced in SP-D(-/-) mice (p = .001) after 12 weeks infection. In vitro uptake of Helicobacter by dendritic cells was significantly enhanced in the presence of SP-D (p = .001). CONCLUSION: In the absence of SP-D, Helicobacter uptake by dendritic cells is impaired. This provides an explanation for the diminished inflammation and immune responses in the SP-D(-/-) mice. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17309747&query_hl=1 ER - TY - JFULL T1 - A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy. A1 - Botoni, FA A1 - Poole-Wilson, PA A1 - Ribeiro, AL A1 - Okonko, DO A1 - Oliveira, BM A1 - Pinto, AS A1 - Teixeira, MM A1 - Teixeira, AL A1 - Reis, AM A1 - Dantas, JB A1 - Ferreira, CS A1 - Tavares, WC A1 - Rocha, MO J1 - Am Heart J Y1 - 2007/04// VL - 153 SN - 1097-6744 SP - 544.e1 EP - 548.e1 N2 - OBJECTIVE: The objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy. BACKGROUND: Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials. METHODS: We conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points. RESULTS: Optimization of RAS inhibition was safe, hemodynamically well tolerated, and associated with improvements in Framingham score (P = .001) and quality of life as well as reductions in the cardiothoracic index (P = .002), brain natriuretic peptide level (P = .032), and RANTES (regulated on activation, normal T expressed and secreted) level (P = .001). Left ventricular ejection fraction increased by 2.3% (P = .25); in patients with an LVEF < or = 45% at baseline, it increased by 2.8% (P = .017). Treatment with carvedilol was associated with a trend toward an increase in LVEF (absolute difference between groups, 2.3%; P = .094). The addition of carvedilol was safe, hemodynamically well tolerated, and not associated with symptomatic bradycardia. CONCLUSIONS: In patients with chronic Chagas cardiomyopathy, optimization of treatment with enalapril and spironolactone and subsequent addition of carvedilol were safe and associated with benefits in cardiac function and clinical status. Larger trials are needed to show effects on mortality and/or hospitalization. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17383291&query_hl=1 ER - TY - JFULL T1 - Interpersonal continuity of care: a cross-sectional survey of primary care patients' preferences and their experiences A1 - Baker, R A1 - Boulton, M A1 - Windridge, K A1 - Tarrant, C A1 - Bankart, J A1 - Freeman, GK J1 - BRIT J GEN PRACT Y1 - 2007/04// VL - 57 SN - 0960-1643 SP - 283 EP - 289 N2 - Background Developments in primary care may make the provision of interpersonal continuity more difficult.Aim To identify those patients who regard interpersonal continuity as important and determine what makes it difficult for them to obtain this. Design of study Cross sectional survey.Setting Twenty-two practices and a walk-in centre in West London and Leicestershire, UK.Method Administration of a questionnaire on preferences for and experiences of interpersonal and informational continuity. Interpersonal continuity was defined in three questions: choosing a particular person; choosing someone known and trusted; and choosing someone who knows the patient and medical condition.Results One thousand four hundred and thirty-seven (46.5%) patients responded. Consulting someone known and trusted was important to 766 (62.6%) responders, although 105 (13.7%) of these reported that they had not experienced it at their last consultation. Seven hundred and eighty-eight (65.2%) responders regarded being able to consult a particular person as important, but 168 (21.3%) of these were unable to. Being in work and consulting for a new problem were associated with failing to obtain interpersonal continuity. Ethnic group was associated with failing to see someone with time to listen when this was preferred.Conclusion In view of the response rate, which was particularly low among young males, some caution is required in applying the findings. Most patients experience the aspects of care important to them, although interpersonal continuity is important to many and certain groups find difficulty in obtaining it. Practices should have flexible appointment systems to account for the difficulties some patients have in negotiating for the type of care they want. ER - TY - JFULL T1 - Haemochromatosis: Rising hospital admission rates but stable mortality 1989/90 to 2002/03 A1 - Cowan, ML A1 - Westlake, S A1 - Majeed, A A1 - Rahman, TM A1 - Maxwell, JD A1 - Kang, J J1 - GUT Y1 - 2007/04// VL - 56 SN - 0017-5749 SP - A123 EP - A124 ER - TY - JFULL T1 - Detection of urinary drug metabolite (xenometabolome) signatures in molecular epidemiology studies via statistical total correlation (NMR) spectroscopy. A1 - Holmes, E A1 - Loo, RL A1 - Cloarec, O A1 - Coen, M A1 - Tang, H A1 - Maibaum, E A1 - Bruce, S A1 - Chan, Q A1 - Elliott, P A1 - Stamler, J A1 - Wilson, ID A1 - Lindon, JC A1 - Nicholson, JK J1 - Anal Chem Y1 - 2007/04/01/ VL - 79 SN - 0003-2700 SP - 2629 EP - 2640 N2 - Western populations use prescription and nonprescription drugs extensively, but large-scale population usage is rarely assessed objectively in epidemiological studies. Here we apply statistical methods to characterize structural pathway connectivities of metabolites of commonly used drugs detected routinely in 1H NMR spectra of urine in a human population study. 1H NMR spectra were measured for two groups of urine samples obtained from U.S. participants in a known population study. The novel application of a statistical total correlation spectroscopy (STOCSY) approach enabled rapid identification of the major and certain minor drug metabolites in common use in the population, in particular, from acetaminophen and ibuprofen metabolites. This work shows that statistical connectivities between drug metabolites can be established in routine "high-throughput" NMR screening of human samples from participants who have randomly self-administered drugs. This approach should be of value in considering interpopulation patterns of drug metabolism in epidemiological and pharmacogenetic studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17323917&query_hl=1 ER - TY - JFULL T1 - Influence of organic diet on the amount of conjugated linoleic acids in breast milk of lactating women in the Netherlands. A1 - Rist, L A1 - Mueller, A A1 - Barthel, C A1 - Snijders, B A1 - Jansen, M A1 - Simões-Wüst, AP A1 - Huber, M A1 - Kummeling, I A1 - von Mandach, U A1 - Steinhart, H A1 - Thijs, C J1 - Br J Nutr Y1 - 2007/04// VL - 97 SN - 0007-1145 SP - 735 EP - 743 N2 - The aim of the present study was to find out whether the incorporation of organic dairy and meat products in the maternal diet affects the contents of the conjugated linoleic acid isomers (CLA) and trans-vaccenic acid (TVA) in human breast milk. To this purpose, milk samples from 312 breastfeeding mothers participating in the KOALA Birth Cohort Study have been analysed. The participants had documented varying lifestyles in relation to the use of conventional or organic products. Breast milk samples were collected 1 month postpartum and analysed for fatty acid composition. The content of rumenic acid (the main CLA) increased in a statistically significant way while going from a conventional diet (no organic dairy/meat products, 0.25 weight % (wt%), n 186) to a moderately organic diet (50-90 % organic dairy/meat, 0.29 wt%, n 33, P = 0.02) and to a strict organic diet (>90 % organic dairy/meat, 0.34 wt%, n 37, P 8 mg/L (indicating that satisfactory peak concentrations were achieved). Ninety-eight percent of samples measured more than 20 h after the dose were <1 mg/L. The best model included weight, and it was found that high base deficit, high creatinine concentration and low temperature (all markers of hypovolaemic shock) reduced clearance (CL/F). Weight influenced volume of the central (V1/F) and peripheral (V2/F) compartments, and high base deficit reduced V2/F and intercompartmental CL (Q/F). Interindividual variability in CL was 26%, in V1/F 33% and in V2/F and Q/F was 52%. Individual estimates of CL/F ranged from 0.02 to 0.16 (median 0.10) L/h/kg and those of Vss/F from 0.26 to 1.31 (median 0.67) L/kg. Initial half-lives had a median of 1.4 h and elimination half-lives and a median of 14.9 h. Excessive concentrations were observed in one patient who had signs of renal impairment and shock. Conclusions: Although a daily dose of 7.5 mg/kg achieves satisfactory gentamicin concentrations in the majority of patients, patients with renal impairment and shock may be at risk of accumulation with 24 hourly dosing. Further studies of gentamicin pharmacokinetics in this group are now needed to inform future international guideline recommendations. ER - TY - JFULL T1 - A long-term study of women with normal colposcopy after referral with low-grade cytological abnormalities - Author's reply A1 - Soutter, WP J1 - BJOG-INT J OBSTET GY Y1 - 2007/04// VL - 114 SN - 1470-0328 ER - TY - JFULL T1 - Approximate disease dynamics in household-structured populations. A1 - Dodd, PJ A1 - Ferguson, NM J1 - J R Soc Interface Y1 - 2007/03/28/ SN - 1742-5689 N2 - We argue that the large-dimensional dynamical systems which frequently occur in biological models can sometimes be effectively reduced to much smaller ones. We illustrate this by applying projection operator techniques to a mean-field model of an infectious disease spreading through a population of households. In this way, we are able to accurately approximate the dynamics of the system in terms of a few key quantities greatly reducing the number of equations required. We investigate linear stability in this framework and find a new way of calculating the familiar threshold criterion for household systems. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17392066&query_hl=1 ER - TY - JFULL T1 - Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe. A1 - Gregson, S A1 - Adamson, S A1 - Papaya, S A1 - Mundondo, J A1 - Nyamukapa, CA A1 - Mason, PR A1 - Garnett, GP A1 - Chandiwana, SK A1 - Foster, G A1 - Anderson, RM J1 - PLoS Med Y1 - 2007/03/27/ VL - 4 SN - 1549-1676 SP - e102 EP - e102 N2 - BACKGROUND: HIV-1 control in sub-Saharan Africa requires cost-effective and sustainable programmes that promote behaviour change and reduce cofactor sexually transmitted infections (STIs) at the population and individual levels. METHODS AND FINDINGS: We measured the feasibility of community-based peer education, free condom distribution, income-generating projects, and clinic-based STI treatment and counselling services and evaluated their impact on the incidence of HIV-1 measured over a 3-y period in a cluster-randomised controlled trial in eastern Zimbabwe. Analysis of primary outcomes was on an intention-to-treat basis. The income-generating projects proved impossible to implement in the prevailing economic climate. Despite greater programme activity and knowledge in the intervention communities, the incidence rate ratio of HIV-1 was 1.27 (95% confidence interval [CI] 0.92-1.75) compared to the control communities. No evidence was found for reduced incidence of self-reported STI symptoms or high-risk sexual behaviour in the intervention communities. Males who attended programme meetings had lower HIV-1 incidence (incidence rate ratio 0.48, 95% CI 0.24-0.98), and fewer men who attended programme meetings reported unprotected sex with casual partners (odds ratio 0.45, 95% CI 0.28-0.75). More male STI patients in the intervention communities reported cessation of symptoms (odds ratio 2.49, 95% CI 1.21-5.12). CONCLUSIONS: Integrated peer education, condom distribution, and syndromic STI management did not reduce population-level HIV-1 incidence in a declining epidemic, despite reducing HIV-1 incidence in the immediate male target group. Our results highlight the need to assess the community-level impact of interventions that are effective amongst targeted population sub-groups. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17388666&query_hl=1 ER - TY - JFULL T1 - Fluvastatin reduces increased blood monocyte Toll-like receptor 4 expression in whole blood from patients with chronic heart failure. A1 - Földes, G A1 - von Haehling, S A1 - Okonko, DO A1 - Jankowska, EA A1 - Poole-Wilson, PA A1 - Anker, SD J1 - Int J Cardiol Y1 - 2007/03/23/ SN - 1874-1754 N2 - BACKGROUND: Innate immune activation mediated by myocardial Toll-like receptors (TLRs) is involved in cardiovascular disease. The function and role of TLRs on peripheral leukocytes in human chronic heart failure (CHF) are not known. METHODS: We measured whole blood TLR4 and TLR2 expressions in 28 patients with CHF (64+/-2 years, New York Heart Association [NYHA] functional class 2.2+/-0.1, left ventricular (LV) ejection fraction 32+/-2%) and 13 healthy subjects of similar age and gender. RESULTS: As assessed by flow cytometry, TLR4 and TLR2 were detected on CD14+ monocytes. Unstimulated monocyte TLR4 expression was significantly higher in CHF patients compared to controls (mean fluorescence intensity, 3.57+/-0.57 vs. 1.72+/-0.32, p<0.05). TLR2 expressions were similar in CHF patients and control subjects (p=0.5). TLR4 levels correlated with the severity of CHF (NYHA class I/II: 2.66+/-0.40, and NYHA class III/IV: 5.08+/-1.24, p<0.01) and with serum lipid levels (total cholesterol, r=-0.44, p<0.01 and high-density lipoprotein, r=-0.68, p<0.001). After stimulation of monocytes by lipopolysaccharide (LPS, 10 ng/ml, 3 h), activated TLR4 was higher in CHF patients (p<0.05). Pre-incubation with fluvastatin for 24 h inhibited dose-dependently ex vivo monocyte TLR4 and TLR2 expressions (p<0.001). CONCLUSIONS: This study suggests that upregulation of monocyte TLR4 may contribute to the pathophysiology of chronic heart failure. Fluvastatin may prevent excessive innate immune response in vitro in chronic heart failure by inhibition of monocyte Toll-like receptor signaling. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17383753&query_hl=1 ER - TY - JFULL T1 - Monocyte-dependent fibroblast CXCL8 secretion occurs in tuberculosis and limits survival of mycobacteria within macrophages. A1 - O'Kane, CM A1 - Boyle, JJ A1 - Horncastle, DE A1 - Elkington, PT A1 - Friedland, JS J1 - J Immunol Y1 - 2007/03/15/ VL - 178 SN - 0022-1767 SP - 3767 EP - 3776 N2 - CXCL8 is a chemokine that is implicated in the formation of tuberculous (TB) granulomas and in immunity to Mycobacterium tuberculosis (Mtb). Fibroblast chemokine secretion is important for modulating inflammatory responses in chronic lung disease and inflammatory arthritis but has not been investigated in the pathophysiology of TB. In this study, we used a cellular model to examine monocyte/macrophage-dependent stimulation of fibroblasts by Mtb in the regulation of chemokine secretion, particularly that of CXCL8. Human lung fibroblasts grown in collagen were stimulated with conditioned medium from Mtb-infected monocytes (CoMTb). CoMTb-induced prolonged dose-dependent, p38-mediated expression of stable CXCL8 mRNA by fibroblasts accompanied by a >10-fold increase in CXCL8 secretion (487 +/- 88 ng/ml vs 48.6 +/- 34 ng/ml in controls) at 120 h. Fibroblasts strongly expressed CXCL8 in vivo in human TB granulomas. Inhibition of TNF-alpha or IL-1 in CoMTb abrogated the induction of CXCL8 at a pretranscriptional level. CXCL8 secretion was NF-kappaB, C/EBP, and JNK dependent. Sustained NF-kappaB activation was demonstrated beyond 24 h in response to CoMTb. Exogenous CXCL8 reduced the survival of Mtb within macrophages, and inhibition of CXCL8 was associated with intracellular mycobacterial proliferation. These data show that fibroblasts have a previously unrecognized role in modulating inflammation in TB by their CXCL8-dependent contribution to cell recruitment and mycobacterial killing within the granuloma. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17339475&query_hl=1 ER - TY - JFULL T1 - Sex ratio and time to pregnancy: analysis of four large European population surveys A1 - Joffe, M A1 - Bennett, J A1 - Best, N A1 - Jensen, TK J1 - BRIT MED J Y1 - 2007/03/10/ VL - 334 SN - 0959-8146 SP - 524 EP - 526A N2 - Objective To test whether the secondary sex ratio (proportion of male births) is associated with time to pregnancy, a marker of fertility.Design Analysis of four large population surveys.Setting Denmark and the United Kingdom. Participants 49 506 pregnancies.Main outcome measure Secondary sex ratio.Results No association was found between the sex ratio and time to pregnancy and no discernible trend was found for sex ratio with time to pregnancy, either within individual datasets or in the pooled analysis. The odds ratios were 0.97 (95% confidence interval 0.90 to 1.04) for contraceptive failures, 1.01 (0.96 to 1.05) for time to pregnancy of 2-4 months, 1.02 (0.97 to 1.08) for 5-10 months, 0.98 (0.93 to 1.03) for 11 months or more, and 0.88 (0.74 to 1.06) for fertility treatment, with 0-1 months as the reference category.Conclusion No association was found between the secondary sex ratio and time to pregnancy. ER - TY - JFULL T1 - Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. A1 - Nadel, S A1 - Goldstein, B A1 - Williams, MD A1 - Dalton, H A1 - Peters, M A1 - Macias, WL A1 - Abd-Allah, SA A1 - Levy, H A1 - Angle, R A1 - Wang, D A1 - Sundin, DP A1 - Giroir, B A1 - REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective (RESOLVE) study group J1 - Lancet Y1 - 2007/03/10/ VL - 369 SN - 1474-547X SP - 836 EP - 843 N2 - BACKGROUND: Drotrecogin alfa (activated) (DrotAA) is used for the treatment of adults with severe sepsis who have a high risk of dying. A phase 1b open-label study has indicated that the pharmacokinetics and pharmacodynamics of DrotAA are similar in children and adults. We initiated the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE) trial to investigate the efficacy and safety of the drug in children. METHODS: Children aged between 38 weeks' corrected gestational age and 17 years with sepsis-induced cardiovascular and respiratory failure were randomly assigned to receive placebo or DrotAA (24 microg/kg/h) for 96 h. We used a prospectively defined, novel primary endpoint of Composite Time to Complete Organ Failure Resolution (CTCOFR) score. Secondary endpoints were 28-day mortality, major amputations, and safety. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov, number NCT00049764. FINDINGS: 477 patients were enrolled; 237 received placebo, and 240 DrotAA. Our results showed no significant difference between groups in CTCOFR score (p=0.72) or in 28-day mortality (placebo 17.5%; DrotAA, 17.2%; p=0.93). Although there was no difference in overall serious bleeding events during the 28-day study period (placebo 6.8%; DrotAA 6.7%; p=0.97), there were numerically more instances of CNS bleeding in the DrotAA group (11 [4.6%], vs 5 [2.1%] in placebo, p=0.13), particularly in children younger than 60 days. For CTCOFR score days 1-14, correlation coefficient was -0.016 (95% CI -0.106 to 0.74); relative risk for 28-day mortality was 1.06 (95% CI 0.66 to 1.46) for DrotAA compared with placebo. INTERPRETATION: Although we did not record any efficacy of DrotAA in children with severe sepsis, serious bleeding events were similar between groups and the overall safety profile acceptable, except in children younger than 60 days. However, we gained important insights into clinical and laboratory characteristics of childhood severe sepsis, and have identified issues that need to be addressed in future trials in critically ill children. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17350452&query_hl=1 ER - TY - JFULL T1 - Sex ratio and time to pregnancy: analysis of four large European population surveys. A1 - Joffe, M A1 - Bennett, J A1 - Best, N A1 - Jensen, TK J1 - BMJ Y1 - 2007/03/10/ VL - 334 SN - 1468-5833 SP - 524 EP - 524 N2 - OBJECTIVE: To test whether the secondary sex ratio (proportion of male births) is associated with time to pregnancy, a marker of fertility. Design Analysis of four large population surveys. Setting Denmark and the United Kingdom. Participants 49 506 pregnancies. MAIN OUTCOME MEASURE: Secondary sex ratio. RESULTS: No association was found between the sex ratio and time to pregnancy and no discernible trend was found for sex ratio with time to pregnancy, either within individual datasets or in the pooled analysis. The odds ratios were 0.97 (95% confidence interval 0.90 to 1.04) for contraceptive failures, 1.01 (0.96 to 1.05) for time to pregnancy of 2-4 months, 1.02 (0.97 to 1.08) for 5-10 months, 0.98 (0.93 to 1.03) for 11 months or more, and 0.88 (0.74 to 1.06) for fertility treatment, with 0-1 months as the reference category. CONCLUSION: No association was found between the secondary sex ratio and time to pregnancy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17277014&query_hl=1 ER - TY - JFULL T1 - A multi-compartment cell repopulation model allowing for inter-compartmental migration following radiation exposure, applied to leukaemia. A1 - Little, MP J1 - J Theor Biol Y1 - 2007/03/07/ VL - 245 SN - 0022-5193 SP - 83 EP - 97 N2 - There is much uncertainty about cancer risks at the high radiation doses used in radiotherapy (RT). It has generally been assumed that cancer induction decreases rapidly at high doses due to cell killing. However, this is not seen in all RT groups, and a model recently developed by Sachs and Brenner [2005. Solid tumor risks after high doses of ionizing radiation. Proc. Natl Acad. Sci. USA 102, 13040-13045] proposed a mechanism for repopulation of cells after radiation exposure that explained why this might happen, at least for solid tumours. In this paper, this model is generalized to allow for heterogeneity in the dose received, and various alternate patterns of repopulation are also considered. The model is fitted to the Japanese atomic bomb survivor leukaemia incidence data, and data for various therapeutically irradiated groups. Two sets of parameters from these model fits are used to assess the sensitivity of model predictions. It is shown that in general allowing for heterogeneity in dose distribution and haematopoietic stem cell migration results in lower risks than the same average dose administered uniformly and without such migration, although this does not hold in the limiting case of complete stem cell repopulation between radiation dose fractions. We also investigate the difference made by assuming a compartmental repopulation signal, and a global repopulation signal. In general we show that in the absence of stochastic extinction, compartmental repopulation always predicts a larger number of mutated cells than global repopulation. However, in certain dose regimes stochastic extinction cannot be ignored, and in these cases the numbers of mutated cells predicted with global repopulation can exceed that for compartmental repopulation. In general, mutant cell numbers are highly overdispersed, with variance much greater than the mean. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17092522&query_hl=1 ER - TY - JFULL T1 - Carvedilol protects better against vascular events than metoprolol in heart failure: results from COMET. A1 - Remme, WJ A1 - Torp-Pedersen, C A1 - Cleland, JG A1 - Poole-Wilson, PA A1 - Metra, M A1 - Komajda, M A1 - Swedberg, K A1 - Di Lenarda, A A1 - Spark, P A1 - Scherhag, A A1 - Moullet, C A1 - Lukas, MA J1 - J Am Coll Cardiol Y1 - 2007/03/06/ VL - 49 SN - 1558-3597 SP - 963 EP - 971 N2 - OBJECTIVES: We explored whether vascular protection by carvedilol could contribute to its superior effects in the treatment of heart failure (HF) compared with metoprolol tartrate in the COMET (Carvedilol Or Metoprolol European Trial) study. BACKGROUND: Full adrenergic blockade by carvedilol and additional (e.g., antioxidative) properties may lead to vascular protection relative to beta-1 blockade alone, and contribute to its efficacy in HF treatment. METHODS: Three thousand twenty-nine patients with HF due to ischemic (51%) or idiopathic cardiomyopathy (44%) were randomized double-blind to carvedilol (n = 1,511) or metoprolol (n = 1,518) and followed for 58 months. Vascular end points were cardiovascular death, stroke, stroke death, myocardial infarction (MI), and unstable angina. RESULTS: The effect of carvedilol on cardiovascular death improved consistently in subgroups with prespecified baseline variables. Myocardial infarctions were reported in 69 carvedilol and 94 metoprolol patients (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52 to 0.97, p = 0.03). Cardiovascular death or nonfatal MI combined were reduced by 19% in carvedilol (HR 0.81, 95% CI 0.72 to 0.92, p = 0.0009 vs. metoprolol). Unstable angina was reported as an adverse event in 56 carvedilol and in 77 metoprolol patients (HR 0.71, 95% CI 0.5