Debbie A Lawlor

Bio: Debbie A Lawlor is an academic researcher from University of Bristol. The author has contributed to research in topics: Population & Body mass index. The author has an hindex of 147, co-authored 1114 publications receiving 101123 citations. Previous affiliations of Debbie A Lawlor include Southampton General Hospital & University of Vermont.

Association of parents’ and children’s physical activity and sedentary time in Year 4 (8–9) and change between Year 1 (5–6) and Year 4: a longitudinal study

Abstract: Parents could be important influences on child physical activity and parents are often encouraged to be more active with their child. This paper examined the association between parent and child physical activity and sedentary time in a UK cohort of children assessed when the children were in Year 1 (5–6 years old) and in Year 4 (8–9 years old). One thousand two hundred twenty three children and parents provided data in Year 4 and of these 685 participated in Year 1. Children and parents wore an accelerometer for five days including a weekend. Mean minutes of sedentary time and moderate-to-vigorous intensity physical activity (MVPA) were derived. Multiple imputation was used to impute all missing data and create complete datasets. Linear regression models examined whether parent MVPA and sedentary time at Year 4 and at Year 1 predicted child MVPA and sedentary time at Year 4. Change in parent MVPA and sedentary time was used to predict change in child MVPA and sedentary time between Year 1 and Year 4. Imputed data showed that at Year 4, female parent sedentary time was associated with child sedentary time (0.13, 95% CI = 0.00 to 0.27 mins/day), with a similar association for male parents (0.15, 95% CI = −0.02 to 0.32 mins/day). Female parent and child MVPA at Year 4 were associated (0.16, 95% CI = 0.08 to 0.23 mins/day) with a smaller association for male parents (0.08, 95% CI = −0.01 to 0.17 mins/day). There was little evidence that either male or female parent MVPA at Year 1 predicted child MVPA at Year 4 with similar associations for sedentary time. There was little evidence that change in parent MVPA or sedentary time predicted change in child MVPA or sedentary time respectively. Parents who were more physically active when their child was 8–9 years old had a child who was more active, but the magnitude of association was generally small. There was little evidence that parental activity from three years earlier predicted child activity at age 8–9, or that change in parent activity predicted change in child activity.

The search for modifiable risk factors for schizophrenia

Abstract: In theory, discovering the causes of schizophrenia should be simple. First, look for gradients in the incidence of schizophrenia across time or within or between populations. Next, scrutinize the findings carefully and generate candidate risk factors that may explain any detected gradient. Take your top candidate exposures, and undertake an integrated research program involving analytical and genetic epidemiology and applied neuroscience in order to unravel the mechanism of action linking the candidate to schizophrenia. Finally, for modifiable risk factors, undertake randomized controlled trials of interventions designed to ameliorate the exposure in order to confirm the causal link and provide effective preventive interventions. What could be simpler? In reality, the search for modifiable risk factors for schizophrenia has been a frustrating and often haphazard affair. For many decades, the schizophrenia research community had a scientific scotoma with respect to variations in the incidence of schizophrenia (1). After convincing gradients were identified, the response of the research community was somewhat ataxic. For example, even after a substantial evidence base had accumulated, the default interpretation of the increased risk of schizophrenia in dark-skinned migrants to the United Kingdom was denial—the findings could not be true and must be the result of methodological biases—rather than an attempt to understand a range of possible reasons for the association, which has been done for physical ill-health, such as hypertension, diabetes, and cardiovascular disease. One of the — most consistent and long-standing risk factors associated with schizophrenia has been winter-spring birth. However, the general response of the research community has been replication of the ecological association without the subsequent testing of plausible modifiable candidate exposures. Have we wasted time and squandered research opportunities by mishandling these important clues? To be fair, these issues are not unique to schizophrenia research or to psychiatry in general. Apart from the need to follow up clues in a timely and efficient manner, the wider role of observational epidemiology in modern health research has come under scrutiny in recent years; some have suggested that epidemiology has \"had its day\" (2). In this issue of the/oumaZ, four articles demonstrate how epidemiology has refined our search space for candidate exposures (3-6). The studies are exemplars of modern epidemiological designs. Clarke et al. (4) have refined our understanding of the antecedents of schizophrenia. Linking various registers, they have confirmed that infants and toddlers who are in the lower end of the normal distribution for motor milestones have an increased risk of schizophrenia. The results suggest that the processes that underlie the emergence of schizophrenia during young adulthood also affect early motor outcomes. Consistent vñth a large body of convergent research, these findings suggest that early-life neurodevelopmental processes contribute to the risk of schizophrenia (7). Importantly, in terms of looking for causal risk factors, the authors note that childhood motor delay is \"neither a necessary nor a sufficient cause of schizophrenia, and these deficits have weak positive predictive power.\" They highlight the importance of their findings in terms of the additive interaction between motor delay and obstetric complications (defined by a low Apgar score). Among 142 case patients and 133 comparison subjects, they found

Missing Data Methods in Mendelian Randomization Studies With Multiple Instruments

Abstract: Mendelian randomization studies typically have low power. Where there are several valid candidate genetic instruments, precision can be gained by using all the instruments available. However, sporadically missing genetic data can offset this gain. The authors describe 4 Bayesian methods for imputing the missing data based on a missing-at-random assumption: multiple imputations, single nucleotide polymorphism (SNP) imputation, latent variables, and haplotype imputation. These methods are demonstrated in a simulation study and then applied to estimate the causal relation between C-reactive protein and each of fibrinogen and coronary heart disease, based on 3 SNPs in British Women's Heart and Health Study participants assessed at baseline between May 1999 and June 2000. A complete-case analysis based on all 3 SNPs was found to be more precise than analyses using any 1 SNP alone. Precision is further improved by using any of the 4 proposed missing data methods; the improvement is equivalent to about a 25% increase in sample size. All methods gave similar results, which were apparently not overly sensitive to violation of the missing-at-random assumption. Programming code for the analyses presented is available online.

Coronary heart disease prevention in clinical practice: are patients with diabetes special? Evidence from two studies of older men and women.

Abstract: Objective: To assess whether the extent of primary and secondary coronary heart disease (CHD) prevention in older British men and women differs between patients with and without diabetes. Design: Two prospective cardiovascular cohort studies. Setting: 24 British towns. Patients: 4252 men and 4286 women aged 60–79 years examined between 1998 and 2001. Main outcome measures: Use of aspirin, statin, and blood pressure lowering treatment and risk factor control, examined by diabetic status and history of established CHD. Results: About 20% of the men and 12% of the women had established CHD at age 60–79 years and 7% of the men and 5% of the women had diabetes. In primary CHD prevention, patients with diabetes were more likely to receive CHD risk reducing medications than those without diabetes, but the proportions receiving preventive treatments in both groups were low. In secondary prevention, diabetic and non-diabetic patients received similar levels of treatment, with the exception of angiotensin converting enzyme inhibitors and (for women only) blood pressure lowering treatment, which were more widely used among diabetic patients. There were no clear differences in blood pressure control or cigarette smoking by diabetic status in primary or secondary prevention. Mean total cholesterol concentrations were lower in diabetic patients independently of treatment with statins. Conclusions: Despite their exceptionally high CHD risk, many opportunities to reduce CHD risk among patients with diabetes have not been taken.

Prediction of uncomplicated pregnancies in obese women: a prospective multicentre study

Abstract: All obese pregnant women are considered at equal high risk with respect to complications in pregnancy and birth, and are commonly managed through resource-intensive care pathways. However, the identification of maternal characteristics associated with normal pregnancy outcomes could assist in the management of these pregnancies. The present study aims to identify the factors associated with uncomplicated pregnancy and birth in obese women, and to assess their predictive performance. Data form obese women (BMI ≥ 30 kg/m2) with singleton pregnancies included in the UPBEAT trial were used in this analysis. Multivariable logistic regression was used to identify sociodemographic, clinical and biochemical factors at 15+0 to 18+6 weeks’ gestation associated with uncomplicated pregnancy and birth, defined as delivery of a term live-born infant without antenatal or labour complications. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Internal validation and calibration were also performed. Women were divided into fifths of risk and pregnancy outcomes were compared between groups. Sensitivity, specificity, and positive and negative predictive values were calculated using the upper fifth as the positive screening group. Amongst 1409 participants (BMI 36.4, SD 4.8 kg/m2), the prevalence of uncomplicated pregnancy and birth was 36% (505/1409). Multiparity and increased plasma adiponectin, maternal age, systolic blood pressure and HbA1c were independently associated with uncomplicated pregnancy and birth. These factors achieved an AUROC of 0.72 (0.68–0.76) and the model was well calibrated. Prevalence of gestational diabetes, preeclampsia and other hypertensive disorders, preterm birth, and postpartum haemorrhage decreased whereas spontaneous vaginal delivery increased across the fifths of increasing predicted risk of uncomplicated pregnancy and birth. Sensitivity, specificity, and positive and negative predictive values were 38%, 89%, 63% and 74%, respectively. A simpler model including clinical factors only (no biomarkers) achieved an AUROC of 0.68 (0.65–0.71), with sensitivity, specificity, and positive and negative predictive values of 31%, 86%, 56% and 69%, respectively. Clinical factors and biomarkers can be used to help stratify pregnancy and delivery risk amongst obese pregnant women. Further studies are needed to explore alternative pathways of care for obese women demonstrating different risk profiles for uncomplicated pregnancy and birth.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …