Identifying signals of potentially harmful medications in pregnancy: use of the double false discovery rate method to adjust for multiple testing.

AIMS: Surveillance of medication use in pregnancy is essential to identify associations between first trimester medications and congenital anomalies (CAs). Medications in the same Anatomical Therapeutic Chemical classes may have similar effects. We aimed to use this information to improve the detection of potential teratogens in CA surveillance data. METHODS: Data on 15 058 malformed fetuses with first trimester medication exposures from 1995-2011 were available from EUROmediCAT, a network of European CA registries. For each medication-CA combination, the proportion of the CA in fetuses with the medication was compared to the proportion of the CA in all other fetuses in the dataset. The Australian classification system was used to identify high-risk medications in order to compare two methods of controlling the false discovery rate (FDR): a single FDR applied across all combinations, and a double FDR incorporating groupings of medications. RESULTS: There were 28 765 potential combinations (523 medications × 55 CAs) for analysis. An FDR cut-off of 50% resulted in a reasonable effective workload, for which single FDR gave rise to eight medication signals (three high-risk medications) and double FDR 50% identified 16 signals (six high-risk). Over a range of FDR cut-offs, double FDR identified more high-risk medications as signals, for comparable effective workloads. CONCLUSIONS: The double FDR method appears to improve the detection of potential teratogens in comparison to the single FDR, while maintaining a low risk of false positives. Use of double FDR is recommended in routine signal detection analyses of CA data

Researching trust in the police and trust in justice: a UK perspective

This paper describes the immediate and more distant origins of a programme of comparative research that is examining cross-national variations in public trust in justice and in the police. The programme is built around a module of the fifth European Social Survey, and evolved from a study funded by the European Commission. The paper describes the conceptual framework within which we are operating – developed in large measure from theories of procedural justice. It reviews some of the methodological issues raised by the use of sample surveys to research issues of public trust in the police, public perceptions of institutional legitimacy and compliance with the law. Finally it gives a flavour of some of the early findings emerging from the programme

Slugs count: assessing citizen scientist engagement and development, and the accuracy of their identifications

•1. How accurately can citizen science participants identify species, and can the information they provide be used to calculate accurate estimates of species richness, abundance and diversity measures? In this paper, we address these questions using data from a citizen science project assessing slug species diversity in gardens. •2. Sixty participants were selected from over 2700 applicants across Britain to sample their gardens regularly for slugs following a standardised method. All slugs collected during the 30-min search were posted to the lead investigator for verification throughout the 12-month project. The resulting data were analysed to explore how accurate participants were in identifying slugs and whether this improved over the study period. Prior experience in slug identification was evaluated as a predictor of accuracy. •3. Participants overestimated slug abundance and species richness, which led to overestimates in species diversity indices, illustrating the importance of verification in citizen science projects involving identification. •4. Accuracy of slug identifications increased significantly over time in quantitative analysis of ecological data. However, self-defined prior experience of identifying slugs before participation was not a good predictor of participant accuracy. •5. Participants reported perceived improvement in slug identification skills to an evaluation survey after the project. However, confidence in identifying and explaining identification of slugs was lower than confidence in understanding and explaining other new science topics. •6. This citizen science approach, including expert verification of physical specimens, illustrates how this method can be used successfully to provide accurate data on species' abundance and richness, alongside improving identification skills among the public for an understudied taxon. Continued engagement and feedback for participants is key in retaining citizen science participation in a project of this type, particularly if the taxon is challenging to identify correctly to species

Evaluating the effects of an exercise program (Staying UpRight) for older adults in long-term care on rates of falls: study protocol for a randomised controlled trial

Background: Falls are two to four times more frequent amongst older adults living in long-term care (LTC) than community-dwelling older adults and have deleterious consequences. It is hypothesised that a progressive exercise program targeting balance and strength will reduce fall rates when compared to a seated exercise program and do so cost effectively. Methods/design: This is a single blind, parallel-group, randomised controlled trial with blinded assessment of outcome and intention-to-treat analysis. LTC residents (age ≥ 65 years) will be recruited from LTC facilities in New Zealand. Participants (n = 528 total, with a 1:1 allocation ratio) will be randomly assigned to either a novel exercise program (Staying UpRight), comprising strength and balance exercises designed specifically for LTC and acceptable to people with dementia (intervention group), or a seated exercise program (control group). The intervention and control group classes will be delivered for 1 h twice weekly over 1 year. The primary outcome is rate of falls (per 1000 person years) within the intervention period. Secondary outcomes will be risk of falling (the proportion of fallers per group), fall rate relative to activity exposure, hospitalisation for fall-related injury, change in gait variability, volume and patterns of ambulatory activity and change in physical performance assessed at baseline and after 6 and 12 months. Cost-effectiveness will be examined using intervention and health service costs. The trial commenced recruitment on 30 November 2018. Discussion: This study evaluates the efficacy and cost-effectiveness of a progressive strength and balance exercise program for aged care residents to reduce falls. The outcomes will aid development of evidenced-based exercise programmes for this vulnerable population. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12618001827224. Registered on 9 November 2018. Universal trial number U1111-1217-7148

A tale of two capitalisms: preliminary spatial and historical comparisons of homicide rates in Western Europe and the USA

This article examines comparative homicide rates in the United States and Western Europe in an era of increasingly globalized neoliberal economics. The main finding of this preliminary analysis is that historical and spatial correlations between distinct forms of political economy and homicide rates are consistent enough to suggest that social democratic regimes are more successful at fostering the socio-cultural conditions necessary for reduced homicide rates. Thus Western Europe and all continents and nations should approach the importation of American neo-liberal economic policies with extreme caution. The article concludes by suggesting that the indirect but crucial causal connection between political economy and homicide rates, prematurely pushed into the background of criminological thought during the ‘cultural turn’, should be returned to the foreground

Imprisonment and internment: Comparing penal facilities North and South

Recent references to the ‘warehouse prison’ in the United States and the prisión-depósito in Latin America seem to indicate that penal confinement in the western hemisphere has converged on a similar model. However, this article suggests otherwise. It contrasts penal facilities in North America and Latin America in terms of six interrelated aspects: regimentation; surveillance; isolation; supervision; accountability; and formalization. Quantitatively, control in North American penal facilities is assiduous (unceasing, persistent and intrusive), while in Latin America it is perfunctory (sporadic, indifferent and cursory). Qualitatively, North American penal facilities produce imprisonment (which enacts penal intervention through confinement), while in Latin America they produce internment (which enacts penal intervention through release). Closely entwined with this qualitative difference are distinct practices of judicial involvement in sentencing and penal supervision. Those practices, and the cultural and political factors that underpin them, represent an interesting starting point for the explanation of the contrasting nature of imprisonment and internment

Post-release reforms for short prison sentences: re-legitimising and widening the net of punishment

Transforming Rehabilitation (TR) promised a ‘revolution’ in the way offenders are managed, providing a renewed focus on short sentence prisoners. The TR reforms extends mandatory post-release supervision and tailored through-the-gate resettlement provisions to a group that has predominately faced a ‘history of neglect’ yet often present with the most acute needs within the criminal justice system. However, existing literature underlines that serving short sentences lack ‘utility’ and can be counter-productive to facilitating effective rehabilitation. This article explores the purposes of providing post release supervision for short sentences, firstly exploring a previous attempt to reform short sentences; (the now defunct) ‘Custody Plus’ within the 2003 Criminal Justice Act and then the Offender Rehabilitation Act 2014 within the TR reforms. This article contends that both post release reforms have sought to re-affirm and re-legitimise prison as the dominant form of punishment in society- or what Carlen refers to as ‘carceral clawback’. This article will also use Cohen’s analysis on social control to establish that post release supervision will serve to ‘widen the net’ extend the period of punishment and oversight and will only reinforce a form of enforced ‘state obligated rehabilitation’ that will undermine efforts made to resettle short sentence prisoners

Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data

Published 10 July 2014To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.Mendelian randomisation meta-analysis of 56 epidemiological studies.261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.Michael V Holmes ... Debbie A Lawlor ... et al. on behalf of The InterAct Consortiu

Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans.

Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms. We performed meta-analysis of Metabochip association results for six RBC traits-hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and red blood cell count (RCC)-in 11 093 Europeans from seven studies of the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium. We identified 394 non-overlapping SNPs in five loci at genome-wide significance: 6p22.1-6p21.33 (with HFE among others), 6q23.2 (with HBS1L among others), 6q23.3 (contains no genes), 9q34.3 (only ABO gene) and 22q13.1 (with TMPRSS6 among others), replicating previous findings of association with RBC traits at these loci and extending them by imputation to 1000 Genomes. We further characterized associations between ABO SNPs and three traits: hemoglobin, hematocrit and red blood cell count, replicating them in an independent cohort. Conditional analyses indicated the independent association of each of these traits with ABO SNPs and a role for blood group O in mediating the association. The 15 most significant RBC-associated ABO SNPs were also associated with five cardiometabolic traits, with discordance in the direction of effect between groups of traits, suggesting that ABO may act through more than one mechanism to influence cardiometabolic risk.British Heart Foundation (Grant ID: RG/10/12/28456, RG/08/013/25942, RG/13/16/30528, RG/98002, RG/07/008/23674); Medical Research Council (Grant ID: G0000934, G0500877, MC_UU_12019/1, K013351); Wellcome Trust (Grant ID: 068545/Z/02, 097451/Z/11/Z); European Commission Framework Programme 6 (Grant ID: 018996); French Ministry of Research; Department of Health Policy Research Programme (England); Chief Scientist Office of Scotland (Grant ID: CZB/4/672, CZQ/1/38); National Institute on Ageing (NIA) (Grant ID: AG1764406S1, 5RO1AG13196); Pfizer plc (Unrestricted Investigator Led Grant); Diabetes UK (Clinical Research Fellowship 10/0003985); Stroke Association; National Heart Lung and Blood Institute (5RO1HL036310); Agency for Health Care Policy Research (HS06516); John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health; Swiss National Science Foundation (33CSCO-122661); GlaxoSmithKline. Faculty of Biology and Medicine of Lausanne,Switzerland.This is the final version of the article. It first appeared from Public Library of Science (PLOS) via http://dx.doi.org/10.1371/journal.pone.015691