Human leukocyte antigen distributions do not share a copula across sub-populations

The distribution of human leukocyte antigens in the population assists in matching solid organ donors and recipients when the typing methods used do not provide sufficiently precise information. This is made possible by linkage disequilibrium (LD), where alleles co-occur more often than random chance would suggest. There is a trade-off between the high bias and low variance of a broad sample from the population and the low bias but high variance of a focused sample. Some of this trade-off could be alleviated if subpopulations shared LD despite having different allele frequencies. These experiments show that Bayesian estimation can balance bias and variance by tuning the effective sample size of the reference panel, but the LD as represented by an additive or multiplicative copula is not shared

Percutaneous Thoracic Intervertebral Disc Nucleoplasty: Technical Notes from 3 Patients with Painful Thoracic Disc Herniations

Symptomatic thoracic disc herniation is an uncommon condition and early surgical approaches were associated with significant morbidity and even mortality. We are the first to describe the technique of percutaneous thoracic nucleoplasty in three patients with severe radicular pain due to thoracic disc herniation. Two of the patients experienced more than 75% pain relief and one patient experienced more than 50% pain relief. Post-procedural pain relief was maintained up to an average of 10 months after nucleoplasty. One patient with preoperative neurological signs improved postoperatively. There were no reported complications in all three patients. In view of the reduced morbidity and shorter operating time, thoracic intervertebral disc nucleoplasty can be considered in patients with pain due to thoracic disc herniation, with no calcification of the herniated disc, and in patients who may be otherwise be unfit for conventional surgery

Prenatal smoking, alcohol and caffeine exposure and offspring externalizing disorders:a systematic review and meta-analysis

BACKGROUND AND AIMS: Several studies have indicated an association between maternal prenatal substance use and offspring externalizing disorders; however, it is uncertain whether this relationship is causal. We conducted a systematic review to determine: (1) if the literature supports a causal role of maternal prenatal substance use on offspring externalizing disorders diagnosis and (2) whether these associations differ across externalizing disorders. METHODS: We searched Web of Science, Embase, PsycINFO and Medline databases. Risk of bias assessment was conducted using the Newcastle-Ottawa Scale (NOS), and where possible meta-analysis was conducted for studies classed as low risk of bias. We included studies of any design that examined prenatal smoking, alcohol or caffeine use. Studies in non-English language, fetal alcohol syndrome and comorbid autism spectrum disorders were excluded. Participants in the included studies were mothers and their offspring. Measurements included prenatal smoking, alcohol or caffeine use as an exposure, and diagnosis of attention-deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD) in offspring as an outcome. RESULTS: We included 63 studies, 46 of which investigated smoking and ADHD. All studies were narratively synthesized, and seven studies on smoking and ADHD were meta-analysed. The largest meta-analysis based on genetically sensitive design included 1 011 546 participants and did not find evidence for an association [odds ratio (OR)  = 0.90, 95% confidence interval (CI) = 0.83-1.11; OR   = 1.04, 95% CI = 0.79-1.36). Studies on alcohol exposure in all the outcomes reported inconsistent findings and no strong conclusions on causality can be made. Studies on caffeine exposure were mainly limited to ADHD and these studies do not support a causal effect. CONCLUSIONS: There appears to be no clear evidence to support a causal relationship between maternal prenatal smoking and offspring attention-deficit hyperactivity disorder. Findings with alcohol and caffeine exposures and conduct disorder and oppositional-defiant disorder need more research, using more genetically sensitive designs

Carrying water may be a major contributor to disability from musculoskeletal disorders in low income countries: a cross-sectional survey in South Africa, Ghana and Vietnam

Background: The Sustainable Development Goals include commitments to end poverty, and promote education for all, gender equality, the availability of water and decent work for all. An important constraint is the fact that each day, many millions of women and children, and much less frequently men, carry their household’s water home from off-plot sources. The burden of fetching water exacerbates gender inequality by keeping women out of education and paid employment. Despite speculation about the potential health impacts of fetching water, there is very little empirical evidence. We report the first large study of the health impacts of carrying water on women and children. Methods: A cross-sectional survey was conducted in South Africa, Ghana and Vietnam during 2012. It investigated water carrying methods and health status. Because areas of self-reported pain were correlated we undertook factor analysis of sites of reported pain, to interpret patterns of pain reporting. Regression analysis using Generalised Estimating Equations (GEE) investigated water carrying as a risk factor for general health and self-reported pain. Findings: People who previously carried water had increased relative risk of reporting pain in the hands (RR 3.62, 95%CI 1.34-9.75) and upper back (RR 2.27, 95%CI 1.17-4.40), as did people who currently carry water (RR hand pain 3.11, 95%CI 1.34-7.23; RR upper back pain 2.16, 95%CI 1.25-3.73). The factor analysis results indicate that factor 1, ‘axial compression’, which is correlated with pain in the head and upper back, chest/ribs, hands, feet and abdomen/stomach, is associated with currently (0.30, 95%CI 0.17-0.43) or previously (0.21, 95%CI 0.01-0.42) carrying water. Factor 2, ‘soft tissue strain’, which is correlated with pain in the neck, shoulders/arms, lower back and hips/pelvis or legs, is marginally negatively associated with currently (-0.18, 95%CI-0.32 - -0.04) carrying water. The factor ‘axial compression’ was more strongly associated with carrying water containers on the head. Conclusions: Participants who reported a history of current or past water carrying more frequently reported pain in locations most likely to be associated with sustained spinal axial compression in the cervical region. Given the fact that cervical spinal conditions are globally one of the more common causes of disability, our findings suggest that water carrying, especially by head loading is a major contributing factor in musculoskeletal disease burden in low income countries. Our findings support the proposed indicator for monitoring SDG6.1: “Percentage of population using safely managed drinking water services at home“ (our emphasis)

Maternal and child genetic liability for smoking and caffeine consumption and child mental health:An intergenerational genetic risk score analysis in the ALSPAC cohort

Background and aims: Previous studies suggest an association between maternal tobacco and caffeine consumption during and outside of pregnancy and offspring mental health. We aimed to separate effects of the maternal environment (intrauterine or postnatal) from pleiotropic genetic effects. Design: Secondary analysis of a longitudinal study. We (i) validated smoking and caffeine genetic risk scores (GRS) derived from published genome-wide association study (GWAS) for use during pregnancy, (ii) compared estimated effects of maternal and offspring GRS on childhood mental health outcomes and (iii) tested associations between maternal and offspring GRS on their respective outcomes. Setting: We used data from a longitudinal birth cohort study from England, the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants: Our sample included 7921 mothers and 7964 offspring. Measurements: Mental health and non-mental health phenotypes were derived from questionnaires and clinical assessments: 79 maternal phenotypes assessed during and outside of pregnancy and 71 offspring phenotypes assessed in childhood (<10years) and adolescence (11–18years). Findings: The maternal smoking and caffeine GRS were associated with maternal smoking and caffeine consumption during pregnancy (2nd trimester: Psmoking=3.0 × 10−7, Pcaffeine=3.28 × 10−5). Both the maternal and offspring smoking GRS showed evidence of association with reduced childhood anxiety symptoms (βmaternal=−0.033; βoffspring=−0.031) and increased conduct disorder symptoms (βmaternal=0.024; βoffspring=0.030), after correcting for multiple testing. Finally, the maternal and offspring smoking GRS were associated with phenotypes related to sensation seeking behaviours in mothers and adolescence (e.g. increased symptoms of externalising disorders, extraversion and monotony avoidance). The caffeine GRS showed weaker evidence for associations with mental health outcomes. Conclusions: We did not find strong evidence that maternal smoking and caffeine genetic risk scores have a causal effect on offspring mental health outcomes. Our results confirm that the smoking genetic risk scores also captures liability for sensation seeking personality traits