Association of multimorbidity and changes in health-related quality of life following myocardial infarction: a UK multicentre longitudinal patient-reported outcomes study.

BACKGROUND: Multimorbidity is prevalent for people with myocardial infarction (MI), yet previous studies investigated single-health conditions in isolation. We identified patterns of multimorbidity in MI survivors and their associations with changes in HRQoL. METHODS: In this national longitudinal cohort study, we analysed data from 9566 admissions with MI from 77 National Health Service hospitals in England between 2011 and 2015. HRQoL was measured using EuroQol 5 dimension (EQ5D) instrument and visual analogue scale (EQVAS) at hospitalisation, 6, and 12 months following MI. Latent class analysis (LCA) of pre-existing long-term health conditions at baseline was used to identify clusters of multimorbidity and associations with changes in HRQoL quantified using mixed effects regression analysis. RESULTS: Of 9566 admissions with MI (mean age of 64.1 years [SD 11.9], 7154 [75%] men), over half (5119 [53.5%] had multimorbidities. LCA identified 3 multimorbidity clusters which were severe multimorbidity (591; 6.5%) with low HRQoL at baseline (EQVAS 59.39 and EQ5D 0.62) which did not improve significantly at 6 months (EQVAS 59.92, EQ5D 0.60); moderate multimorbidity (4301; 47.6%) with medium HRQoL at baseline (EQVAS 63.08, EQ5D 0.71) and who improved at 6 months (EQVAS 71.38, EQ5D 0.76); and mild multimorbidity (4147, 45.9%) at baseline (EQVAS 64.57, EQ5D 0.75) and improved at 6 months (EQVAS 76.39, EQ5D 0.82). Patients in the severe and moderate groups were more likely to be older, women, and presented with NSTEMI. Compared with the mild group, increased multimorbidity was associated with lower EQ-VAS scores (adjusted coefficient: -5.12 [95% CI -7.04 to -3.19] and -0.98 [-1.93 to -0.04] for severe and moderate multimorbidity, respectively. The severe class was more likely than the mild class to report problems in mobility, OR 9.62 (95% confidence interval: 6.44 to 14.36), self-care 7.87 (4.78 to 12.97), activities 2.41 (1.79 to 3.26), pain 2.04 (1.50 to 2.77), and anxiety/depression 1.97 (1.42 to 2.74). CONCLUSIONS: Among MI survivors, multimorbidity clustered into three distinct patterns and was inversely associated with HRQoL. The identified multimorbidity patterns and HRQoL domains that are mostly affected may help to identify patients at risk of poor HRQoL for which clinical interventions could be beneficial to improve the HRQoL of MI survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT01808027 and NCT01819103.

The association of mode of location activity and mobility with acute coronary syndrome: a nationwide ecological study.

BACKGROUND: We aimed to study the effect of social containment mandates on ACS presentation during COVID-19 pandemic using location activity and mobility data from mobile phone map services. METHODS: We conducted a cross-sectional study using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) including all ACS presentations during the pandemic until 7 May 2020. Using a count regression model, we adjusted for day of the week, daily weather and incidence of COVID-19. RESULTS: A 10% increase in activity around areas of residence was associated with 38% lower rates of ACS hospitalizations, whereas increased activity relating to retail and recreation, grocery stores and pharmacies, workplaces and mode of mobility was associated with 10-20% higher rates of ACS hospitalizations. CONCLUSION: Government policy regarding social containment mandates has important public health implications for medical emergencies such as ACS and may explain the decline in ACS presentations observed during COVID-19 pandemic.

Phenomenological Constraints on the Transport Properties of QCD Matter with Data-Driven Model Averaging.

Using combined data from the Relativistic Heavy Ion and Large Hadron Colliders, we constrain the shear and bulk viscosities of quark-gluon plasma (QGP) at temperatures of ∼150-350 MeV. We use Bayesian inference to translate experimental and theoretical uncertainties into probabilistic constraints for the viscosities. With Bayesian model averaging we propagate an estimate of the model uncertainty generated by the transition from hydrodynamics to hadron transport in the plasma's final evolution stage, providing the most reliable phenomenological constraints to date on the QGP viscosities.

Psychosocial factors and hospitalisations for COVID-19: Prospective cohort study based on a community sample.

BACKGROUND: While certain infectious diseases have been linked to socioeconomic disadvantage, mental health problems, and lower cognitive function, relationships with COVID-19 are either uncertain or untested. Our objective was to examine the association of a range of psychosocial factors with hospitalisation for COVID-19. METHODS: UK Biobank, a prospective cohort study, comprises around half a million people who were aged 40-69 years at study induction between 2006 and 2010 when information on psychosocial factors and covariates were captured. Hospitalisations for COVID-19 were ascertained between 16th March and 26th April 2020. RESULTS: There were 908 hospitalisations for COVID-19 in an analytical sample of 431,051 England-based study members. In age- and sex-adjusted analyses, an elevated risk of COVID-19 was related to disadvantaged levels of education (odds ratio; 95% confidence interval: 2.05; 1.70, 2.47), income (2.00; 1.63, 2,47), area deprivation (2.20; 1.86, 2.59), occupation (1.39; 1.14, 1.69), psychological distress (1.58; 1.32, 1.89), mental health (1.50; 1.25, 1.79), neuroticism (1.19; 1.00, 1.42), and performance on two tests of cognitive function - verbal and numerical reasoning (2.66; 2.06, 3.34) and reaction speed (1.27; 1.08, 1.51). These associations were graded (p-value for trend ≤ 0.038) such that effects were apparent across the full psychosocial continua. After mutual adjustment for these characteristics plus ethnicity, comorbidity, and lifestyle factors, only the relationship between lower cognitive function as measured using the reasoning test and risk of the infection remained (1.98; 1.38, 2.85). CONCLUSIONS: A range of psychosocial factors revealed associations with hospitalisation for COVID-19 of which the relation with cognitive function, a marker of health literacy, was most robust.

A combined analysis of genetically correlated traits identifies 187 loci and a role for neurogenesis and myelination in intelligence.

Intelligence, or general cognitive function, is phenotypically and genetically correlated with many traits, including a wide range of physical, and mental health variables. Education is strongly genetically correlated with intelligence (rg = 0.70). We used these findings as foundations for our use of a novel approach-multi-trait analysis of genome-wide association studies (MTAG; Turley et al. 2017)-to combine two large genome-wide association studies (GWASs) of education and intelligence, increasing statistical power and resulting in the largest GWAS of intelligence yet reported. Our study had four goals: first, to facilitate the discovery of new genetic loci associated with intelligence; second, to add to our understanding of the biology of intelligence differences; third, to examine whether combining genetically correlated traits in this way produces results consistent with the primary phenotype of intelligence; and, finally, to test how well this new meta-analytic data sample on intelligence predicts phenotypic intelligence in an independent sample. By combining datasets using MTAG, our functional sample size increased from 199,242 participants to 248,482. We found 187 independent loci associated with intelligence, implicating 538 genes, using both SNP-based and gene-based GWAS. We found evidence that neurogenesis and myelination-as well as genes expressed in the synapse, and those involved in the regulation of the nervous system-may explain some of the biological differences in intelligence. The results of our combined analysis demonstrated the same pattern of genetic correlations as those from previous GWASs of intelligence, providing support for the meta-analysis of these genetically-related phenotypes.

A core outcome set for pre-eclampsia research: an international consensus development study.

OBJECTIVE: To develop a core outcome set for pre-eclampsia. DESIGN: Consensus development study. SETTING: International. POPULATION: Two hundred and eight-one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. METHODS: Modified Delphi method and Modified Nominal Group Technique. RESULTS: A long-list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre-eclampsia trials with those derived from thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. Forty-seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small-for-gestational-age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. CONCLUSIONS: The core outcome set for pre-eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies. TWEETABLE ABSTRACT: 281 healthcare professionals, 41 researchers and 110 women have developed #preeclampsia core outcomes @HOPEoutcomes @jamesmnduffy. [Correction added on 29 June 2020, after first online publication: the order has been corrected.].

Genetic contributions to self-reported tiredness.

Self-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8.4% (s.e.=0.6%). GWAS identified one genome-wide significant hit (Affymetrix id 1:64178756_C_T; P=1.36 × 10-11). Linkage disequilibrium score regression and polygenic profile score analyses were used to test for shared genetic aetiology between tiredness and up to 29 physical and mental health traits from GWAS consortia. Significant genetic correlations were identified between tiredness and body mass index (BMI), C-reactive protein, high-density lipoprotein (HDL) cholesterol, forced expiratory volume, grip strength, HbA1c, longevity, obesity, self-rated health, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder, neuroticism, schizophrenia and verbal-numerical reasoning (absolute rg effect sizes between 0.02 and 0.78). Significant associations were identified between tiredness phenotypic scores and polygenic profile scores for BMI, HDL cholesterol, low-density lipoprotein cholesterol, coronary artery disease, C-reactive protein, HbA1c, height, obesity, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, childhood cognitive ability, neuroticism, bipolar disorder, major depressive disorder and schizophrenia (standardised ß's had absolute values<0.03). These results suggest that tiredness is a partly heritable, heterogeneous and complex phenomenon that is phenotypically and genetically associated with affective, cognitive, personality and physiological processes.

Genetic contributions to Trail Making Test performance in UK Biobank.

The Trail Making Test (TMT) is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the TMT and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The single-nucleotide polymorphism-based heritability estimates for trail-making measures were 7.9% (part A), 22.4% (part B) and 17.6% (part B-part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg>0.6), general cognitive function (rg>0.6), processing speed (rg>0.7) and memory (rg>0.3). Polygenic profile analysis indicated considerable shared genetic aetiology between trail making, general cognitive function, processing speed and memory (standardized ß between 0.03 and 0.08). These results suggest that trail making is both phenotypically and genetically strongly associated with general cognitive function and processing speed.

Genetic contributions to self-reported tiredness.

This corrects the article DOI: 10.1038/mp.2017.5.

Correlates of Level and Loss of Grip Strength in Later Life: Findings from the English Longitudinal Study of Ageing and the Hertfordshire Cohort Study.

Characterisation of grip strength (GS) using isometric dynamometry is central to the definition of sarcopenia. Determinants of low GS include: older age, shorter stature, low physical activity, poor nutrition, socioeconomic disadvantage and multimorbidity. Less is known about risk factors for accelerated loss of GS. We investigated determinants of level and 8-year loss of GS in 3703 men and women (aged 52-82 years) in the English Longitudinal Study of Ageing (ELSA). Four hundred and forty-one men and women (aged 59-71 years) who participated in a 10-year follow-up of the Hertfordshire Cohort Study (HCS) were used for replication. Variables were harmonised between cohorts. Change in GS was characterised using mixed-effects models in ELSA and a residual change approach in HCS and analysed for men and women combined. Men in ELSA and HCS had higher average levels of GS at baseline, and accelerated rates of loss, compared with women. In ELSA, older age, shorter stature and multimorbidity were correlated with lower level, and accelerated rate of loss, of GS in both sexes (accelerated loss of 0.04 (95% CI 0.00-0.08) standard deviation scores per additional morbidity after multivariable adjustment). Socioeconomic disadvantage, low level of physical activity and poorer self-reported health were also correlated with low GS level, but not loss rate, after multivariable adjustment. Analysis in HCS yielded similar results. Our results identify multimorbidity as a modifiable determinant of loss of muscle strength in later life, and raise the possibility that developmental influences may impact on rate of involutional decline in muscle strength.

Systematic comparative validation of self-report measures of sedentary time against an objective measure of postural sitting (activPAL).

BACKGROUND: Sedentary behaviour is a public health concern that requires surveillance and epidemiological research. For such large scale studies, self-report tools are a pragmatic measurement solution. A large number of self-report tools are currently in use, but few have been validated against an objective measure of sedentary time and there is no comparative information between tools to guide choice or to enable comparison between studies. The aim of this study was to provide a systematic comparison, generalisable to all tools, of the validity of self-report measures of sedentary time against a gold standard sedentary time objective monitor. METHODS: Cross sectional data from three cohorts (N = 700) were used in this validation study. Eighteen self-report measures of sedentary time, based on the TAxonomy of Self-report SB Tools (TASST) framework, were compared against an objective measure of postural sitting (activPAL) to provide information, generalizable to all existing tools, on agreement and precision using Bland-Altman statistics, on criterion validity using Pearson correlation, and on data loss. RESULTS: All self-report measures showed poor accuracy compared with the objective measure of sedentary time, with very wide limits of agreement and poor precision (random error > 2.5 h). Most tools under-reported total sedentary time and demonstrated low correlations with objective data. The type of assessment used by the tool, whether direct, proxy, or a composite measure, influenced the measurement characteristics. Proxy measures (TV time) and single item direct measures using a visual analogue scale to assess the proportion of the day spent sitting, showed the best combination of precision and data loss. The recall period (e.g. previous week) had little influence on measurement characteristics. CONCLUSION: Self-report measures of sedentary time result in large bias, poor precision and low correlation with an objective measure of sedentary time. Choice of tool depends on the research context, design and question. Choice can be guided by this systematic comparative validation and, in the case of population surveillance, it recommends to use a visual analog scale and a 7 day recall period. Comparison between studies and improving population estimates of average sedentary time, is possible with the comparative correction factors provided.

Development of a core outcome set for trials on induction of labour: an international multistakeholder Delphi study.

OBJECTIVE: To develop a set of core outcomes to be minimally reported in trials on induction of labour. DESIGN: Two-round Delphi survey and consensus meeting. POPULATION: Four stakeholder groups: midwives, obstetricians, neonatologists, and women's representatives. METHODS: Protocol registered with COMET (Registration Number: 695). Stakeholders rated reported outcomes for importance (1-limited to 9-critical). The median rating of each outcome was calculated. The consensus criteria to include outcomes were as follows: ≥70% participants rated outcomes as critical and <15% rated outcomes as limited importance. Outcomes that did not achieve consensus were taken to round two and, if there was still no consensus, to the final consensus meeting. MAIN OUTCOME MEASURES: Outcomes in trials of induction of labour. RESULTS: Of the 159 invited participants, 54% (86/159) completed the first round, and 83% completed the second round (71/86). The core outcome set included 28 core outcomes in four domains: Short-term maternal outcomes (n = 18)-cardiorespiratory arrest, damage to internal organs, death, haemorrhage, hysterectomy, infection, intensive care admission, length of hospital stay, mode of delivery, need for more than one induction agent, oxytocin augmentation, postnatal depression, pulmonary embolus, satisfaction with care, stroke, time from induction to delivery, uterine hyperstimulation, uterine scar dehiscence/rupture; short-term offspring outcomes (n = 8)-admission to the neonatal unit, birth trauma, death, hypoxic ischaemic encephalopathy/need for therapeutic hypothermia, meconium aspiration syndrome, need for respiratory support, infection, and seizures; long-term maternal outcomes (n = 1)-operative pelvic floor repair; long-term offspring outcomes (n = 1)-disability including neurodevelopmental delay. CONCLUSION: Trials on induction of labour should include this core outcome set to standardise reporting. TWEETABLE ABSTRACT: International multistakeholder Delphi study identifies a core outcome set for trials on induction of labour.

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151).

People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal-numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal-numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia.

Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia.

Causes of the well-documented association between low levels of cognitive functioning and many adverse neuropsychiatric outcomes, poorer physical health and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular-metabolic, neuropsychiatric, physiological-anthropometric and cognitive traits in the participants of UK Biobank, a very large population-based sample (N=112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics and to the method of linkage disequilibrium score regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.

Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci.

Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10(-15)) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.

Core outcome sets in women's and newborn health: a systematic review.

BACKGROUND: Variation in outcome collection and reporting is a serious hindrance to progress in our specialty; therefore, over 80 journals have come together to support the development, dissemination, and implementation of core outcome sets. OBJECTIVE: This study systematically reviewed and characterised registered, progressing, or completed core outcome sets relevant to women's and newborn health. SEARCH STRATEGY: Systematic search using the Core Outcome Measures in Effectiveness Trial initiative and the Core Outcomes in Women's and Newborn Health initiative databases. SELECTION CRITERIA: Registry entries, protocols, systematic reviews, and core outcome sets. DATA COLLECTION AND ANALYSIS: Descriptive statistics to describe characteristics and results. RESULTS: There were 49 core outcome sets registered in maternal and newborn health, with the majority registered in 2015 (n = 22; 48%) or 2016 (n = 16; 32%). Benign gynaecology (n = 8; 16%) and newborn health (n = 3; 6%) are currently under-represented. Twenty-four (52%) core outcome sets were funded by international (n = 1; <1%), national (n = 18; 38%), and regional (n = 4; 8%) bodies. Seven protocols were published. Twenty systematic reviews have characterised the inconsistency in outcome reporting across a broad range of relevant healthcare conditions. Four core outcome sets were completed: reconstructive breast surgery (11 outcomes), preterm birth (13 outcomes), epilepsy in pregnancy (29 outcomes), and maternity care (48 outcomes). The quantitative, qualitative, and consensus methods used to develop core outcome sets varied considerably. CONCLUSIONS: Core outcome sets are currently being developed across women's and newborn health, although coverage of topics is variable. Development of further infrastructure to develop, disseminate, and implement core outcome sets is urgently required. TWEETABLE ABSTRACT: Forty-nine women's and newborn core outcome sets registered. 50% funded. 7 protocols, 20 systematic reviews, and 4 core outcome sets published. @coreoutcomes @jamesmnduffy.

Outcome reporting across randomised controlled trials evaluating therapeutic interventions for pre-eclampsia.

BACKGROUND: Standardising outcome collection and reporting in pre-eclampsia trials requires an appraisal of current outcome reporting. OBJECTIVES: To map maternal and offspring outcome reporting across randomised trials evaluating therapeutic interventions for pre-eclampsia. SEARCH STRATEGY: Randomised trials were identified by searching bibliographical databases from inception to January 2016. SELECTION CRITERIA: Randomised controlled trials. DATA COLLECTION AND ANALYSIS: We systematically extracted and categorised outcome reporting. MAIN RESULTS: Seventy-nine randomised trials, reporting data from 31 615 maternal participants and 28 172 of their offspring, were included. Fifty-five different interventions were evaluated. Included trials reported 119 different outcomes, including 72 maternal outcomes and 47 offspring outcomes. Maternal outcomes were inconsistently reported across included trials; for example, 11 trials (14%) reported maternal mortality, reporting data from 12 422 participants, and 16 trials (20%) reported cardiovascular morbidity, reporting data from 14 963 maternal participants. Forty-three trials (54%) reported fetal outcomes and 23 trials (29%) reported neonatal outcomes. Twenty-eight trials (35%) reported offspring mortality. There was poor reporting of childhood outcomes: six trials (8%) reported neurodevelopmental outcomes. Less than half of included trials reported any relevant information regarding harms for maternal participants and their offspring. CONCLUSIONS: Most randomised trials evaluating interventions for pre-eclampsia are missing information on clinically important outcomes, and in particular have neglected to evaluate efficacy and safety in the offspring of participants. Developing and implementing a minimum data set, known as a core outcome set, in future pre-eclampsia trials could help to address these issues. TWEETABLE ABSTRACT: Future #preeclampsia research requires a core outcome set to reduce #research waste. @coreoutcomes @jamesmnduffy International Prospective Register of Systematic Reviews: CRD42015015529; www.crd.york.ac.uk/PROSPERO/display_record.aspID=CRD42015015529.

Sexual dimorphism in relation to adipose tissue and intrahepatocellular lipid deposition in early infancy.

Sexual dimorphism in adiposity is well described in adults, but the age at which differences first manifest is uncertain. Using a prospective cohort, we describe longitudinal changes in directly measured adiposity and intrahepatocellular lipid (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63 days, infants underwent quantification of adipose tissue depots by whole-body magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys and 30 girls). In the neonatal period girls are more adipose in relation to body size than boys. At follow-up (median age 63 days), girls remained significantly more adipose. The greater relative adiposity that characterises girls is explained by more subcutaneous adipose tissue and this becomes increasingly apparent by follow-up. No significant sex differences were seen in IHCL. Sex-specific differences in infant adipose tissue distribution are in keeping with those described in later life, and suggest that sexual dimorphism in adiposity is established in early infancy.

Importance of the Bulk Viscosity of QCD in Ultrarelativistic Heavy-Ion Collisions.

We investigate the consequences of a nonzero bulk viscosity coefficient on the transverse momentum spectra, azimuthal momentum anisotropy, and multiplicity of charged hadrons produced in heavy ion collisions at LHC energies. The agreement between a realistic 3D hybrid simulation and the experimentally measured data considerably improves with the addition of a bulk viscosity coefficient for strongly interacting matter. This paves the way for an eventual quantitative determination of several QCD transport coefficients from the experimental heavy ion and hadron-nucleus collision programs.

Cardiovascular sequelae in long-term survivors of young peoples' cancer: a linked cohort study.

BACKGROUND: We aimed to define the incidence and risk of cardiovascular late effects (LEs) identified from inpatient hospital episode statistics (HES) among long-term survivors of cancer in young people by age at diagnosis (0-14 and 15-29 years). METHODS: Records from the Yorkshire Specialist Register of Cancer in Children and Young People (1991-2006) were linked to inpatient HES data (1996-2011) to assess rates of cardiovascular LEs. Rates were compared with the general population in Yorkshire using age-sex-matched HES records for the entire region. RESULTS: Of 3247 survivors of cancer, 3.6% had at least one cardiovascular LE. Overall, cardiovascular hospitalisations for the childhood cohort were threefold higher compared with the general population, but did not differ for young adults. For young adults, increased rates were limited to pericardial disease, cardiomyopathy and heart failure, pulmonary heart disease, hypertension and conduction disorders. CONCLUSIONS: Survivors of childhood and young adult cancer remain at increased risk of cardiovascular LEs compared with the general population.