Validity, practical utility, and reliability of the activPAL in preschool children

<p>Purpose: With the increasing global prevalence of childhood obesity, it is important to have appropriate measurement tools for investigating factors (e.g. sedentary time) contributing to positive energy balance in early childhood. For pre-school children, single unit monitors such as the activPALTM are promising. However, validation is required as activity patterns differ from adults.</p> <p>Methods: Thirty pre-school children participated in a validation study. Children were videoed for one hour undertaking usual nursery activity while wearing an activPALTM. Video (criterion method) was analyzed on a second-by-second basis to categorise posture and activity. This was compared with the corresponding activPALTM output. In a subsequent sub-study investigating practical utility and reliability, 20 children wore an activPALTM for seven consecutive 24-hour periods.</p> <p>Results: A total of 97,750 seconds of direct observation from 30 children were categorized as sit/lie (46%), stand (35%), walk (16%); with 3% of time in nonsit/lie/upright postures (e.g. crawl/crouch/kneel-up). Sensitivity for the overall total time matched seconds detected as activPALTM ‘sit/lie’ was 86.7%, specificity 97.1%, and positive predictive value (PPV) 96.3%. For individual children, the median (interquartile range) sensitivity for activPALTM sit/lie was 92.8% (76.1-97.4), specificity 97.3% (94.9-99.2), PPV 97.0% (91.5-99.1). The activPALTM underestimated total time spent sitting (mean difference -4.4%, p<0.01), and overestimated time standing (mean difference 7.1%, p<0.01). There was no difference in overall % time categorised as ‘walk’ (p=0.2). The monitors were well tolerated by children during a seven day period of free-living activity. In the reliability study, at least five days of monitoring were required to obtain an intraclass correlation coefficient of ≥0.8 for time spent sit/lie according to activPALTM output.</p> <p>Conclusion: The activPAL had acceptable validity, practical utility, and reliability for the measurement of posture and activity during freeliving activities in pre-school children.</p&gt

Trust, guilds and kinship in London, 1330-1680

How was trust created and reinforced between the inhabitants of medieval and early modern cities? And how did the social foundations of trusting relationships change over time? Current research highlights the role of kinship, neighbourhood and associations, particularly guilds, in creating ‘relationships of trust’ and social capital in the face of high levels of migration, mortality and economic volatility, but tells us little about their relative importance or how they developed. We uncover a profound shift in the contribution of family and guilds to trust networks among the middling and elite of one of Europe’s major cities, London, over three centuries, from the 1330s to the 1680s. We examine the networks of sureties created to secure the inheritances of children whose fathers died while they were minors, surviving in the records of London’s Orphans Court. Our analysis of almost fifteen thousand networks evaluates the presence of trusting relationships connected with guild membership, family and place over several centuries. We show a profound increase in the role of kinship – a re-embedding of trust within the family - and a decline of the importance of shared guild membership in connecting Londoner’s who secured orphans’ inheritances together. We suggest these developments are best explained as a result of the impact of the Reformation on the form and intensity of sociability fostered by guilds and the enormous growth of the metropolis

Trust, guilds and kinship in London, 1330-1680

How was trust created and reinforced between the inhabitants of medieval and early modern cities? And how did the social foundations of trusting relationships change over time? Current research highlights the role of kinship, neighbourhood and associations, particularly guilds, in creating ‘relationships of trust’ and social capital in the face of high levels of migration, mortality and economic volatility, but tells us little about their relative importance or how they developed. We uncover a profound shift in the contribution of family and guilds to trust networks among the middling and elite of one of Europe’s major cities, London, over three centuries, from the 1330s to the 1680s. We examine almost 15,000 networks of sureties created to secure orphans’ inheritances to measure the presence of trusting relationships connected by guild membership, family and place. We uncover a profound increase in the role of kinship – a re-embedding of trust within the family - and a decline of the importance of shared guild membership in connecting Londoner’s who secured orphans’ inheritances together. These developments indicate a profound transformation in the social fabric of urban society

The influence of minimum sitting period of the ActivPAL™ on the measurement of breaks in sitting in young children

Sitting time and breaks in sitting influence cardio-metabolic health. New monitors (e.g. activPAL™) may be more accurate for measurement of sitting time and breaks in sitting although how to optimize measurement accuracy is not yet clear. One important issue is the minimum sitting/upright period (MSUP) to define a new posture. Using the activPAL™, we investigated the effect of variations in MSUP on total sitting time and breaks in sitting, and also determined the criterion validity of different activPAL™ settings for both construct

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Trust, Guilds and Kinship in London, 1330-1680

How was trust created and reinforced between the inhabitants of medieval and early modern cities? And how did the social foundations of trusting relationships change over time? Current research highlights the role of kinship, neighbourhood and associations, particularly guilds, in creating ‘relationships of trust’ and social capital in the face of high levels of migration, mortality and economic volatility, but tells us little about their relative importance or how they developed. We uncover a profound shift in the contribution of family and guilds to trust networks among the middling and elite of one of Europe’s major cities, London, over three centuries, from the 1330s to the 1680s. We examine almost 15,000 networks of sureties created to secure orphans’ inheritances to measure the presence of trusting relationships connected by guild membership, family and place. We uncover a profound increase in the role of kinship – a re-embedding of trust within the family - and a decline of the importance of shared guild membership in connecting Londoner’s who secured orphans’ inheritances together. These developments indicate a profound transformation in the social fabric of urban society