Enabling Torts

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Towards Reliable Automatic Protein Structure Alignment

A variety of methods have been proposed for structure similarity calculation, which are called structure alignment or superposition. One major shortcoming in current structure alignment algorithms is in their inherent design, which is based on local structure similarity. In this work, we propose a method to incorporate global information in obtaining optimal alignments and superpositions. Our method, when applied to optimizing the TM-score and the GDT score, produces significantly better results than current state-of-the-art protein structure alignment tools. Specifically, if the highest TM-score found by TMalign is lower than (0.6) and the highest TM-score found by one of the tested methods is higher than (0.5), there is a probability of (42%) that TMalign failed to find TM-scores higher than (0.5), while the same probability is reduced to (2%) if our method is used. This could significantly improve the accuracy of fold detection if the cutoff TM-score of (0.5) is used. In addition, existing structure alignment algorithms focus on structure similarity alone and simply ignore other important similarities, such as sequence similarity. Our approach has the capacity to incorporate multiple similarities into the scoring function. Results show that sequence similarity aids in finding high quality protein structure alignments that are more consistent with eye-examined alignments in HOMSTRAD. Even when structure similarity itself fails to find alignments with any consistency with eye-examined alignments, our method remains capable of finding alignments highly similar to, or even identical to, eye-examined alignments.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

Nipah Virus Infection in Dogs, Malaysia, 1999

The 1999 outbreak of Nipah virus encephalitis in humans and pigs in Peninsular Malaysia ended with the evacuation of humans and culling of pigs in the epidemic area. Serologic screening showed that, in the absence of infected pigs, dogs were not a secondary reservoir for Nipah virus

Family Composition and Stability for Orphans: A Longitudinal Study of Well-Being in 5 Low- and Middle-Income Countries

Objectives: Many orphaned children in low- and middle-income countries live with family. Yet, their household composition and its stability are not well-characterized, nor is impact of stability on longer-term outcomes. Methods: We used the longitudinal, multi-country Positive Outcomes for Orphans cohort to describe adult family living with orphans. Stability was measured by changes in presence of six familial relations over time, and related to three outcomes: 1) incident abuse, 2) cognitive functioning, 3) emotional difficulties. Associations were estimated using generalized linear models fit with generalized estimating equations. For abuse, Poisson regression estimated risk ratios. For continuous scores of cognitive functioning and emotional difficulties, linear models estimated mean differences (MDs) with 95% confidence intervals. Results: Among 1,359 orphans, 53–61% reported living with their mother each year; 7–13% with father; nearly 60% reported ≥1 change in composition over follow-up. Compared to 0 changes, difficulties increased with 1 change [MD: 0.23 (−0.33, 0.79)], 2 changes [MD: 0.57 (0.00, 1.16)] and ≥3 changes [MD: 0.73 (0.18, 1.29)]. No associations were found with abuse or cognitive functioning. Conclusion: Orphan well-being may be improved through supports stabilizing household composition or targeting emotional resilience

Random Convex Hulls and Extreme Value Statistics

In this paper we study the statistical properties of convex hulls of $N$ random points in a plane chosen according to a given distribution. The points may be chosen independently or they may be correlated. After a non-exhaustive survey of the somewhat sporadic literature and diverse methods used in the random convex hull problem, we present a unifying approach, based on the notion of support function of a closed curve and the associated Cauchy's formulae, that allows us to compute exactly the mean perimeter and the mean area enclosed by the convex polygon both in case of independent as well as correlated points. Our method demonstrates a beautiful link between the random convex hull problem and the subject of extreme value statistics. As an example of correlated points, we study here in detail the case when the points represent the vertices of $n$ independent random walks. In the continuum time limit this reduces to $n$ independent planar Brownian trajectories for which we compute exactly, for all $n$, the mean perimeter and the mean area of their global convex hull. Our results have relevant applications in ecology in estimating the home range of a herd of animals. Some of these results were announced recently in a short communication [Phys. Rev. Lett. {\bf 103}, 140602 (2009)].Comment: 61 pages (pedagogical review); invited contribution to the special issue of J. Stat. Phys. celebrating the 50 years of Yeshiba/Rutgers meeting

Gendering the careers of young professionals: some early findings from a longitudinal study. in Organizing/theorizing: developments in organization theory and practice

Wonders whether companies actually have employees best interests at heart across physical, mental and spiritual spheres. Posits that most organizations ignore their workforce – not even, in many cases, describing workers as assets! Describes many studies to back up this claim in theis work based on the 2002 Employment Research Unit Annual Conference, in Cardiff, Wales

Cardiometabolic Pregnancy Complications in Association With Autism-Related Traits as Measured by the Social Responsiveness Scale in ECHO

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Inf luences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998–2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (β = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (β = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may inf luence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council