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.
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 (r
= 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.
It is challenging to conduct and quickly disseminate findings from in-depth qualitative analyses, which can impede timely implementation of interventions because of its time-consuming methods. To ...better understand tradeoffs between the need for actionable results and scientific rigor, we present our method for conducting a framework-guided rapid analysis (RA) and a comparison of these findings to an in-depth analysis of interview transcripts.
Set within the context of an evaluation of a successful academic detailing (AD) program for opioid prescribing in the Veterans Health Administration, we developed interview guides informed by the Consolidated Framework for Implementation Research (CFIR) and interviewed 10 academic detailers (clinical pharmacists) and 20 primary care providers to elicit detail about successful features of the program. For the RA, verbatim transcripts were summarized using a structured template (based on CFIR); summaries were subsequently consolidated into matrices by participant type to identify aspects of the program that worked well and ways to facilitate implementation elsewhere. For comparison purposes, we later conducted an in-depth analysis of the transcripts. We described our RA approach and qualitatively compared the RA and deductive in-depth analysis with respect to consistency of themes and resource intensity.
Integrating the CFIR throughout the RA and in-depth analysis was helpful for providing structure and consistency across both analyses. Findings from the two analyses were consistent. The most frequently coded constructs from the in-depth analysis aligned well with themes from the RA, and the latter methods were sufficient and appropriate for addressing the primary evaluation goals. Our approach to RA was less resource-intensive than the in-depth analysis, allowing for timely dissemination of findings to our operations partner that could be integrated into ongoing implementation.
In-depth analyses can be resource-intensive. If consistent with project needs (e.g., to quickly produce information to inform ongoing implementation or to comply with a policy mandate), it is reasonable to consider using RA, especially when faced with resource constraints. Our RA provided valid findings in a short timeframe, enabling identification of actionable suggestions for our operations partner.
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.
Vitamin D insufficiency is common in women of childbearing age and increasing evidence suggests that the risk of osteoporotic fracture in adulthood could be determined partly by environmental factors ...during intrauterine and early postnatal life. We investigated the effect of maternal vitamin D status during pregnancy on childhood skeletal growth.
In a longitudinal study, we studied 198 children born in 1991–92 in a hospital in Southampton, UK; the body build, nutrition, and vitamin D status of their mothers had been characterised during pregnancy. The children were followed up at age 9 years to relate these maternal characteristics to their body size and bone mass.
49 (31%) mothers had insufficient and 28 (18%) had deficient circulating concentrations of 25(OH)-vitamin D during late pregnancy. Reduced concentration of 25(OH)-vitamin D in mothers during late pregnancy was associated with reduced whole-body (
r=0·21, p=0·0088) and lumbar-spine (
r=0·17, p=0·03) bone-mineral content in children at age 9 years. Both the estimated exposure to ultraviolet B radiation during late pregnancy and the maternal use of vitamin D supplements predicted maternal 25(OH)-vitamin D concentration (p<0·0001 and p=0·0110, respectively) and childhood bone mass (p=0·0267). Reduced concentration of umbilical-venous calcium also predicted reduced childhood bone mass (p=0·0286).
Maternal vitamin D insufficiency is common during pregnancy and is associated with reduced bone-mineral accrual in the offspring during childhood; this association is mediated partly through the concentration of umbilical venous calcium. Vitamin D supplementation of pregnant women, especially during winter months, could lead to longlasting reductions in the risk of osteoporotic fracture in their offspring.
Objective: To investigate whether exposure to high maternal concentrations of 25(OH)-vitamin D in pregnancy poses any risk to the child. Design: Prospective study. Setting: Princess Anne Maternity ...Hospital, Southampton, UK. Subjects: A group of 596 pregnant women were recruited. A total of 466 (78%) children were examined at birth, 440 (74%) at age 9 months and 178 (30%) at age 9 years. Methods: Maternal 25 (OH)-vitamin D concentrations were measured in late pregnancy. Anthropometry of the child was recorded at birth, 9 months and 9 years. At 9 months, atopic eczema was assessed. At 9 years, children had an echocardiogram and a dual energy x-ray absorptiometry scan, blood pressure, arterial compliance and carotid intima-media thickness were measured and intelligence and psychological function assessed. Results: There were no associations between maternal 25(OH)-vitamin D concentrations and the child's body size or measures of the child's intelligence, psychological health or cardiovascular system. Children whose mothers had a 25(OH)-vitamin D concentration in pregnancy >75 nmol/l had an increased risk of eczema on examination at 9 months (OR 3.26, 95% CI 1.15-9.29, P=0.025) and asthma at age 9 years (OR 5.40, 95% CI, 1.09-26.65, P=0.038) compared to children whose mothers had a concentration of <30 nmol/l. Conclusion: Exposure to maternal concentrations of 25(OH)-vitamin D in pregnancy in excess of 75 nmol/l does not appear to influence the child's intelligence, psychological health or cardiovascular system; there could be an increased risk of atopic disorders, but this needs confirmation in other studies.
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.
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.
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.
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.
Observations that older people who enjoy life more tend to live longer suggest that psychological well-being may be a potential resource for healthier ageing. We investigated whether psychological ...well-being was associated with incidence of physical frailty.
We used multinomial logistic regression to examine the prospective relationship between psychological well-being, assessed using the CASP-19, a questionnaire that assesses perceptions of control, autonomy, self-realization and pleasure, and incidence of physical frailty or pre-frailty, defined according to the Fried criteria (unintentional weight loss, weakness, self-reported exhaustion, slow walking speed and low physical activity), in 2557 men and women aged 60 to ≥ 90 years from the English Longitudinal Study of Ageing (ELSA).
Men and women with higher levels of psychological well-being were less likely to become frail over the 4-year follow-up period. For a standard deviation higher score in psychological well-being at baseline, the relative risk ratio (RR) for incident frailty, adjusted for age, sex and baseline frailty status, was 0.46 95% confidence interval (CI) 0.40-0.54. There was a significant association between psychological well-being and risk of pre-frailty (RR 0.69, 95% CI 0.63-0.77). Examination of scores for hedonic (pleasure) and eudaimonic (control, autonomy and self-realization) well-being showed that higher scores on both were associated with decreased risk. Associations were partially attenuated by further adjustment for other potential confounding factors but persisted. Incidence of pre-frailty or frailty was associated with a decline in well-being, suggesting that the relationship is bidirectional.
Maintaining a stronger sense of psychological well-being in later life may protect against the development of physical frailty. Future research needs to establish the mechanisms underlying these findings.
The development of effective vaccines that can be rapidly manufactured and distributed worldwide is necessary to mitigate the devastating health and economic impacts of pandemics like COVID‐19. The ...receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein, which mediates host cell entry of the virus, is an appealing antigen for subunit vaccines because it is efficient to manufacture, highly stable, and a target for neutralizing antibodies. Unfortunately, RBD is poorly immunogenic. While most subunit vaccines are commonly formulated with adjuvants to enhance their immunogenicity, clinically‐relevant adjuvants Alum, AddaVax, and CpG/Alum are found unable to elicit neutralizing responses following a prime‐boost immunization. Here, it has been shown that sustained delivery of an RBD subunit vaccine comprising CpG/Alum adjuvant in an injectable polymer‐nanoparticle (PNP) hydrogel elicited potent anti‐RBD and anti‐spike antibody titers, providing broader protection against SARS‐CoV‐2 variants of concern compared to bolus administration of the same vaccine and vaccines comprising other clinically‐relevant adjuvant systems. Notably, a SARS‐CoV‐2 spike‐pseudotyped lentivirus neutralization assay revealed that hydrogel‐based vaccines elicited potent neutralizing responses when bolus vaccines did not. Together, these results suggest that slow delivery of RBD subunit vaccines with PNP hydrogels can significantly enhance the immunogenicity of RBD and induce neutralizing humoral immunity.
An injectable hydrogel‐based COVID‐19 vaccine is developed using the receptor‐binding domain (RBD) antigen of the SARS‐CoV‐2 virus and clinically de‐risked adjuvants. Sustained delivery of the subunit vaccine containing a CpG/Alum complex as an adjuvant from this hydrogel depot increases titers, provides broader protection against spike variants, and leads to more robust neutralization compared to a dose‐matched bolus control.
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