Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r
...≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h
) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h
could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A). ...RS is characterized by skeletal dysplasia and distinctive facial and physical characteristics. To further explore the genetic heterogeneity, paralog contribution, and phenotypic variability of RS, we investigated a cohort of 22 individuals clinically diagnosed with RS from 18 unrelated families. Pathogenic or likely pathogenic variants in genes associated with RS or RS phenocopies were identified in all 22 individuals, including the first variant to be reported in DVL2. We retrospectively collected medical records of 16 individuals from this cohort and extracted clinical descriptions from 52 previously published cases. We performed Human Phenotype Ontology (HPO) based quantitative phenotypic analyses to dissect allele-specific phenotypic differences. Individuals with FZD2 variants clustered into two groups with demonstrable phenotypic differences between those with missense and truncating alleles. Probands with biallelic NXN variants clustered together with the majority of probands carrying DVL1, DVL2, and DVL3 variants, demonstrating no phenotypic distinction between the NXN-autosomal recessive and dominant forms of RS. While phenotypically similar diseases on the RS differential matched through HPO analysis, clustering using phenotype similarity score placed RS-associated phenotypes in a unique cluster containing WNT5A, FZD2, and ROR2 apart from non-RS-associated paralogs. Through human phenotype analyses of this RS cohort and OMIM clinical synopses of Mendelian disease, this study begins to tease apart specific biologic roles for non-canonical WNT-pathway proteins.
Robinow syndrome (RS) is a genetically heterogeneous disorder caused by WNT/PCP-signaling dysfunction. We identified pathogenic variants in RS individuals (n = 22), including the first DVL2 variant. Quantitative HPO-term-based analyses unveiled gene/allele-specific correlations to disease traits, providing a model for delineating the phenotypic consequences of variants affecting paralogs in the same pathway.
Few population-based studies in the US collected individual-level data from families during the COVID-19 pandemic.
To examine differences in COVID-19 pandemic-related experiences in a large ...sociodemographically diverse sample of children and caregivers.
The Environmental influences on Child Health Outcomes (ECHO) multi-cohort consortium is an ongoing study that brings together 64 individual cohorts with participants (24 757 children and 31 700 caregivers in this study) in all 50 US states and Puerto Rico. Participants who completed the ECHO COVID-19 survey between April 2020 and March 2022 were included in this cross-sectional analysis. Data were analyzed from July 2021 to September 2022.
Exposures of interest were caregiver education level, child life stage (infant, preschool, middle childhood, and adolescent), and urban or rural (population <50 000) residence. Dependent variables included COVID-19 infection status and testing; disruptions to school, child care, and health care; financial hardships; and remote work. Outcomes were examined separately in logistic regression models mutually adjusted for exposures of interest and race, ethnicity, US Census division, sex, and survey administration date.
Analyses included 14 646 children (mean SD age, 7.1 4.4 years; 7120 49% female) and 13 644 caregivers (mean SD age, 37.6 7.2 years; 13 381 98% female). Caregivers were racially (3% Asian; 16% Black; 12% multiple race; 63% White) and ethnically (19% Hispanic) diverse and comparable with the US population. Less than high school education (vs master's degree or more) was associated with more challenges accessing COVID-19 tests (adjusted odds ratio aOR, 1.88; 95% CI, 1.06-1.58), lower odds of working remotely (aOR, 0.04; 95% CI, 0.03-0.07), and more food access concerns (aOR, 4.14; 95% CI, 3.20-5.36). Compared with other age groups, young children (age 1 to 5 years) were least likely to receive support from schools during school closures, and their caregivers were most likely to have challenges arranging childcare and concerns about work impacts. Rural caregivers were less likely to rank health concerns (aOR, 0.77; 95% CI, 0.69-0.86) and social distancing (aOR, 0.82; 95% CI, 0.73-0.91) as top stressors compared with urban caregivers.
Findings in this cohort study of US families highlighted pandemic-related burdens faced by families with lower socioeconomic status and young children. Populations more vulnerable to public health crises should be prioritized in recovery efforts and future planning.
Pandemic Kelly, Heath A; Mercer, Geoff N; Fielding, James E ...
PloS one,
06/2010, Letnik:
5, Številka:
6
Journal Article
Recenzirano
In mid-June 2009 the State of Victoria in Australia appeared to have the highest notification rate of pandemic (H1N1) 2009 influenza in the world. We hypothesise that this was because community ...transmission of pandemic influenza was already well established in Victoria at the time testing for the novel virus commenced. In contrast, this was not true for the pandemic in other parts of Australia, including Western Australia (WA). We used data from detailed case follow-up of patients with confirmed infection in Victoria and WA to demonstrate the difference in the pandemic curve in two Australian states on opposite sides of the continent. We modelled the pandemic in both states, using a susceptible-infected-removed model with Bayesian inference accounting for imported cases. Epidemic transmission occurred earlier in Victoria and later in WA. Only 5% of the first 100 Victorian cases were not locally acquired and three of these were brothers in one family. By contrast, 53% of the first 102 cases in WA were associated with importation from Victoria. Using plausible model input data, estimation of the effective reproductive number for the Victorian epidemic required us to invoke an earlier date for commencement of transmission to explain the observed data. This was not required in modelling the epidemic in WA. Strong circumstantial evidence, supported by modelling, suggests community transmission of pandemic influenza was well established in Victoria, but not in WA, at the time testing for the novel virus commenced in Australia. The virus is likely to have entered Victoria and already become established around the time it was first identified in the US and Mexico.
Genomic mismatch scanning (GMS) is a technique that enriches for regions of identity by descent (IBD) between two individuals without the need for genotyping or sequencing. Regions of IBD selected by ...GMS are mapped by hybridization to a microarray containing ordered clones of genomic DNA from chromosomes of interest. Here we demonstrate the feasibility and efficacy of this form of linkage-mapping, using congenital hyperinsulinism (HI), an autosomal recessive disease, whose relatively high frequency in Ashkenazi Jews suggests a founder effect. The gene responsible (SUR1) encodes the sulfonylurea receptor, which maps to chromosome 11p15.1. We show that the combination of GMS and hybridization of IBD products to a chromosome-11 microarray correctly maps the HI gene to a 2-Mb region, thereby demonstrating linkage-disequilibrium mapping without genotyping.
NASA's Transiting Exoplanet Survey Satellite (TESS) is an all-sky survey mission designed to find transiting exoplanets orbiting nearby bright stars. It has identified more than 329 transiting ...exoplanets, and almost 6,000 candidates remain unvalidated. In this manuscript, we discuss the findings from the ongoing VaTEST (Validation of Transiting Exoplanets using Statistical Tools) project, which aims to validate new exoplanets for further characterization. We validated 11 new exoplanets by examining the light curves of 24 candidates using the LATTE and TESS-Plot tools and computing the False Positive Probabilities using the statistical validation tool TRICERATOPS. These include planets suitable for atmospheric characterization using transmission spectroscopy (TOI-2194b), emission spectroscopy (TOI-3082b and TOI-5704b) and for both transmission and emission spectroscopy (TOI-672b, TOI- 1694b, and TOI-2443b); One super-Earth (TOI-2194b) orbiting a bright (V = 8.42 mag), metal-poor (Fe/H = -0.3720 \(\pm\) 0.1) star; one short-period Neptune-like planet (TOI-5704) in the Hot Neptune Desert. In total, we validated 1 super-Earth, 7 sub-Neptunes, 1 Neptune-like, and 2 sub-Saturn or super-Neptune-like exoplanets. Additionally, we identify five likely planet candidates (TOI-323, TOI- 1180, TOI-2200, TOI-2408 and TOI-3913) which can be further studied to establish their planetary nature.
The 3M Petrifilm Staph Express Count plate method was compared with AOAC Official Method 975.55 for the enumeration of Staphylococcus aureus in selected foods. Four foods--cooked, diced chicken; ...cured ham; smoked salmon; and pepperoni--were analyzed for S. aureus by 12 collaborating laboratories. For each food tested, the collaborators received 8 blind test samples consisting of a control sample, a low inoculation level, a medium inoculation level, and a medium inoculation level with background flora, each in duplicate. The mean log10 counts for the methods were comparable for all 4 foods. The repeatability and reproducibility variances of the 24 h Petrifilm Staph Express Count plate method were similar to those of the 72 h standard method.
Multi-planet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf ...(\(\rm{V=11.6,~K=9.9}\)) and four transiting sub-Neptunes identified by TESS with orbital periods of \(4.31~\rm{d},~5.90~\rm{d},~18.66~\rm{d}\), and \(~37.92~\rm{d}\). We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (\(\rm{2.97 \pm 0.06~R_\oplus},\rm{2.47 \pm 0.08~R_\oplus}, \rm{3.46 \pm 0.09~R_\oplus}\), \(\rm{3.72 \pm 0.16~R_\oplus}\)), and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (\(\rm{8.1 \pm 1.1 M_\oplus}\), \(\rm{8.8 \pm 1.2 M_\oplus}\), \(\rm{5.3 \pm 1.7 M_\oplus}\), \(\rm{14.8 \pm 2.3 M_\oplus}\)). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (\(\rm{P_{e}/P_{d}=2.03}\)) and exhibit transit timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only six systems with measured masses and radii for all four transiting planets. The planet densities range from \(\rm{0.70 \pm 0.24}\) to \(3.21 \pm 0.44 \rm{g/cm^3}\), implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 \(\pm\) 3.6 \(\rm{M_\oplus}\). This planet candidate is exterior to TOI-1246 e with a candidate period of 93.8 d, and we discuss the implications if it is confirmed to be planetary in nature.
The idea that male and female observers would have different reactions to the use of touch by a nurse towards a patient in a hospital situation was tested. There was an overall pattern for observers ...to react more favorably to the nurse who used touch compared to no touch in interacting with a patient.
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