Self-reported extracurricular activity, academic success, and quality of life in UK medical students.

OBJECTIVES: To explore the relationship between academic performance, extracurricular activity, and quality of life at medical school in the UK to aid our understanding of students' work-life balance. METHODS: A cross-sectional study, using an electronic questionnaire distributed to UK final year medical students across 20 medical schools (4478 students). Participants reported the hours of self-regulated learning and extracurricular activities undertaken each year at medical school; along with their academic decile (1 = highest, 10 = lowest). Self-reported quality of life (QoL) was assessed using an established screening tool (7 = highest, 1 = lowest). RESULTS: Seven hundred responses were obtained, across 20 participating medical schools, response rate 16% (700/4478). Factors associated with higher academic achievement were: graduate entry course students (2 deciles higher, p < 0.0001), more hours academic study during term and revision periods (rho=-0.1, p < 0.01), and involvement in teaching or research. Increased hours of study was associated with lower QoL (rho = -0.13, p < 0.01). CONCLUSIONS: Study skills may be more important than duration spent studying, for academic achievement and QoL. Graduate-entry students attain higher decile scores despite similar self-reported duration of study

<i>TESS</i> Spots a Compact System of Super-Earths around the Naked-eye Star HR 858

Transiting Exoplanet Survey Satellite (TESS) observations have revealed a compact multiplanet system around the sixth-magnitude star HR 858 (TIC 178155732, TOI 396), located 32 pc away. Three planets, each about twice the size of Earth, transit this slightly evolved, late F-type star, which is also a member of a visual binary. Two of the planets may be in mean motion resonance. We analyze the TESS observations, using novel methods to model and remove instrumental systematic errors, and combine these data with follow-up observations taken from a suite of ground-based telescopes to characterize the planetary system. The HR 858 planets are enticing targets for precise radial velocity observations, secondary eclipse spectroscopy, and measurements of the Rossiter–McLaughlin effect

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

TOI-257b (HD 19916b): a warm sub-saturn orbiting an evolved F-type star

ABSTRACT We report the discovery of a warm sub-Saturn, TOI-257b (HD 19916b), based on data from NASA’s Transiting Exoplanet Survey Satellite (TESS). The transit signal was detected by TESS and confirmed to be of planetary origin based on radial velocity observations. An analysis of the TESS photometry, the Minerva-Australis, FEROS, and HARPS radial velocities, and the asteroseismic data of the stellar oscillations reveals that TOI-257b has a mass of MP = 0.138 ± 0.023 $\rm {M_J}$ (43.9 ± 7.3 $\, M_{\rm \oplus}$), a radius of RP = 0.639 ± 0.013 $\rm {R_J}$ (7.16 ± 0.15 $\, \mathrm{ R}_{\rm \oplus}$), bulk density of $0.65^{+0.12}_{-0.11}$ (cgs), and period $18.38818^{+0.00085}_{-0.00084}$ $\rm {days}$. TOI-257b orbits a bright (V = 7.612 mag) somewhat evolved late F-type star with M* = 1.390 ± 0.046 $\rm {M_{sun}}$, R* = 1.888 ± 0.033 $\rm {R_{sun}}$, Teff = 6075 ± 90 $\rm {K}$, and vsin i = 11.3 ± 0.5 km s−1. Additionally, we find hints for a second non-transiting sub-Saturn mass planet on a ∼71 day orbit using the radial velocity data. This system joins the ranks of a small number of exoplanet host stars (∼100) that have been characterized with asteroseismology. Warm sub-Saturns are rare in the known sample of exoplanets, and thus the discovery of TOI-257b is important in the context of future work studying the formation and migration history of similar planetary systems

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Self-reported extracurricular activity, academic success, and quality of life in UK medical students

Objectives: To explore the relationship between academic performance, extracurricular activity, and quality of life at medical school in the UK to aid our understanding of students’ work-life balance. Methods: A cross-sectional study, using an electronic questionnaire distributed to UK final year medical students across 20 medical schools (4478 students). Participants reported the hours of self-regulated learning and extracurricular activities undertaken each year at medical school; along with their academic decile (1 = highest, 10 = lowest). Self-reported quality of life (QoL) was assessed using an established screening tool (7 = highest, 1 = lowest). Results: Seven hundred responses were obtained, across 20 participating medical schools, response rate 16% (700/4478). Factors associated with higher academic achievement were: graduate entry course students (2 deciles higher, p< 0.0001), more hours academic study during term and revision periods (rho=-0.1, p< 0.01), and involvement in teaching or research. Increased hours of study was associated with lower QoL (rho = -0.13, p<0.01). Conclusions: Study skills may be more important than duration spent studying, for academic achievement and QoL. Graduate-entry students attain higher decile scores despite similar self-reported duration of study

The global prevalence and genetic spectrum of lysosomal acid lipase deficiency: A rare condition that mimics NAFLD.

BACKGROUND & AIMS: Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive condition that may present in a mild form (cholesteryl ester storage disease [CESD]), which mimics non-alcoholic fatty liver disease (NAFLD). It has been suggested that CESD may affect 1 in 40,000 and is under-diagnosed in NAFLD clinics. Therefore, we aimed to estimate the prevalence of LAL-D using analysis of genetic variation in LIPA. METHODS: MEDLINE and EMBASE were systematically searched for previously reported disease variants and prevalence estimates. Previous prevalence estimates were meta-analysed. Disease variants in LIPA were annotated with allele frequencies from gnomAD and combined with unreported major functional variants found in humans. Pooled ethnicity-specific prevalences for LAL-D and CESD were calculated using the Hardy-Weinberg equation. RESULTS: Meta-analysis of existing genetic studies estimated the prevalence of LAL-D as 1 per 160,000 (95% CI 1 per 65,025-761,652) using the allele frequency of c.894G>A in LIPA. A total of 98 previously reported disease variants in LIPA were identified, of which 32/98 were present in gnomAD, giving a prevalence of 1 per 307,482 (95% CI 257,672-366,865). Wolman disease was associated with more loss-of-function variants than CESD. When this was combined with 22 previously unreported major functional variants in LIPA identified in humans, the pooled prevalence of LAL-D was 1 per 177,452 (95% CI 149,467-210,683) with a carrier frequency of 1 per 421. The prevalence is lowest in those of East Asian, South Asian, and Finnish ancestry. CONCLUSION: Using 120 disease variants in LIPA, these data can reassure clinicians that LAL-D is an ultra-rare disorder. Given the therapeutic capability of sebelipase alpha, investigation for LAL-D might be included in second-line metabolic screening in NAFLD. LAY SUMMARY: Lysosomal Acid Lipase Deficiency (LAL-D) is a rare genetic condition that can cause severe liver disease, but it is difficult to diagnose and sometimes can look like simple fatty liver. It was not clear how common LAL-D was and whether many cases were being missed. To study this, we searched for all genetic mutations that could cause LAL-D, calculated how common those mutations were, and added them up. This let us estimate that LAL-D affects roughly 1 in 175,000 people. We conclude that LAL-D is a very rare condition, but it is treatable so may be included in a 'second-line' of tests for causes of fatty liver

Clinical outcomes in pediatric intestinal failure: a meta-analysis and meta-regression.

BACKGROUND: Intestinal failure (IF) is associated with significant morbidity and mortality, yet specific parameters that determine medium- and long-term outcomes remain ill defined. OBJECTIVE: The aim of this study was to determine the long-term outcomes in childhood IF and identify patient characteristics associated with clinical endpoints. DESIGN: MEDLINE and EMBASE were searched for cohorts of >10 pediatric-onset IF patients with >12 mo follow-up. Random-effects meta-analysis and meta-regression weighted by follow-up duration were used to calculate clinical outcome rates and patient factors associated with outcomes. Primary outcome was mortality rate; secondary outcomes included neurodevelopmental status, transplantation, IF-associated liver disease (IFALD), enteral autonomy, and sepsis. RESULTS: In total, 175 cohorts (9318 patients and 34,549 y follow-up) were included in the meta-analysis. Overall mortality was 5.2% per y (95% CI: 4.3, 6.0) and was associated with sepsis and IFALD on meta-regression. Mortality rate improved with time from 5.9% per y pre-2000 to 4.5% per y post-2005. Sepsis rate was also predictive of IFALD and liver failure. Enteral autonomy was associated with small bowel length but not presence of ileo-cecal valve. There was a relative lack of data on neurodevelopmental outcomes. CONCLUSIONS: Sepsis is the primary modifiable factor associated with mortality and liver failure, whereas enteral autonomy correlates with small-bowel length. No clear parameters have been identified that accurately predict neurodevelopmental outcomes, and hence further research is needed. Together, our findings are helpful for parental counseling and resource planning, and support targeting reduction in sepsis.Wellcome Trust Fellowship (216329/Z/19/Z