Explore the vast range of titles available.

Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type. We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2-7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2-7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England. Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.

A mutation that is common in northern Europe is less so in Africa.

A mutation that is common in northern Europe is less so in Africa.

A mutation that is common in northern Europe is less so in Africa.

People sometimes experience a strong emotional response to artworks. Previous studies have demonstrated that the peak emotional experience of chills (goose bumps or shivers) when listening to music involves psychophysiological arousal and a rewarding effect. However, many aspects of peak emotion are still not understood. The current research takes a new perspective of peak emotional response of tears (weeping, lump in the throat). A psychophysiological experiment showed that self-reported chills increased electrodermal activity and subjective arousal whereas tears produced slow respiration during heartbeat acceleration, although both chills and tears induced pleasure and deep breathing. A song that induced chills was perceived as being both happy and sad whereas a song that induced tears was perceived as sad. A tear-eliciting song was perceived as calmer than a chill-eliciting song. These results show that tears involve pleasure from sadness and that they are psychophysiologically calming; thus, psychophysiological responses permit the distinction between chills and tears. Because tears may have a cathartic effect, the functional significance of chills and tears seems to be different. We believe that the distinction of two types of peak emotions is theoretically relevant and further study of tears would contribute to more understanding of human peak emotional response.

Bacteremia, a critical condition that can lead to sepsis, is often diagnosed using blood cultures, which may yield false positives, leading to unnecessary treatments. Although clinical indicators, such as shaking chills and food consumption, have been identified as predictors of bacteremia, their diagnostic accuracy in outpatients, particularly when considering the timing of blood collection, remains unclear. This study aimed to assess the diagnostic accuracy of self-reported food consumption and shaking chills in detecting bacteremia, focusing on the time interval between the last meal and blood culture collection. This prospective, multicenter, observational study included outpatients aged > 16 years who could eat orally and underwent blood cultures in the emergency or general medicine department from April 2019 to March 2021. Food consumption before blood culture was self-reported using a medical questionnaire and categorized as \"normal\" (≥80%) or \"poor\" (<80%). The presence of chills was also assessed. Among 534 patients (mean age 68.3 ± 21.9 years, 51.3% men), 68 had bacteremia. The absence of poor food consumption (i.e., normal food consumption) had a negative predictive value of 91.2% (95% confidence interval, 88.8-93.6) and a negative likelihood ratio of 0.66 (0.23-1.94). Excluding the blood cultures collected between 10 pm and 8 am, these values increased to 96.2% (94.5-97.8) and 0.32 (0.12-0.89), respectively. Shaking chills had a positive likelihood ratio of 3.74 (2.75-4.73), increasing to 4.21 (3.22-5.19) after the same exclusion. Self-reported shaking chills were good positive predictors of bacteremia in outpatients, whereas self-reported normal food consumption, when accounting for the time between meals, ruled out bacteremia. These findings could help improve the early diagnosis and management of bacteremia, particularly in outpatient settings, and may contribute to the development of self-report tools for clinical decision-making.

BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E -mutated advanced rare cancers: anaplastic thyroid carcinoma ( n  = 36), biliary tract cancer ( n  = 43), gastrointestinal stromal tumor ( n  = 1), adenocarcinoma of the small intestine ( n  = 3), low-grade glioma ( n  = 13), high-grade glioma ( n  = 45), hairy cell leukemia ( n  = 55) and multiple myeloma ( n  = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E -mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110 . In the final analysis of all cohorts in the phase 2 ROAR basket trial, dabrafenib plus trametinib exhibited tumor-agnostic clinical activity in patients with rare BRAFV800E -mutated cancers, including anaplastic thyroid carcinoma, biliary tract cancer, low-grade glioma and hairy cell leukemia.

Epistasis—nonlinear genetic interactions between polymorphic loci—is the genetic basis of canalization and speciation, and epistatic interactions can be used to infer genetic networks affecting quantitative traits. However, the role that epistasis plays in the genetic architecture of quantitative traits is controversial. Here, we compared the genetic architecture of three Drosophila life history traits in the sequenced inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and a large outbred, advanced intercross population derived from 40 DGRP lines (Flyland). We assessed allele frequency changes between pools of individuals at the extremes of the distribution for each trait in the Flyland population by deep DNA sequencing. The genetic architecture of all traits was highly polygenic in both analyses. Surprisingly, none of the SNPs associated with the traits in Flyland replicated in the DGRP and vice versa. However, the majority of these SNPs participated in at least one epistatic interaction in the DGRP. Despite apparent additive effects at largely distinct loci in the two populations, the epistatic interactions perturbed common, biologically plausible, and highly connected genetic networks. Our analysis underscores the importance of epistasis as a principal factor that determines variation for quantitative traits and provides a means to uncover genetic networks affecting these traits. Knowledge of epistatic networks will contribute to our understanding of the genetic basis of evolutionarily and clinically important traits and enhance predictive ability at an individualized level in medicine and agriculture.

To minimize the carbon footprint of the transportation industry, manufacturers and engineers are continuously trying to improve the efficiency of the combustion engine. However, due to the presence of iron cylinder liners in the engine block, high tensile residual stresses are generated during the manufacturing process which leads to a large reduction of the alloy’s useable strength. Thus, the present study utilized neutron diffraction to study, for the first time, the evolution of residual stress of sand-cast aluminum engine blocks that have eliminated the iron cylinder liners from the casting process and mechanically inserted them after heat treatment and machining operations. Moreover, this study also examined the effects that cylinder bore chills have on the resulting residual stress profiles. The replacement of the iron liners shifted the stress mode from purely tension to purely compression until the bore chills were removed. Following the removal of the bore chills, the maximum tensile stress at the top of the cylinder bridge was ~ 70% lower than the engine’s predecessor which was produced with iron liners. Moreover, in the production-ready state (i.e., T7 heat treated and press-fit liners inserted), the stress mode maintains the partially compressive nature, thereby lowering the material’s susceptibility to crack growth and propagation. Graphical Abstract