Diversity of symptom phenotypes in SARS-CoV-2 community infections observed in multiple large datasets

Variability in case severity and in the range of symptoms experienced has been apparent from the earliest months of the COVID-19 pandemic. From a clinical perspective, symptom variability might indicate various routes/mechanisms by which infection leads to disease, with different routes requiring potentially different treatment approaches. For public health and control of transmission, symptoms in community cases were the prompt on which action such as PCR testing and isolation was taken. However, interpreting symptoms presents challenges, for instance in balancing sensitivity and specificity of individual symptoms with the need to maximise case finding, whilst managing demand for limited resources such as testing. For both clinical and transmission control reasons, we require an approach that allows for the possibility of distinct symptom phenotypes, rather than assuming variability along a single dimension. Here we address this problem by bringing together four large and diverse datasets deriving from routine testing, a population-representative household survey and participatory smartphone surveillance in the United Kingdom. Through use of cutting-edge unsupervised classification techniques from statistics and machine learning, we characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases, making comparisons across datasets and by age bands. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. In this way, we are able to demonstrate the deep structure of symptoms of COVID-19 without usual biases due to study design.Comment: 52 pages; 25 figure

Absorption Troughs of Lyα Emitters in HETDEX

The Hobby-Eberly Telescope Dark Energy Experiment (HETDEX) is designed to detect and measure the redshifts of more than 1 million Lyα emitting galaxies (LAEs) 1.88 < z < 3.52. In addition to its cosmological measurements, these data enable studies of Lyα spectral profiles and the underlying radiative transfer. Using the roughly half a million LAEs in the HETDEX Data Release 3, we stack various subsets to obtain the typical Lyα profile for the z ∼ 2-3 epoch and to understand their physical properties. We find clear absorption wings around Lyα emission, which extend ∼2000 km s−1 both redward and blueward of the central line. Using far-UV spectra of nearby (0.002 < z < 0.182) LAEs in the COS Legacy Archive Spectroscopic Survey treasury and optical/near-IR spectra of 2.8 < z < 6.7 LAEs in the Multi Unit Spectroscopic-Wide survey, we observe absorption profiles in both redshift regimes. Dividing the sample by volume density shows that the troughs increase in higher-density regions. This trend suggests that the depth of the absorption is dependent on the local density of objects near the LAE, a geometry that is similar to damped Lyα systems. Simple simulations of Lyα radiative transfer can produce similar troughs due to absorption of light from background sources by H i gas surrounding the LAEs

Liax Is a Surrogate Marker For Cell Envelope Stress and Daptomycin Non-Susceptibility in Enterococcus Faecium

Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistan

Role of Adjuvant Multimodality Therapy After Curative-Intent Resection of Ampullary Carcinoma

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, setting, and participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main outcomes and measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41). Conclusions and relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined

HETDEX Public Source Catalog 1 -- Stacking 50K Lyman Alpha Emitters

We describe the ensemble properties of the $1.9 < z < 3.5$ Lyman Alpha Emitters (LAEs) found in the HETDEX survey's first public data release, HETDEX Public Source Catalog 1 (Mentuch Cooper et al. 2023). Stacking the low-resolution ($R \sim$ 800) spectra greatly increases the signal-to-noise ratio, revealing spectral features otherwise hidden by noise, and we show that the stacked spectrum is representative of an average member of the set. The flux limited, Ly$\alpha$ signal-to-noise ratio restricted stack of 50K HETDEX LAEs shows the ensemble biweight ``average" $z \sim 2.6$ LAE to be a blue (UV continuum slope $\sim -2.4$ and E(B-V) $< 0.1$), moderately bright (M$_{\text{UV}} \sim -19.7$) star forming galaxy with strong Ly$\alpha$ emission (log $L_{Ly\alpha}$ $\sim$ 42.8 and $W_{\lambda}$(Ly$\alpha$) $\sim$ 114\AA), and potentially significant leakage of ionizing radiation. The restframe UV light is dominated by a young, metal poor stellar population with an average age 5-15 Myr and metallicity of 0.2-0.3 Z$_{\odot}$.Comment: 17 pages, 11 figures, 2 data files (ApJ Accepted

Water quality is a poor predictor of recreational hotspots in England

Maintaining and improving water quality is key to the protection and restoration of aquatic ecosystems, which provide important benefits to society. In Europe, the Water Framework Directive (WFD) defines water quality based on a set of biological, hydro-morphological and chemical targets, and aims to reach good quality conditions in all river bodies by the year 2027. While recently it has been argued that achieving these goals will deliver and enhance ecosystem services, in particular recreational services, there is little empirical evidence demonstrating so. Here we test the hypothesis that good water quality is associated with increased utilization of recreational services, combining four surveys covering walking, boating, fishing and swimming visits, together with water quality data for all water bodies in eight River Basin Districts (RBDs) in England. We compared the percentage of visits in areas of good water quality to a set of null models accounting for population density, income, age distribution, travel distance, public access, and substitutability. We expect such association to be positive, at least for fishing (which relies on fish stocks) and swimming (with direct contact to water). We also test if these services have stronger association with water quality relative to boating and walking alongside rivers, canals or lakeshores. In only two of eight RBDs (Northumbria and Anglian) were both criteria met (positive association, strongest for fishing and swimming) when comparing to at least one of the null models. This conclusion is robust to variations in dataset size. Our study suggests that achieving the WFD water quality goals may not enhance recreational ecosystem services, and calls for further empirical research on the connection between water quality and ecosystem services

Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK

Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations