Phosphine gas in the cloud decks of Venus

Measurements of trace gases in planetary atmospheres help us explore chemical conditions different to those on Earth. Our nearest neighbour, Venus, has cloud decks that are temperate but hyperacidic. Here we report the apparent presence of phosphine (PH3) gas in Venus’s atmosphere, where any phosphorus should be in oxidized forms. Single-line millimetre-waveband spectral detections (quality up to ~15σ) from the JCMT and ALMA telescopes have no other plausible identification. Atmospheric PH3 at ~20 ppb abundance is inferred. The presence of PH3 is unexplained after exhaustive study of steady-state chemistry and photochemical pathways, with no currently known abiotic production routes in Venus’s atmosphere, clouds, surface and subsurface, or from lightning, volcanic or meteoritic delivery. PH3 could originate from unknown photochemistry or geochemistry, or, by analogy with biological production of PH3 on Earth, from the presence of life. Other PH3 spectral features should be sought, while in situ cloud and surface sampling could examine sources of this gas

The extent and variability of storm-induced temperature changes in lakes measured with long-term and high-frequency data

The intensity and frequency of storms are projected to increase in many regions of the world because of climate change. Storms can alter environmental conditions in many ecosystems. In lakes and reservoirs, storms can reduce epilimnetic temperatures from wind-induced mixing with colder hypolimnetic waters, direct precipitation to the lake's surface, and watershed runoff. We analyzed 18 long-term and high-frequency lake datasets from 11 countries to assess the magnitude of wind- vs. rainstorm-induced changes in epilimnetic temperature. We found small day-to-day epilimnetic temperature decreases in response to strong wind and heavy rain during stratified conditions. Day-to-day epilimnetic temperature decreased, on average, by 0.28 degrees C during the strongest windstorms (storm mean daily wind speed among lakes: 6.7 +/- 2.7 m s(-1), 1 SD) and by 0.15 degrees C after the heaviest rainstorms (storm mean daily rainfall: 21.3 +/- 9.0 mm). The largest decreases in epilimnetic temperature were observed >= 2 d after sustained strong wind or heavy rain (top 5(th) percentile of wind and rain events for each lake) in shallow and medium-depth lakes. The smallest decreases occurred in deep lakes. Epilimnetic temperature change from windstorms, but not rainstorms, was negatively correlated with maximum lake depth. However, even the largest storm-induced mean epilimnetic temperature decreases were typicallyPeer reviewe

Storm impacts on phytoplankton community dynamics in lakes

In many regions across the globe, extreme weather events, such as storms, have increased in frequency, intensity and duration. Ecological theory predicts that such extreme events should have large impacts on ecosystem structure and function. For lake ecosystems, high winds and rainfall associated with storms are linked by short term runoff events from catchments and physical mixing of the water column. Although we have a well-developed understanding of how such wind and precipitation events alter lake physical processes, our mechanistic understanding of how these short-term disturbances 48 translate from physical forcing to changes in phytoplankton communities is poor. Here, we provide a conceptual model that identifies how key storm features (i.e., the frequency, intensity, and duration of wind and precipitation) interact with attributes of lakes and their watersheds to generate changes in a lake’s physical and chemical environment and subsequently phytoplankton community structure and dynamics. We summarize the current understanding of storm-phytoplankton dynamics, identify knowledge gaps with a systematic review of the literature, and suggest future research directions by generating testable hypotheses across a global gradient of lake types and environmental conditions.Fil: Stockwell, Jason D.. University of Vermont; Estados UnidosFil: Adrian, Rita. Leibniz Institute of Freshwater Ecology and Inland Fisheries; AlemaniaFil: Andersen, Mikkel. Dundalk Institute of Technology; IrlandaFil: Anneville, Orlane. Institut National de la Recherche Agronomique; FranciaFil: Bhattacharya, Ruchi. University of Missouri; Estados UnidosFil: Burns, Wilton G.. University of Vermont; Estados UnidosFil: Carey, Cayelan C.. Virginia Tech University; Estados UnidosFil: Carvalho, Laurence. Freshwater Restoration & Sustainability Group; Reino UnidoFil: Chang, ChunWei. National Taiwan University; República de ChinaFil: De Senerpont Domis, Lisette N.. Netherlands Institute of Ecology; Países BajosFil: Doubek, Jonathan P.. University of Vermont; Estados UnidosFil: Dur, Gaël. Shizuoka University; JapónFil: Frassl, Marieke A.. Griffith University; AustraliaFil: Gessner, Mark O.. Leibniz Institute of Freshwater Ecology and Inland Fisheries; AlemaniaFil: Hejzlar, Josef. Biology Centre of the Czech Academy of Sciences; República ChecaFil: Ibelings, Bas W.. University of Geneva; SuizaFil: Janatian, Nasim. Estonian University of Life Sciences; EstoniaFil: Kpodonu, Alfred T. N. K.. City University of New York; Estados UnidosFil: Lajeunesse, Marc J.. University of South Florida; Estados UnidosFil: Lewandowska, Aleksandra M.. Tvarminne Zoological Station; FinlandiaFil: Llames, Maria Eugenia del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Matsuzaki, Shin-ichiro S.. National Institute for Environmental Studies; JapónFil: Nodine, Emily R.. Rollins College; Estados UnidosFil: Nõges, Peeter. Estonian University of Life Sciences; EstoniaFil: Park, Ho-Dong. Shinshu University; JapónFil: Patil, Vijay P.. US Geological Survey; Estados UnidosFil: Pomati, Francesco. Swiss Federal Institute of Water Science and Technology; SuizaFil: Rimmer, Alon. Kinneret Limnological Laboratory; IsraelFil: Rinke, Karsten. Helmholtz-Centre for Environmental Research; AlemaniaFil: Rudstam, Lars G.. Cornell University; Estados UnidosFil: Rusak, James A.. Ontario Ministry of the Environment and Climate Change; CanadáFil: Salmaso, Nico. Research and Innovation Centre - Fondazione Mach; ItaliaFil: Schmitt, François. Laboratoire d’Océanologie et de Géosciences; FranciaFil: Seltmann, Christian T.. Dundalk Institute of Technology; IrlandaFil: Souissi, Sami. Universite Lille; FranciaFil: Straile, Dietmar. University of Konstanz; AlemaniaFil: Thackeray, Stephen J.. Lancaster Environment Centre; Reino UnidoFil: Thiery, Wim. Vrije Unviversiteit Brussel; Bélgica. Institute for Atmospheric and Climate Science; SuizaFil: Urrutia Cordero, Pablo. Uppsala University; SueciaFil: Venail, Patrick. Universidad de Ginebra; SuizaFil: Verburg, Piet. 8National Institute of Water and Atmospheric Research; Nueva ZelandaFil: Williamson, Tanner J.. Miami University; Estados UnidosFil: Wilson, Harriet L.. Dundalk Institute of Technology; IrlandaFil: Zohary, Tamar. Israel Oceanographic & Limnological Research; IsraelGLEON 20: All Hands' MeetingRottnest IslandAustraliaUniversity of Western AustraliaUniversity of AdelaideGlobal Lake Ecological Observatory Networ

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

[Letter from Emily Rimmer Vasquez to John J. Herrera - November 23, 1954]

Letter from Emily Rimmer Vasquez, Junior Director to John J. Herrera where she addresses Herrera as Johnnie and inquires about Herrera's job duties as National Organizer for LULAC. Vasquez also mentions Albert Armendariz's position as an organizer and questions Herrera about it