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Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

The North Atlantic Climate System Integrated Study (ACSIS) was a large multidisciplinary research programme funded by the UK's Natural Environment Research Council (NERC). ACSIS ran from 2016 to 2022 and brought together around 80 scientists from seven leading UK-based environmental research institutes to deliver major advances in the understanding of North Atlantic climate variability and extremes. Here, we present an overview of the data generated by the ACSIS programme. The datasets described cover the North Atlantic Ocean, the atmosphere above it (including its composition), and Arctic sea ice. Atmospheric composition datasets include measurements from seven aircraft campaigns (45 flights in total, 0–10 km altitude range) in the northeastern Atlantic (∼ 15–55° N, ∼ 40° W–5° E) made at intervals of 6 months to 2 years between February 2017 and May 2022. The flights measured chemical species (including greenhouse gases; ozone precursors; and volatile organic compounds – VOCs) and aerosols (organic aerosol – OA; SO4; NH4; NO3; and non-sea salt chloride – nss-Cl) (https://doi.org/10.5285/6285564c34a246fc9ba5ce053d85e5e7, FAAM et al., 2024). Ground-based stations at the Cape Verde Atmospheric Observatory (CVAO), Penlee Point Atmospheric Observatory (PPAO), and Plymouth Marine Laboratory (PML) recorded ozone, ozone precursors, halocarbons, greenhouse gases (CO2 and methane), SO2, and photolysis rates (CVAO; http://catalogue.ceda.ac.uk/uuid/81693aad69409100b1b9a247b9ae75d5, National Centre for Atmospheric Science et al., 2010); O3 and CH4 (PPAO, https://catalogue.ceda.ac.uk/uuid/8f1ff8ea77534e08b03983685990a9b0 (Plymouth Marine Laboratory and Yang, 2017); and aerosols (PML, https://doi.org/10.5285/e74491c96ef24df29a9342a3d57b5939, Smyth, 2024), respectively. Complementary model simulations of atmospheric composition were performed with the UK Earth System Model (UKESM1) for the period from 1982 to 2020 using Coupled Model Intercomparison Project Phase 6 (CMIP6) historical forcing up to 2014 and Shared Socioeconomic Pathways (SSP) scenario SSP3-7.0 from 2015 to 2020. Model temperature and winds were relaxed towards ERA reanalysis. Monthly mean model data for ozone, NO, NO2, CO, methane, stratospheric ozone tracers, and 30 regionally emitted tracers are available for download (https://data.ceda.ac.uk/badc/acsis/UKESM1-hindcasts, Abraham, 2024). ACSIS also generated new ocean heat content diagnostics (https://doi.org/10/g6wm, https://doi.org/10/g8g2, Moat et al., 2021a–b) and gridded temperature and salinity based on objectively mapped Argo measurements (https://doi.org/10.5285/fe8e524d-7f04-41f3-e053-6c86abc04d51 King, 2023). An ensemble of atmosphere-forced global-ocean sea-ice simulations using the NEMO-CICE model was performed with horizontal resolutions of 1/4 and 1/12° covering the period from 1958 to 2020 using several different atmosphere-reanalysis-based surface forcing datasets, supplemented by additional global simulations and stand-alone sea-ice model simulations with advanced sea-ice physics using the CICE model (http://catalogue.ceda.ac.uk/uuid/770a885a8bc34d51ad71e87ef346d6a8, Megann et al., 2021e). Output is stored as monthly averages and includes 3D potential temperature, salinity, zonal velocity, meridional velocity, and vertical velocity; 2D sea-surface height, mixed-layer depth, surface heat, and freshwater fluxes; ice concentration and thickness; and a wide variety of other variables. In addition to the data presented here, we provide a very brief overview of several other datasets that were generated during ACSIS and have been described previously in the literature.

Music educators and clinicians from Ohio and across the country gather annually for the Ohio Music Education Association (OMEA) Professional Development Conference. Dr. Sarah J. Bartolome, Associate Professor of Music Education at Northwestern University, was the featured keynote speaker of the Graduate Research Forum in February 2024. In addition to her teaching and scholarship in the areas of participatory music making as social capital, world music pedagogy, gender expansive music education, and trauma-informed approaches in music education, Dr. Bartolome serves as the Co-Lead for the Music for Childhood Wellbeing Initiative, an interdisciplinary research effort sponsored by the Buffett Institute for Global Affairs at Northwestern University. In this research forum, Dr. Bartolome discussed the research design of the Music for Childhood Wellbeing Initiative, its progress thus far, and the interdisciplinary collaboration that has made it possible.

The interstellar object (ISO) population of the Milky Way is a product of its stars. However, what is in fact a complex structure in the solar neighborhood has traditionally in ISO studies been described as smoothly distributed. Using a debiased stellar population derived from the Gaia Data Release 3 stellar sample, we predict that the velocity distribution of ISOs is far more textured than a smooth Gaussian. The moving groups caused by Galactic resonances dominate the distribution. 1I/‘Oumuamua and 2I/Borisov have entirely normal places within these distributions; 1I is within the noncoeval moving group that includes the Matariki (Pleiades) cluster, and 2I within the Coma Berenices moving group. We show that for the composition of planetesimals formed beyond the ice line, these velocity structures also have a chemodynamic component. This variation will be visible on the sky. We predict that this richly textured distribution will be differentiable from smooth Gaussians in samples that are within the expected discovery capacity of the Vera C. Rubin Observatory. Solar neighborhood ISOs will be of all ages and come from a dynamic mix of many different populations of stars, reflecting their origins from all around the Galactic disk.

We report the detection of water vapor associated with main-belt comet 358P/PANSTARRS on UT 2024 January 8–9 using the NIRSPEC instrument on board JWST. We derive a water production rate of ${Q}_{{{\rm{H}}}_{2}{\rm{O}}}=(5.0\pm 0.2)\,\times {10}^{25}$ molecules s ^−1 , marking only the second direct detection of sublimation products of any kind from a main-belt comet, after 238P/Read. Similar to 238P, we find a remarkable absence of hypervolatile species, finding ${Q}_{{\mathrm{CO}}_{2}}\lt 7.6\times {10}^{22}$ molecules s ^−1 , corresponding to ${Q}_{{\mathrm{CO}}_{2}}/{Q}_{{{\rm{H}}}_{2}{\rm{O}}}\lt 0.2$ %. Upper limits on CH _3 OH and CO emission are also estimated. Photometry from ground-based observations shows that the dust coma brightened and faded slowly over ∼250 days in 2023–2024, consistent with photometric behavior observed in 2012–2013, but also indicates a ∼2.5× decline in the dust production rate between these two periods. Dynamical dust modeling shows that the coma’s morphology as imaged by JWST's NIRCam instrument on 2023 November 22 can be reproduced by asymmetric dust emission from a nucleus with a midrange obliquity ( ε ∼ 80°) with a steady-state mass-loss rate of ∼0.8 kg s ^−1 . Finally, we find similar Af ρ -to-gas ratios of ${\mathrm{log}}_{10}({Af}\rho /{Q}_{{{\rm{H}}}_{2}{\rm{O}}})=-24.8\pm 0.2$ for 358P and ${\mathrm{log}}_{10}({Af}\rho /{Q}_{{{\rm{H}}}_{2}{\rm{O}}})=-24.4\pm 0.2$ for 238P, suggesting that Af ρ could serve as an effective proxy for estimating water production rates in other active main-belt comets. The confirmation of water vapor outgassing in both main-belt comets observed by JWST to date reinforces the use of recurrent activity near perihelion as an indicator of sublimation-driven activity in active asteroids.

Abstract NLRP3 induces caspase-1-dependent pyroptotic cell death to drive inflammation. Aberrant activity of NLRP3 occurs in many human diseases. NLRP3 activation induces ASC polymerization into a single, micron-scale perinuclear punctum. Higher resolution imaging of this signaling platform is needed to understand how it induces pyroptosis. Here, we apply correlative cryo-light microscopy and cryo-electron tomography to visualize ASC/caspase-1 in NLRP3-activated cells. The puncta are composed of branched ASC filaments, with a tubular core formed by the pyrin domain. Ribosomes and Golgi-like or endosomal vesicles permeate the filament network, consistent with roles for these organelles in NLRP3 activation. Mitochondria are not associated with ASC but have outer-membrane discontinuities the same size as gasdermin D pores, consistent with our data showing gasdermin D associates with mitochondria and contributes to mitochondrial depolarization.

Abstract Faecal or biopsy samples are frequently used to analyse the gut microbiota, but issues remain with the provision and collection of such samples. Rectal swabs are widely-utilised in clinical practice and previous data demonstrate their potential role in microbiota analyses; however, studies to date have been heterogenous, and there are a particular lack of data concerning the utility of swabs for the analysis of the microbiota’s functionality and metabolome. We compared paired stool and rectal swab samples from healthy individuals to investigate whether rectal swabs are a reliable proxy for faecal sampling. There were no significant differences in key alpha and beta diversity measures between swab and faecal samples, and inter-subject variability was preserved. Additionally, no significant differences were demonstrated in abundance of major annotated phyla. Inferred gut functionality using Tax4Fun2 showed excellent correlation between the two sampling techniques (Pearson’s coefficient r = 0.9217, P

The photostationary state (PSS) equilibrium between NO and NO2 is reached within minutes in the atmosphere and can be described by the PSS parameter, φ. Deviations from expected values of φ have previously been used to infer missing oxidants in diverse locations, from highly polluted regions to the extremely clean conditions observed in the remote marine boundary layer (MBL), and have been interpreted as missing understanding of fundamental photochemistry. Here, contrary to these previous observations, we observe good agreement between PSS-derived NO2 ([NO2]PSS ext.), calculated from measured NO, O3, and jNO2 and photochemical box model predictions of peroxy radicals (RO2 and HO2), and observed NO2 ([NO2]Obs.) in extremely clean air containing low levels of CO ( ppbV) and VOCs (volatile organic compounds). However, in clean air containing small amounts of aged pollution (CO > 100 ppbV), we observed higher levels of NO2 than inferred from the PSS, with [NO2]Obs. / [NO2]PSS ext. of 1.12–1.68 (25th–75th percentile), implying underestimation of RO2 radicals by 18.5–104 pptV. Potential NO2 measurement artefacts have to be carefully considered when comparing PSS-derived NO2 to observed NO2, but we show that the NO2 artefact required to explain the deviation would have to be ∼ 4 times greater than the maximum calculated from known interferences. If the additional RO2 radicals inferred from the PSS convert NO to NO2 with a reaction rate equivalent to that of methyl peroxy radicals (CH3O2), then the calculated net ozone production rate (NOPR, ppbV h−1) including these additional oxidants is similar to the average change in O3 observed, within estimated uncertainties, once halogen oxide chemistry is accounted for. This implies that such additional peroxy radicals cannot be excluded as a missing oxidant in clean marine air containing aged pollution and that modelled RO2 concentrations are significantly underestimated under these conditions.

Rising but fluctuating oxygen levels in the Early Palaeozoic provide an environmental context for the radiation of early metazoans, but little is known about how mechanistically early animals satisfied their oxygen requirements. Here we propose that the countercurrent gaseous exchange, a highly efficient respiratory mechanism, was effective in the gills of the Late Ordovician trilobite Triarthrus eatoni. In order to test this, we use computational fluid dynamics to simulate water flow around its gills and show that water velocity decreased distinctly in front of and between the swollen ends, which first encountered the oxygen-charged water, and slowed continuously at the mid-central region, forming a buffer zone with a slight increase of the water volume. In T. eatoni respiratory surface area was maximized by extending filament height and gill shaft length. In comparison with the oxygen capacity of modern fish and crustaceans, a relatively low weight specific area in T. eatoni may indicate its low oxygen uptake, possibly related to a less active life mode. Exceptionally preserved respiratory structures in the Cambrian deuterostome Haikouella are also consistent with a model of countercurrent gaseous exchange, exemplifying the wide adoption of this strategy among early animals.

Fast radio bursts (FRBs) are transient radio events with millisecond-scale durations and debated origins. Collisions between planetesimals and neutron stars (NSs) have been proposed as a mechanism to produce FRBs; the planetesimal strength, size, and density determine the time duration and energy of the resulting event. One source of planetesimals is the population of interstellar objects (ISOs), free-floating objects expected to be extremely abundant in galaxies across the Universe as products of planetary formation. We explore using the ISO population as a reservoir of planetesimals for FRB production, finding that the expected ISO–NS collision rate is comparable with the observed FRB event rate. Using a model linking the properties of planetesimals and the FRBs they produce, we further show that observed FRB durations are consistent with the sizes of known ISOs, and the FRB energy distribution is consistent with the observed size distributions of solar system planetesimal populations. Finally, we argue that the rate of ISO–NS collisions must increase with cosmic time, matching the observed evolution of the FRB rate. Thus, ISO–NS collisions are a feasible mechanism for producing FRBs.

Some taxa occupy our imaginations as “living fossils” because they were known from the fossil record before being discovered alive today. Other taxa are considered “living fossils” because modern relatives bear a strong morphological resemblance to fossil relatives, or because they occupy a contracted geographic range or have less diversity now than in the past, or because they represent phylogenetic diversity that requires conservation. A characterizing feature of living fossils–and thus an implicit assumption of all criteria–is that the “living fossil” of interest is extant. However, the general research questions that “living fossils” inspire–Why do rates of evolution vary across organisms, across traits, and across time? Why do some clades decline in diversity over extended periods?–may be applied to any clade, including completely extinct clades. We propose that there is nothing special about “now” when it comes to pursuing these questions and that it is unnecessarily limiting to restrict research programs to clades for which an extant member meets some conception of the “living fossil” moniker. To this end, we investigate the extent to which Permian trilobites might resemble “living fossils,” albeit from the perspective of 253 million years ago, when the last trilobites were still alive. We do so by comparing the taxonomic diversity, geographic range, and morphological disparity of trilobites living in the Permian to earlier time periods. We find that Permian trilobites meet most definitions of living fossils, although our assessment of morphological change and character retention depend on taxonomic scale.

Anthropogenic secondary organic aerosol (ASOA), formed from anthropogenic emissions of organic compounds, constitutes a substantial fraction of the mass of submicron aerosol in populated areas around the world and contributes to poor air quality and premature mortality. However, the precursor sources of ASOA are poorly understood, and there are large uncertainties in the health benefits that might accrue from reducing anthropogenic organic emissions. We show that the production of ASOA in 11 urban areas on three continents is strongly correlated with the reactivity of specific anthropogenic volatile organic compounds. The differences in ASOA production across different cities can be explained by differences in the emissions of aromatics and intermediate- and semi-volatile organic compounds, indicating the importance of controlling these ASOA precursors. With an improved model representation of ASOA driven by the observations, we attribute 340 000 PM2.5-related premature deaths per year to ASOA, which is over an order of magnitude higher than prior studies. A sensitivity case with a more recently proposed model for attributing mortality to PM2.5 (the Global Exposure Mortality Model) results in up to 900 000 deaths. A limitation of this study is the extrapolation from cities with detailed studies and regions where detailed emission inventories are available to other regions where uncertainties in emissions are larger. In addition to further development of institutional air quality management infrastructure, comprehensive air quality campaigns in the countries in South and Central America, Africa, South Asia, and the Middle East are needed for further progress in this area.

Trilobites are organized in packages; the adult trilobite body plan is composed of a cephalon (head), thorax (midsection), and pygidium (tail). These packages, or modules, are composed of traits that evolve semi-independently such that change in one module does not necessarily beget change in another module. At the macroevolutionary level, this decoupling and relaxation of evolutionary constraints is thought to promote evolvability. Thus, it is thought that modularity facilitates rapid diversification in diverse evolutionary directions, the hallmark of an adaptive radiation, as evolutionary rates among modules can vary along phylogenetic branches. Trilobites provide an unmatched fossil record, due to their biomineralized exoskeleton, to examine the long-term relationship between macroevolutionary diversification and modularity. However, the lack of a phylogenetic framework for major trilobite groups hampers the study of macroevolutionary questions. For instance, the trilobite family Pterygometopidae diversified during the Middle and Late Ordovician in Baltica, Avalonia, Laurentia, and Siberia. This group traditionally comprises four subfamilies with strong biogeographic signal including Pterygometopinae, Chasmopinae, Eomonorachinae, and Monokainae. However, relationships between and within subfamilies remain unresolved. Further, relationships with other families in the suborder Phacopina, especially with Phacopidae, remain unclear. To even begin tackling the relationship between macroevolution and modularity, phylogenetic relationships must be resolved in this trilobite group. To do so, we constructed a comprehensive character matrix comprising >240 characters including discrete, meristic, and continuous characters. Analyses include taxa from all 36 genera assigned to Pterygometopidae and include Ordovician exemplars from the trilobite families Diaphanometopidae, Phacopidae, Dalmanitidae, and Acastidae. We ran Bayesian phylogenetic analyses to produce trees that would co-estimate topology and evolutionary rates using the birth-death model. Further, we quantified the 3D morphology of the trilobite head using high-density geometric morphometrics for exemplar taxa within Pterygometopidae to identify the structure and degree of modularity of the trilobite head in this group. Future work will assess evolutionary rates for the trilobite head and, importantly, evolutionary rates of individual modules over the Ordovician Radiation to determine an increase or decrease in modularity over this diversification event.

Abstract Anopheles mosquitoes transmit malaria, which affects one-fifth of the world population. A comprehensive understanding of mosquito behaviour is essential for the development of novel tools for vector control and surveillance. Despite abundant research on mosquito behaviour, little is known on the stimuli that drive malaria vectors during the landing phase of host-seeking. Using behavioural assays with a multimodal step approach we quantified both the individual and the combined effect of three host-associated stimuli in eliciting landing in Anopheles coluzzii females. We demonstrated that visual, olfactory and thermal sensory stimuli interact synergistically to increase the landing response. Furthermore, if considering only the final outcome (i.e. landing response), our insect model can bypass the absence of either a thermal or a visual stimulus, provided that at least one of these is presented simultaneously with the olfactory stimuli, suggesting that landing is the result of a flexible but accurate stimuli integration. These results have important implications for the development of mosquito control and surveillance tools.

Abstract Background Mosquito-borne diseases are a global health problem, causing hundreds of thousands of deaths per year. Pathogens are transmitted by mosquitoes feeding on the blood of an infected host and then feeding on a new host. Monitoring mosquito host-choice behaviour can help in many aspects of vector-borne disease control. Currently, it is possible to determine the host species and an individual human host from the blood meal of a mosquito by using genotyping to match the blood profile of local inhabitants. Epidemiological models generally assume that mosquito biting behaviour is random; however, numerous studies have shown that certain characteristics, e.g. genetic makeup and skin microbiota, make some individuals more attractive to mosquitoes than others. Analysing blood meals and illuminating host-choice behaviour will help re-evaluate and optimise disease transmission models. Methods We describe a new blood meal assay that identifies the sex of the person that a mosquito has bitten. The amelogenin locus (AMEL), a sex marker located on both X and Y chromosomes, was amplified by polymerase chain reaction in DNA extracted from blood-fed Aedes aegypti and Anopheles coluzzii. Results AMEL could be successfully amplified up to 24 h after a blood meal in 100% of An. coluzzii and 96.6% of Ae. aegypti, revealing the sex of humans that were fed on by individual mosquitoes. Conclusions The method described here, developed using mosquitoes fed on volunteers, can be applied to field-caught mosquitoes to determine the host species and the biological sex of human hosts on which they have blood fed. Two important vector species were tested successfully in our laboratory experiments, demonstrating the potential of this technique to improve epidemiological models of vector-borne diseases. This viable and low-cost approach has the capacity to improve our understanding of vector-borne disease transmission, specifically gender differences in exposure and attractiveness to mosquitoes. The data gathered from field studies using our method can be used to shape new transmission models and aid in the implementation of more effective and targeted vector control strategies by enabling a better understanding of the drivers of vector-host interactions.

While the entire Arctic Ocean is warming rapidly, the Barents Sea in particular is experiencing significant warming and sea ice retreat. An increase in ocean heat transport from the Atlantic is causing the Barents Sea to be transformed from a cold, salinity-stratified system into a warmer, less-stratified Atlantic-dominated climate regime. Productivity in the Barents Sea shelf is fuelled by waters of Atlantic origin (AW) which are ultimately exported to the Arctic Basin. The consequences of this current regime shift on the nutrient characteristics of the Barents Sea are poorly defined. Here we use the stable isotopic ratios of nitrate (δ15N-NO3, δ18O-NO3) to determine the uptake and modification of AW nutrients in the Barents Sea. In summer months, phytoplankton consume nitrate, surface waters become nitrate depleted, and particulate nitrogen (δ15N-PN) reflects the AW nitrate source. The ammonification of organic matter in shallow sediments resupplies N to the water column and replenishes the nitrate inventory for the following season. Low δ18O-NO3 in the northern Barents Sea reveals that the nitrate in lower-temperature Arctic waters is > 80 % regenerated through seasonal nitrification. During on-shelf nutrient uptake and regeneration, there is no significant change to δ15N-NO3 or N*, suggesting that benthic denitrification does not impart an isotopic imprint on pelagic nitrate. Our results demonstrate that the Barents Sea is distinct from other Arctic shelves where benthic denitrification enriches δ15N-NO3 and decreases N*. As nutrients are efficiently recycled in the Barents Sea and there is no significant loss of N through benthic denitrification, changes to Barents Sea productivity are unlikely to alter N availability on shelf or the magnitude of N advected to the central Arctic Basin. However, we suggest that the AW nutrient source ultimately determines Barents Sea productivity and that changes to AW delivery have the potential to alter Barents Sea primary production and subsequent nutrient supply to the central Arctic Ocean.

Abstract Hotspots constitute the major reservoir for residual malaria transmission, with higher malaria incidence than neighbouring areas, and therefore, have the potential to form the cornerstone for successful intervention strategies. Detection of malaria hotspots is hampered by their heterogenous spatial distribution, and the laborious nature and low sensitivity of the current methods used to assess transmission intensity. We adopt ecological theory underlying foraging in herbivorous insects to vector mosquito host seeking and modelling of fine-scale landscape features at the village level. The overall effect of environmental variables on the density of indoor mosquitoes, sporozoite infected mosquitoes, and malaria incidence, was determined using generalized linear models. Spatial analyses were used to identify hotspots for malaria incidence, as well as malaria vector density and associated sporozoite prevalence. We identify household occupancy and location as the main predictors of vector density, entomological inoculation rate and malaria incidence. We propose that the use of conventional vector control and malaria interventions, integrated with their intensified application targeting predicted hotspots, can be used to reduce malaria incidence in endemic and residual malaria settings.

Abstract Background The bacterium Bacillus thuringiensis serovar israelensis (Bti) is used in many countries as a biological larvicide to control dipteran insects of the suborder Nematocera, especially mosquitoes and black flies. Bti is generally accepted to be target-specific and efficient, with low potential for development of resistance among the target species. However, even though Bti may have minimal direct effects on non-target organisms, it might potentially be associated with knock-on effects on food webs and other ecosystem properties, including biodiversity and ecosystem functioning. Evidence from previous research is mixed, with some finding no evidence for indirect effects on biodiversity and ecosystem-level properties, but others indicating that such effects are possible. The fact that many studies have been conducted by organisations coordinating the control programs, and that many of those studies have been published outside peer reviewed scientific journals, highlights the challenges for decision makers and others to assess the results of the existing studies. In this protocol we outline how we aim to systematically and transparently synthesise all available evidence in a forthcoming systematic review. Methods We will use six bibliographic databases/platforms and the online search engines Google and Google Scholar in searches for literature. Searches will also be made on specialist websites. We will screen the search results for eligibility in stage one based on title and abstract, and in stage two based on the full text of the material. At stage one, after testing and clarifying the eligibility criteria, two reviewers will split and single screen the search results. At stage two the articles will be screened independently by two reviewers. We have developed a preliminary critical appraisal tool that will be used as basis for assessing study validity. Each study will be critically appraised independently by two reviewers. Disagreements will be reconciled through discussions seeking to reach consensus. It is unclear whether a quantitative synthesis based on meta-analysis will be feasible. A narrative synthesis will include descriptive statistics outlining the evidence base in terms of bibliographic information and study metadata. A narrative synthesis table in the form of an Excel spreadsheet will be provided.

Summary: Zoonotic pathogens, such as COVID-19, reside in animal hosts before jumping species to infect humans. The Carnivora, like mink, carry many zoonoses, yet how diversity in host immune genes across species affect pathogen carriage is poorly understood. Here, we describe a progressive evolutionary downregulation of pathogen-sensing inflammasome pathways in Carnivora. This includes the loss of nucleotide-oligomerization domain leucine-rich repeat receptors (NLRs), acquisition of a unique caspase-1/-4 effector fusion protein that processes gasdermin D pore formation without inducing rapid lytic cell death, and the formation of a caspase-8 containing inflammasome that inefficiently processes interleukin-1β. Inflammasomes regulate gut immunity, but the carnivorous diet has antimicrobial properties that could compensate for the loss of these immune pathways. We speculate that the consequences of systemic inflammasome downregulation, however, can impair host sensing of specific pathogens such that they can reside undetected in the Carnivora.

Background: Increasing evidence indicates a role for Epstein–Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment.Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy.Methods: We assessed participants 2 and 3 years after completion of T cell therapy.Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product.Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.

Interleukin-12 (IL-12) is a potent, pro-inflammatory type 1 cytokine that has long been studied as a potential immunotherapy for cancer. Unfortunately, IL-12's remarkable antitumor efficacy in preclinical models has yet to be replicated in humans. Early clinical trials in the mid-1990's showed that systemic delivery of IL-12 incurred dose-limiting toxicities. Nevertheless, IL-12's pleiotropic activity, i.e., its ability to engage multiple effector mechanisms and reverse tumor-induced immunosuppression, continues to entice cancer researchers. The development of strategies which maximize IL-12 delivery to the tumor microenvironment while minimizing systemic exposure are of increasing interest. Diverse IL-12 delivery systems, from immunocytokine fusions to polymeric nanoparticles, have demonstrated robust antitumor immunity with reduced adverse events in preclinical studies. Several localized IL-12 delivery approaches have recently reached the clinical stage with several more at the precipice of translation. Taken together, localized delivery systems are supporting an IL-12 renaissance which may finally allow this potent cytokine to fulfill its considerable clinical potential. This review begins with a brief historical account of cytokine monotherapies and describes how IL-12 went from promising new cure to ostracized black sheep following multiple on-study deaths. The bulk of this comprehensive review focuses on developments in diverse localized delivery strategies for IL-12-based cancer immunotherapies. Advantages and limitations of different delivery technologies are highlighted. Finally, perspectives on how IL-12-based immunotherapies may be utilized for widespread clinical application in the very near future are offered.

Time calibrated trees are challenging to estimate for many extinct groups of species due to the incompleteness of the rock and fossil records. Additionally, the precise age of a sample is typically not known as it may have occurred at any time during the time interval spanned by the rock layer. Bayesian phylogenetic approaches provide a coherent framework for incorporating multiple sources of evidence and uncertainty. In this study, we simulate datasets with characteristics typical of Palaeozoic marine invertebrates, in terms of character and taxon sampling. We use these datasets to examine the impact of different age handling methods on estimated topologies and divergence times obtained using the fossilized birth-death process. Our results reiterate the importance of modeling fossil age uncertainty, although we find that the relative impact of fossil age uncertainty depends on both fossil taxon sampling and character sampling. Sampling the fossil ages as part of the inference gives topology and divergence time estimates that are as good as those obtained by fixing ages to the truth, whereas fixing fossil ages to incorrect values results in higher error and lower coverage. The relative effect increases with increased fossil and character sampling. Modeling fossil age uncertainty is thus critical, as fixing incorrect fossil ages will negate the benefits of improved fossil and character sampling.

Abstract Previous work has found that people are drawn to explanations of psychological phenomena when these explanations contain neuroscience information, even when that information is irrelevant. This preference may be due to a general preference for reductive explanations; however, prior work has not investigated whether people indeed prefer such explanations or whether this preference varies by scientific discipline. The current study asked 82 participants to choose which methods would be most appropriate for investigating topics in six scientific fields. Participants generally preferred methods that either matched the field of investigation (e.g., biology for biology) or that came from the immediately more reductive field (e.g., chemistry for biology). Both of these patterns were especially evident for the pairing of psychology and neuroscience. Additionally, participants selected significantly more methods as being useful for explaining neuroscience phenomena. These results suggest that people’s sense of the relations among scientific fields are fairly well calibrated but display some general attraction to neuroscience.

Abstract Background Understanding the ecology of exophilic anophelines is a key step toward developing outdoor control strategies to complement existing indoor control tools against malaria vectors. This study was conducted to assess the movement pattern of exophilic Anopheles mosquitoes between blood meal sources and resting habitats, and the landscape factors dictating their resting habitat choice. Results Resting clay pots were placed at 5 m, 25 m, 50 m, 75 m and 100 m away from isolated focal houses, radiating from them in four directions. The locations of the clay pots represent heterogeneous land cover types at a relatively fine spatial scale in the landscape. The effect of the landscape characters on the number of both female and male anophelines caught was modelled using zero-inflated negative binomial regression with a log link function. A total of 420 Anopheles mosquitoes (353 females and 67 males) belonging to three species; Anopheles arabiensis, Anopheles pharoensis, and Anopheles tenebrosus were caught in the resting clay pots, with An. arabiensis being the dominant species. Canopy cover, distance from the house, and land cover type were the significant landscape characters influencing the aggregation of resting mosquitoes. Both the count and binary models showed that canopy cover was the strongest predictor variable on the counts and the presence of Anopheles mosquitoes in the clay pots. Female Anopheles were most frequently found resting in the pots placed in banana plantations, and at sampling points that were at the greater distances (75 m and 100 m) from the focal house. Conclusions This study showed that exophilic Anopheles mosquitoes tend to rest in shaded areas some distance away from human habitation. These findings are important when targeting mosquitoes outdoors, complementing the existing effort being made to control malaria vectors indoors.

The biological production of calcium carbonate (CaCO3), a process termed calcification, is a key term in the marine carbon cycle. A major planktonic group responsible for such pelagic CaCO3 production (CP) is the coccolithophores, single-celled haptophytes that inhabit the euphotic zone of the ocean. Satellite-based estimates of areal CP are limited to surface waters and open-ocean areas, with current algorithms utilising the unique optical properties of the cosmopolitan bloom-forming species Emiliania huxleyi, whereas little understanding of deep-water ecology, optical properties or environmental responses by species other than E. huxleyi is currently available to parameterise algorithms or models. To aid future areal estimations and validate future modelling efforts we have constructed a database of 2765 CP measurements, the majority of which were measured using 12 to 24 h incorporation of radioactive carbon (14C) into acid-labile inorganic carbon (CaCO3). We present data collated from over 30 studies covering the period from 1991 to 2015, sampling the Atlantic, Pacific, Indian, Arctic and Southern oceans. Globally, CP in surface waters ( −3 d−1 (with a geometric mean of 16.1 µmol C m−3 d−1). An integral value for the upper euphotic zone (herein surface to the depth of 1 % surface irradiance) ranged from −2 d−1 (geometric mean 1.19 mmol C m−2 d−1). The full database is available for download from PANGAEA at https://doi.org/10.1594/PANGAEA.888182.

We present a characterization of the chemical composition of the atmosphere of the Brazilian Amazon rainforest based on trace gas measurements carried out during the South AMerican Biomass Burning Analysis (SAMBBA) airborne experiment in September 2012. We analyzed the observations of primary biomass burning emission tracers, i.e., carbon monoxide (CO), nitrogen oxides (NOx), ozone (O3), isoprene, and its main oxidation products, methyl vinyl ketone (MVK), methacrolein (MACR), and isoprene hydroxy hydroperoxide (ISOPOOH). The focus of SAMBBA was primarily on biomass burning emissions, but there were also several flights in areas of the Amazon forest not directly affected by biomass burning, revealing a background with a signature of biomass burning in the chemical composition due to long-range transport of biomass burning tracers from both Africa and the eastern part of Amazonia. We used the [MVK + MACR + ISOPOOH] ∕ [isoprene] ratio and the hydroxyl radical (OH) indirect calculation to assess the oxidative capacity of the Amazon forest atmosphere. We compared the background regions (CO 3] ∕ [CO]), to evaluate the impact of biomass burning emissions on the oxidative capacity of the Amazon forest atmosphere. We observed that biomass burning emissions disturb the isoprene oxidation reactions, especially for fresh plumes ([MVK + MACR + ISOPOOH] ∕ [isoprene]  =   7) downwind. The oxidation of isoprene is higher in fresh smoke plumes at lower altitudes (∼ 500 m) than in aged smoke plumes, anticipating near the surface a complex chain of oxidation reactions which may be related to secondary organic aerosol (SOA) formation. We proposed a refinement of the OH calculation based on the sequential reaction model, which considers vertical and horizontal transport for both biomass burning regimes and background environment. Our approach for the [OH] estimation resulted in values on the same order of magnitude of a recent observation in the Amazon rainforest [OH] ≅ 106 (molecules cm−3). During the fresh plume regime, the vertical profile of [OH] and the [MVK + MACR + ISOPOOH] ∕ [isoprene] ratio showed evidence of an increase in the oxidizing power in the transition from planetary boundary layer to cloud layer (1000–1500 m). These high values of [OH] (1.5 × 106 molecules cm−3) and [MVK + MACR + ISOPOOH] ∕ [isoprene] (7.5) indicate a significant change above and inside the cloud decks due to cloud edge effects on photolysis rates, which have a major impact on OH production rates.

The Great Calcite Belt (GCB) of the Southern Ocean is a region of elevated summertime upper ocean calcite concentration derived from coccolithophores, despite the region being known for its diatom predominance. The overlap of two major phytoplankton groups, coccolithophores and diatoms, in the dynamic frontal systems characteristic of this region provides an ideal setting to study environmental influences on the distribution of different species within these taxonomic groups. Samples for phytoplankton enumeration were collected from the upper mixed layer (30 m) during two cruises, the first to the South Atlantic sector (January–February 2011; 60° W–15° E and 36–60° S) and the second in the South Indian sector (February–March 2012; 40–120° E and 36–60° S). The species composition of coccolithophores and diatoms was examined using scanning electron microscopy at 27 stations across the Subtropical, Polar, and Subantarctic fronts. The influence of environmental parameters, such as sea surface temperature (SST), salinity, carbonate chemistry (pH, partial pressure of CO2 (pCO2), alkalinity, dissolved inorganic carbon), macronutrients (nitrate + nitrite, phosphate, silicic acid, ammonia), and mixed layer average irradiance, on species composition across the GCB was assessed statistically. Nanophytoplankton (cells 2–20 µm) were the numerically abundant size group of biomineralizing phytoplankton across the GCB, with the coccolithophore Emiliania huxleyi and diatoms Fragilariopsis nana, F. pseudonana, and Pseudo-nitzschia spp. as the most numerically dominant and widely distributed. A combination of SST, macronutrient concentrations, and pCO2 provided the best statistical descriptors of the biogeographic variability in biomineralizing species composition between stations. Emiliania huxleyi occurred in silicic acid-depleted waters between the Subantarctic Front and the Polar Front, a favorable environment for this species after spring diatom blooms remove silicic acid. Multivariate statistics identified a combination of carbonate chemistry and macronutrients, covarying with temperature, as the dominant drivers of biomineralizing nanoplankton in the GCB sector of the Southern Ocean.

Age-related deficits in the immune system have been associated with an increased incidence of infections, autoimmune diseases, and cancer. Human B cell populations change quantitatively and qualitatively in the elderly. However, the function of human B-1 cells, which play critical anti-microbial and housekeeping roles, have not been studied in the older age population. In the present work, we analyzed how the frequency, function and repertoire of human peripheral blood B-1 cells (CD19+CD20+CD27+CD38low/intCD43+) change with age. Our results show that not only the percentage of B-1 cells but also their ability to spontaneously secrete IgM decreased with age. Further, expression levels of the transcription factors XBP-1 and Blimp-1 were significantly lower, while PAX-5, characteristic of non-secreting B cells, was significantly higher, in healthy donors over 65 years (old) as compared to healthy donors between 20 and 45 years (young). To further characterize the B-1 cell population in older individuals, we performed single cell sequencing analysis of IgM heavy chains from healthy young and old donors. We found reduced repertoire diversity of IgM antibodies in B-1 cells from older donors as well as differences in usage of certain VH and DH specific genes, as compared to younger. Overall, our results show impairment of the human B-1 cell population with advancing age, which might impact the quality of life and onset of disease within the elderly population.

Total peroxy nitrate ( ∑ PN) concentrations have been measured using a thermal dissociation laser-induced fluorescence (TD-LIF) instrument during the BORTAS campaign, which focused on the impact of boreal biomass burning (BB) emissions on air quality in the Northern Hemisphere. The strong correlation observed between the ∑ PN concentrations and those of carbon monoxide (CO), a well-known pyrogenic tracer, suggests the possible use of the ∑ PN concentrations as marker of the BB plumes. Two methods for the identification of BB plumes have been applied: (1) ∑ PN concentrations higher than 6 times the standard deviation above the background and (2) ∑ PN concentrations higher than the 99th percentile of the ∑ PNs measured during a background flight (B625); then we compared the percentage of BB plume selected using these methods with the percentage evaluated, applying the approaches usually used in literature. Moreover, adding the pressure threshold ( ∼ 750 hPa) as ancillary parameter to ∑ PNs, hydrogen cyanide (HCN) and CO, the BB plume identification is improved. A recurrent artificial neural network (ANN) model was adapted to simulate the concentrations of ∑ PNs and HCN, including nitrogen oxide (NO), acetonitrile (CH3CN), CO, ozone (O3) and atmospheric pressure as input parameters, to verify the specific role of these input data to better identify BB plumes.

Abstract Background In this study, we examined the association between American Society of Anesthesiologists Physical Status (ASA PS) designation and 48-h mortality for both elective and emergent procedures in a large contemporary dataset (patient encounters between 2009 and 2014) and compared this association with data from a landmark study published by Vacanti et al. in 1970. Methods Patient history, hospital characteristics, anesthetic approach, surgical procedure, efficiency and quality indicators, and patient outcomes were prospectively collected for 732,704 consecutive patient encounters between January 1, 2009, and December 31, 2014, at 233 anesthetizing locations across 19 facilities in two US states and stored in the Quantum™ Clinical Navigation System (QCNS) database. The outcome (death within 48 h of procedure) was tabulated against ASA PS designations separately for patients with and without “E” status labels. To maintain consistency with the historical cohort from the landmark study performed by Vacanti et al. on adult men at US naval hospitals in 1970, we then created a comparison cohort in the contemporary dataset that consisted of 242,103 adult male patients (with/without E designations) undergoing elective and emergent procedures. Differences in the relationship between ASA PS and 48-h mortality in the historical and contemporary cohorts were assessed for patients undergoing elective and emergent procedures. Results As reported nearly five decades ago, we found a significant trend toward increased mortality with increasing ASA PS for patients undergoing both elective and emergent procedures in a large contemporary cohort (p

The observations collected during the BOReal forest fires on Tropospheric oxidants over the Atlantic using Aircraft and Satellites (BORTAS) campaign in summer 2011 over Canada are analysed to study the impact of forest fire emissions on the formation of ozone (O3) and total peroxy nitrates ∑PNs, ∑ROONO2). The suite of measurements on board the BAe-146 aircraft, deployed in this campaign, allows us to calculate the production of O3 and of ∑PNs, a long-lived NOx reservoir whose concentration is supposed to be impacted by biomass burning emissions. In fire plumes, profiles of carbon monoxide (CO), which is a well-established tracer of pyrogenic emission, show concentration enhancements that are in strong correspondence with a significant increase of concentrations of ∑PNs, whereas minimal increase of the concentrations of O3 and NO2 is observed. The ∑PN and O3 productions have been calculated using the rate constants of the first- and second-order reactions of volatile organic compound (VOC) oxidation. The ∑PN and O3 productions have also been quantified by 0-D model simulation based on the Master Chemical Mechanism. Both methods show that in fire plumes the average production of ∑PNs and O3 are greater than in the background plumes, but the increase of ∑PN production is more pronounced than the O3 production. The average ∑PN production in fire plumes is from 7 to 12 times greater than in the background, whereas the average O3 production in fire plumes is from 2 to 5 times greater than in the background. These results suggest that, at least for boreal forest fires and for the measurements recorded during the BORTAS campaign, fire emissions impact both the oxidized NOy and O3, but (1 ∑PN production is amplified significantly more than O3 production and (2) in the forest fire plumes the ratio between the O3 production and the ∑PN production is lower than the ratio evaluated in the background air masses, thus confirming that the role played by the ∑PNs produced during biomass burning is significant in the O3 budget. The implication of these observations is that fire emissions in some cases, for example boreal forest fires and in the conditions reported here, may influence more long-lived precursors of O3 than short-lived pollutants, which in turn can be transported and eventually diluted in a wide area.