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Abstract Natural systems exhibit high spatial variability across multiple scales. Models that can capture ecosystem dynamics across space and time by explicitly incorporating major biological mechanisms are crucial, both for management and for ecological insight. In the case of coral reef systems, much focus has been on modelling variability between reefs, despite substantial variability also existing within reefs. We developed C~scape, a coral metacommunity modelling framework that integrates the demography of corals with population-level responses to physical and environmental spatial layers, to facilitate spatiotemporal predictions of coral dynamics across reefs at fine (100s of metres to kilometres) scales. We used satellite-derived habitat maps to modulate community growth spatially, as a proxy for the many interacting physical and environmental factors—e.g., depth, light, wave exposure, temperature, and substrate type—that drive within-reef variability in coral demography. With a case study from the Great Barrier Reef, we demonstrate the model’s capability for producing hindcasts of coral cover dynamics and show that overlooking within-reef variability may lead to misleading conclusions about metacommunity dynamics. C~scape provides a valuable framework for exploring a range of management and restoration scenarios at relevant spatial scales.

BackgroundAcute respiratory distress syndrome (ARDS) is highly heterogeneous, both in its clinical presentation and in the patient’s physiological responses to changes in mechanical ventilator settings, such as PEEP. This study investigates the clinical efficacy of a physiological model-based ventilatory decision support system (DSS) to personalize ventilator therapy in ARDS patients.MethodsThis international, multicenter, randomized, open-label study enrolled patients with ARDS during the COVID-19 pandemic. Patients were randomized to either receive active advice from the DSS (intervention) or standard care without DSS advice (control). The primary outcome was to detect a reduction in average driving pressure between groups. Secondary outcomes included several clinically relevant measures of respiratory physiology, ventilator-free days, time from control mode to support mode, number of changes in ventilator settings per day, percentage of time in control and support mode ventilation, ventilation- and device-related adverse events, and the number of times the advice was followed.ResultsA total of 95 patients were randomized in this study. The DSS showed no significant effect on average driving pressure between groups. However, patients in the intervention arm had a statistically improved oxygenation index when in support mode ventilation (−1.41, 95% CI: −2.76, −0.08; p = 0.0370). Additionally, the ventilatory ratio significantly improved in the intervention arm for patients in control mode ventilation (−0.63, 95% CI: −1.08, −0.17, p = 0.0068). The application of the DSS led to a significantly increased number of ventilator changes for pressure settings and respiratory frequency.ConclusionThe use of a physiological model-based decision support system for providing advice on mechanical ventilation in patients with COVID-19 and non-COVID-19 ARDS showed no significant difference in driving pressure as a primary outcome measure. However, the application of approximately 60% of the DSS advice led to improvements in the patient’s physiological state.Clinical trial registrationclinicaltrials.gov, NCT04115709.

Understanding how small molecules bind to specific protein complexes in living cells is critical to understanding their mechanism-of-action. Unbiased chemical biology strategies for direct readout of protein interactome remodelling by small molecules would provide advantages over target-focused approaches, including the ability to detect previously unknown ligand targets and complexes. However, there are few current methods for unbiased profiling of small molecule interactomes. To address this, we envisioned a technology that would combine the sensitivity and live-cell compatibility of proximity labelling coupled to mass spectrometry, with the specificity and unbiased nature of chemoproteomics. In this manuscript, we describe the BioTAC system, a small-molecule guided proximity labelling platform that can rapidly identify both direct and complexed small molecule binding proteins. We benchmark the system against µMap, photoaffinity labelling, affinity purification coupled to mass spectrometry and proximity labelling coupled to mass spectrometry datasets. We also apply the BioTAC system to provide interactome maps of Trametinib and analogues. The BioTAC system overcomes a limitation of current approaches and supports identification of both inhibitor bound and molecular glue bound complexes.

The mechanisms underlying the complications of mild traumatic brain injury, including post-concussion syndrome, post-impact catastrophic death, and delayed neurodegeneration remain poorly understood. This limited pathophysiological understanding has hindered the development of diagnostic and prognostic biomarkers and has prevented the advancement of treatments for the sequelae of mild traumatic brain injury. We aimed to characterize the early electrophysiological and neurovascular alterations following repetitive mild traumatic brain injury and sought to identify new targets for the diagnosis and treatment of individuals at risk of severe post-impact complications. We combined behavioural, electrophysiological, molecular, and neuroimaging techniques in a rodent model of repetitive mild traumatic brain injury. In humans, we used dynamic contrast-enhanced MRI to quantify blood-brain barrier dysfunction after exposure to sport-related concussive mild traumatic brain injury. Rats could clearly be classified based on their susceptibility to neurological complications, including life-threatening outcomes, following repetitive injury. Susceptible animals showed greater neurological complications and had higher levels of blood-brain barrier dysfunction, transforming growth factor β (TGFβ) signalling, and neuroinflammation compared to resilient animals. Cortical spreading depolarizations were the most common electrophysiological events immediately following mild traumatic brain injury and were associated with longer recovery from impact. Triggering cortical spreading depolarizations in mild traumatic brain injured rats (but not in controls) induced blood-brain barrier dysfunction. Treatment with a selective TGFβ receptor inhibitor prevented blood-brain barrier opening and reduced injury complications. Consistent with the rodent model, blood-brain barrier dysfunction was found in a subset of human athletes following concussive mild traumatic brain injury. We provide evidence that cortical spreading depolarization, blood-brain barrier dysfunction, and pro-inflammatory TGFβ signalling are associated with severe, potentially life-threatening outcomes following repetitive mild traumatic brain injury. Diagnostic-coupled targeting of TGFβ signalling may be a novel strategy in treating mild traumatic brain injury.

Abstract Understanding how small molecules bind to specific protein complexes in living cells is critical to understanding their mechanism-of-action. Unbiased chemical biology strategies for direct readout of protein interactome remodelling by small molecules would provide advantages over target-focused approaches, including the ability to detect previously unknown ligand targets and complexes. However, there are few current methods for unbiased profiling of small molecule interactomes. To address this, we envisioned a technology that would combine the sensitivity and live-cell compatibility of proximity labelling coupled to mass spectrometry, with the specificity and unbiased nature of chemoproteomics. In this manuscript, we describe the BioTAC system, a small-molecule guided proximity labelling platform that can rapidly identify both direct and complexed small molecule binding proteins. We benchmark the system against µMap, photoaffinity labelling, affinity purification coupled to mass spectrometry and proximity labelling coupled to mass spectrometry datasets. We also apply the BioTAC system to provide interactome maps of Trametinib and analogues. The BioTAC system overcomes a limitation of current approaches and supports identification of both inhibitor bound and molecular glue bound complexes.

The proportional cover of rubble on reefs is predicted to increase as disturbances increase in intensity and frequency. Unstable rubble can kill coral recruits and impair binding processes that transform rubble into a stable substrate for coral recruitment. A clearer understanding of the mechanisms of inhibited coral recovery on rubble requires characterisation of the hydrodynamic conditions that trigger rubble mobilisation. Here, we investigated rubble mobilisation under regular wave conditions in a wave flume and irregular wave conditions in situ on a coral reef in the Maldives. We examined how changes in near-bed wave orbital velocity influenced the likelihood of rubble motion (e.g. rocking) and transport (by walking, sliding or flipping). Rubble mobilisation was considered as a function of rubble length, branchiness (branched vs. unbranched) and underlying substrate (rubble vs. sand). The effect of near-bed wave orbital velocity on rubble mobilisation was comparable between flume and reef observations. As near-bed wave orbital velocity increased, rubble was more likely to rock, be transported and travel greater distances. Averaged across length, branchiness and substrate, loose rubble had a 50 % chance of transport when near-bed wave orbital velocities reached 0.30 m s−1 in both the wave flume and on the reef. However, small and/or unbranched rubble pieces were generally mobilised more and at lower velocities than larger, branched rubble. Rubble also travelled further distances per day (∼2 cm) on substrates composed of sand than rubble. Importantly, if rubble was interlocked, it was very unlikely to move (< 7 % chance) even at the highest velocity tested (0.4 m s−1). Furthermore, the probability of rubble transport declined over 3 d deployments in the field, suggesting rubble had snagged or settled into more hydrodynamically stable positions within the first days of deployment. We expect that snagged or settled rubble is transported more commonly in locations with higher-energy events and more variable wave environments. At our field site in the Maldives, we expect recovery windows for binding (when rubble is stable) to predominantly occur during the calmer north-eastern monsoon when wave energy impacting the atoll is less and wave heights are smaller. Our results show that rubble beds comprised of small rubble pieces and/or pieces with fewer branches are more likely to have shorter windows of recovery (stability) between mobilisation events, and thus be good candidates for rubble stabilisation interventions to enhance coral recruitment and binding.

People with acquired apraxia of speech (AOS) and aphasia commonly experience long-term communication disability without support for their ongoing recovery or self-management. Little is known about their lived experience of metalinguistic abilities and capacity to harness them for self-management of speech production. The author, a speech and language therapist (SLT), revisited her previous qualitative study after her own more recent lived experience of recovering from mild aphasia. Participant perspectives were explored from a longitudinal case series (eleven people with confirmed AOS and aphasia discharged from SLT), with full ethical approval. The anonymized data comprised detailed transcripts from videoed semi-structured interviews, participant assessments, field notes and reflections, member checking, and reflexivity. The original systematic thematic analysis of these data in NVivo software was re-interrogated by the author, deriving three overarching themes: Metalinguistic awareness of spoken communication breakdown, Self-management, and Therapeutic assessment. The participants conveyed the nature, occurrence, context, mechanism, and purpose underlying errors in spoken communication (themes of What, When, Where, How and Why). They generated compensatory strategies, elucidated via subthemes with quotations, verified contemporaneously by an original participant volunteer. The findings support the value of metalinguistic co-construction during in-depth assessments of communication disability, offering fresh avenues for long-term self-management in aphasia and AOS.

Abstract Recurrent mass bleaching events threaten the future of coral reefs. To persist under climate change, corals will need to endure progressively more intense and frequent marine heatwaves, yet it remains unknown whether their thermal tolerance can keep pace with warming. Here, we reveal an emergent increase in the thermal tolerance of coral assemblages at a rate of 0.1 °C/decade for a remote Pacific coral reef system. This led to less severe bleaching impacts than would have been predicted otherwise, indicating adaptation, acclimatisation or shifts in community structure. Using future climate projections, we show that if thermal tolerance continues to rise over the coming century at the most-likely historic rate, substantial reductions in bleaching trajectories are possible. High-frequency bleaching can be fully mitigated at some reefs under low-to-middle emissions scenarios, yet can only be delayed under high emissions scenarios. Collectively, our results indicate a potential ecological resilience to climate change, but still highlight the need for reducing carbon emissions in line with Paris Agreement commitments to preserve coral reefs.

Abstract Background Acute skeletal muscle wasting during critical illness is common and causes significant morbidity and functional limitation. Myofibre necrosis is a major histological finding but is often considered an unprogrammed by‐product of muscle inflammation. This study sought to evaluate if a form of programmed necrosis, necroptosis, is activated in skeletal muscle during critical illness. Methods A cohort of 28 patients from the MUSCLE‐UK study (ClinicalTrials.gov: NCT01106300) with serum and skeletal muscle biopsy samples were identified. Samples were available from ICU admission (T1) and between day 7–10 post admission (T2). Skeletal muscle was stratified by a histopathologist in the original study as necrotic (NEC, N = 14) or non‐necrotic (NONEC, N = 14) using haematoxylin and eosin staining. We used phosphorylated mixed‐lineage kinase domain‐like (pMLKL) protein (a key terminal effector protein) and receptor‐interacting protein kinase 3 (RIPK3) as markers of necroptosis activation using Western blotting and immunohistochemistry. Results We show that pMLKL expression is significantly higher in the NEC group [NEC: T2:T1 expression; 9.1 (IQR 3.9–22.3) vs. NONEC: T2:T1 expression; 0.9 (IQR 0.6–1.1), P = 0.003]. We then confirm this upregulation and describe co‐localization with receptor interacting protein kinase 3 (RIPK3) in skeletal muscle using immunohistochemistry. We show that both RIPK3 and pMLKL are present within intact myofibres at the intermediate timepoint day 3 without cellular infiltrate. At T2, pMLKL is also present in the interstitial space where there is infiltrate of CD68 positive immune cells. The observed necroptosis may originate from both internal and infiltrating sources. These findings were absent in samples from patients who did not exhibit histopathological features of necrosis. Conclusions We show that necroptosis machinery, RIPK3 and pMLKL, are associated with conventional histopathological features of myonecrosis in a critically ill cohort.

Abstract Background Pulmonary arterial hypertension (PAH) encompasses a group of diseases characterized by raised pulmonary vascular resistance, resulting from vascular remodelling and inflammation. Bromodomain and extra-terminal (BET) proteins are required for the expression of a subset of NF-κB-induced inflammatory genes which can be inhibited by the BET mimic JQ1+. We hypothesised that JQ+ would supress TNFα-driven inflammatory responses in human pulmonary vascular cells from PAH patients. Methods Immunohistochemical staining of human peripheral lung tissue (N = 14 PAH and N = 12 non-PAH) was performed for the BET proteins BRD2 and 4. Human pulmonary microvascular endothelial cells (HPMEC) and pulmonary artery smooth muscle cells (HPASMC) from PAH patients (N = 4) and non-PAH controls (N = 4) were stimulated with TNFα in presence or absence of JQ1+ or its inactive isomer JQ1–. IL-6 and -8 mRNA was measured by RT-qPCR and protein levels by ELISA. Chromatin immunoprecipitation analysis was performed using EZ-ChIP™ and NF-κB p65 activation determined using a TransAm kit. MTT assay was used to measure cell viability. Results Nuclear staining of BRD2 and BRD4 was significantly (p

Translational research needs to show value through impact on measures that matter to the public, including health and societal benefits. To this end, the Translational Science Benefits Model (TSBM) identified four categories of impact: Clinical, Community, Economic, and Policy. However, TSBM offers limited guidance on how these areas of impact relate to equity. Central to the structure of our Center for American Indian and Alaska Native Diabetes Translation Research are seven regional, independent Satellite Centers dedicated to community-engaged research. Drawing on our collective experience, we provide empirical evidence about how TSBM applies to equity-focused research that centers community partnerships and recognizes Indigenous knowledge. For this special issue – “Advancing Understanding and Use of Impact Measures in Implementation Science” – our objective is to describe and critically evaluate gaps in the fit of TSBM as an evaluation approach with sensitivity to health equity issues. Accordingly, we suggest refinements to the original TSBM Logic model to add: 1) community representation as an indicator of providing community partners “a seat at the table” across the research life cycle to generate solutions (innovations) that influence equity and to prioritize what to evaluate, and 2) assessments of the representativeness of the measured outcomes and benefits.

Captive and domestic animals are often required to engage in physical activity initiated or organised by humans, which may impact their body temperature, with consequences for their health and welfare. This is a particular concern for animals such as elephants that face thermoregulatory challenges because of their body size and physiology. Using infrared thermography, we measured changes in skin temperature associated with two types of physical activity in ten female Asian elephants (Elephas maximus) at an eco-tourism lodge in Nepal. Six elephants took part in an activity relatively unfamiliar to the elephants-a polo tournament-and four participated in more familiar ecotourism activities. We recorded skin temperatures for four body regions affected by the activities, as well as an average skin temperature. Temperature change was used as the response variable in the analysis and calculated as the difference in elephant temperature before and after activity. We found no significant differences in temperature change between the elephants in the polo-playing group and those from the non-polo playing group. However, for both groups, when comparing the average skin body temperature and several different body regions, we found significant differences in skin temperature change before and after activity. The ear pinna was the most impacted region and was significantly different to all other body regions. This result highlights the importance of this region in thermoregulation for elephants during physical activity. However, as we found no differences between the average body temperatures of the polo and non-polo playing groups, we suggest that thermoregulatory mechanisms can counteract the effects of both physical activities the elephants engaged in.

Corals are experiencing unprecedented decline from climate change-induced mass bleaching events. Dispersal not only contributes to coral reef persistence through demographic rescue but can also hinder or facilitate evolutionary adaptation. Locations of reefs that are likely to survive future warming therefore remain largely unknown, particularly within the context of both ecological and evolutionary processes across complex seascapes that differ in temperature range, strength of connectivity, network size, and other characteristics. Here, we used eco-evolutionary simulations to examine coral adaptation to warming across reef networks in the Caribbean, the Southwest Pacific, and the Coral Triangle. We assessed the factors associated with coral persistence in multiple reef systems to understand which results are general and which are sensitive to particular geographic contexts. We found that evolution can be critical in preventing extinction and facilitating the long-term recovery of coral communities in all regions. Furthermore, the strength of immigration to a reef (destination strength) and current sea surface temperature robustly predicted reef persistence across all reef networks and across temperature projections. However, we found higher initial coral cover, slower recovery, and more evolutionary lag in the Coral Triangle, which has a greater number of reefs and more larval settlement than the other regions. We also found the lowest projected future coral cover in the Caribbean. These findings suggest that coral reef persistence depends on ecology, evolution, and habitat network characteristics, and that, under an emissions stabilization scenario (RCP 4.5), recovery may be possible over multiple centuries.

Global environmental change is challenging species with novel conditions, such that demographic and evolutionary trajectories of populations are often shaped by the exchange of organisms and alleles across landscapes. Current ecological theory predicts that random networks with dispersal shortcuts connecting distant sites can promote persistence when there is no capacity for evolution. Here, we show with an eco-evolutionary model that dispersal shortcuts across environmental gradients instead hinder persistence for populations that can evolve because long-distance migrants bring extreme trait values that are often maladaptive, short-circuiting the adaptive response of populations to directional change. Our results demonstrate that incorporating evolution and environmental heterogeneity fundamentally alters theoretical predictions regarding persistence in ecological networks.

Abstract As marine species adapt to climate change, their heat tolerance will likely be under strong selection. Yet trade-offs between heat tolerance and other life history traits could compromise natural adaptation or assisted evolution. This is particularly important for ecosystem engineers, such as reef-building corals, which support biodiversity yet are vulnerable to heatwave-induced mass bleaching and mortality. Here, we exposed 70 colonies of the reef-building coral Acropora digitifera to a long-term marine heatwave emulation experiment. We tested for trade-offs between heat tolerance and three traits measured from the colonies in situ – colony growth, fecundity, and symbiont community composition. Despite observing remarkable within-population variability in heat tolerance, all colonies were dominated by Cladocopium C40 symbionts. We found no evidence for trade-offs between heat tolerance and fecundity or growth. Contrary to expectations, positive associations emerged with growth, such that faster-growing colonies tended to bleach and die at higher levels of heat stress. Collectively, our results suggest that these corals exist on an energetic continuum where some high-performing individuals excel across multiple traits. Within populations, trade-offs between heat tolerance and growth or fecundity may not be major barriers to natural adaptation or the success of assisted evolution interventions.

While urban areas may not seem conducive to human-wildlife interactions (HWI), rapid land use transformations can result in frequent encounters with wildlife in the context of changing habitats, as well as encounters with species that thrive in urban settings. In Asia, the processes of rapid land-use change can bring into sharp relief the juxtaposition of biodiversity hotspots with urban space. This provides an interesting context to study human-wildlife interactions, and also gives considerable scope for input into sustainable urban design worldwide. We conducted a structured review of published literature on HWI across urban southern and eastern Asia. Within the extracted literature, we investigated the framing of the interactions, as HWI have been predominantly perceived through the lens of dualistic antagonism and framed by paradigms of conflict, however there is also substantial discourse emphasizing interspecific coexistence. Invertebrates, mammals and birds occurred most commonly in the abstracts included in our review, with examples of conflict and coexistence common among all three taxonomic groups. Very few studies mentioned amphibians, reptiles and fish. Within each taxonomic group excluding amphibians, at least 50 % of interactions with humans were framed as conflicts. Humans were presented as causing conflict or negative impact on animals in the majority of studies on amphibians, birds, fish and insects, while mammals and lizards were more often considered to negatively impact humans. Our study illustrates the variety and complexity of human-wildlife interactions in Asia that need to be taken into account when planning sustainable urban designs.

Sustainable development (SD) policies targeting marine economic sectors, designed to alleviate poverty and conserve marine ecosystems, have proliferated in recent years. Many developing countries are providing poor fishing households with new fishing boats (fishing capital) that can be used further offshore as a means to improve incomes and relieve fishing pressure on nearshore fish stocks. These kinds of policies are a marine variant of traditional SD policies focused on agriculture. Here, we evaluate ex ante economic and environmental impacts of provisions of fishing and agricultural capital, with and without enforcement of fishing regulations that prohibit the use of larger vessels in nearshore habitats. Combining methods from development economics, natural resource economics, and marine ecology, we use a unique dataset and modeling framework to account for linkages between households, business sectors, markets, and local fish stocks. We show that the policies investing capital in local marine fisheries or agricultural sectors achieve income gains for targeted households, but knock-on effects lead to increased harvest of nearshore fish, making them unlikely to achieve conservation objectives in rural coastal economies. However, pairing an agriculture stimulus with increasing enforcement of existing fisheries' regulations may lead to a win-win situation. While marine-based policies could be an important tool to achieve two of the United Nations Sustainable Development Goals (alleviate poverty and protect vulnerable marine resources), their success is by no means assured and requires consideration of land and marine socioeconomic linkages inherent in rural economies.

Repetitive mild traumatic brain injury in American football players has garnered increasing public attention following reports of chronic traumatic encephalopathy, a progressive tauopathy. While the mechanisms underlying repetitive mild traumatic brain injury-induced neurodegeneration are unknown and antemortem diagnostic tests are not available, neuropathology studies suggest a pathogenic role for microvascular injury, specifically blood-brain barrier dysfunction. Thus, our main objective was to demonstrate the effectiveness of a modified dynamic contrast-enhanced MRI approach we have developed to detect impairments in brain microvascular function. To this end, we scanned 42 adult male amateur American football players and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. MRI scans were also performed in 51 patients with brain pathologies involving the blood-brain barrier, namely malignant brain tumours, ischaemic stroke and haemorrhagic traumatic contusion. Based on data from prolonged scans, we generated maps that visualized the permeability value for each brain voxel. Our permeability maps revealed an increase in slow blood-to-brain transport in a subset of amateur American football players, but not in sex- and age-matched controls. The increase in permeability was region specific (white matter, midbrain peduncles, red nucleus, temporal cortex) and correlated with changes in white matter, which were confirmed by diffusion tensor imaging. Additionally, increased permeability persisted for months, as seen in players who were scanned both on- and off-season. Examination of patients with brain pathologies revealed that slow tracer accumulation characterizes areas surrounding the core of injury, which frequently shows fast blood-to-brain transport. Next, we verified our method in two rodent models: rats and mice subjected to repeated mild closed-head impact injury, and rats with vascular injury inflicted by photothrombosis. In both models, slow blood-to-brain transport was observed, which correlated with neuropathological changes. Lastly, computational simulations and direct imaging of the transport of Evans blue-albumin complex in brains of rats subjected to recurrent seizures or focal cerebrovascular injury suggest that increased cellular transport underlies the observed slow blood-to-brain transport. Taken together, our findings suggest dynamic contrast-enhanced-MRI can be used to diagnose specific microvascular pathology after traumatic brain injury and other brain pathologies.

Mangrove forests protect communities from storms and support fisheries. Here, the authors show that the association with economic growth has shifted from negatively impacting mangroves to enabling mangrove expansion, and that community forestry is promoting mangrove expansion.

Abstract COPD is driven by exogenous and endogenous oxidative stress derived from inhaled cigarette smoke, air pollution and reactive oxygen species from dysregulated mitochondria in activated inflammatory cells within the airway and lung. This is compounded by the loss in antioxidant defences including FOXO and NRF2 and other antioxidant transcription factors together with various key enzymes that attenuate oxidant effects. Oxidative stress enhances inflammation; airway remodelling including fibrosis and emphysema; post-translational protein modifications leading to autoantibody generation; DNA damage and cellular senescence. Recent studies using various omics technologies in the airways, lungs and blood of COPD patients has emphasised the importance of oxidative stress, particularly that derived from dysfunctional mitochondria in COPD and its role in immunity, inflammation, mucosal barrier function and infection. Therapeutic interventions targeting oxidative stress should overcome the deleterious pathologic effects of COPD if targeted to the lung. We require novel, more efficacious antioxidant COPD treatments among which mitochondria-targeted antioxidants and Nrf2 activators are promising.

Abstract Crown‐of‐thorns starfish (CoTS) naturally occur on coral reefs throughout the Indo‐Pacific region. On Australia's Great Barrier Reef (GBR), outbreaks of CoTS populations are responsible for ecologically significant losses of corals, and while they have been documented for decades, they now undermine coral recovery from multiple stressors, especially anthropogenic warming. Culling interventions are currently the best approach to control CoTS outbreaks on the GBR, but assessing control effectiveness under multiple stressors is complicated. Using an ensemble of two reef community models simulating the temporal and spatial dynamics of CoTS and corals under future climate scenarios, we evaluate the present‐day and future effectiveness of the current implementation of the GBR CoTS Control Program. Specifically, we determine the culling effort needed (i.e., number of vessels) to achieve the maximum ecological benefits as predicted by the models under possible warming futures. Benefits were measured by comparing projections of coral cover and CoTS densities under scenarios of increasing control effort and baseline scenarios where no control was simulated. Projections of present‐day control efforts (five vessels) show that the number of individual reefs subject to CoTS outbreaks is reduced by 50%–65% annually, yielding a benefit of 5%–7% of healthy GBR coral area per decade, equivalent to gaining 104–150 km2 of live corals by 2035. A threefold increase in current control efforts is sufficient to reach more than 80% of the maximum coral benefits predicted by each model, but the future amount of effort required to control CoTS effectively depends on the intensity of warming and the early detection of CoTS outbreaks. While culling CoTS across the entire GBR is unfeasible, we provide a framework for maximizing ecosystem‐wide benefits of CoTS control and guide management decisions on the required culling effort needed to reduce CoTS outbreaks to levels that may ensure coral persistence in the face of future climate change impacts.

We estimated the particle number distributions (PNDs), particle number concentrations (PNCs), physicochemical characteristics, meteorological effects, and respiratory deposition doses (RDD) in the human respiratory tract for three different particle modes: nucleation (N6–30), accumulation (N30–300), and coarse (N300–10,000) modes. This study was conducted in three different microenvironments (MEs) in London (indoor, IN; traffic intersection, TI; park, PK) measuring particles in the range of 6 nm–10,000 nm using an electrical low-pressure impactor (ELPI+). Mean PNCs were 1.68 ± 1.03 × 104 #cm−3, 7.00 ± 18.96 × 104 #cm−3, and 0.76 ± 0.95 × 104 #cm−3 at IN, TI, and PK, respectively. The PNDs were high for nucleation-mode particles at the TI site, especially during peak traffic hours. Wind speeds ranging from 0 to 6 ms−1 exhibit higher PNCs for nucleation- and accumulation-mode particles at TI and PK sites. Physicochemical characterisation shows trace metals, including Fe, O, and inorganic elements, that were embedded in a matrix of organic material in some samples. Alveolar RDD was higher for the nucleation and accumulation modes than the coarse-mode particles. The chemical signatures from the physicochemical characterisation indicate the varied sources at different MEs. These findings enhance our understanding of the different particle profiles at each ME and should help devise ways of reducing personal exposure at each ME.

Abstract Background The acute respiratory distress syndrome (ARDS) occurs in response to a variety of insults, and mechanical ventilation is life-saving in this setting, but ventilator-induced lung injury can also contribute to the morbidity and mortality in the condition. The Beacon Caresystem is a model-based bedside decision support system using mathematical models tuned to the individual patient’s physiology to advise on appropriate ventilator settings. Personalised approaches using individual patient description may be particularly advantageous in complex patients, including those who are difficult to mechanically ventilate and wean, in particular ARDS. Methods We will conduct a multi-centre international randomised, controlled, allocation concealed, open, pragmatic clinical trial to compare mechanical ventilation in ARDS patients following application of the Beacon Caresystem to that of standard routine care to investigate whether use of the system results in a reduction in driving pressure across all severities and phases of ARDS. Discussion Despite 20 years of clinical trial data showing significant improvements in ARDS mortality through mitigation of ventilator-induced lung injury, there remains a gap in its personalised application at the bedside. Importantly, the protective effects of higher positive end-expiratory pressure (PEEP) were noted only when there were associated decreases in driving pressure. Hence, the pressures set on the ventilator should be determined by the diseased lungs’ pressure-volume relationship which is often unknown or difficult to determine. Knowledge of extent of recruitable lung could improve the ventilator driving pressure. Hence, personalised management demands the application of mechanical ventilation according to the physiological state of the diseased lung at that time. Hence, there is significant rationale for the development of point-of-care clinical decision support systems which help personalise ventilatory strategy according to the current physiology. Furthermore, the potential for the application of the Beacon Caresystem to facilitate local and remote management of large numbers of ventilated patients (as seen during this COVID-19 pandemic) could change the outcome of mechanically ventilated patients during the course of this and future pandemics. Trial registration ClinicalTrials.gov identifier NCT04115709. Registered on 4 October 2019, version 4.0

Abstract Patterns of movement of marine species can reflect strategies of reproduction and dispersal, species' interactions, trophodynamics, and susceptibility to change, and thus critically inform how we manage populations and ecosystems. On coral reefs, the density and diversity of metazoan taxa are greatest in dead coral and rubble, which are suggested to fuel food webs from the bottom up. Yet, biomass and secondary productivity in rubble is predominantly available in some of the smallest individuals, limiting how accessible this energy is to higher trophic levels. We address the bioavailability of motile coral reef cryptofauna based on small‐scale patterns of emigration in rubble. We deployed modified RUbble Biodiversity Samplers (RUBS) and emergence traps in a shallow rubble patch at Heron Island, Great Barrier Reef, to detect community‐level differences in the directional influx of motile cryptofauna under five habitat accessibility regimes. The mean density (0.13–4.5 ind cm−3) and biomass (0.14–5.2 mg cm−3) of cryptofauna were high and varied depending on microhabitat accessibility. Emergent zooplankton represented a distinct community (dominated by the Appendicularia and Calanoida) with the lowest density and biomass, indicating constraints on nocturnal resource availability. Mean cryptofauna density and biomass were greatest when interstitial access within rubble was blocked, driven by the rapid proliferation of small harpacticoid copepods from the rubble surface, leading to trophic simplification. Individuals with high biomass (e.g., decapods, gobies, and echinoderms) were greatest when interstitial access within rubble was unrestricted. Treatments with a closed rubble surface did not differ from those completely open, suggesting that top‐down predation does not diminish rubble‐derived resources. Our results show that conspecific cues and species' interactions (e.g., competition and predation) within rubble are most critical in shaping ecological outcomes within the cryptobiome. These findings have implications for prey accessibility through trophic and community size structuring in rubble, which may become increasingly relevant as benthic reef complexity shifts in the Anthropocene.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast, the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Research on memory reconsolidation has relied heavily on the use of Pavlovian auditory cued-fear conditioning. Here, an auditory cue (CS) is paired with a footshock (US) and the CS is later able to evoke a freezing response when presented alone. Some treatments, when administered to conditioned subjects immediately following a CS-alone (memory reactivation) trial, can attenuate the freezing they display on subsequent CS-alone (test) trials, in the absence of the treatment. This reduction in conditioned freezing is usually taken as evidence that the treatment disrupts post-reactivation reconsolidation of the memory trace representing the pairing of CS and US. We suggest an alternative interpretation that may account, either in whole or in part, for the attenuated freezing. The standard reconsolidation protocol (SRP) for auditory fear-conditioning has a design feature that results in second-order conditioning of fear to the test context, as this context is paired with the fear-evoking CS on the reactivation trial. Since freezing during the CS on the test will reflect the compound influence of contextual-fear and cued-fear, a post-reactivation treatment might attenuate freezing on the test by disrupting consolidation of second-order contextual-fear conditioning, even if it has little or no effect on the stability of the original cued-fear memory. This experiment confirmed that rats tested according to the SRP, in which the reactivation and test trials occur in the same context, freeze more on the test trial than rats that receive the reactivation and test trials in different contexts. This confound could lead to false-positive evidence of disrupted reconsolidation if it is not avoided or minimized, which can be accomplished with a modified protocol.