Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults.

BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).

An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study.

BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .

Leaf Shelters Facilitate the Colonisation of Arthropods and Enhance Microbial Diversity on Plants.

Shelter-building insects are important ecosystem engineers, playing critical roles in structuring arthropod communities. Nonetheless, the influence of leaf shelters and arthropods on plant-associated microbiota remains largely unexplored. Arthropods that visit or inhabit plants can contribute to the leaf microbial community, resulting in significant changes in plant-microbe interactions. By artificially constructing leaf shelters, we provide evidence that shelter-building insects influence not only the arthropod community structure but also impact the phyllosphere microbiota. Leaf shelters exhibited higher abundance and richness of arthropods, changing the associated arthropod community composition. These shelters also altered the composition and community structure of phyllosphere microbiota, promoting greater richness and diversity of bacteria at the phyllosphere. In leaf shelters, microbial diversity positively correlated with the richness and diversity of herbivores. These findings demonstrate the critical role of leaf shelters in structuring both arthropod and microbial communities through altered microhabitats and species interactions.

Predators control pests and increase yield across crop types and climates: a meta-analysis.

Pesticides have well-documented negative consequences to control crop pests, and natural predators are alternatives and can provide an ecosystem service as biological control agents. However, there remains considerable uncertainty regarding whether such biological control can be a widely applicable solution, especially given ongoing climatic variation and climate change. Here, we performed a meta-analysis focused on field studies with natural predators to explore broadly whether and how predators might control pests and in turn increase yield. We also contrasted across studies pest suppression by a single and multiple predators and how climate influence biological control. Predators reduced pest populations by 73% on average, and increased crop yield by 25% on average. Surprisingly, the impact of predators did not depend on whether there were many or a single predator species. Precipitation seasonality was a key climatic influence on biological control: as seasonality increased, the impact of predators on pest populations increased. Taken together, the positive contribution of predators in controlling pests and increasing yield, and the consistency of such responses in the face of precipitation variability, suggest that biocontrol has the potential to be an important part of pest management and increasing food supplies as the planet precipitation patterns become increasingly variable.

Habitat Diversity Mitigates the Impacts of Human Pressure on Stream Biodiversity.

Recent decades have witnessed substantial changes in freshwater biodiversity worldwide. Although research has shown that freshwater biodiversity can be shaped by changes in habitat diversity and human-induced pressure, the potentials for interaction between these drivers and freshwater biodiversity at large spatial extents remain unclear. To address these issues, we employed a spatially extensive multitrophic fish and insect database from 3323 stream sites across the United States, to investigate the ability of habitat diversity to modulate the effect of human pressure on the richness and abundance of fish and insects. We found evidence that high levels of habitat diversity were associated with increased richness and abundance of fish and insects (including whole-assemblage and individual trophic guilds). We also show that the effects of human pressure on the richness and abundance of fish and insects tend to become positive at high levels of habitat diversity. Where habitat diversity is low, human pressure strongly reduces insect richness and abundance, whereas these reductions are attenuated at high levels of habitat diversity. Structural equation modeling revealed that human pressure reduced habitat diversity, indirectly negatively affecting the richness and abundance of fish and insects. These findings illustrate that, in addition to promoting greater fish and insect biodiversity, habitat diversity may mitigate the deleterious effects of human pressures on these two stream assemblages. Overall, our study suggests that maintaining high levels of habitat diversity is a useful way to protect freshwater biodiversity from ongoing increases in human pressure. However, if human pressures continue to increase, this will reduce habitat diversity, further threatening stream assemblages.

Trophic cascades within and across ecosystems: The role of anti-predatory defences, predator type and detritus quality.

Species in one ecosystem can indirectly affect multiple biodiversity components and ecosystem functions of adjacent ecosystems. The magnitude of these cross-ecosystem effects depends on the attributes of the organisms involved in the interactions, including traits of the predator, prey and basal resource. However, it is unclear how predators with cross-ecosystem habitat interact with predators with single-ecosystem habitat to affect their shared ecosystem. Also, unknown is how such complex top-down effects may be mediated by the anti-predatory traits of prey and quality of the basal resource. We used the aquatic invertebrate food webs in tank bromeliads as a model system to investigate these questions. We manipulated the presence of a strictly aquatic predator (damselfly larvae) and a predator with both terrestrial and aquatic habitats (spider), and examined effects on survival of prey (detritivores grouped by anti-predator defence), detrital decomposition (of two plant species differing in litter quality), nitrogen flux and host plant growth. To evaluate the direct and indirect effects each predator type on multiple detritivore groups and ultimately on multiple ecosystem processes, we used piecewise structural equation models. For each response variable, we isolated the contribution of different detritivore groups to overall effects by comparing alternate model formulations. Alone, damselfly larvae and spiders each directly decreased survival of detritivores and caused multiple indirect negative effects on detritus decomposition, nutrient cycling and host plant growth. However, when predators co-occurred, the spider caused a negative non-consumptive effect on the damselfly larva, diminishing the net direct and indirect top-down effects on the aquatic detritivore community and ecosystem functioning. Both detritivore traits and detritus quality modulated the strength and mechanism of these trophic cascades. Predator interference was mediated by undefended or partially defended detritivores as detritivores with anti-predatory defences evaded consumption by damselfly larvae but not spiders. Predators and detritivores affected ecosystem decomposition and nutrient cycling only in the presence of high-quality detritus, as the low-quality detritus was consumed more by microbes than invertebrates. The complex responses of this system to predators from both recipient and adjacent ecosystems highlight the critical role of maintaining biodiversity components across multiple ecosystems.

As espécies em um ecossistema podem afetar indiretamente múltiplos componentes da biodiversidade e funções ecossistêmicas em ecossistemas adjacentes. A magnitude destes efeitos entre ecossistemas depende dos atributos dos organismos envolvidos nas interações, incluindo características do predador, da presa e do recurso basal. No entanto, não está claro como os predadores com habitat em múltiplos ecossistemas interagem com predadores de um ecossistema único, e como isso afeta o ecossistema partilhado entre eles. Além disso, não se sabe como esses efeitos complexos do tipo top­down podem ser mediados pelas características antipredatórias da presa e pela qualidade do recurso basal. Usamos as teias alimentares de invertebrados aquáticos de bromélias­tanque como um sistema modelo para investigar essas questões. Nós manipulamos a presença de um predador estritamente aquático (larvas de zigópteros) e um predador com habitats terrestre e aquático (aranha), e examinamos os efeitos na sobrevivência de presas (grupos de detritívoros com diferentes estratégias de defesa antipredatória), decomposição de detritos foliares (de duas espécies de plantas diferindo na qualidade foliar), fluxo de nitrogênio e crescimento da planta hospedeira. Para avaliar os efeitos diretos e indiretos de cada tipo de predador em múltiplos grupos de detritívoros e, finalmente, em múltiplos processos ecossistêmicos, utilizamos modelos de equações estruturais por partes (piecewiseSEM). Para cada variável resposta, isolamos a contribuição de diferentes grupos de detritívoros bem como seus efeitos globais, comparando modelos alternativos. Larvas de zigópteros e aranhas diminuíram diretamente a sobrevivência dos detritívoros e causaram múltiplos efeitos negativos indiretos na decomposição de detritos, na ciclagem de nutrientes e no crescimento da planta hospedeira. No entanto, quando os predadores coocorreram, a aranha causou um efeito negativo não consumível na larva de zigóptero, diminuindo os efeitos líquidos, diretos e indiretos, do tipo top­down na comunidade de detritívoros aquáticos e no funcionamento do ecossistema. Tanto os atributos antipredatórios dos detritívoros quanto a qualidade dos detritos modularam a força e o mecanismo dessas cascatas tróficas. A interferência do predador foi mediada por detritívoros indefesos ou com defesa parcial. Entretanto, os detritívoros com defesas antipredatórias escaparam do consumo por larvas de zigópteros, mas não por aranhas. Predadores e detritívoros afetaram a decomposição do ecossistema e a ciclagem de nutrientes apenas na presença de detritos de alta qualidade, uma vez que os detritos de baixa qualidade foram consumidos mais por micróbios do que por invertebrados. As respostas complexas deste sistema aos predadores tanto de ecossistemas receptores quanto adjacentes destacam o papel crítico da manutenção dos componentes da biodiversidade em múltiplos ecossistemas.

Tropical and temperate differences in the trophic structure and aquatic prey use of riparian predators.

The influence of aquatic resource-inputs on terrestrial communities is poorly understood, particularly in the tropics. We used stable isotope analysis of carbon and nitrogen to trace aquatic prey use and quantify the impact on trophic structure in 240 riparian arthropod communities in tropical and temperate forests. Riparian predators consumed more aquatic prey and were more trophically diverse in the tropics than temperate regions, indicating tropical riparian communities are both more reliant on and impacted by aquatic resources than temperate communities. This suggests they are more vulnerable to disruption of aquatic-terrestrial linkages. Although aquatic resource use declined strongly with distance from water, we observed no correlated change in trophic structure, suggesting trophic flexibility to changing resource availability within riparian predator communities in both tropical and temperate regions. Our findings highlight the importance of aquatic resources for riparian communities, especially in the tropics, but suggest distance from water is less important than resource diversity in maintaining terrestrial trophic structure.

Human land-uses homogenize stream assemblages and reduce animal biomass production.

Human land-use change is a major threat to natural ecosystems worldwide. Nonetheless, the effects of human land-uses on the structure of plant and animal assemblages and their functional characteristics need to be better understood. Furthermore, the pathways by which human land uses affect ecosystem functions, such as biomass production, still need to be clarified. We compiled a unique dataset of fish, arthropod and macrophyte assemblages from 61 stream ecosystems in two Neotropical biomes: Amazonian rainforest and Uruguayan grasslands. We then tested how the cover of agriculture, pasture, urbanization and afforestation affected the taxonomic richness and functional diversity of those three species assemblages, and the consequences of these effects for animal biomass production. Single trait categories and functional diversity were evaluated, combining recruitment and life-history, resource and habitat-use, and body size. The effects of intensive human land-uses on taxonomic and functional diversities were as strong as other drivers known to affect biodiversity, such as local climate and environmental factors. In both biomes, the taxonomic richness and functional diversity of animal and macrophyte assemblages decreased with increasing cover of agriculture, pasture, and urbanization. Human land-uses were associated with functional homogenization of both animal and macrophyte assemblages. Human land-uses reduced animal biomass through direct and indirect pathways mediated by declines in taxonomic and functional diversities. Our findings indicate that converting natural ecosystems to supply human demands results in species loss and trait homogenization across multiple biotic assemblages, ultimately reducing animal biomass production in streams.

The role of pets in SARS-CoV-2 transmission: an exploratory analysis.

PURPOSE: There is evidence that humans can transmit SARS-CoV-2 to cats and dogs. However, there is no evidence that they can transmit it back to humans or play any role in SARS-CoV-2 transmission. Here, we present an exploratory analysis on that matter. METHODS: We conducted a case-control study with participants with flu-like symptoms seeking care at a primary healthcare unit to be tested for COVID-19. They were asked if they owned pet cats and/or dogs in their residences, and this variable was evaluated as exposure. RESULTS: The odds ratio of "having dogs and/or cats in the residence" was 1.29 (95% CI 1.08-1.54) of "having only dogs and no cats" was 1.26 (1.05-1.52), and "no dogs and only cats" was 1.29 (0.95-1.75). CONCLUSION: Having a cat/dog in the house can affect the risk of infection by SARS-CoV-2.

Decomposing the Intraurban Malnutrition Gap Between Poor and Non-poor Children in Colombia : Decomposing the Intraurban Malnutrition Gap Between Poor and Non-poor Children in Colombia.

In Colombia, although it can be said that, on average children living in urban areas have better quality of life than their rural peers, it is also true that within cities, there are high levels of socioeconomic inequality. Our objective is to identify the contribution of the factors that explain the gap in stunting and excess weight between poor and non-poor children under 5 years of age in urban areas of Colombia. We use data from the 2015 National Nutritional Status Survey, and two nonlinear decomposition techniques based on the classical decomposition method developed by Blinder-Oaxaca. With a sample of 6877 observations, the results show that the intraurban gap of stunting between poor and non-poor children in urban areas is 4.8 percentage points. Its main determinants are the mother's educational level (46.5%), affiliation to the health system by the mother (19.4%), and assisted delivery in a medical institution (16.6%). For excess weight, the gap is - 2.1 percentage points, and its main determinants are the mother's educational level (39.2%) and birth attended by a physician (21.8%). This study suggests the coexistence of a double burden of malnutrition (DBM) in children under 5 years of age living in urban areas of Colombia. Stunting is associated with low-income levels while excess weight is associated with higher income levels. The identification of the main determinants of DBM and its relative importance, constitutes a contribution for public policy makers aimed at reducing socioeconomic gaps.

Baseline Severity and Inflammation Would Influence the Effect of Simvastatin on Clinical Outcomes in Cirrhosis Patients.

BACKGROUND: Simvastatin administration to decompensated cirrhosis patients improved Child-Pugh (CP) at the end of a safety trial (EST). AIM: To evaluate whether simvastatin reduces cirrhosis severity through a secondary analysis of the safety trial. METHODS: Thirty patients CP class (CPc) CPc A (n = 6), CPc B (n = 22), and CPc C (n = 2) received simvastatin for one year. PRIMARY ENDPOINT: cirrhosis severity. Secondary endpoints: health-related quality of life (HRQoL) and hospitalizations for cirrhosis complications. RESULTS: Cirrhosis severity decreased baseline versus EST only across CP score (7.3 ± 1.3 versus 6.7 ± 1.7, P = 0.041), and CPc: 12 patients lessened from CPc B to CPc A, and three patients increased from CPc A to CPc B (P = 0.029). Due to cirrhosis severity changes and differences in clinical outcomes, 15 patients completed the trial as CPc AEST and another 15 as CPc B/C. At baseline, CPc AEST showed greater albumin and high-density lipoprotein cholesterol concentrations than CPc B/C (P = 0.036 and P = 0.028, respectively). Comparing EST versus baseline, only in CPc AEST, there was a reduction in white-cell blood (P = 0.012), neutrophils (P = 0.029), monocytes (P = 0.035), and C-reactive protein (P = 0.046); an increase in albumin (P = 0.011); and a recovery in HRQoL (P < 0.030). Finally, admissions for cirrhosis complications decreased in CPc AEST versus CPc B/C (P = 0.017). CONCLUSIONS: Simvastatin would reduce cirrhosis severity only in CPc B at baseline in a suitable protein and lipid milieu, possibly due to its anti-inflammatory effects. Furthermore, only in CPc AEST would improve HRQoL and reduce admissions by cirrhosis complications. However, as these outcomes were not primary endpoints, they require validation.

ERS statement: a core outcome set for clinical trials evaluating the management of COPD exacerbations.

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use.

Predator responses to prey camouflage strategies: a meta-analysis.

Although numerous studies about camouflage have been conducted in the last few decades, there is still a significant gap in our knowledge about the magnitude of protective value of different camouflage strategies in prey detection and survival. Furthermore, the functional significance of several camouflage strategies remains controversial. Here we carried out a comprehensive meta-analysis including comparisons of different camouflage strategies as well as predator and prey types, considering two response variables: mean predator search time (ST) (63 studies) and predator attack rate (AR) of camouflaged prey (28 studies). Overall, camouflage increased the predator ST by 62.56% and decreased the AR of prey by 27.34%. Masquerade was the camouflage strategy that most increased predator ST (295.43%). Background matching and disruptive coloration did not differ from each other. Motion camouflage did not increase ST but decreases AR on prey. We found no evidence that eyespot increases ST and decreases AR by predators. The different types of predators did not differ from each other, but caterpillars were the type of prey that most influenced the magnitude of camouflage's effect. We highlight the potential evolutionary mechanisms that led camouflage to be a highly effective anti-predatory adaptation, as well as potential discrepancies or redundancies among strategies, predator and prey types.

Climate variability and aridity modulate the role of leaf shelters for arthropods: A global experiment.

Current climate change is disrupting biotic interactions and eroding biodiversity worldwide. However, species sensitive to aridity, high temperatures, and climate variability might find shelter in microclimatic refuges, such as leaf rolls built by arthropods. To explore how the importance of leaf shelters for terrestrial arthropods changes with latitude, elevation, and climate, we conducted a distributed experiment comparing arthropods in leaf rolls versus control leaves across 52 sites along an 11,790 km latitudinal gradient. We then probed the impact of short- versus long-term climatic impacts on roll use, by comparing the relative impact of conditions during the experiment versus average, baseline conditions at the site. Leaf shelters supported larger organisms and higher arthropod biomass and species diversity than non-rolled control leaves. However, the magnitude of the leaf rolls' effect differed between long- and short-term climate conditions, metrics (species richness, biomass, and body size), and trophic groups (predators vs. herbivores). The effect of leaf rolls on predator richness was influenced only by baseline climate, increasing in magnitude in regions experiencing increased long-term aridity, regardless of latitude, elevation, and weather during the experiment. This suggests that shelter use by predators may be innate, and thus, driven by natural selection. In contrast, the effect of leaf rolls on predator biomass and predator body size decreased with increasing temperature, and increased with increasing precipitation, respectively, during the experiment. The magnitude of shelter usage by herbivores increased with the abundance of predators and decreased with increasing temperature during the experiment. Taken together, these results highlight that leaf roll use may have both proximal and ultimate causes. Projected increases in climate variability and aridity are, therefore, likely to increase the importance of biotic refugia in mitigating the effects of climate change on species persistence.

Warming and top predator loss drive direct and indirect effects on multiple trophic groups within and across ecosystems.

The interspecific interactions within and between adjacent ecosystems strongly depend on the changes in their abiotic and biotic components. However, little is known about how climate change and biodiversity loss in a specific ecosystem can impact the multiple trophic interactions of different biological groups within and across ecosystems. We used natural microecosystems (tank-bromeliads) as a model system to investigate the main and interactive effects of aquatic warming and aquatic top predator loss (i.e. trophic downgrading) on trophic relationships in three integrated food web compartments: (a) aquatic micro-organisms, (b) aquatic macro-organisms and (c) terrestrial predators (i.e. via cross-ecosystem effects). The aquatic top predator loss substantially impacted the three food web compartments. In the aquatic macrofauna compartment, trophic downgrading increased the filter feeder richness and abundance directly and indirectly via an increase in detritivore richness, likely through a facilitative interaction. For the microbiota compartment, aquatic top predator loss had a negative effect on algae richness, probably via decreasing the input of nutrients from predator biological activities. Furthermore, the more active terrestrial predators responded more to aquatic top predator loss, via an increase in some components of aquatic macrofauna, than more stationary terrestrial predators. The aquatic trophic downgrading indirectly altered the richness and abundance of cursorial terrestrial predators, but these effects had different direction according to the aquatic functional group, filter feeder or other detritivores. The web-building predators were indirectly affected by aquatic trophic downgrading due to increased filter feeder richness. Aquatic warming did not affect the aquatic micro- or macro-organisms but did positively affect the abundance of web-building terrestrial predators. These results allow us to raise a predictive framework of how different anthropogenic changes predicted for the next decades, such as aquatic warming and top predator loss, could differentially affect multiple biological groups through interactions within and across ecosystems.

As interações interespecíficas dentro e entre ecossistemas adjacentes dependem fortemente das mudanças de seus componentes abióticos e bióticos. Entretanto, pouco se sabe sobre como mudanças climáticas e a perda de biodiversidade em um ecossistema específico pode impactar as múltiplas interações tróficas de diferentes grupos biológicos dentro e entre ecossistemas. Nós utilizamos micro ecossistemas naturais (bromélias-tanque) como sistema modelo para investigar os efeitos individuais e interativos do aquecimento e da perda de predadores aquáticos (simplificação trófica) nas relações tróficas em três compartimentos integrados da teia alimentar: i) micro-organismos aquáticos, ii) macroorganismos aquáticos e iii) predadores terrestres (via efeito entre ecossistemas). A perda de predadores de topo aquáticos afetou substancialmente os três compartimentos da rede trófica. No compartimento da macrofauna aquática, a simplificação trófica aumentou a riqueza e abundância de filtradores, direta e indiretamente, por meio de um aumento da riqueza de espécies de detritívoros, provavelmente através de uma interação de facilitação. Para o compartimento da microbiota, a perda de predadores de topo aquáticos teve um efeito negativo sobre a riqueza de espécies de algas, provavelmente por meio da diminuição da entrada de nutrientes provenientes das atividades biológicas dos predadores. Além disso, os predadores terrestres mais ativos responderam mais à perda de predadores de topo aquáticos, por meio de um aumento de alguns componentes da macrofauna aquática, do que predadores terrestres mais estacionários. A simplificação trófica aquática alterou indiretamente a riqueza e abundância de predadores cursoriais terrestres, mas esses efeitos tiveram direção diferente de acordo com o grupo funcional aquático, filtradores ou outros detritívoros. Os predadores construtores de teias foram indiretamente afetados pela simplificação trófica aquática devido ao aumento da riqueza de filtradores. O aquecimento aquático não afetou os micro ou macro organismos aquáticos, mas afetou positivamente a abundância de predadores terrestres construtores de teias. Esses resultados nos permitem levantar um quadro preditivo de como diferentes mudanças antropogênicas preditas para as próximas décadas, como o aquecimento e a perda de predadores de topo aquáticos, podem afetar diferencialmente vários grupos biológicos por meio de interações dentro e entre os ecossistemas.

Regime shifts in a shallow lake over 12 years: Consequences for taxonomic and functional diversities, and ecosystem multifunctionality.

Under increasing nutrient loading, shallow lakes may shift from a state of clear water dominated by submerged macrophytes to a turbid state dominated by phytoplankton or a shaded state dominated by floating macrophytes. How such regime shifts mediate the relationship between taxonomic and functional diversities (FD) and lake multifunctionality is poorly understood. We employed a detailed database describing a shallow lake over a 12-year period during which the lake has displayed all the three states (clear, turbid and shaded) to investigate how species richness, FD of fish and zooplankton, ecosystem multifunctionality and five individual ecosystem functions (nitrogen and phosphorus concentrations, standing fish biomass, algae production and light availability) differ among states. We also evaluated how the relationship between biodiversity (species richness and FD) and multifunctionality is affected by regime shifts. We showed that species richness and the FD of fish and zooplankton were highest during the clear state. The clear state also maintained the highest values of multifunctionality as well as standing fish biomass production, algae biomass and light availability, whereas the turbid and shaded states had higher nutrient concentrations. Functional diversity was the best predictor of multifunctionality. The relationship between FD and multifunctionality was strongly positive during the clear state, but such relationship became flatter after the shift to the turbid or shaded state. Our findings illustrate that focusing on functional traits may provide a more mechanistic understanding of how regime shifts affect biodiversity and the consequences for ecosystem functioning. Regime shifts towards a turbid or shaded state negatively affect the taxonomic diversity and FD of fish and zooplankton, which in turn impairs the multifunctionality of shallow lakes.

Local drivers of heterogeneity in a tropical forest: epiphytic tank bromeliads affect the availability of soil resources and conditions and indirectly affect the structure of seedling communities.

Environmental heterogeneity is a key component in explaining the megadiversity of tropical forests. Despite its importance, knowledge about local drivers of environmental heterogeneity remains a challenge for ecologists. In Neotropical forests, epiphytic tank bromeliads store large amounts of water and nutrients in the tree canopy, and their tank overflow may create nutrient-rich patches in the soil. However, the effects of this nutrient flux on environmental heterogeneity and plant community structure in the understory remain unexplored. In a Brazilian coastal sandy forest, we investigated the effects of the presence of epiphytic tank bromeliads on throughfall chemistry, soil chemistry, soil litter biomass, light, and seedling community structure. In the presence of epiphytic tank bromeliads, the throughfall nitrogen concentration increased twofold, the throughfall phosphorus concentration increased threefold, and the soil patches had a 3.96% higher pH, a 50% higher calcium concentration, and 11.88% less light. By altering the availability of soil resources and conditions, the presence of bromeliads partially shifted the available niche spaces for plant species and indirectly affected the structure of the seedling communities, decreasing their diversity, density, and biomass. For the first time, we showed that the presence of tank bromeliads in the canopy can create characteristic soil patches in the understory, affecting the structure of seedling communities via fertilization. Our results reveal a novel local driver of environmental heterogeneity, reinforcing and expanding the key role of tank bromeliads both in nutrient cycling and plant community structuring of Neotropical coastal sandy forests.

Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial.

BACKGROUND: Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. METHODS: A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. RESULTS: From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. CONCLUSIONS: The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. CLINICAL TRIALS REGISTRATION: NCT04343729.

Trophic downgrading decreases species asynchrony and community stability regardless of climate warming.

Theory and some evidence suggest that biodiversity promotes stability. However, evidence of how trophic interactions and environmental changes modulate this relationship in multitrophic communities is lacking. Given the current scenario of biodiversity loss and climate changes, where top predators are disproportionately more affected, filling these knowledge gaps is crucial. We simulated climate warming and top predator loss in natural microcosms to investigate their direct and indirect effects on temporal stability of microbial communities and the role of underlying stabilising mechanisms. Community stability was insensitive to warming, but indirectly decreased due to top predator loss via increased mesopredator abundance and consequent reduction of species asynchrony and species stability. The magnitude of destabilising effects differed among trophic levels, being disproportionally higher at lower trophic levels (e.g. producers). Our study unravels major patterns and causal mechanisms by which trophic downgrading destabilises large food webs, regardless of climate warming scenarios.

Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study.

BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).