Latitudinal patterns in stabilizing density dependence of forest communities.

Numerous studies have shown reduced performance in plants that are surrounded by neighbours of the same species1,2, a phenomenon known as conspecific negative density dependence (CNDD)3. A long-held ecological hypothesis posits that CNDD is more pronounced in tropical than in temperate forests4,5, which increases community stabilization, species coexistence and the diversity of local tree species6,7. Previous analyses supporting such a latitudinal gradient in CNDD8,9 have suffered from methodological limitations related to the use of static data10-12. Here we present a comprehensive assessment of latitudinal CNDD patterns using dynamic mortality data to estimate species-site-specific CNDD across 23 sites. Averaged across species, we found that stabilizing CNDD was present at all except one site, but that average stabilizing CNDD was not stronger toward the tropics. However, in tropical tree communities, rare and intermediate abundant species experienced stronger stabilizing CNDD than did common species. This pattern was absent in temperate forests, which suggests that CNDD influences species abundances more strongly in tropical forests than it does in temperate ones13. We also found that interspecific variation in CNDD, which might attenuate its stabilizing effect on species diversity14,15, was high but not significantly different across latitudes. Although the consequences of these patterns for latitudinal diversity gradients are difficult to evaluate, we speculate that a more effective regulation of population abundances could translate into greater stabilization of tropical tree communities and thus contribute to the high local diversity of tropical forests.

Identification of molecular subphenotypes in two cohorts of paediatric ARDS.

BACKGROUND: Two subphenotypes of acute respiratory distress syndrome (ARDS), hypoinflammatory and hyperinflammatory, have been reported in adults and in a single paediatric cohort. The relevance of these subphenotypes in paediatrics requires further investigation. We aimed to identify subphenotypes in two large observational cohorts of paediatric ARDS and assess their congruence with prior descriptions. METHODS: We performed latent class analysis (LCA) separately on two cohorts using biomarkers as inputs. Subphenotypes were compared on clinical characteristics and outcomes. Finally, we assessed overlap with adult cohorts using parsimonious classifiers. FINDINGS: In two cohorts from the Children's Hospital of Philadelphia (n=333) and from a multicentre study based at the University of California San Francisco (n=293), LCA identified two subphenotypes defined by differential elevation of biomarkers reflecting inflammation and endotheliopathy. In both cohorts, hyperinflammatory subjects had greater illness severity, more sepsis and higher mortality (41% and 28% in hyperinflammatory vs 11% and 7% in hypoinflammatory). Both cohorts demonstrated overlap with adult subphenotypes when assessed using parsimonious classifiers. INTERPRETATION: We identified hypoinflammatory and hyperinflammatory subphenotypes of paediatric ARDS from two separate cohorts with utility for prognostic and potentially predictive, enrichment. Future paediatric ARDS trials should identify and leverage biomarker-defined subphenotypes in their analysis.

Damage to tropical forests caused by cyclones is driven by wind speed but mediated by topographical exposure and tree characteristics.

Each year, an average of 45 tropical cyclones affect coastal areas and potentially impact forests. The proportion of the most intense cyclones has increased over the past four decades and is predicted to continue to do so. Yet, it remains uncertain how topographical exposure and tree characteristics can mediate the damage caused by increasing wind speed. Here, we compiled empirical data on the damage caused by 11 cyclones occurring over the past 40 years, from 74 forest plots representing tropical regions worldwide, encompassing field data for 22,176 trees and 815 species. We reconstructed the wind structure of those tropical cyclones to estimate the maximum sustained wind speed (MSW) and wind direction at the studied plots. Then, we used a causal inference framework combined with Bayesian generalised linear mixed models to understand and quantify the causal effects of MSW, topographical exposure to wind (EXP), tree size (DBH) and species wood density (ρ) on the proportion of damaged trees at the community level, and on the probability of snapping or uprooting at the tree level. The probability of snapping or uprooting at the tree level and, hence, the proportion of damaged trees at the community level, increased with increasing MSW, and with increasing EXP accentuating the damaging effects of cyclones, in particular at higher wind speeds. Higher ρ decreased the probability of snapping and to a lesser extent of uprooting. Larger trees tended to have lower probabilities of snapping but increased probabilities of uprooting. Importantly, the effect of ρ decreasing the probabilities of snapping was more marked for smaller than larger trees and was further accentuated at higher MSW. Our work emphasises how local topography, tree size and species wood density together mediate cyclone damage to tropical forests, facilitating better predictions of the impacts of such disturbances in an increasingly windier world.

Transgender and non-binary peoples experiences of cervical cancer screening: A scoping review.

AIM(S): To synthesise the literature about transgender and non-binary people's experiences of cervical cancer screening and identify ways to improve screening. BACKGROUND: Transgender people often face barriers to accessing health services including cervical screening, where transgender people have a lower uptake than cisgender women. DESIGN: A scoping review was undertaken following the Arksey and O'Malley (2005) framework and the PRISMA-ScR checklist. Following database searching of Medline via PubMed, Web of Science, Scopus and CINHAL, 23 papers published between 2008 and 2003 were included. Papers were included if they shared trans and non-binary people's experiences of cervical screening and were written in English. There were no date or geographical data restrictions due to the paucity of research. RESULTS: Transgender people experience barriers to cervical screening including gender dysphoria, a history of sexual trauma, and mistrust in health professionals or health services, which can result in having negative experiences of screening or avoiding screening. Health professionals can help to create a positive experience by informing themselves about best practices for trans+ health. CONCLUSION: Changes are required to improve transgender people's experiences and uptake of cervical screening. Improving medical education about trans health and updating health systems would help to combat issues discussed. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Having an understanding of the reasons why accessing health services can be more difficult for transgender people will help health professionals to provide appropriate care for transgender patients. This paper details this in the context of cervical cancer screening and can be applied to other areas of healthcare. REPORTING METHOD: We have adhered to relevant EQUATOR guidelines and used the PRISMA-ScR reporting method. No Patient or Public Contribution.

'Moving on' for Adults With a Learning Disability and Their Families: A Constructivist Grounded Theory Study.

Ending familial co-residence, termed 'moving on' by participants, is an increasingly relevant life transition for people with a learning disability due to increasing life expectancy and policy developments. Nevertheless, there is an absence of research exploring this transition experience in a United Kingdom (UK) context. This constructivist grounded theory study therefore aimed to explore, conceptualise, and theorise the 'moving on' experiences of adults with a learning disability and their families. This article reports the experiences of five adults with a learning disability and nine family members in England, UK. Narrative interviews and creative storybook methods were used to collect data between April 2015 and May 2016. Constant comparative methods, theoretical sampling, and memo writing were used throughout data collection and analysis. Participants with a learning disability presented personal growth and greater life fulfilment over the course of the transition; they flourished. In parallel, family members relinquished their care responsibilities. Importantly, the iterative and reciprocal relationship between flourishing and relinquishing shows that ongoing family member involvement is crucial during and following relocation. Family members identified factors that potentially inhibit relinquishing: pressure to 'let go', different perceptions of independence between family members and service providers, inadequate future investment, and rapport with professional carers. These novel insights led to the generation of the first known mid-range theory concerning this transition, entitled 'Moving on: flourishing and relinquishing'. Findings will guide future research in this field and facilitate the design of appropriate support for people with a learning disability and their families.

Demographic trade-offs and functional shifts in a hurricane-impacted tropical forest.

BACKGROUND AND AIMS: Understanding shifts in the demographic and functional composition of forests after major natural disturbances has become increasingly relevant given the accelerating rates of climate change and elevated frequency of natural disturbances. Although plant demographic strategies are often described across a slow-fast continuum, severe and frequent disturbance events influencing demographic processes may alter the demographic trade-offs and the functional composition of forests. We examined demographic trade-offs and the shifts in functional traits in a hurricane-disturbed forest using long-term data from the Luquillo Forest Dynamics Plot (LFPD) in Puerto Rico. METHODS: We analysed information on growth, survival, seed rain and seedling recruitment for 30 woody species in the LFDP. In addition, we compiled data on leaf, seed and wood functional traits that capture the main ecological strategies for plants. We used this information to identify the main axes of demographic variation for this forest community and evaluate shifts in community-weighted means for traits from 2000 to 2016. KEY RESULTS: The previously identified growth-survival trade-off was not observed. Instead, we identified a fecundity-growth trade-off and an axis representing seedling-to-adult survival. Both axes formed dimensions independent of resprouting ability. Also, changes in tree species composition during the post-hurricane period reflected a directional shift from seedling and tree communities dominated by acquisitive towards conservative leaf economics traits and large seed mass. Wood specific gravity, however, did not show significant directional changes over time. CONCLUSIONS: Our study demonstrates that tree demographic strategies coping with frequent storms and hurricane disturbances deviate from strategies typically observed in undisturbed forests, yet the shifts in functional composition still conform to the expected changes from acquisitive to conservative resource-uptake strategies expected over succession. In the face of increased rates of natural and anthropogenic disturbance in tropical regions, our results anticipate shifts in species demographic trade-offs and different functional dimensions.

Biomarker-Based Risk Stratification in Pediatric Sepsis From a Low-Middle Income Country.

OBJECTIVES: Most biomarker studies of sepsis originate from high-income countries, whereas mortality risk is higher in low- and middle-income countries. The second version of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has been validated in multiple North American PICUs for prognosis. Given differences in epidemiology, we assessed the performance of PERSEVERE-II in septic children from Pakistan, a low-middle income country. Due to uncertainty regarding how well PERSEVERE-II would perform, we also assessed the utility of other select biomarkers reflecting endotheliopathy, coagulopathy, and lung injury. DESIGN: Prospective cohort study. SETTING: PICU in Aga Khan University Hospital in Karachi, Pakistan. PATIENTS: Children (< 18 yr old) meeting pediatric modifications of adult Sepsis-3 criteria between November 2020 and February 2022 were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma was collected within 24 hours of admission and biomarkers quantified. The area under the receiver operating characteristic curve for PERSEVERE-II to discriminate 28-day mortality was determined. Additional biomarkers were compared between survivors and nonsurvivors and between subjects with and without acute respiratory distress syndrome. In 86 subjects (20 nonsurvivors, 23%), PERSEVERE-II discriminated mortality (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.72-0.94) and stratified the cohort into low-, medium-, and high-risk of mortality. Biomarkers reflecting endotheliopathy (angiopoietin 2, intracellular adhesion molecule 1) increased across worsening risk strata. Angiopoietin 2, soluble thrombomodulin, and plasminogen activator inhibitor 1 were higher in nonsurvivors, and soluble receptor for advanced glycation end-products and surfactant protein D were higher in children meeting acute respiratory distress syndrome criteria. CONCLUSIONS: PERSEVERE-II performs well in septic children from Aga Khan University Hospital, representing the first validation of PERSEVERE-II in a low-middle income country. Patients possessed a biomarker profile comparable to that of sepsis from high-income countries, suggesting that biomarker-based enrichment strategies may be effective in this setting.

The role of family in supporting adherence to diabetes self-care management practices: An umbrella review.

AIMS: Synthesize a review of reviews of the family's role in supporting adherence to diabetes self-care management practices (DSMP) for adults with type 2 diabetes (DM2). DESIGN: An umbrella review. DATA SOURCES: Scopus, Web of Science including MEDLINE, CINAHL via EBSCO, PubMed and Science Direct were searched for systematic reviews from their year of establishment until June 2021. REVIEW METHODS: The review followed the Joanna Briggs Institute (JBI) guidelines for umbrella reviews. The JBI data extraction form for systematic reviews and research syntheses was used for data extraction. Methodological quality was assessed using the JBI Critical Appraisal Checklist for Systematic reviews and Research Syntheses. RESULTS: Nineteen reviews met the inclusion criteria. The key findings were summarized using a narrative and thematic analysis methods. Four main themes were identified: family interactions and diabetes self-management, family support as informal social support, factors affecting families' roles, and tailoring culturally sensitive family-based interventions. CONCLUSION: There appears to be a consensus regarding the impact of family on adults' self-management of DM2. Additional research is needed to comprehend the role of the family in underrepresented populations and examine what constitutes a family and the diverse family functions in different groups. IMPACT: Enhancing adherence to self-care management practices is crucial for the well-being of adults with DM2. Family support is a key to successful self-care management at home. However, understanding the unique needs of adults with DM2 and their families can help healthcare professionals plan appropriate support strategies and sustainable family-based interventions. NO PATIENT OR PUBLIC CONTRIBUTION: This review did not incorporate direct patients or public input as it summarizes evidence from previously published systematic reviews.

Differentiating children with sepsis with and without acute respiratory distress syndrome using proteomics.

Both sepsis and acute respiratory distress syndrome (ARDS) rely on imprecise clinical definitions leading to heterogeneity, which has contributed to negative trials. Because circulating protein/DNA complexes have been implicated in sepsis and ARDS, we aimed to develop a proteomic signature of DNA-bound proteins to discriminate between children with sepsis with and without ARDS. We performed a prospective case-control study in 12 children with sepsis with ARDS matched to 12 children with sepsis without ARDS on age, severity of illness score, and source of infection. We performed co-immunoprecipitation and downstream proteomics in plasma collected ≤ 24 h of intensive care unit admission. Expression profiles were generated, and a random forest classifier was used on differentially expressed proteins to develop a signature which discriminated ARDS. The classifier was tested in six independent blinded samples. Neutrophil and nucleosome proteins were over-represented in ARDS, including two S100A proteins, superoxide dismutase (SOD), and three histones. Random forest produced a 10-protein signature that accurately discriminated between children with sepsis with and without ARDS. This classifier perfectly assigned six independent blinded samples as having ARDS or not. We validated higher expression of the most informative discriminating protein, galectin-3-binding protein, in children with ARDS. Our methodology has applicability to isolation of DNA-bound proteins from plasma. Our results support the premise of a molecular definition of ARDS, and give preliminary insight into why some children with sepsis, but not others, develop ARDS.

Imatinib alleviates lung injury and prolongs survival in ventilated rats.

Imatinib, a tyrosine kinase inhibitor, attenuates pulmonary edema and inflammation in lung injury. However, the physiological effects of this drug and their impact on outcomes are poorly characterized. Using serial computed tomography (CT), we tested the hypothesis that imatinib reduces injury severity and improves survival in ventilated rats. Hydrochloric acid (HCl) was instilled in the trachea (pH 1.5, 2.5 mL/kg) of anesthetized, intubated supine rats. Animals were randomized (n = 17 each group) to receive intraperitoneal imatinib or vehicle immediately prior to HCl. All rats then received mechanical ventilation. CT was performed hourly for 4 h. Images were quantitatively analyzed to assess the progression of radiological abnormalities. Injury severity was confirmed via hourly blood gases, serum biomarkers, bronchoalveolar lavage (BAL), and histopathology. Serial blood drug levels were measured in a subset of rats. Imatinib reduced mortality while delaying functional and radiological injury progression: out of 17 rats per condition, 2 control vs. 8 imatinib-treated rats survived until the end of the experiment (P = 0.02). Imatinib attenuated edema after lung injury (P < 0.05), and survival time in both groups was negatively correlated with increased lung mass (R2 = 0.70) as well as other physiological and CT parameters. Capillary leak (BAL protein concentration) was significantly lower in the treated group (P = 0.04). Peak drug concentration was reached after 70 min, and the drug half-life was 150 min. Imatinib decreased both mortality and lung injury severity in mechanically ventilated rats. Pharmacological inhibition of edema could be used during mechanical ventilation to improve the severity and outcome of lung injury.

Hurricanes increase tropical forest vulnerability to drought.

Rapid changes in climate and disturbance regimes, including droughts and hurricanes, are likely to influence tropical forests, but our understanding of the compound effects of disturbances on forest ecosystems is extremely limited. Filling this knowledge gap is necessary to elucidate the future of these ecosystems under a changing climate. We examined the relationship between hurricane response (damage, mortality, and resilience) and four hydraulic traits of 13 dominant woody species in a wet tropical forest subject to periodic hurricanes. Species with high resistance to embolisms (low P50 values) and higher safety margins ( SMP50 ) were more resistant to immediate hurricane mortality and breakage, whereas species with higher hurricane resilience (rapid post-hurricane growth) had high capacitance and P50 values and low SMP50 . During 26 yr of post-hurricane recovery, we found a decrease in community-weighted mean values for traits associated with greater drought resistance (leaf turgor loss point, P50 , SMP50 ) and an increase in capacitance, which has been linked with lower drought resistance. Hurricane damage favors slow-growing, drought-tolerant species, whereas post-hurricane high resource conditions favor acquisitive, fast-growing but drought-vulnerable species, increasing forest productivity at the expense of drought tolerance and leading to higher overall forest vulnerability to drought.

Distribution of biomass dynamics in relation to tree size in forests across the world.

Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4-52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1-10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models.

Demographic composition, not demographic diversity, predicts biomass and turnover across temperate and tropical forests.

The growth and survival of individual trees determine the physical structure of a forest with important consequences for forest function. However, given the diversity of tree species and forest biomes, quantifying the multitude of demographic strategies within and across forests and the way that they translate into forest structure and function remains a significant challenge. Here, we quantify the demographic rates of 1961 tree species from temperate and tropical forests and evaluate how demographic diversity (DD) and demographic composition (DC) differ across forests, and how these differences in demography relate to species richness, aboveground biomass (AGB), and carbon residence time. We find wide variation in DD and DC across forest plots, patterns that are not explained by species richness or climate variables alone. There is no evidence that DD has an effect on either AGB or carbon residence time. Rather, the DC of forests, specifically the relative abundance of large statured species, predicted both biomass and carbon residence time. Our results demonstrate the distinct DCs of globally distributed forests, reflecting biogeography, recent history, and current plot conditions. Linking the DC of forests to resilience or vulnerability to climate change, will improve the precision and accuracy of predictions of future forest composition, structure, and function.

Interactions between all pairs of neighboring trees in 16 forests worldwide reveal details of unique ecological processes in each forest, and provide windows into their evolutionary histories.

When Darwin visited the Galapagos archipelago, he observed that, in spite of the islands' physical similarity, members of species that had dispersed to them recently were beginning to diverge from each other. He postulated that these divergences must have resulted primarily from interactions with sets of other species that had also diverged across these otherwise similar islands. By extrapolation, if Darwin is correct, such complex interactions must be driving species divergences across all ecosystems. However, many current general ecological theories that predict observed distributions of species in ecosystems do not take the details of between-species interactions into account. Here we quantify, in sixteen forest diversity plots (FDPs) worldwide, highly significant negative density-dependent (NDD) components of both conspecific and heterospecific between-tree interactions that affect the trees' distributions, growth, recruitment, and mortality. These interactions decline smoothly in significance with increasing physical distance between trees. They also tend to decline in significance with increasing phylogenetic distance between the trees, but each FDP exhibits its own unique pattern of exceptions to this overall decline. Unique patterns of between-species interactions in ecosystems, of the general type that Darwin postulated, are likely to have contributed to the exceptions. We test the power of our null-model method by using a deliberately modified data set, and show that the method easily identifies the modifications. We examine how some of the exceptions, at the Wind River (USA) FDP, reveal new details of a known allelopathic effect of one of the Wind River gymnosperm species. Finally, we explore how similar analyses can be used to investigate details of many types of interactions in these complex ecosystems, and can provide clues to the evolution of these interactions.

Plant functional traits have globally consistent effects on competition.

Phenotypic traits and their associated trade-offs have been shown to have globally consistent effects on individual plant physiological functions, but how these effects scale up to influence competition, a key driver of community assembly in terrestrial vegetation, has remained unclear. Here we use growth data from more than 3 million trees in over 140,000 plots across the world to show how three key functional traits--wood density, specific leaf area and maximum height--consistently influence competitive interactions. Fast maximum growth of a species was correlated negatively with its wood density in all biomes, and positively with its specific leaf area in most biomes. Low wood density was also correlated with a low ability to tolerate competition and a low competitive effect on neighbours, while high specific leaf area was correlated with a low competitive effect. Thus, traits generate trade-offs between performance with competition versus performance without competition, a fundamental ingredient in the classical hypothesis that the coexistence of plant species is enabled via differentiation in their successional strategies. Competition within species was stronger than between species, but an increase in trait dissimilarity between species had little influence in weakening competition. No benefit of dissimilarity was detected for specific leaf area or wood density, and only a weak benefit for maximum height. Our trait-based approach to modelling competition makes generalization possible across the forest ecosystems of the world and their highly diverse species composition.

IRE1A Stimulates Hepatocyte-Derived Extracellular Vesicles That Promote Inflammation in Mice With Steatohepatitis.

BACKGROUND & AIMS: Endoplasmic reticulum to nucleus signaling 1 (ERN1, also called IRE1A) is a sensor of the unfolded protein response that is activated in the livers of patients with nonalcoholic steatohepatitis (NASH). Hepatocytes release ceramide-enriched inflammatory extracellular vesicles (EVs) after activation of IRE1A. We studied the effects of inhibiting IRE1A on release of inflammatory EVs in mice with diet-induced steatohepatitis. METHODS: C57BL/6J mice and mice with hepatocyte-specific disruption of Ire1a (IRE1αΔhep) were fed a diet high in fat, fructose, and cholesterol to induce development of steatohepatitis or a standard chow diet (controls). Some mice were given intraperitoneal injections of the IRE1A inhibitor 4µ8C. Mouse liver and primary hepatocytes were transduced with adenovirus or adeno-associated virus that expressed IRE1A. Livers were collected from mice and analyzed by quantitative polymerase chain reaction and chromatin immunoprecipitation assays; plasma samples were analyzed by enzyme-linked immunosorbent assay. EVs were derived from hepatocytes and injected intravenously into mice. Plasma EVs were characterized by nanoparticle-tracking analysis, electron microscopy, immunoblots, and nanoscale flow cytometry; we used a membrane-tagged reporter mouse to detect hepatocyte-derived EVs. Plasma and liver tissues from patients with NASH and without NASH (controls) were analyzed for EV concentration and by RNAscope and gene expression analyses. RESULTS: Disruption of Ire1a in hepatocytes or inhibition of IRE1A reduced the release of EVs and liver injury, inflammation, and accumulation of macrophages in mice on the diet high in fat, fructose, and cholesterol. Activation of IRE1A, in the livers of mice, stimulated release of hepatocyte-derived EVs, and also from cultured primary hepatocytes. Mice given intravenous injections of IRE1A-stimulated, hepatocyte-derived EVs accumulated monocyte-derived macrophages in the liver. IRE1A-stimulated EVs were enriched in ceramides. Chromatin immunoprecipitation showed that IRE1A activated X-box binding protein 1 (XBP1) to increase transcription of serine palmitoyltransferase genes, which encode the rate-limiting enzyme for ceramide biosynthesis. Administration of a pharmacologic inhibitor of serine palmitoyltransferase to mice reduced the release of EVs. Levels of XBP1 and serine palmitoyltransferase were increased in liver tissues, and numbers of EVs were increased in plasma, from patients with NASH compared with control samples and correlated with the histologic features of inflammation. CONCLUSIONS: In mouse hepatocytes, activated IRE1A promotes transcription of serine palmitoyltransferase genes via XBP1, resulting in ceramide biosynthesis and release of EVs. The EVs recruit monocyte-derived macrophages to the liver, resulting in inflammation and injury in mice with diet-induced steatohepatitis. Levels of XBP1, serine palmitoyltransferase, and EVs are all increased in liver tissues from patients with NASH. Strategies to block this pathway might be developed to reduce liver inflammation in patients with NASH.

Vesicular Stomatitis Virus Encoding a Destabilized Tumor Antigen Improves Activation of Anti-tumor T Cell Responses.

Enhancing the immunogenicity of tumor-associated antigens would represent a major advance for anti-tumor vaccination strategies. Here, we investigated structure-directed antigen destabilization as a strategy to improve the degradation, immunogenic epitope presentation, and T cell activation against a vesicular stomatitis virus (VSV)-encoded tumor antigen. We used the crystal structure of the model antigen ovalbumin to identify charge-disrupting amino acid mutations that were predicted to decrease the stability of the protein. One mutation, OVA-C12R, significantly reduced the half-life of the protein and was preferentially degraded in a 26-S proteasomal-dependent manner. The destabilized ovalbumin protein exhibited enhanced presentation of the major histocompatibility complex (MHC) class I immunogenic epitope, SIINFEKL, on the surface of B16F10 cells or murine bone marrow-derived dendritic cells (BMDCs) in vitro. Enhanced presentation correlated with better recognition by cognate CD8 OT-I T cells as measured by activation, proliferation, and effector cytokine production. Finally, VSV encoding the degradation-prone antigen was better able to prime an antigen ovalbumin-specific CD8 T cell response in vivo without altering the anti-viral CD8 T cell response. Our studies highlight that not only is the choice of antigen in cancer vaccines of importance, but that emphasis should be placed on modifying antigen quality to ensure optimal priming of anti-tumor responses.

Children's perspectives and experiences of the COVID-19 pandemic and UK public health measures.

BACKGROUND: The COVID-19 pandemic has had profound impacts on how we live our lives; yet, the implications for children and the effects on children's everyday lives have been relatively underacknowledged. Understanding children's views on COVID-19 and related restrictions on their lives provides an important opportunity to understand how children have responded to the pandemic, including the impacts on their social and emotional well-being. OBJECTIVE: This study explored the experiences and perspectives of children in relation to the COVID-19 pandemic and related restrictions on everyday life. METHOD: A qualitative study using semistructured online interviews with participatory drawings was undertaken between May and July 2020. Eighteen children from England and Wales, aged 7-11 years, participated in interviews. FINDINGS: Themes included children's reflections on (1) COVID-19 as a deadly contagion; (2) fears and sadness and (3) social responsibility and opportunities to respond positively. CONCLUSIONS: Young children offer insightful reflections on their experiences during the first wave of the COVID-19 pandemic in the United Kingdom. Children and young people's perspectives must be considered in future public health discourse. PATIENT OR PUBLIC CONTRIBUTION: This work was informed by conversations with my own three primary school-aged children and the children of friends. A formal Patient and Public Involvement (PPI) group was not established due to the speed with which the project was undertaken. Any future research in this area would benefit from formal PPI in the design, methods and questions.

Health of African Refugee Children Outside Africa: A Scoping Review.

PROBLEM: Africa is the largest source continent of refugee children. However, we found no published synthesis of the literature on the health of African refugee children outside Africa. Conducting a review of the literature on this particular population will help illuminate the particular contextual health issues faced by African child refugees who live outside Africa. The purpose of this review is to synthesize what is known from the existing literature regarding the health of sub-Saharan African refugee children who live outside Africa. METHODS: We completed a scoping review of the published literature. We included articles published in English with a focus on the health of sub-Saharan African refugee children living outside Africa. We excluded studies of refugees in Africa as the living conditions of these refugees, most of whom reside in camps, are very different from those outside Africa. Using relevant keywords, we searched 10 databases to identify and screen 6602 articles after duplicates were eliminated. SAMPLE: A total of 20 studies were included in this review. FINDINGS: Published research articles on sub-Saharan African child refugees living outside Africa focus on infectious diseases, mental health and neurodevelopmental disorders, food insecurity and psychosocial adjustment, physical health (including obesity), and health promotion strategies. This population is characterized by a high rate of infectious diseases (e.g., malaria), obesity, and mental health problems, especially post-traumatic stress disorder (PTSD). CONCLUSIONS AND IMPLICATIONS: To attend to the health needs of sub-Saharan African refugee children who live outside Africa, interventions should address pre-migration factors as well as post-migration factors (including income and community belonging) while employing a strengths-based perspective.

Temporal population variability in local forest communities has mixed effects on tree species richness across a latitudinal gradient.

Among the local processes that determine species diversity in ecological communities, fluctuation-dependent mechanisms that are mediated by temporal variability in the abundances of species populations have received significant attention. Higher temporal variability in the abundances of species populations can increase the strength of temporal niche partitioning but can also increase the risk of species extinctions, such that the net effect on species coexistence is not clear. We quantified this temporal population variability for tree species in 21 large forest plots and found much greater variability for higher latitude plots with fewer tree species. A fitted mechanistic model showed that among the forest plots, the net effect of temporal population variability on tree species coexistence was usually negative, but sometimes positive or negligible. Therefore, our results suggest that temporal variability in the abundances of species populations has no clear negative or positive contribution to the latitudinal gradient in tree species richness.