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Background: The COVID-19 pandemic has caused unprecedented health care challenges mandating surgical service reconfiguration. Within our hospital, emergency and elective streams were separated and self-contained Protected Elective Surgical Units were developed to mitigate against infection-related morbidity. Aims of this study were to determine the risk of COVID-19 transmission and mortality and whether the development of Protected Elective Surgical Units can result in significant reduction in risk. Methods: A retrospective observational study of consecutive patients from 18 specialties undergoing elective or emergency surgery under general, spinal, or epidural anaesthetic over a 12-month study period was undertaken. Primary outcome measures were 30-day postoperative COVID-19 transmission rate and mortality. Secondary adjusted analyses were performed to ascertain hospital and Protected Elective Surgical Unit transmission rates. Results: Between 15 March 2020 and 14 March 2021, 9,925 patients underwent surgery: 6,464 (65.1%) elective, 5,116 (51.5%) female, and median age 57 (39–70). A total of 69.5% of all procedures were performed in Protected Elective Surgical Units. Overall, 30-day postoperative COVID-19 transmission was 2.8% (3.4% emergency vs 1.2% elective P 70, male sex, American Society of Anesthesiologists grade >2, and emergency surgery were all independently associated with mortality. Conclusion: This study has demonstrated that Protected Elective Surgical Units can facilitate high-volume elective surgical services throughout peaks of the COVID-19 pandemic while minimising viral transmission and mortality. However, mortality risk associated with perioperative COVID-19 infection remains high.

Objectives The psychological impact of the COVID-19 pandemic on doctors is a significant concern. Due to the emergence of multiple pandemic waves, longitudinal data on the impact of COVID-19 are vital to ensure an adequate psychological care response. The primary aim was to assess the prevalence and degree of psychological distress and trauma in frontline doctors during the acceleration, peak and deceleration of the COVID-19 first wave. Personal and professional factors associated with psychological distress are also reported.Design A prospective online three-part longitudinal survey.Setting Acute hospitals in the UK and Ireland.Participants Frontline doctors working in emergency medicine, anaesthetics and intensive care medicine during the first wave of the COVID-19 pandemic in March 2020.Primary outcome measures Psychological distress and trauma measured using the General Health Questionnaire-12 and the Impact of Events-Revised.Results The initial acceleration survey distributed across networks generated a sample of 5440 doctors. Peak and deceleration response rates from the original sample were 71.6% (n=3896) and 56.6% (n=3079), respectively. Prevalence of psychological distress was 44.7% (n=1334) during the acceleration, 36.9% (n=1098) at peak and 31.5% (n=918) at the deceleration phase. The prevalence of trauma was 23.7% (n=647) at peak and 17.7% (n=484) at deceleration. The prevalence of probable post-traumatic stress disorder was 12.6% (n=343) at peak and 10.1% (n=276) at deceleration. Worry of family infection due to clinical work was the factor most strongly associated with both distress (R2=0.06) and trauma (R2=0.10).Conclusion Findings reflect a pattern of elevated distress at acceleration and peak, with some natural recovery. It is essential that policymakers seek to prevent future adverse effects through (a) provision of vital equipment to mitigate physical and psychological harm, (b) increased awareness and recognition of signs of psychological distress and (c) the development of clear pathways to effective psychological care.Trial registration number ISRCTN10666798.

BackgroundIsoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude "regular and heavy alcohol drinkers" from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use.SettingThe Immune Suppression Syndrome Clinic of Mbarara, Uganda.MethodsWe defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). We evaluated the associations of current alcohol use and other variables of interest (sex, body mass index, and ART regimen) with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI).ResultsAmong 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% (95% CI: 16.8-21.1) had elevated transaminases pre-IPT, with few (1.1%) severe (≥5X the ULN). The proportion with any elevation among those currently using alcohol and those abstaining was 22.3% and 11.6%, respectively (pConclusionsPre-IPT elevated transaminases among PLWH receiving ART were common, similar to prior estimates, but severe elevations were rare. Current drinking and male sex were independently associated with elevated transaminases. Further research is needed to determine the implications of such transaminase elevations and alcohol use on providing IPT.

Residential land is expanding in the United States, and lawn now covers more area than the country's leading irrigated crop by area. Given that lawns are widespread across diverse climatic regions and there is rising concern about the environmental impacts associated with their management, there is a clear need to understand the geographic variation, drivers, and outcomes of common yard care practices. We hypothesized that 1) income, age, and the number of neighbors known by name will be positively associated with the odds of having irrigated, fertilized, or applied pesticides in the last year, 2) irrigation, fertilization, and pesticide application will vary quadratically with population density, with the highest odds in suburban areas, and 3) the odds of irrigating will vary by climate, but fertilization and pesticide application will not. We used multi-level models to systematically address nested spatial scales within and across six U.S. metropolitan areas-Boston, Baltimore, Miami, Minneapolis-St. Paul, Phoenix, and Los Angeles. We found significant variation in yard care practices at the household (the relationship with income was positive), urban-exurban gradient (the relationship with population density was an inverted U), and regional scales (city-to-city variation). A multi-level modeling framework was useful for discerning these scale-dependent outcomes because this approach controls for autocorrelation at multiple spatial scales. Our findings may guide policies or programs seeking to mitigate the potentially deleterious outcomes associated with water use and chemical application, by identifying the subpopulations most likely to irrigate, fertilize, and/or apply pesticides.

Abstract Preliminary evidence suggests perturbations of the kynurenine pathway (KP) of tryptophan metabolism in infants with single ventricle heart disease (SVHD). In 72 infants with SVHD undergoing stage 2 palliation (S2P) and 41 controls, we quantified serum KP metabolite concentrations via tandem mass spectroscopy pre‐S2P and post‐S2P at 2, 24, and 48 h and assessed metabolite relationships with post‐S2P outcomes (length of stay, hypoxemia burden, and intubation duration). Pre‐S2P, SVHD infants had lower tryptophan and serotonin levels and higher kynurenic acid, 3‐hydroxykynurenine, and picolinic acid levels than controls. Post‐S2P, metabolites peaked at 2 h, with return to baseline by 48 h for all except kynurenic acid, which remained elevated. Metabolite concentrations pre‐S2P were poorly associated with outcomes. A lower serotonin peak 2 h post‐S2P was associated with longer length of stay and intubation duration. Multiple metabolites at 24 and 48 h correlated with outcomes; notably, elevated kynurenic acid was associated with worse results for all three outcomes. Our results confirm that interstage SVHD infants have altered KP activity compared to controls. Further, the link between outcomes and KP metabolites post‐S2P—but not at baseline—demonstrates that acute, perioperative changes in tryptophan catabolism may be more important to tolerating S2P physiology than chronic interstage changes.

Each year wildland fires kill and injure trees on millions of forested hectares globally, affecting plant and animal biodiversity, carbon storage, hydrologic processes, and ecosystem services. The underlying mechanisms of fire-caused tree mortality remain poorly understood, however, limiting the ability to accurately predict mortality and develop robust modeling applications, especially under novel future climates. Virtually all post-fire tree mortality prediction systems are based on the same underlying empirical model described in Ryan and Reinhardt (1988 Can. J. For. Res. 18 1291–7), which was developed from a limited number of species, stretching model assumptions beyond intended limits. We review the current understanding of the mechanisms of fire-induced tree mortality, provide recommended standardized terminology, describe model applications and limitations, and conclude with key knowledge gaps and future directions for research. We suggest a two-pronged approach to future research: (1) continued improvements and evaluations of empirical models to quantify uncertainty and incorporate new regions and species and (2) acceleration of basic, physiological research on the proximate and ultimate causes of fire-induced tree mortality to incorporate processes of tree death into models. Advances in both empirical and process fire-induced tree modeling will allow creation of hybrid models that could advance understanding of how fire injures and kills trees, while improving prediction accuracy of fire-driven feedbacks on ecosystems and landscapes, particularly under novel future conditions.

This study examines the distributional equity of urban tree canopy (UTC) cover for Baltimore, MD, Los Angeles, CA, New York, NY, Philadelphia, PA, Raleigh, NC, Sacramento, CA, and Washington, D.C. using high spatial resolution land cover data and census data. Data are analyzed at the Census Block Group levels using Spearman's correlation, ordinary least squares regression (OLS), and a spatial autoregressive model (SAR). Across all cities there is a strong positive correlation between UTC cover and median household income. Negative correlations between race and UTC cover exist in bivariate models for some cities, but they are generally not observed using multivariate regressions that include additional variables on income, education, and housing age. SAR models result in higher r-square values compared to the OLS models across all cities, suggesting that spatial autocorrelation is an important feature of our data. Similarities among cities can be found based on shared characteristics of climate, race/ethnicity, and size. Our findings suggest that a suite of variables, including income, contribute to the distribution of UTC cover. These findings can help target simultaneous strategies for UTC goals and environmental justice concerns.

Plant species and communities often reflect historic fire regimes via ecological and evolutionary responses to recurrent fires. Plant communities of the southeastern USA experience a wide array of fire regimes, perhaps nowhere more marked than the juxtaposition of fire-prone uplands and adjacent mesic ravines along Florida's Apalachicola River. The ravines contain many endemic and disjunct species, most notably the endangered endemic conifer Torreya taxifolia. A rapid decline in T. taxifolia over the past 60 years has been associated with widespread replacement by other tree species. To understand the changes accompanying the shift in ravine composition, we compared leaf litter flammability of nine historic and contemporary species. We measured maximum flame height, flame duration, smoldering duration, mass loss, absorptive capacity, and drying rate. Ordination and perMANOVA suggest the nine species segregated into three distinct groups: the fire-impeding T. taxifolia and Taxus floridana; an intermediate group of three deciduous angiosperms; and a mixed cluster of four flammable species. Results suggest T. taxifolia and T. floridana were fire-impeding species in these communities, while contemporary dominants burn similarly to the upslope pyric species. The increasing presence of fire-facilitating species may portend a shifting fire regime that further imperils T. taxifolia and other rare species in the formerly fire-safe ravines.

Background/Objectives: Antibody light chains form amyloid fibrils that lead to progressive tissue damage in amyloid light chain (AL) amyloidosis. The properties of each patient’s unique light chain appear to determine its propensity to form amyloid. One factor is N-glycosylation, which is more frequent in amyloid-associated light chains than in light chains from the normal immune repertoire. However, the mechanisms underlying this association are unknown. Here, we investigate the frequency and position within the light chain sequence of the N-glycosylation sequence motif, or sequon. Methods: Monoclonal light chains from AL amyloidosis and multiple myeloma were identified from the AL-Base repository. Polyclonal light chains were obtained from the Observed Antibody Space resource. We compared the fraction of light chains from each group harboring an N-glycosylation sequon, and the positions of these sequons within the sequences. Results: Sequons are enriched among AL-associated light chains derived from a subset of precursor germline genes. Sequons are observed at multiple positions, which differ between the two types of light chains, κ and λ, but are similar between light chains from AL amyloidosis and multiple myeloma. Positions of sequons map to residues with surface-exposed sidechains that are compatible with the folded structures of light chains. Within the known structures of λ AL amyloid fibrils, many residues where sequons are observed are buried, inconsistent with N-glycosylation. Conclusions: There is no clear structural rationale for why N-glycosylation of κ light chains is associated with AL amyloidosis. A better understanding of the roles of N-glycosylation in AL amyloidosis is required before it can be used as a marker for disease risk.

Oxidized low density lipoprotein (LDL) may play a significant role in atherosclerosis. We have investigated the effect of pH on the oxidation of LDL by iron or copper. When LDL was oxidized by iron in the presence of cysteine in either Hanks' balanced salt solution (HBSS) or Ham's F-10 medium, an acidic pH greatly decreased the lag period and increased the rate of formation of hydroperoxides and thiobarbituric acid-reactive substances (TBARS), and increased its uptake by macrophages. There was a dose-dependent increase of LDL oxidation at acidic pH in the presence of increasing concentrations of cysteine. When LDL was oxidized by copper in HBSS, an acidic pH increased the lag phase before the rapid formation of conjugated dienes, hydroperoxides, and TBARS, but increased its uptake by macrophages. Similar results were obtained using Ham's F-10 medium. Cysteine (100 microM) inhibited the modification of LDL by copper in HBSS at both pH 7.4 and 5.5 As atherosclerotic lesions may be acidic, these observations may help to explain why LDL oxidation occurs locally at these sites.

Residential yards across the US look remarkably similar despite marked variation in climate and soil, yet the drivers of this homogenization are unknown. Telephone surveys of fertilizer and irrigation use and satisfaction with the natural environment, and measurements of inherent water and nitrogen availability in six US cities (Boston, Baltimore, Miami, Minneapolis-St. Paul, Phoenix, Los Angeles) showed that the percentage of people using irrigation at least once in a year was relatively invariant with little difference between the wettest (Miami, 85%) and driest (Phoenix, 89%) cities. The percentage of people using fertilizer at least once in a year also ranged narrowly (52%–71%), while soil nitrogen supply varied by 10x. Residents expressed similar levels of satisfaction with the natural environment in their neighborhoods. The nature and extent of this satisfaction must be understood if environmental managers hope to effect change in the establishment and maintenance of residential ecosystems.

Fire is an integral component of ecosystems globally and a tool that humans have harnessed for millennia. Altered fire regimes are a fundamental cause and consequence of global change, impacting people and the biophysical systems on which they depend. As part of the newly emerging Anthropocene, marked by human-caused climate change and radical changes to ecosystems, fire danger is increasing, and fires are having increasingly devastating impacts on human health, infrastructure, and ecosystem services. Increasing fire danger is a vexing problem that requires deep transdisciplinary, trans-sector, and inclusive partnerships to address. Here, we outline barriers and opportunities in the next generation of fire science and provide guidance for investment in future research. We synthesize insights needed to better address the long-standing challenges of innovation across disciplines to (i) promote coordinated research efforts; (ii) embrace different ways of knowing and knowledge generation; (iii) promote exploration of fundamental science; (iv) capitalize on the "firehose" of data for societal benefit; and (v) integrate human and natural systems into models across multiple scales. Fire science is thus at a critical transitional moment. We need to shift from observation and modeled representations of varying components of climate, people, vegetation, and fire to more integrative and predictive approaches that support pathways toward mitigating and adapting to our increasingly flammable world, including the utilization of fire for human safety and benefit. Only through overcoming institutional silos and accessing knowledge across diverse communities can we effectively undertake research that improves outcomes in our more fiery future.

BackgroundIsoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude "regular and heavy alcohol drinkers" from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use.SettingThe Immune Suppression Syndrome Clinic of Mbarara, Uganda.MethodsWe defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). We evaluated the associations of current alcohol use and other variables of interest (sex, body mass index, and ART regimen) with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI).ResultsAmong 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% (95% CI: 16.8-21.1) had elevated transaminases pre-IPT, with few (1.1%) severe (≥5X the ULN). The proportion with any elevation among those currently using alcohol and those abstaining was 22.3% and 11.6%, respectively (p

Wildland fires have a multitude of ecological effects in forests, woodlands, and savannas across the globe. A major focus of past research has been on tree mortality from fire, as trees provide a vast range of biological services. We assembled a database of individual-tree records from prescribed fires and wildfires in the United States. The Fire and Tree Mortality (FTM) database includes records from 164,293 individual trees with records of fire injury (crown scorch, bole char, etc.), tree diameter, and either mortality or top-kill up to ten years post-fire. Data span 142 species and 62 genera, from 409 fires occurring from 1981-2016. Additional variables such as insect attack are included when available. The FTM database can be used to evaluate individual fire-caused mortality models for pre-fire planning and post-fire decision support, to develop improved models, and to explore general patterns of individual fire-induced tree death. The database can also be used to identify knowledge gaps that could be addressed in future research.

The Earth's population will become more than 80% urban during this century. This threshold is often regarded as sufficient justification for pursuing urban ecology. However, pursuit has primarily focused on building empirical richness, and urban ecology theory is rarely discussed. The Baltimore Ecosystem Study (BES) has been grounded in theory since its inception and its two decades of data collection have stimulated progress toward comprehensive urban theory. Emerging urban ecology theory integrates biology, physical sciences, social sciences, and urban design, probes interdisciplinary frontiers while being founded on textbook disciplinary theories, and accommodates surprising empirical results. Theoretical growth in urban ecology has relied on refined frameworks, increased disciplinary scope, and longevity of interdisciplinary interactions. We describe the theories used by BES initially, and trace ongoing theoretical development that increasingly reflects the hybrid biological-physical-social nature of the Baltimore ecosystem. The specific mix of theories used in Baltimore likely will require modification when applied to other urban areas, but the developmental process, and the key results, will continue to benefit other urban social-ecological research projects.

The oxygen-redox mechanism in lithium-rich disordered rocksalt cathode materials is still not well understood. Here, the authors show that in Li2MnO2F, molecular oxygen forms in the bulk during charge and is re-incorporated into the structure as oxygen anions on discharge, but this process is associated with irreversible Mn migration, causing voltage hysteresis.

Abstract The all-oral combination of ixazomib, cyclophosphamide, and dexamethasone (ICD) is well tolerated and effective in newly diagnosed and relapsed multiple myeloma (MM). We carried out MUKeight, a randomised, controlled, open, parallel group, multi-centre phase II trial in patients with relapsed MM after prior treatment with thalidomide, lenalidomide, and a proteasome inhibitor (ISRCTN58227268), with the primary objective to test whether ICD has improved clinical activity compared to cyclophosphamide and dexamethasone (CD) in terms of progression-free survival (PFS). Between January 2016 and December 2018, 112 participants were randomised between ICD (n = 58) and CD (n = 54) in 33 UK centres. Patients had a median age of 70 years and had received a median of four prior lines of therapy. 74% were classed as frail. Median PFS in the ICD arm was 5.6 months, compared to 6.7 months with CD (hazard ratio (HR) = 1.21, 80% CI 0.9–1.6, p = 0.3634). Response rates and overall survival were not significantly different between ICD and CD. Dose modifications or omissions, and serious adverse events (SAEs), occurred more often in the ICD arm. In summary, the addition of ixazomib to cyclophosphamide and dexamethasone did not improve outcomes in the comparatively frail patients enroled in the MUKeight trial.

BACKGROUND:Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV) and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in 3 high TB-/HIV-burden countries. METHODS:We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda. Outcomes included nonfatal toxicity, fatal toxicity, life expectancy, TB cases, and TB death. RESULTS:In this simulation, 6 months of IPT + ART (IPT6) extended life expectancy over both ART alone and 36 months of IPT + ART (IPT36) in India and Uganda, but ART alone dominated in Brazil in 51.5% of simulations. Toxicity occurred in 160/1000 persons on IPT6 and 415/1000 persons on IPT36, with fatal toxicity in 8/1000 on IPT6 and 21/1000 on IPT36. Sensitivity analyses favored IPT6 in India and Uganda with high toxicity thresholds. CONCLUSIONS:The benefits of IPT for heavy drinkers outweighed its risks in India and Uganda when given for a 6-month course. The toxicity/efficacy trade-off was less in Brazil where TB incidence is lower. IPT6 resulted in fatal toxicity in 8/1000 people, whereas even higher toxicities of IPT36 negated its benefits in all countries. Data to better characterize IPT toxicity among HIV-infected drinkers are needed to improve guidance.

BACKGROUND:Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV) and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in 3 high TB-/HIV-burden countries. METHODS:We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda. Outcomes included nonfatal toxicity, fatal toxicity, life expectancy, TB cases, and TB death. RESULTS:In this simulation, 6 months of IPT + ART (IPT6) extended life expectancy over both ART alone and 36 months of IPT + ART (IPT36) in India and Uganda, but ART alone dominated in Brazil in 51.5% of simulations. Toxicity occurred in 160/1000 persons on IPT6 and 415/1000 persons on IPT36, with fatal toxicity in 8/1000 on IPT6 and 21/1000 on IPT36. Sensitivity analyses favored IPT6 in India and Uganda with high toxicity thresholds. CONCLUSIONS:The benefits of IPT for heavy drinkers outweighed its risks in India and Uganda when given for a 6-month course. The toxicity/efficacy trade-off was less in Brazil where TB incidence is lower. IPT6 resulted in fatal toxicity in 8/1000 people, whereas even higher toxicities of IPT36 negated its benefits in all countries. Data to better characterize IPT toxicity among HIV-infected drinkers are needed to improve guidance.

Understanding how livestock grazing strategies of native warm season grasses (NWSG) can impact facultative grassland bird nesting can provide insight for conservation efforts. We compared pre and post treatment effects of rotational grazing (ROT) and patch-burn grazing (PBG) for facultative grassland bird species nest success and nest-site selection on NWSG pastures at three Mid-South research sites. We established 14, 9.7 ha NWSG pastures and randomly assigned each to either ROT or PBG and monitored avian nest-site selection and nest success, 2014–2016. We collected nesting and vegetation data in 2014, before treatment implementation, as an experimental pre-treatment. We implemented treatments across all research sites in spring 2015. We used a step-wise model selection framework to estimate treatment effect for ROT or PBG on avian nest daily survival rate (DSR) and resource selection function (RSF) at the temporal scale and within-field variables. Daily survival rates were 0.93% (SE = 0.006) for field sparrow (Spizella pusilla), 0.96% (SE = 0.008) for red-winged blackbird (Agelaius phoeniceus), and 0.92% (SE = 0.01) for indigo bunting (Passerina cyanea). Model support for PBG treatment and vegetation height were indicated as negative and positive influences for field sparrow DSR, respectively. Red-winged blackbirds’ DSR were negatively influenced by ROT while vegetation height positively affected DSR, and DSR for indigo bunting did not differ among treatments. Combined RSF models indicated nest-site selection for all species was positively related to vegetation height and only weakly associated with other within-field variables. We provide evidence that ROT and/or PBG effects vary by species for DSR for these three facultative grassland birds, and vegetation characteristics affected their nest-site selection in the Mid-South USA. A lack of disturbance in Mid-South grasslands can lead to higher successional stages (i.e., mix shrub-grassland), but some combination of ROT, PBG, and unburned/ungrazed areas can provide adequate nesting habitat on small pasture lands (∼1.8 –7.8 ha) for various facultative grassland birds and potentially offer the opportunity to simultaneously maintain livestock production and grassland bird nesting habitat.

Characterizing the extent of genetic differentiation among individuals and its distribution across the genome is increasingly important to inform both conservation and management of exploited species. The Greenland Halibut is one of the main demersal fish species to be commercially exploited in Eastern Canada, and accurate information on geographic population structure and local adaptation is required to ensure the long-term presence of this species. We generated high-quality whole-genome sequencing data for 1,297 Greenland Halibut sampled across 32 locations throughout the Northwest Atlantic (from Arctic Canadian and Greenlandic coasts to the Gulf of St Lawrence). Population genetic structure was analyzed, revealing an absence of population differentiation between Canada and west Greenland but significant genetic differentiation between the Gulf of Saint Lawrence and the remainder of the Northwest Atlantic. Except for Gulf of Saint Lawrence, Greenland Halibut thus appear to be panmictic throughout the Northwest Atlantic. Environmental Association Analyses revealed that the environment explained up to 51 % might be replaced by 51% of the differentiation observed between the two stocks, with both ocean-bottom and surface variables (e.g., temperature and oxygen) involved in the observed genomic differentiation. Altogether, these results indicate that phenotypic differences previously observed between the Gulf of Saint Lawrence and the Northwest Atlantic likely resulted from functional adaptive divergence to their respective environmental conditions. Using coalescent simulations, we also assessed how high levels of migration between the two stocks would allow Greenland Halibut to potentially escape unfavorable environmental conditions in the Gulf of Saint Lawrence. In addition to supporting the management of this important exploited species, this work highlights the utility of using comprehensive genomic datasets to characterize the effects of climate change across a wider range of species.

Abstract Recent wildfires across western North America have burned with uncharacteristically high severity, representing a substantial departure from natural fire regimes. In mixed‐conifer and pine–oak ecosystems of the southern Cascade Range, widespread shifts in stand structure and composition have led to a diversity of post‐wildfire vegetation responses. When recent wildfire “footprints” reburn in subsequent fires, their recovery pathways are complex. In order to understand the effects of overlapping mixed‐severity fires, we quantified changes in overstory and midstory structure and species composition for time periods prior to and following two large overlapping wildfires in the southern Cascades: the 2000 Storrie and 2012 Chips Fires. Plots were stratified into 16 severity combinations (unburned, low, moderate, and high in the Storrie Fire combined with the same four categories in the Chips Fire: e.g., moderate Storrie/high Chips) across the 9000‐ha overlapping burned area. Following the two fires, tree quadratic mean diameter and stand density declined for most species, but changes were species‐specific. Compared with preburn values, importance values for fire‐sensitive white fir (Abies concolor) were reduced by 66%, while resprouting fire‐resilient California black oak (Quercus kelloggii) importance values increased by 37% in severity combinations that included at least one high‐severity fire. Greatest shifts were documented in sites that burned twice at high severity, where resulting vegetation was dominated by oak sprout clumps and resprouting and fire‐stimulated montane chaparral species, while unburned and low‐severity strata retained a substantial component of Douglas‐fir (Pseudotsuga menziesii) and white fir. Results suggest that repeated moderate‐ and high‐severity fires can result in ecosystem state shifting toward fire‐resilient oak‐shrub communities in this fire‐prone landscape. Managers seeking greater landscape resilience can implement treatments such as thinning and prescribed burning, while taking advantage of fire‐created patches such as these in areas where the likelihood of a hotter and drier future makes the reestablishment of continuous forest cover unrealistic.

Overstory trees serve multiple functions in grassy savannas. Past research has shown that understory species can vary along gradients of canopy cover and basal area in savannas. This variation is frequently associated with light availability but could also be related to other mechanisms, such as heterogeneity in soil and litter depth and fire intensity. Several savanna studies have found differences in understory plant functional groups within the local environment near trees versus away from them in canopy openings. Although small‐scale variation is known to be high in southeastern U.S. pine savannas, patterns in understory species diversity have not been examined at the scale of individual overstory pine trees in this system. We conducted an observational study of the relationship between understory plant communities and proximity to individual pine trees in xeric and mesic pine savannas in frequently burned sites (1–3 year intervals). We recorded the plant community composition in plots adjacent to tree boles (basal) or outside crown driplines (open). Within each environment, raw species richness was significantly greater in open locations, where light transmittance was greater. In contrast, rarified species richness did not differ. Multivariate analyses showed that community composition differed significantly between basal and open plots. One native, woody species in each environment, Serenoa repens (W. Bartram) Small in mesic and Diospyros virginiana L. in xeric, was more abundant in basal plots. In mesic environments, eight species had greater occurrence in open plots. In xeric environments, four understory forbs were more abundant in open plots. Our results support previous research indicating that individual pine trees are associated with significant variation in understory vegetation in pine savannas. [ABSTRACT FROM AUTHOR]

Background: Hypercalciuria is the most common risk factor for kidney stone formation, including in pediatric patients. However, the etiology is often unknown and children are frequently diagnosed with idiopathic hypercalciuria. Nearly 50% of children with hypercalciuria have a first-degree relative with kidney stones, suggesting a strong genetic basis for this disease. A failure of calcium reabsorption from the proximal nephron is implicated in the pathogenesis of hypercalciuria. Claudin-2 is a tight junction protein abundantly expressed in the proximal tubule. It confers paracellular permeability to calcium that is essential for transport across the proximal tubule where the majority of filtered calcium is reabsorbed. Objective: Our objective was to examine the frequency of coding variations in CLDN2 in a cohort of children with idiopathic hypercalciuria. Design: Mixed method including retrospective chart review and patient interview, followed by genetic sequencing. Setting: Three tertiary care centers in Canada. Patients: Children (age 1-18 years) with idiopathic hypercalciuria. Patients with other causes of hypercalciuria were excluded. Methods: Data were collected from 40 patients with idiopathic hypercalciuria. Informed consent to collect DNA was obtained from 13 patients, and the final and only coding exon of CLDN2 was sequenced. Results: The majority of patients were male, white, and had a positive family history of kidney stones. Parathyroid hormone levels were significantly lower than the reference range ( P < .001). The levels of 1,25-dihydroxyvitamin D were also significantly higher in our patient cohort, relative to the reference range ( P < .001). Sequence analysis of CLDN2 did not identify any coding variations. Limitations: Sequencing analysis was limited to the final coding exon and small sample size. Conclusions: CLDN2 coding variations are not a common cause of idiopathic hypercalciuria in Canadian children. Further study is needed to determine the causes of hypercalciuria in pediatric patients and develop targeted therapies.

Introduction: Bortezomib has been reported to favourably impact the outcomes of t (4;14) and del(17p) in multiple myeloma (MM), but its impact on gain 1q (+1q) is unknown. Methods: To address this, 250 patients treated with bortezomib-based induction were analysed. All myeloma samples had fluorescence in situ hybridization (FISH) performed on CD138-sorted bone marrow aspirate, and plasma cells were analysed using DNA probes specific for the following chromosomal aberrations: del(13q14), del(17p), t (14;16), t (4;14), and +1q. Presence of +1q was defined as the presence of at least three copies of 1q21 at the cut off level of 20% of bone marrow plasma cells. Results: +1q identified in 167 (66.8%) and associated with t (4;14) and high lactate dehydrogenase (LDH). +1q was not associated with response rate but shorter event-free survival (EFS) (median EFS 35 vs 55 months, p = 0.05) and overall survival (OS) (median OS 74 vs 168 months, p = 0.00025). Copy number and clone size did not impact survival. Multivariate analysis showed +1q was an independent adverse factor for OS together with International Staging System (ISS)3, high LDH, del(17p) and t (4;14). When a risk score of 1 was assigned to each independent adverse factor, OS was shortened incrementally by a risk score from 0 to 4. Post-relapse/progression survival was inferior in those with +1q (median 60 vs 118 months, p = 0.000316). Autologous stem cell transplantation (ASCT) improved OS for those with +1q (median OS 96 vs 49 months, p = 0.000069). Conclusion: +1q is an adverse factor for OS in MM uniformly treated with bortezomib-based induction but was partially mitigated by ASCT. A risk scoring system comprising +1q, LDH, high-risk FISH, and ISS is a potential tool for risk stratification in MM.

Traditional methods of fieldwork delivery can present learners with a range of physical, cognitive and social challenges which may subsequently hinder their ability to engage effectively with learning. We developed a residential geoscience field course designed to be physically accessible to, and socially inclusive of, a diverse range of learners including those with limited physical mobility and neurodiverse conditions. This paper presents the logistical and pedagogical challenges involved in delivering such a field course. In terms of pedagogic design scheduling, pace and timing, and the ability to access content in multiple ways were critical to ensuring that all students were included in the learning. The most effective mitigations were the simplest and benefitted the whole group. Practical interventions found to support access and inclusion for the benefit of all participants included using an audio tour-guide system to communicate with students at field locations, using a four-wheel drive vehicle to improve access to specific locations, providing alternative exercises such as prepared photomicrographs and rock specimens, providing electronic tablets with suitable apps, and selecting accommodation with accessible common-room spaces, and a dedicated quiet room.

This study examines the distributional equity of urban tree canopy (UTC) cover for Baltimore, MD, Los Angeles, CA, New York, NY, Philadelphia, PA, Raleigh, NC, Sacramento, CA, and Washington, D.C. using high spatial resolution land cover data and census data. Data are analyzed at the Census Block Group levels using Spearman's correlation, ordinary least squares regression (OLS), and a spatial autoregressive model (SAR). Across all cities there is a strong positive correlation between UTC cover and median household income. Negative correlations between race and UTC cover exist in bivariate models for some cities, but they are generally not observed using multivariate regressions that include additional variables on income, education, and housing age. SAR models result in higher r-square values compared to the OLS models across all cities, suggesting that spatial autocorrelation is an important feature of our data. Similarities among cities can be found based on shared characteristics of climate, race/ethnicity, and size. Our findings suggest that a suite of variables, including income, contribute to the distribution of UTC cover. These findings can help target simultaneous strategies for UTC goals and environmental justice concerns.

Temperature varies on multiple timescales and ectotherms must adjust to these changes to survive. These adjustments may lead to energetic trade-offs between self-maintenance and reproductive investment. However, we know little about how diurnal and seasonal temperature changes impact energy allocation. Here we used a combination of empirical data and modeling of both thermoregulatory behaviors and body temperature to examine potential energetic trade-offs in the dung beetle Onthophagus taurus. Beginning in March 2020, universities and laboratories were officially closed due to the COVID-19 pandemic. We thus performed experiments at a private residence near Knoxville, Tennessee, USA, leveraging the heating, ventilation and air conditioning of the home to manipulate temperature and compare beetle responses to stable indoor temperatures versus variable outdoor temperatures. We collected O. taurus beetles in the early-, mid-, and late-breeding seasons to examine energetics and reproductive output in relation to diurnal and seasonal temperature fluctuations. We recorded the mass of field fresh beetles before and after a 24-h fast and used the resulting change in mass as a proxy for energetic costs of self-maintenance across seasons. To understand the impacts of diurnal fluctuations on energy allocation, we held beetles either indoors or outdoors for 14-day acclimation trials, fed them cow dung, and recorded mass change and reproductive output. Utilizing biophysical models, we integrated individual-level biophysical characteristics, microhabitat-specific performance, respirometry data, and thermoregulatory behaviors to predict temperature-induced changes to the allocation of energy toward survival and reproduction. During 24 h of outdoor fasting, we found that beetles experiencing reduced temperature variation lost more mass than those experiencing greater temperature variation, and this was not affected by season. By contrast, during the 14-day acclimation trials, we found that beetles experiencing reduced temperature variation (i.e., indoors) gained more mass than those experiencing greater temperature variation (i.e., outdoors). This effect may have been driven by shifts in the metabolism of the beetles during acclimation to increased temperature variation. Despite the negative relationship between temperature variation and energetic reserves, the only significant predictor of reproductive output was mean temperature. Taken together, we find that diurnal temperature fluctuations are important for driving energetics, but not reproductive output. [ABSTRACT FROM AUTHOR]

Fluxes of halogenated volatile organic compounds (VOCs) over the Southern Ocean remain poorly understood, and few atmospheric measurements exist to constrain modeled emissions of these compounds. We present observations of CHBr3, CH2Br2, CH3I, CHClBr2, CHBrCl2, and CH3Br during the O2∕N2 Ratio and CO2 Airborne Southern Ocean (ORCAS) study and the second Atmospheric Tomography mission (ATom-2) in January and February of 2016 and 2017. Good model–measurement correlations were obtained between these observations and simulations from the Community Earth System Model (CESM) atmospheric component with chemistry (CAM-Chem) for CHBr3, CH2Br2, CH3I, and CHClBr2 but all showed significant differences in model : measurement ratios. The model : measurement comparison for CH3Br was satisfactory and for CHBrCl2 the low levels present precluded us from making a complete assessment. Thereafter, we demonstrate two novel approaches to estimate halogenated VOC fluxes; the first approach takes advantage of the robust relationships that were found between airborne observations of O2 and CHBr3, CH2Br2, and CHClBr2. We use these linear regressions with O2 and modeled O2 distributions to infer a biological flux of halogenated VOCs. The second approach uses the Stochastic Time-Inverted Lagrangian Transport (STILT) particle dispersion model to explore the relationships between observed mixing ratios and the product of the upstream surface influence of sea ice, chl a, absorption due to detritus, and downward shortwave radiation at the surface, which in turn relate to various regional hypothesized sources of halogenated VOCs such as marine phytoplankton, phytoplankton in sea-ice brines, and decomposing organic matter in surface seawater. These relationships can help evaluate the likelihood of particular halogenated VOC sources and in the case of statistically significant correlations, such as was found for CH3I, may be used to derive an estimated flux field. Our results are consistent with a biogenic regional source of CHBr3 and both nonbiological and biological sources of CH3I over these regions.

Abstract Background While genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS). Results GWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80–491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus. Conclusions Our findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.