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Background: Secure messaging use is associated with improved diabetes-related outcomes. However, it is less clear how secure messaging supports diabetes management., Objective: We examined secure message topics between patients and clinical team members in a national sample of veterans with type 2 diabetes to understand use of secure messaging for diabetes management and potential associations with glycemic control., Methods: We surveyed and analyzed the content of secure messages between 448 US Veterans Health Administration patients with type 2 diabetes and their clinical teams. We also explored the relationship between secure messaging content and glycemic control., Results: Explicit diabetes-related content was the most frequent topic (72.1% of participants), followed by blood pressure (31.7% of participants). Among diabetes-related conversations, 90.7% of patients discussed medication renewals or refills. More patients with good glycemic control engaged in 1 or more threads about blood pressure compared to those with poor control (37.5% vs 27.2%, P=.02). More patients with good glycemic control engaged in 1 more threads intended to share information with their clinical team about an aspect of their diabetes management compared to those with poor control (23.7% vs 12.4%, P=.009)., Conclusions: There were few differences in secure messaging topics between patients in good versus poor glycemic control. Those in good control were more likely to engage in informational messages to their team and send messages related to blood pressure. It may be that the specific topic content of the secure messages may not be that important for glycemic control. Simply making it easier for patients to communicate with their clinical teams may be the driving influence between associations previously reported in the literature between secure messaging and positive clinical outcomes in diabetes., (©Stephanie A Robinson, Mark Zocchi, Carolyn Purington, Linda Am, Kathryn DeLaughter, Varsha G Vimalananda, Dane Netherton, Arlene S Ash, Timothy P Hogan, Stephanie L Shimada. Originally published in JMIR Diabetes (https://diabetes.jmir.org), 23.03.2023.)

Sleep disturbances, including chronic insomnia and sleep apnea, are major concerns for US veterans, with rising rates and detrimental effects on physical, mental, and social well-being. Sleep disturbances in veterans are also underdiagnosed and undertreated for reasons that include limited sleep clinician availability, long wait times, and the time commitment for treatment. Greater use of sleep health information technologies could improve access to assessment and treatment of sleep disturbances. However, the assessment of acceptance of these technologies among veterans is still ongoing. This mixed-method study combines data from two separate but similar randomized controlled trials to assess acceptance of sleep health information technologies for veterans with chronic insomnia. Sleep health information technologies included in these trials were the following: (1) a WatchPAT sleep monitor for home-based sleep assessment, including detection of sleep apnea, and (2) the VA mobile app Cognitive Behavioral Therapy for Insomnia (CBT-i Coach), which supports self-management of insomnia. The combined sample of 37 veterans receiving care within one New England VA medical center completed a six-week trial using both health information technology tools. Participants completed a survey and interview at the end of the 6 weeks. Overall, participants found the tools acceptable, easy to use, and useful and reported they would use them in the future. Thus, these sleep health information technologies appear to provide an acceptable remote option for assessing and managing sleep issues for veterans. ClinicalTrials.gov NCT02392000; http://clinicaltrials.gov/ct2/show/NCT02392000 and ClinicalTrials.gov NCT03305354; https://clinicaltrials.gov/ct2/show/NCT03305354., Competing Interests: Competing InterestsThe authors declare no competing interests., (© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022.)

Understanding the toxicity of organic compounds in oil sands process-affected water (OSPW) is necessary to inform the development of environmental guidelines related to wastewater management in Canada's oil sands region. In the present study, we investigated the effects of naphthenic acid fraction compounds (NAFCs), one of the most toxic components of OSPW, on mating behaviour, fertility, and offspring viability in the wood frog (Rana sylvatica). Wild adult wood frogs were exposed separately from the opposite sex to 0, 5, or 10 mg/L of OSPW-derived NAFCs for 24 h and then combined in outdoor lake water mesocosms containing the same NAFC concentrations (n = 2 males and 1 female per mesocosm, n = 3 mesocosms per treatment). Mating events were recorded for 48 h and egg masses were measured to determine adult fertility. NAFC exposure had no significant effect on mating behaviour (probability of amplexus and oviposition, amplexus and oviposition latency, total duration of amplexus and number of amplectic events) or fertility (fertilization success and clutch size). Tadpoles (50 individuals per mesocosm at hatching, and 15 individuals per mesocosm from 42 d post-hatch) were reared in the same mesocosms under chronic NAFC exposure until metamorphic climax (61-85 d after hatching). Offspring exposed to 10 mg/L NAFCs during development were less likely to survive and complete metamorphosis, grew at a reduced rate, and displayed more frequent morphological abnormalities. These abnormalities included limb anomalies at metamorphosis, described for the first time after NAFC exposure. The results of this study suggest that NAFCs reduce wood frog reproductive success through declines in offspring viability and therefore raise the concern that exposure to NAFCs during reproduction and development may affect the recruitment of native amphibian populations in the oil sands region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Antarctic terrestrial biodiversity faces multiple threats, from invasive species to climate change. Yet no large-scale assessments of threat management strategies exist. Applying a structured participatory approach, we demonstrate that existing conservation efforts are insufficient in a changing world, estimating that 65% (at best 37%, at worst 97%) of native terrestrial taxa and land-associated seabirds are likely to decline by 2100 under current trajectories. Emperor penguins are identified as the most vulnerable taxon, followed by other seabirds and dry soil nematodes. We find that implementing 10 key threat management strategies in parallel, at an estimated present-day equivalent annual cost of US$23 million, could benefit up to 84% of Antarctic taxa. Climate change is identified as the most pervasive threat to Antarctic biodiversity and influencing global policy to effectively limit climate change is the most beneficial conservation strategy. However, minimising impacts of human activities and improved planning and management of new infrastructure projects are cost-effective and will help to minimise regional threats. Simultaneous global and regional efforts are critical to secure Antarctic biodiversity for future generations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Amphibians have been facing global declines over the last decades from direct and indirect effects of anthropogenic activities. A contributor to declines is waterway contamination from agricultural runoffs of pesticides such as neonicotinoids. Beyond direct and indirect effects of the pesticide, few studies have investigated the possible interactions between neonicotinoids and natural environmental stressors across larval development, which could alter the strength and direction of observed neonicotinoid effects. The present study used a fully crossed design to investigate how a concentration of imidacloprid (a neonicotinoid; 10 µg/L) measured in surface waters interacted with low and high population densities (0.33 and 1 tadpole/L, respectively), an important environmental stressor, to influence behavior and development across metamorphosis in wood frogs (Rana sylvatica), known to breed in agricultural landscapes. Behaviors were measured in the absence and presence of predation cues using open-field tests at three distinct developmental stages, up to the metamorph stage. We found that imidacloprid did not interact with population density or independently affect behaviors in the absence of predation cues. However, individuals raised at high density compared with low density were more active at an early developmental stage but less active at metamorphic climax. Furthermore, both density and imidacloprid independently decreased the natural freezing response of tadpoles to predation cues. Finally, we found that distance traveled in the open-field test was weakly repeatable between aquatic stages but not repeatable across metamorphosis, a pattern that was not affected by treatments. The present study provides novel insights on the ecotoxicology of imidacloprid in the presence of a natural stressor, highlighting the importance of including behavioral assays and natural stressors in studies of amphibian ecotoxicology. Environ Toxicol Chem 2022;41:2968-2980. © 2022 SETAC., (© 2022 SETAC.)

Anthropogenic climate change is causing observable changes in Antarctica and the Southern Ocean including increased air and ocean temperatures, glacial melt leading to sea-level rise and a reduction in salinity, and changes to freshwater water availability on land. These changes impact local Antarctic ecosystems and the Earth's climate system. The Antarctic has experienced significant past environmental change, including cycles of glaciation over the Quaternary Period (the past ~2.6 million years). Understanding Antarctica's paleoecosystems, and the corresponding paleoenvironments and climates that have shaped them, provides insight into present day ecosystem change, and importantly, helps constrain model projections of future change. Biological archives such as extant moss beds and peat profiles, biological proxies in lake and marine sediments, vertebrate animal colonies, and extant terrestrial and benthic marine invertebrates, complement other Antarctic paleoclimate archives by recording the nature and rate of past ecological change, the paleoenvironmental drivers of that change, and constrain current ecosystem and climate models. These archives provide invaluable information about terrestrial ice-free areas, a key location for Antarctic biodiversity, and the continental margin which is important for understanding ice sheet dynamics. Recent significant advances in analytical techniques (e.g., genomics, biogeochemical analyses) have led to new applications and greater power in elucidating the environmental records contained within biological archives. Paleoecological and paleoclimate discoveries derived from biological archives, and integration with existing data from other paleoclimate data sources, will significantly expand our understanding of past, present, and future ecological change, alongside climate change, in a unique, globally significant region., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Antarctic biodiversity faces an unknown future with a changing climate. Most terrestrial biota is restricted to limited patches of ice-free land in a sea of ice, where they are adapted to the continent's extreme cold and wind and exploit microhabitats of suitable conditions. As temperatures rise, ice-free areas are predicted to expand, more rapidly in some areas than others. There is high uncertainty as to how species' distributions, physiology, abundance, and survivorship will be affected as their habitats transform. Here we use current knowledge to propose hypotheses that ice-free area expansion (i) will increase habitat availability, though the quality of habitat will vary; (ii) will increase structural connectivity, although not necessarily increase opportunities for species establishment; (iii) combined with milder climates will increase likelihood of non-native species establishment, but may also lengthen activity windows for all species; and (iv) will benefit some species and not others, possibly resulting in increased homogeneity of biodiversity. We anticipate considerable spatial, temporal, and taxonomic variation in species responses, and a heightened need for interdisciplinary research to understand the factors associated with ecosystem resilience under future scenarios. Such research will help identify at-risk species or vulnerable localities and is crucial for informing environmental management and policymaking into the future., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Objective: To assess anti-Ro52 and anti-Ro60 serologic profiles as markers of clinically relevant phenotypic subsets of patients with Sjögren's syndrome (SS)., Methods: From a cohort of 839 consecutive patients with suspected or established SS seen in our multidisciplinary SS center, we compared the association of key phenotypic features in 390 patients who fulfilled SS classification criteria and in the parent cohort, stratifed by the presence of both anti-Ro60 and anti-Ro52, anti-Ro60 alone, and anti-Ro52 alone., Results: The SS cohort included 227 patients (58%) with both anti-Ro60 and anti-Ro52, 65 (17%) with anti-Ro60 alone, 58 (15%) with anti-Ro52 alone, and 40 (10%) with neither antibody. Those with both anti-Ro60 and anti-Ro52 had a significantly increased prevalence of abnormal ocular surface staining, focal lymphocytic sialadenitis with focus score ≥1, antinuclear antibody ≥1:320, anti-SSB/La, rheumatoid factor, and IgG ≥15.6 gm/liter (P < 0.0016 for all). The groups with isolated anti-Ro52 and anti-Ro60 were equivalent to each other in their phenotypic associations, except for rheumatoid factor, which was higher in the anti-Ro52 alone group. The associations of these Ro antibody serologic profiles were similar in the parent cohort, except for additional associations with salivary gland enlargement and parotid gland ultrasound score., Conclusion: SS patients with both anti-Ro60 and anti-Ro52 antibodies are distinguished by a higher prevalence of markers of B-cell hyperactivity and glandular inflammation. Antibody reactivity to both Ro60 and Ro52 may thus serve as an important inclusion criterion for SS patients in clinical trials where the therapeutic agent targets pathways mediating these pathogenic abnormalities., (© 2021 American College of Rheumatology.)

Objective: To estimate the cost savings associated with a pedometer-based, web-mediated physical activity intervention in a cohort of US veterans with chronic obstructive pulmonary disease (COPD)., Study Design: Economic analysis., Methods: We constructed a decision tree from the health care system perspective incorporating adjusted relative risk of a pedometer-based, web-mediated intervention for COPD-related acute exacerbations, acute exacerbation-related costs (ie, emergency department visits and hospitalizations), and intervention-related costs. Total COPD-related costs were estimated per patient across 12 months. Probabilistic sensitivity analysis with Monte Carlo simulation was used to estimate uncertainty in the model findings., Results: In the deterministic (base case) model, the model estimated costs to be $4236 per participant who used the pedometer-based, web-mediated intervention compared with $7913 per participant in the control group (estimated $3677 saved in 1 year compared with the control group). The model findings were robust to probabilistic sensitivity analysis, with a difference in mean costs of $4582 (95% probability interval, $4084-$5080; P < .001). Cost savings in the model were driven by the adjusted relative risk of the web-based intervention, probability of a COPD-related acute exacerbation, rate of hospitalization, probability of hospitalization, and cost of hospitalization., Conclusions: A pedometer-based, web-mediated physical activity intervention yielded substantial cost savings. Increased implementation of the intervention could markedly reduce the economic burden of COPD for payers and patients.

Successful conservation of threatened species and ecosystems in a rapidly changing world requires scientifically sound decision-making tools that are readily accessible to conservation practitioners. Physiological applications that examine how plants and animals interact with their environment are now widely used when planning, implementing and monitoring conservation. Among these tools, stable-isotope physiology is a potentially powerful, yet under-utilized cornerstone of current and future conservation efforts of threatened and endangered plants. We review the underlying concepts and theory of stable-isotope physiology and describe how stable-isotope applications can support plant conservation. We focus on stable isotopes of carbon, hydrogen, oxygen and nitrogen to address plant ecophysiological responses to changing environmental conditions across temporal scales from hours to centuries. We review examples from a broad range of plant taxa, life forms and habitats and provide specific examples where stable-isotope analysis can directly improve conservation, in part by helping identify resilient, locally adapted genotypes or populations. Our review aims to provide a guide for practitioners to easily access and evaluate the information that can be derived from stable-isotope signatures, their limitations and how stable isotopes can improve conservation efforts., (© The Author(s) 2022. Published by Oxford University Press and the Society for Experimental Biology.)

Bryophytes are the group of land plants with the lowest photosynthetic rates, which was considered to be a consequence of their higher anatomical CO2 diffusional limitation compared with tracheophytes. However, the most recent studies assessing limitations due to biochemistry and mesophyll conductance in bryophytes reveal discrepancies based on the methodology used. In this study, we compared data calculated from two different methodologies for estimating mesophyll conductance: variable J and the curve-fitting method. Although correlated, mesophyll conductance estimated by the curve-fitting method was on average 4-fold higher than the conductance obtained by the variable J method; a large enough difference to account for the scale of differences previously shown between the biochemical and diffusional limitations to photosynthesis. Biochemical limitations were predominant when the curve-fitting method was used. We also demonstrated that variations in bryophyte relative water content during measurements can also introduce errors in the estimation of mesophyll conductance, especially for samples which are overly desiccated. Furthermore, total chlorophyll concentration and soluble proteins were significantly lower in bryophytes than in tracheophytes, and the percentage of proteins quantified as Rubisco was also significantly lower in bryophytes (<6.3% in all studied species) than in angiosperms (>16% in all non-stressed cases). Photosynthetic rates normalized by Rubisco were not significantly different between bryophytes and angiosperms. Our data suggest that the biochemical limitation to photosynthesis in bryophytes is more relevant than so far assumed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Induction of non-photochemical quenching (NPQ) of chlorophyll fluorescence in leaves affords photoprotection to the photosynthetic apparatus when, for whatever reason, photon capture in the antennae of photosystems exceeds their capacity to utilise this excitation in photochemistry and ultimately in CO2 assimilation. Here we augment traditional monitoring of NPQ using the fast time resolution, remote and relatively non-intrusive light induced fluorescence transient (LIFT) technique (Kolber et al . 2005 ; Osmond et al . 2017 ) that allows direct measurement of functional (σ'PSII ) and optical cross-sections (a 'PSII ) of PSII in situ , and calculates the half saturation light intensity for ETR (E k ). These parameters are obtained from the saturation and relaxation phases of fluorescence transients elicited by a sequence of 270, high intensity 1 μs flashlets at controlled time intervals over a period of 30 ms in the QA flash at intervals of a few seconds. We report that although σ'PSII undergoes large transient increases after transfer from dark to strong white light (WL) it declines little in steady-state as NPQ is induced in shade- and sun-grown spinach and Arabidopsis genotypes Col , OEpsbs , pgr 5bkg , stn 7 and stn 7/8. In contrast, σ'PSII increases by ~30% when induction of NPQ in spinach is inhibited by dithiothreitol and by inhibition of NPQ in Arabidopsis npq 1, npq 4 and pgr 5. We propose this increase in σ'PSII arises as some excitation from closed PSII reaction centres is transferred to open centres when excitation partitioning to photochemistry (Y II ) and NPQ (Y NP ) declines, and is indicated by an increased excitation dissipation from closed PSII centres (Y NO , including fluorescence emission). Although E k increases following dissipation of excitation as heat when NPQ is engaged, it declines when NPQ is inhibited. Evidently photochemistry becomes more easily light saturated when excitation is transferred from closed RCIIs to open centres with larger σ'PSII . The NPQ mutant pgr 5 is an exception; E k increases markedly in strong light as electron transport QA → PQ and PQ → PSI accelerate and the PQ pool becomes strongly reduced. These novel in situ observations are discussed in the context of contemporary evidence for functional and structural changes in the photosynthetic apparatus during induction of NPQ.

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km 2 resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km 2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Physical activity (PA) is suggested as an easily accessible adjunctive lifestyle intervention for insomnia. It is not clear if PA is equally beneficial across different levels of insomnia severity. The current study examined the relationship between daily PA (steps) and sleep (duration, efficiency, and quality) across the spectrum of insomnia severity. Multilevel models estimated day-to-night relationships between PA and sleep, and if insomnia severity moderated these relationships. Days with greater PA were associated with nights with longer sleep duration. This was moderated by insomnia severity; PA was associated with longer sleep that night in participants with mild insomnia and associated with less sleep in those with severe insomnia. PA was not associated with sleep efficiency or quality. PA is potentially an easily accessible and impactful intervention to promote sleep duration in participants who are experiencing less severe sleep disturbance. More complex, resource-intensive interventions may be needed as insomnia severity increases., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Many chemicals in commonly used household and industrial products are being released into the environment, yet their toxicity is poorly understood. The synthetic phenolic antioxidant, 4,4'-thiobis(6-t-butyl-m-cresol) (CAS 96-69-5; TBBC) is present in many common products made of rubber and plastic. Yet, this phenolic antioxidant has not been tested for potential toxicity and developmental disruption in amphibians, a sensitive and susceptible class. We investigated whether acute and chronic exposure to TBBC would interfere with thyroid hormone-dependent developmental processes in the frog Silurana tropicalis and thus affect its early life-stage development. We exposed S. tropicalis embryos at the Nieuwkoop-Faber (NF) 9-10 stage to TBBC at nominal concentrations (0, 25, 50, 75, 100, 200 and 400 μg/L) to determine the 96h lethal concentrations and sublethal effects. We conducted a chronic exposure starting at stage NF47-48 to three sublethal TBBC nominal concentrations (0, 0.002, 0.1 and 5 μg/L) for 48-52 days to evaluate effects on growth and metamorphosis. The 96h lethal and effective (malformations) TBBC concentrations (LC 50 and EC 50 ) were 70.5 and 76.5 μg/L, respectively. Acute exposure to all TBBC concentrations affected S. tropicalis growth and was lethal at 200 and 400 μg/L. Chronic exposure to sublethal TBBC concentrations reduced body size by 8% at 5 μg/L and body mass by 17% at 0.002 μg/L when metamorphosis was completed. This study demonstrates that TBBC is toxic, induces malformations and inhibits tadpole growth after acute and chronic exposures. These findings call for further investigations on the mode of actions of TBBC and related antioxidants for developmental disruption in amphibians., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth's surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1-67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change., (© 2022. The Author(s).)

There has been increased incentivization to develop remote exercise training programs for those living with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD). Remote programs offer patients an opportunity to overcome barriers to accessing traditional in-person programs, such as pulmonary rehabilitation (PR). Methods to deliver exercise training remotely range in complexity and types of technological modalities, including phone calls, real-time video conferencing, web- and app-based platforms, video games, and virtual reality (VR). There are a number of studies demonstrating the effectiveness of these programs on exercise capacity, dyspnea, and health-related quality of life (HRQL). However, there is great variation in these programs, making it difficult to assess findings across studies. Other aspects that contribute to the effectiveness of these programs include stakeholder perceptions, such as motivation and willingness to engage, and adherence. Finally, while the intent of these remote programs is to overcome barriers to access, they may inadvertently exacerbate access disparities. Future program development efforts should focus on standardizing how remote exercise training is delivered, engaging stakeholders early on to develop patient-centered programs that patients will want to use, and understanding the heterogeneous preferences and needs of those living with chronic respiratory disease in order to facilitate engagement with these programs.

Therapeutic monoclonal antibodies and their derivatives are key components of clinical pipelines in the global biopharmaceutical industry. The availability of large datasets of antibody sequences, structures, and biophysical properties is increasingly enabling the development of predictive models and computational tools for the "developability assessment" of antibody drug candidates. Here, we provide an overview of the antibody informatics tools applicable to the prediction of developability issues such as stability, aggregation, immunogenicity, and chemical degradation. We further evaluate the opportunities and challenges of using biopharmaceutical informatics for drug discovery and optimization. Finally, we discuss the potential of developability guidelines based on in silico metrics that can be used for the assessment of antibody stability and manufacturability.

Glucocorticoid hormones (GCs) help vertebrates maintain homeostasis during and following challenging events. Short-term elevations in GC levels are necessary for survival, whereas longer-term changes can lead to reduced reproductive output and immunosuppression. Persistent environmental contaminants (ECs) are widespread globally. Experimental exposure of individuals to ECs is associated with varying GC responses, within, and across, species and contaminants. Individuals exposed to ECs over long durations are expected to have prolonged GC elevations, which likely affect their health. We conducted a meta-analysis to test for a relationship between fish GC levels and experimental exposure to ECs, and to explore potential moderators, including duration of exposure, that could help explain the variation in effect sizes within and between studies. We report almost exclusively on cortisol responses of teleost fish to ECs. Although there was much variation in effect sizes, captive-bred fish exposed to ECs had baseline GC levels 1.5× higher than unexposed fish, and fish exposed to pharmaceuticals (estradiols and stimulants being mainly considered) had baseline GC levels approximately 2.5× higher than unexposed fish. We found that captive-bred and wild-caught fish did not differ in GC levels after exposure to the same classes of ECs - studies on captive bred fish may thus enable inferences about GC responses to ECs for wild species. Furthermore, effect sizes did not differ between baseline and challenge-induced GC measures. In different analyses, duration of exposure was negatively correlated to effect size, suggesting that the GC response may acclimate after chronic exposure to some ECs which could potentially alter the GC response of EC-exposed fish to novel stressors. Future studies should explore the effect of multiple stressors on the fish GC response and perform tests on a broader array of contaminant types and vertebrate classes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Identifying the epitope of an antibody is a key step in understanding its function and its potential as a therapeutic. Sequence-based clonal clustering can identify antibodies with similar epitope complementarity, however, antibodies from markedly different lineages but with similar structures can engage the same epitope. We describe a novel computational method for epitope profiling based on structural modelling and clustering. Using the method, we demonstrate that sequence dissimilar but functionally similar antibodies can be found across the Coronavirus Antibody Database, with high accuracy (92% of antibodies in multiple-occupancy structural clusters bind to consistent domains). Our approach functionally links antibodies with distinct genetic lineages, species origins, and coronavirus specificities. This indicates greater convergence exists in the immune responses to coronaviruses than is suggested by sequence-based approaches. Our results show that applying structural analytics to large class-specific antibody databases will enable high confidence structure-function relationships to be drawn, yielding new opportunities to identify functional convergence hitherto missed by sequence-only analysis., Competing Interests: The authors have declared that no competing interests exist.

Background: Insomnia is a prevalent and debilitating disorder among veterans. Cognitive behavioral therapy for insomnia (CBTI) can be effective for treating insomnia, although many cannot access this care. Technology-based solutions and lifestyle changes, such as physical activity (PA), offer affordable and accessible self-management alternatives to in-person CBTI., Objective: This study aims to extend and replicate prior pilot work to examine whether the use of a mobile app for CBTI (cognitive behavioral therapy for insomnia coach app [CBT-i Coach]) improves subjective and objective sleep outcomes. This study also aims to investigate whether the use of the CBT-i Coach app with adjunctive PA improves sleep outcomes more than CBT-i Coach alone., Methods: A total of 33 veterans (mean age 37.61 years, SD 9.35 years) reporting chronic insomnia were randomized to use either the CBT-i Coach app alone or the CBT-i Coach app with a PA intervention over 6 weeks, with outcome measures of objective and subjective sleep at pre- and posttreatment., Results: Although the PA manipulation was unsuccessful, both groups of veterans using the CBT-i Coach app showed significant improvement from baseline to postintervention on insomnia (P<.001), sleep quality (P<.001), and functional sleep outcomes (P=.002). Improvements in subjective sleep outcomes were similar in those with and without posttraumatic stress disorder and mild-to-moderate sleep apnea. We also observed a significant but modest increase in objective sleep efficiency (P=.02)., Conclusions: These findings suggest that the use of a mobile app-delivered CBTI is feasible and beneficial for improving sleep outcomes in veterans with insomnia, including those with comorbid conditions such as posttraumatic stress disorder or mild-to-moderate sleep apnea., Trial Registration: ClinicalTrials.gov NCT03305354; https://clinicaltrials.gov/ct2/show/NCT03305354., (©Erin Dawna Reilly, Stephanie A Robinson, Beth Ann Petrakis, Melissa M Gardner, Renda Soylemez Wiener, Carmen Castaneda-Sceppa, Karen S Quigley. Originally published in JMIR Formative Research (https://formative.jmir.org), 09.12.2021.)

Background: Novel strategies to complement current methods of education delivery by healthcare providers in clinic encounters or in pulmonary rehabilitation are needed to promote COPD self-management., Methods: We developed a COPD web-based platform that delivers education as part of a physical activity intervention. We examined COPD knowledge in persons with COPD who used a web-mediated, pedometer-based physical activity intervention. Knowledge was assessed with the Bristol COPD Knowledge Questionnaire (BCKQ) at baseline, 3, 6, 9, and 12 months. Scores range from 0 to 100, with higher scores indicating greater knowledge. Repeated measures ANOVA (PROC MIXED, SAS 9.4) examined trends across the 12 months and identified changes from baseline at 3, 6, 9, and 12 months., Results: We enrolled 72 participants with COPD, 93% males with mean ± sd age of 69 ± 7 years and FEV1% predicted of 60 ± 23%. There was a significant increase from baseline to 9 months (p = 0.012), although this increase did not persist at 12 months. Among the 13 topics, participants scored the highest at baseline on smoking knowledge (65.3 ± 17.4) and the lowest on inhaled steroids (9.7 ± 15.4). Across the 12 months, there were significant increases in knowledge about inhaled bronchodilators (p = 0.011) and inhaled steroids (p = 0.035). At 12 months, there were significant improvements in knowledge about exercise (p = 0.004), vaccination (p = 0.027), inhaled bronchodilators (p = 0.002), and inhaled steroids (p = 0.002)., Conclusion: An internet-mediated intervention may provide another option for COPD education delivery and support for disease self-management., (Published by Elsevier Ltd.)

Background: Rural patients with diabetes have difficulty accessing care and are at higher risk for poor diabetes management. Sustained use of patient portal features such as secure messaging (SM) can provide accessible support for diabetes self-management., Objective: This study explored whether rural patients' self-management and glycemic control was associated with the use of SM., Methods: This secondary, cross-sectional, mixed methods analysis of 448 veterans with diabetes used stratified random sampling to recruit a diverse sample from the United States (rural vs urban and good vs poor glycemic control). Administrative, clinical, survey, and interview data were used to determine patients' rurality, use of SM, diabetes self-management behaviors, and glycemic control. Moderated mediation analyses assessed these relationships., Results: The sample was 51% (n=229) rural and 49% (n=219) urban. Mean participant age was 66.4 years (SD 7.7 years). More frequent SM use was associated with better diabetes self-management (P=.007), which was associated with better glycemic control (P<.001). Among rural patients, SM use was indirectly associated with better glycemic control through improved diabetes self-management (95% CI 0.004-0.927). These effects were not observed among urban veterans with diabetes (95% CI -1.039 to 0.056). Rural patients were significantly more likely than urban patients to have diabetes-related content in their secure messages (P=.01)., Conclusions: More frequent SM use is associated with engaging in diabetes self-management, which, in turn, is associated with better diabetes control. Among rural patients with diabetes, SM use is indirectly associated with better diabetes control. Frequent patient-team communication through SM about diabetes-related content may help rural patients with diabetes self-management, resulting in better glycemic control., (©Stephanie A Robinson, Dane Netherton, Mark Zocchi, Carolyn Purington, Arlene S Ash, Stephanie L Shimada. Originally published in JMIR Diabetes (https://diabetes.jmir.org), 19.11.2021.)

Objective: To evaluate the cost-effectiveness of a technology-based physical activity (PA) intervention for chronic obstructive pulmonary disease (COPD). Design: A secondary data analysis was performed from a randomized controlled trial in COPD of an activity monitor alone or an activity monitor plus a web-based PA intervention. Models estimated cost per quality-adjusted life year (QALY) and incremental cost-effectiveness ratios (ICERs) compared with usual care. Results: The estimated ICER for both groups was below the willingness-to-pay threshold of $50,000/QALY (activity monitor alone = $10,437/QALY; website plus activity monitor intervention = $13,065/QALY). A probabilistic simulation estimated 76% of the activity monitor-alone group and 78% of the intervention group simulations to be cost-effective. Conclusion(s): Both the activity monitor-alone group and the activity monitor plus website group were cost-effective at the base case by using conventional willingness-to-pay thresholds. Further research would benefit from a more direct estimate of health utilities and downstream health care costs. Clinical Trials.gov NCT01102777.

Objective: The study sought to investigate whether consistent use of the Veterans Health Administration's My HealtheVet (MHV) online patient portal is associated with improvement in diabetes-related physiological measures among new portal users., Materials and Methods: We conducted a retrospective cohort study of new portal users with type 2 diabetes that registered for MHV between 2012 and 2016. We used random-effect linear regression models to examine associations between months of portal use in a year (consistency) and annual means of the physiological measures (hemoglobin A1c [HbA1c], low-density lipoproteins [LDLs], and blood pressure [BP]) in the first 3 years of portal use., Results: For patients with uncontrolled HbA1c, LDL, or BP at baseline, more months of portal use in a year was associated with greater improvement. Compared with 1 month of use, using the portal 12 months in a year was associated with annual declines in HbA1c of -0.41% (95% confidence interval [CI], -0.46% to -0.36%) and in LDL of -6.25 (95% CI, -7.15 to -5.36) mg/dL. Twelve months of portal use was associated with minimal improvements in BP: systolic BP of -1.01 (95% CI, -1.33 to -0.68) mm Hg and diastolic BP of -0.67 (95% CI, -0.85 to -0.49) mm Hg. All associations were smaller or not present for patients in control of these measures at baseline., Conclusions: We found consistent use of the patient portal among new portal users to be associated with modest improvements in mean HbA1c and LDL for patients at increased risk at baseline. For patients with type 2 diabetes, self-management supported by online patient portals may help control HbA1c, LDL, and BP., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2021. This work is written by US Government employees and is in the public domain in the US.)

Neonicotinoid pesticide use is widespread and highly debated, as evidenced by recent attention received from the public, academics and pesticide regulatory agencies. However, relatively little is known about the physiological effects of neonicotinoid insecticides on aquatic vertebrates. Amphibians (larval stages in particular) are excellent vertebrate bioindicators in aquatic systems due to their risk of exposure and sensitivity to environmental stressors. Previous work with wood frog (Rana sylvatica) tadpoles exposed to formulated products containing thiamethoxam or clothianidin in outdoor mesocosms found significant shifts in leukocyte profiles, suggesting the tadpoles were physiologically stressed. The main objective of the present study was to characterize this stress response further using complementary measures of stress after exposure to clothianidin on northern leopard frogs (Rana pipiens) during their aquatic larval stages. Laboratory static-renewal exposures were conducted over eight weeks with the technical product clothianidin at 0, 0.23, 1, 10 and 100 μg/L, and diquat dibromide at 532 μg/L was used as a positive control. We assessed tadpole leukocyte profiles and measures of oxidative stress as these sub-lethal alterations could affect amphibian fitness. We found changes in several types of leukocytes at 1 and 10 μg/L, suggesting that these tadpoles exhibited signs of mild physiological stress. Clothianidin also induced an oxidative stress response at 0.23, 1 and 100 μg/L. However, we found no differences in survival, growth, development time or hepatosomatic index in frogs exposed to clothianidin. Our study indicates that tadpoles chronically exposed to clothianidin have increased stress responses, but in the absence of concentration-response relationships and effects on whole-organism endpoints, the implications on the overall health and fitness of these changes are unclear., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Improving exercise capacity is a primary objective in COPD. Declines in exercise capacity result in reduced physical activity and health-related quality of life (HRQoL). Self-management interventions can teach patients skills and behaviours to manage their disease. Technology-mediated interventions have the potential to provide easily accessible support for disease self-management. We evaluated the effectiveness of a web-based self-management intervention, focused on physical activity promotion, on exercise capacity in COPD. This 6-month randomised controlled trial (NCT02099799) enrolled 153 persons with COPD at two US sites (VABoston, n=108; VABirmingham, n=45). Participants were allocated (1:1) to the web-based self-management intervention (physical activity promotion through personalised, progressive step-count goals, feedback, online COPD-related education and social support via an online community) or usual care. The primary outcome was exercise capacity (6-min walk distance (6 MWD)). Secondary outcomes included physical activity (daily steps per day), HRQoL (St. George's Respiratory Questionnaire Total Score), dyspnoea, COPD-related knowledge and social support. Change in step-count goals reflected intervention engagement. Participants' mean age was 69 (sd=7), and mean forced expiratory volume in 1 s % predicted was 61% (sd=21%). Change in 6MWD did not differ between groups. Intervention participants improved their mean daily step counts by 1312 more than those in the usual care group (p<0.001). Groups did not differ on other secondary outcomes. VABirmingham participants were significantly more engaged with the intervention, although site did not modify the effect of the intervention on 6MWD or secondary outcomes. The intervention did not improve exercise capacity but improved physical activity at 6 months. Additional intervention modifications are needed to optimise its COPD self-management capabilities., Competing Interests: Conflict of interest: J.A. Cooper Jr has nothing to disclose. Conflict of interest: R.L. Goldstein has nothing to disclose. Conflict of interest: M. Polak has nothing to disclose. Conflict of interest: P.N. Cruz Rivera has nothing to disclose. Conflict of interest: D.R. Gagnon has nothing to disclose. Conflict of interest: A. Samuelson has nothing to disclose. Conflict of interest: S. Moore has nothing to disclose. Conflict of interest: R. Kadri has nothing to disclose. Conflict of interest: C.R. Richardson has nothing to disclose. Conflict of interest: M.L. Moy has nothing to disclose., (Copyright ©The authors 2021.)

Background: Pain is a common but underappreciated symptom experienced by people with Chronic Obstructive Pulmonary Disease (COPD). The relationships between pain and physical activity (PA) and exercise capacity are poorly understood., Methods: This retrospective secondary analysis includes three cohorts of Veterans with COPD who participated in longitudinal studies evaluating PA and exercise capacity with objective measures of daily step counts and 6-min walk test (6MWT) distance, respectively. Pain was assessed using the bodily pain domain of the Veterans RAND-36. In two cohorts, participants were randomly assigned to a web-based, pedometer-mediated PA intervention which has previously been demonstrated to improve PA., Results: Three-hundred and seventy-three (373) unique study participants were included in this analysis. Eighty-three percent (n = 311) of the population reported at least mild pain and/or at least a little bit of interference due to pain at baseline. Cross-sectionally, greater bodily pain was associated with lower 6MWT distance (β = 0.51; 95% CI 0.20, 0.82; p = 0.0013). Longitudinally, worsening bodily pain was associated with a decline in 6MWT distance (β = 0.30; 95% CI 0.03, 0.58; p = 0.0312). There was no association between baseline bodily pain and baseline daily step counts, baseline bodily pain and change in PA, or change in bodily pain and change in PA. Compared to usual care, our PA intervention improved bodily pain scores (β = 6.17; 95% CI 1.84, 10.45; p = 0.0054). Bodily pain scores did not affect the impact of the intervention on daily step counts., Conclusion: Pain is highly prevalent and significantly associated with lower exercise capacity among Veterans with COPD. Worsening pain co-occurred with decline in exercise capacity but not PA. Our intervention reduced pain, although pain did not affect the impact of the intervention on PA., (© 2021. The Author(s).)

Agricultural drainage ditches help remove excess water from fields and provide habitat for wildlife. Drainage ditch management, which includes various forms of vegetation clearing and sediment dredging, can variably affect the ecological function of these systems. To determine whether ditch conditions following dredging/vegetation clearing management affected the survival, growth, and development of embryos and tadpoles of northern leopard frogs (Lithobates pipiens), we conducted three field studies using in situ cages over 2 years. We measured nutrients, pesticides, and other water quality properties in vegetated/unmanaged (i.e., no clearing or dredging) and newly cleared/dredged (i.e., treeless, then dredged), clay-bottomed drainage ditches in a river basin in Eastern Ontario, Canada. Nutrients, atrazine, and total neonicotinoid concentrations were generally lower at the cleared/dredged sites, whereas glyphosate was at higher concentrations. In contrast, water-quality variables measured in situ, particularly temperature, dissolved oxygen, and turbidity, tended to be higher in the cleared/dredged sites. Total phosphorous and total organic carbon concentrations at all sites were above the recommended limits for amphibian assays. No significant differences were detected in the survival, hatching success, or development of embryos among the ditch management treatments, but premature hatching was observed at one vegetated/unmanaged site where high specific conductivity may have been formative. We found the cleared/dredged sites supported earlier tadpole growth and development, likely as a result of the higher water temperatures. Increased temperature may have offset other growth/development stressors, such as those related to water chemistry. However, the long-term consequences of these differences on amphibian populations requires further study.

Habitat loss, climate change, environmental contaminants, and parasites and pathogens are among the main factors thought to act singly or together in causing amphibian declines. We tested for combined effects of neonicotinoid pesticides and parasites (versus parasites-only) on mortality, growth, and white blood cell profiles of a model amphibian: the northern leopard frog (Rana pipiens). We first exposed infectious stages of frog trematodes (cercariae of Echinostoma spp.) to low and high concentrations of thiamethoxam or clothianidin versus water-only controls. There were no differences in survival of trematode cercariae between treatments. For the main experiment, we exposed tadpoles to clean water versus high concentrations of clothianidin or thiamethoxam for 2 weeks and added trematode cercariae to all tanks after 1 week. Exposure of tadpoles and parasites to high concentrations of thiamethoxam or clothianidin did not affect parasite infection success. Tadpole survival was not different between treatments before or after parasite addition and there were no significant differences in tadpole snout-to-vent lengths or developmental stages between treatments. Tadpoles exposed to thiamethoxam + parasites had smaller widths than parasite-only tadpoles, whereas tadpoles exposed to clothianidin + parasites had higher eosinophil to leukocyte ratios compared to parasite-only tadpoles. Tadpoles of both neonicotinoid + parasite treatments had significantly lower monocyte to leukocyte ratios relative to parasite-only tadpoles. High concentrations of neonicotinoid combined with parasites appear to influence tadpole immune function important for further defense against parasites and pathogens. This work highlights the need for more holistic approaches to ecotoxicity studies, using multiple stressors.

Amphibians are declining globally. Exposure to pesticides has been implicated in decreasing amphibian immune function, thus increasing their susceptibility to parasites and disease and thereby negatively affecting individuals and populations. Amphibians are likely exposed to neonicotinoids because these widely used insecticides are highly soluble in water and because amphibian freshwater habitats are often embedded in agroecosystems. Herein, we investigate the effects of long-term exposure to two individual neonicotinoids (clothianidin or thiamethoxam) at either low or high concentrations (2.5 or 250 µg/L) on northern leopard frog (Lithobates pipiens) blood cell profiles and concentrations of corticosterone, an energy-mediating hormone associated with stress. Larval frogs from Gosner stage 25 to 46 were exposed to pesticide and control treatments in outdoor mesocosms. Corticosterone concentrations were measured after 6 d of exposure, and blood cell profiles were assessed once frogs reached Gosner stage 46 (following 8 w of exposure). No significant changes were found in erythrocyte counts, leukocyte counts, monocyte to leukocyte ratios or corticosterone concentrations between treatments. However, exposure to either 2.5 or 250 µg/L of clothianidin, or 250 µg/L of thiamethoxam decreased neutrophil to lymphocyte ratios and neutrophil to leukocyte ratios, and exposure to 2.5 µg/L of clothianidin or 250 µg/L of thiamethoxam decreased eosinophil to leukocyte ratios. Our results indicate that long-term exposure to neonicotinoids can alter leukocyte profiles, indicative of a stress response. Future studies should investigate whether chronic exposure to neonicotinoids affect multiple measures of stress differently or influences the susceptibility of amphibians to parasites and pathogens. Our work underscores the importance of continued use of multiple measures of stress for different amphibian species when undertaking ecotoxicological assessments., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Globally, collapse of ecosystems-potentially irreversible change to ecosystem structure, composition and function-imperils biodiversity, human health and well-being. We examine the current state and recent trajectories of 19 ecosystems, spanning 58° of latitude across 7.7 M km 2 , from Australia's coral reefs to terrestrial Antarctica. Pressures from global climate change and regional human impacts, occurring as chronic 'presses' and/or acute 'pulses', drive ecosystem collapse. Ecosystem responses to 5-17 pressures were categorised as four collapse profiles-abrupt, smooth, stepped and fluctuating. The manifestation of widespread ecosystem collapse is a stark warning of the necessity to take action. We present a three-step assessment and management framework (3As Pathway Awareness, Anticipation and Action) to aid strategic and effective mitigation to alleviate further degradation to help secure our future., (© 2021 John Wiley & Sons Ltd.)

Environmental change and biodiversity loss are but two of the complex challenges facing conservation practitioners and policy makers. Relevant and robust scientific knowledge is critical for providing decision-makers with the actionable evidence needed to inform conservation decisions. In the Anthropocene, science that leads to meaningful improvements in biodiversity conservation, restoration and management is desperately needed. Conservation Physiology has emerged as a discipline that is well-positioned to identify the mechanisms underpinning population declines, predict responses to environmental change and test different in situ and ex situ conservation interventions for diverse taxa and ecosystems. Here we present a consensus list of 10 priority research themes. Within each theme we identify specific research questions (100 in total), answers to which will address conservation problems and should improve the management of biological resources. The themes frame a set of research questions related to the following: (i) adaptation and phenotypic plasticity; (ii) human-induced environmental change; (iii) human-wildlife interactions; (iv) invasive species; (v) methods, biomarkers and monitoring; (vi) policy, engagement and communication; (vii) pollution; (viii) restoration actions; (ix) threatened species; and (x) urban systems. The themes and questions will hopefully guide and inspire researchers while also helping to demonstrate to practitioners and policy makers the many ways in which physiology can help to support their decisions., (© The Author(s) 2021. Published by Oxford University Press and the Society for Experimental Biology.)

Bovines have evolved a subset of antibodies with ultra-long heavy chain complementarity determining regions that harbour cysteine-rich knob domains. To produce high-affinity peptides, we previously isolated autonomous 3-6 kDa knob domains from bovine antibodies. Here, we show that binding of four knob domain peptides elicits a range of effects on the clinically validated drug target complement C5. Allosteric mechanisms predominated, with one peptide selectively inhibiting C5 cleavage by the alternative pathway C5 convertase, revealing a targetable mechanistic difference between the classical and alternative pathway C5 convertases. Taking a hybrid biophysical approach, we present C5-knob domain co-crystal structures and, by solution methods, observed allosteric effects propagating >50 Å from the binding sites. This study expands the therapeutic scope of C5, presents new inhibitors, and introduces knob domains as new, low molecular weight antibody fragments, with therapeutic potential., Competing Interests: AM, ZA, JB, MS, BH, VO, JS, VE, AL employee of UCB and may hold shares and/or stock options, ML, MG, SC, SR, PN, DS, Jv No competing interests declared, TM T.E.M is a Board member of Ra Pharmaceuticals, Inc, CD Reviewing editor, eLife, (© 2021, Macpherson et al.)

Solving the structure of an antibody-antigen complex gives atomic level information of the interactions between an antibody and its antigen, but such structures are expensive and hard to obtain. Alternative experimental sources include epitope mapping and binning experiments, which can be used as a surrogate to identify key interacting residues. However, their resolution is usually not sufficient to identify if two antibodies have identical interactions. Computational approaches to this problem have so far been based on the premise that antibodies with similar sequences behave similarly. Such approaches will fail to identify sequence-distant antibodies that target the same epitope. Here, we present Ab-Ligity, a structure-based similarity measure tailored to antibody-antigen interfaces. Using predicted paratopes on model antibody structures, we assessed its ability to identify those antibodies that target highly similar epitopes. Most antibodies adopting similar binding modes can be identified from sequence similarity alone, using methods such as clonotyping. In the challenging subset of antibodies whose sequences differ significantly, Ab-Ligity is still able to predict antibodies that would bind to highly similar epitopes (precision of 0.95 and recall of 0.69). We compared Ab-Ligity's performance to an existing tool for comparing general protein interfaces, InterComp, and showed improved performance on antibody cases achieved in a substantially reduced time. These results suggest that Ab-Ligity will allow the identification of diverse (sequence-dissimilar) antibodies that bind to the same epitopes from large datasets such as immune repertoires. The tool is available at http://opig.stats.ox.ac.uk/resources.

Combined enhanced UV-B radiation and drought may induce different morphological and physiological alterations in plants than either abiotic stress alone. We evaluated morphology, biomass, and primary and secondary metabolism changes in seedlings of two common bean cultivars, IAC Imperador (drought-resistant) and IAC Milênio. To test the hypothesis that cultivars responded differently to combined stresses in a controlled environment, seedlings of the examined been cultivars were exposed to UV-B and/or drought treatments for three weeks. The cultivars behaved differently, especially to the drought treatment, suggesting that they use different mechanisms to cope with unfavorable environmental conditions. IAC Imperador showed a stronger protective response, modifying wax composition and primary metabolism, and improving its resistance to UV-B radiation. For IAC Imperador, the accumulation of cuticular wax and alkane was higher under combined stress but production of primary alcohols was reduced, suggesting a possible fatty acyl switch. Root/shoot length and biomass ratios increased in both cultivars, particularly for the combined stress, indicating a common plant response. We show that these two bean cultivars responded more strongly to UV-B and combined stress than drought alone as evident in changes to their chemistry and biology. This shows the importance of investigating plant morphological and physiological responses to combined stress., (© 2020 American Society for Photobiology.)

This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive assessment (Photochemical and Photobiological Sciences, 2019, 18, 595-828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.

Restrictions on the production and use of some highly toxic and persistent flame retardants has resulted in the increased use of alternative phosphate flame retardants that are less-well characterized. The brominated organophosphate ester flame retardant, tris(tribromoneopentyl) phosphate (CAS 19186-97-1, molecular formula C15H24Br9O4P, molecular weight 1018.47 g/mol, acronym TTBrNP) is a compound with potential to bioaccumulate and disrupt endocrine functions. To determine the toxicity of TTBrNP, two Canadian native amphibian species, Lithobates sylvaticus and L. pipiens, were acutely (embryos and Gosner stage 25 (GS25) tadpoles) or sub-chronically (GS25-41 tadpoles) exposed to the following nominal concentrations of TTBrNP: 0 (water and solvent controls), 30.6, 61.3, 122.5 and 245.0 μg/L. Note, measured concentrations declined with time (i.e., 118%-30% of nominal). There was high survival for both species after acute and sub-chronic exposures, where 75%-100% survived the exposures, respectively. There were no differences in the occurrence of abnormalities or hatchling size between controls and TTBrNP treatments for either species exposed acutely as embryos or tadpoles. Furthermore, after 30 d of sub-chronic exposure of L. pipiens tadpoles to TTBrNP there were no effects on size, developmental stage, liver somatic index or sex ratio. Bioconcentration factors were low at 26 ± 3.1 L/kg ww in tadpoles from all treatments, suggesting biotransformation or limited bioavailability via aquatic exposures. Thus, using two species of anurans at different early larval stages, we found TTBrNP up to 245 μg/L to have no overt detrimental effects on survival or morphological responses that would suggest fitness-relevant consequences., Competing Interests: Declaration of competing interest None., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

This study examined the role of personality traits in a 5-week physical activity intervention study for working adults. We tested whether personality traits predicted individual differences in change in daily steps over time. Fifty-two participants ages 35 to 69 ( M age = 49.71, SD = 8.64) wore a Fitbit Zip step counter for 35 days and completed a personality questionnaire. Participants were randomly assigned to either an implementation intention group or a control group. Both groups wore a Fitbit and had the goal to increase their daily steps. For the present study, the sample was collapsed across groups. Higher conscientiousness was associated with greater increases in daily steps. Also, individuals with healthy neuroticism , the combination of higher neuroticism and higher conscientiousness, showed greater increases in daily steps. The findings highlight that the efficacy of physical activity interventions may depend on personality traits. Intervention outcomes may be improved if personality is taken into account when designing the programs.

Peptide insertions in the primary sequence of proteins expand functionality by introducing new binding sequences, chemical handles, or membrane disrupting motifs. With these properties, proteins can be engineered as scaffolds for vaccines or targeted drug delivery vehicles. Virus-like particles (VLPs) are promising platforms for these applications since they are genetically simple, mimic viral structure for cell uptake, and can deliver multiple copies of a therapeutic agent to a given cell. Peptide insertions in the coat protein of VLPs can increase VLP uptake in cells by increasing cell binding, but it is difficult to predict how an insertion affects monomer folding and higher order assembly. To this end, we have engineered the MS2 VLP using a high-throughput technique, called Systematic Mutagenesis and Assembled Particle Selection (SyMAPS). In this work, we applied SyMAPS to investigate a highly mutable loop in the MS2 coat protein to display 9,261 non-native tripeptide insertions. This library generates a discrete map of three amino acid insertions permitted at this location, validates the FG loop as a valuable position for peptide insertion, and illuminates how properties such as charge, flexibility, and hydrogen bonding can interact to preserve or disrupt capsid assembly. Taken together, the results highlight the potential to engineer VLPs in a systematic manner, paving the way to exploring the applications of peptide insertions in biomedically relevant settings.

Background: Diabetes is a complex, chronic disease that requires patients' effective self-management between clinical visits; this in turn relies on patient self-efficacy. The support of patient autonomy from healthcare providers is associated with better self-management and greater diabetes self-efficacy. Effective provider-patient secure messaging (SM) through patient portals may improve disease self-management and self-efficacy. SM that supports patients' sense of autonomy may mediate this effect by providing patients ready access to their health information and better communication with their clinical teams., Objective: We examined the association between healthcare team-initiated SM and diabetes self-management and self-efficacy, and whether this association was mediated by patients' perceptions of autonomy support from their healthcare teams., Design: We surveyed and analyzed content of messages sent to a sample of patients living with diabetes who use the SM feature on the VA's My HealtheVet patient portal., Participants: Four hundred forty-six veterans with type 2 diabetes who were sustained users of SM., Main Measures: Proactive (healthcare team-initiated) SM (0 or ≥ 1 messages); perceived autonomy support; diabetes self-management; diabetes self-efficacy., Key Results: Patients who received at least one proactive SM from their clinical team were significantly more likely to engage in better diabetes self-management and report a higher sense of diabetes self-efficacy. This relationship was mediated by the patient's perception of autonomy support. The majority of proactive SM discussed scheduling, referrals, or other administrative content. Patients' responses to team-initiated communication promoted patient engagement in diabetes self-management behaviors., Conclusions: Perceived autonomy support is important for diabetes self-management and self-efficacy. Proactive communication from clinical teams to patients can help to foster a patient's sense of autonomy and encourage better diabetes self-management and self-efficacy.