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Background and Purpose: The efficacy and safety of ravulizumab, a terminal complement C5 inhibitor, in adults with anti‐acetylcholine receptor antibody‐positive (AChR Ab+) generalized myasthenia gravis (gMG) were demonstrated in the CHAMPION MG study (NCT03920293). This analysis aimed to characterize the latency to onset of a clinically meaningful therapeutic effect for ravulizumab. Methods: Post hoc analysis of data collected for up to 60 weeks from CHAMPION MG was performed to assess the timing of response to ravulizumab. Response was analyzed based on reductions of ≥2 and ≥3 points (minimal clinically important differences [MCIDs]) in Myasthenia Gravis–Activities of Daily Living (MG‐ADL) and Quantitative Myasthenia Gravis (QMG) total scores, respectively, and on more rigorous reductions of ≥3 and ≥5 points, respectively. Time to first response was assessed using the Kaplan–Meier product‐limit method. Results: The median (95% confidence interval) time to first response was 2.1 (2.1–2.6) and 4.1 (2.3–10.0) weeks for reductions of ≥2 and ≥3 points in MG‐ADL total score, respectively (n = 139), and 4.1 (2.1–10.0) and 18.3 (11.0–33.4) weeks for reductions of ≥3 and ≥5 points in QMG total score, respectively (n = 134). Cumulative response rates at Week 60 (data cut‐off) were 88% and 82% for ≥2‐ and ≥3‐point MG‐ADL score reductions, respectively, and 86% and 59% for ≥3‐ and ≥5‐point QMG score reductions, respectively. Conclusions: The median times to MCID with ravulizumab treatment in patients with AChR Ab+ gMG were ~2 weeks and ~4 weeks based on MCID MG‐ADL and QMG total score reductions, respectively. [ABSTRACT FROM AUTHOR]

It is important to understand the effects of environmental factors such as air pollution on mitochondrial structure and function, especially when these changes increase cardiovascular disease risk. Although lifestyle choices directly determine many mitochondrial diseases, increasingly, it is becoming clear that the structure and function of mitochondria may be affected by pollutants found in the atmosphere (e.g., gases, pesticides herbicide aerosols, or microparticles). To date, the role of such agents on mitochondria and the potential impact on cardiovascular fitness is neglected. Here we offer a review of airborne stressors and pollutants, that may contribute to impairments in mitochondrial function and structure to cause heart disease. [ABSTRACT FROM AUTHOR]

Chronic systemic inflammation significantly increases myocardial infarction risk in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the risk of vasoconstriction, inflammation, and thrombosis, contributing to cardiovascular disease. We aimed to characterize endothelial cell (EC) chemokines, cytokine, and chemokine receptors of PLWH, hypothesizing that in our cohort, glucose intolerance contributes to their differential expression implicated in endothelial dysfunction. Using single‐cell transcriptomic analysis, we phenotyped chemokine and cytokine receptor expression on arterial ECs, capillary ECs, venous ECs, and vascular smooth muscle cells (VSMCs) in subcutaneous adipose tissue of 59 PLWH with and without glucose intolerance. Our results show that arterial and capillary ECs express significantly higher interferon and tumor necrosis factor (TNF) receptors than venous ECs and VSMCs. Venous ECs exhibited more interleukin (IL)1R1 and ACKR1 receptors, and VSMCs showed significant IL6R expression than arterial and capillary ECs. When stratified by group, arterial ECs from PLWH with glucose intolerance expressed significantly higher IL1R1, IL6R, CXCL12, CCL14, and ICAM2 transcripts than arterial ECs from PLWH without diabetes. Of the different vascular cell types studied, arterial ECs as a proportion of all ECs in adipose tissue were positively correlated with plasma fasting blood glucose. In contrast, venous ECs and VSMCs were positively correlated with plasma IL6. To directly assess the effect of plasma from PLWH on endothelial function, we cultured human arterial ECs (HAECs) in plasma‐conditioned media from PLWH and performed bulk RNA sequencing. Plasma from PLWH stimulated ECs with the upregulation of genes that enrich for the oxidative phosphorylation and the TNF‐α via NFK‐β pathways. In conclusion, ECs in PLWH show heterogeneous cytokine and chemokine receptor expression, and arterial ECs were the most influenced by glucose intolerance. Further research must explicate cytokine and chemokine roles in EC dysfunction and identify biomarkers for disease progression and therapeutic response. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Materials and Methods Results Conclusion and Clinical Relevance Anal sac impaction is common in dogs. Manual expression may be effective, yet recurrence can be problematic. To facilitate physiological emptying of the sacs, it is important to maintain bulky stool consistency.The study evaluated if supplementation with a complementary feed product formulated as a chew containing Bacillus velezensis C‐3102 and fibre sources, reduced anal sac impaction recurrence.Thirty‐five client‐owned dogs with anal sac impaction were enrolled.Prospective, randomised, negative controlled field clinical trial with 22 dogs receiving the chew orally for 90 consecutive days and 13 dogs with no treatment. Dogs were evaluated on Day (D) 30, 60, 90 and 120 for the presence of clinical signs of anal sac impaction and the need to empty the sacs. Any animal that required manual expression of the sacs was classified as a failure and was withdrawn from the study.The cumulative percentage of failures in the untreated group increased steadily from the first follow‐up visit on D30 (15%) to the last visit on D120 (61.5%). However, in the group receiving the chew the cumulative percentage of failures increased at a much slower rate and stabilised at 19% from the D90 visit (last administration day) until the end of the study on D120, with statistically significant differences (p = 0.025). Animals receiving the chew also showed reduction in clinical signs.The probiotic and fibre chew was a safe and effective management option for recurrent anal sac impaction in dogs. [ABSTRACT FROM AUTHOR]

The Irrawaddy dolphin (Orcaella brevirostris) is an endangered cetacean that ranges throughout much of Southeast Asia and lives in coastal, estuarine, and riverine habitats including three river systems: Ayeyarwady, Mekong, and Mahakam. Many populations face risks from human interference, but overall rangewide diversity and connectivity is not well‐understood. Here we sequenced 77 complete mitogenomes from across the range of the Irrawaddy dolphin including all obligate riverine populations; eighteen of these were sequenced from historical museum specimens. Phylogenetic analysis showed haplotypes from each riverine population formed separate clades nested within the wider species implying each river system was separately invaded only once. All Irrawaddy dolphin mitogenomes were dated to a last common ancestor ~764 kya. Most lineages appeared after inundation cycles of the Sunda Shelf were initiated ~400 kya. Despite the lack of monophyly among many haplotypes from the same population, no population shared any haplotypes. Rangewide nucleotide diversity was average compared to other odontocetes, but riverine populations were especially low. Differentiation was significant among all populations analyzed with the most divergence occurring between isolated riverine populations. These analyses add more evidence for the necessity of conservation efforts directed towards riverine and other isolated populations of the Irrawaddy dolphin. [ABSTRACT FROM AUTHOR]

Summary Lameness in the horse is one of the most common reasons a horse is seen by a veterinarian. As the foot is frequently the source of lameness, research utilising reversible methods of foot lameness induction is vital to improving knowledge in this area. This literature review aims to describe published methods of reversible foot lameness induction, identify any limitations and summarise research findings where these methods have been utilised. [ABSTRACT FROM AUTHOR]

CA 4011 (Reg. no. GP‐1149, PI 705597) is a noncommercial breeding line of cotton (Gossypium hirsutum L.) jointly released by Texas A&M AgriLife Research and the Agricultural Experiment Station at the University of Georgia‐Tifton. This cotton germplasm is a selection from CA 3084, a germplasm line released by Texas Agricultural Experiment Station in 1987. CA 3084 was derived from a cross of EPSM‐75‐AAAA‐3 and EPSM‐1224‐1‐74‐2‐4‐2‐1, historical breeding lines developed by the cotton breeding program at Texas Agricultural Experiment Station in El Paso. Progeny row of CA 4011 was selected for 2008 preliminary yield testing in Southern High Plains by the Texas A&M AgriLife Research cotton breeding program in Lubbock. In 2012, CA 4011 had less damage from thrips feeding injury than 22 other genotypes tested in a greenhouse assay but was equal to the resistant check TX110 (PI 163608). Performance testing for yield, fiber quality, and other related agronomic properties was conducted under organic management and on certified organic farms during 2012, 2013, and 2014 growing seasons. CA 4011 showed comparable yield and fiber quality to standard check cultivars grown in the Southern High Plains. Subsequent testing was done at the University of Georgia Coastal Plains Experiment Station in Tifton, GA, to evaluate for resistance to the foliar diseases areolate mildew and target spot. Disease ratings were taken in 2018 and 2019 growing seasons. CA 4011 showed favorable resistance to areolate mildew in comparison to susceptible checks, providing less leaf infection and defoliation. Core Ideas: CA 4011 had less damage from thrips feeding injury than 22 other genotypes but was equal to the resistant check.CA 4011 shows resistance to areolate mildew.CA 4011 has acceptable yield and fiber quality. [ABSTRACT FROM AUTHOR]

In this paper, we present a heuristic for the non‐unicost set covering problem using local branching. Local branching eliminates the need to define a problem specific search neighbourhood for any particular (zero‐one) optimisation problem. It does this by incorporating a generalised Hamming distance neighbourhood into the problem, and this leads naturally to an appropriate neighbourhood search procedure. We apply our approach to the non‐unicost set covering problem. Computational results are presented for 65 test problems that have been widely considered in the literature. Our results indicate that our heuristic is better than six of the eight other heuristics we examined, slightly worse than that of one heuristic, but that there is a single heuristic that outperforms all others. We believe that the work described here illustrates that the potential for using local branching, operating as a stand‐alone matheuristic, has not been fully exploited in the literature. [ABSTRACT FROM AUTHOR]

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LDs) within the brown adipocytes and a high abundance of iron‐containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle‐to‐organelle contacts. For example, the contact sites that mediate mitochondria–LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and the proteins that modulate organelle contact sites. However, how mitochondria–LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age‐related changes in LD morphology and mitochondria–lipid interactions in BAT. We examined the three‐dimensional morphology of mitochondria and LDs in young (3‐month) and aged (2‐year) murine BAT using serial block face‐scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Our analyses showed reductions in LD volume, area, and perimeter in aged samples in comparison to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for the mitochondria interacting with LDs. Overall, these data define the nature of LD morphology and organelle–organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology with mitochondrial function, metabolism, and bioactivity in aged BAT. [ABSTRACT FROM AUTHOR]

BACKGROUND: Biological invasions are a leading cause of reductions in global biodiversity. Islands are particularly sensitive to invasions, which often result in cascading impacts throughout island communities. Wild pigs (Sus scrofa) are globally invasive and pose threats to numerous taxa and ecosystems, particularly for islands where they have contributed to declines of many endemic species. However, the impacts of wild pig diet on the flora and fauna remain understudied in many island systems. RESULTS: We used DNA metabarcoding of wild pig fecal samples to quantify the seasonal diet composition of wild pigs on three barrier islands in the southeastern United States. Wild pigs exhibited a diverse diet dominated by plants, but also including marine and terrestrial animals. The diet composition of plants varied seasonally and between islands. Consumption of invertebrates also changed seasonally, with a shift to coastal invertebrates, particularly crabs, in spring and summer. Vertebrates were found in <10% of samples, but spanned broad taxa including amphibians, fish, mammals, and reptiles. Species consumed by wild pigs indicate that wild pigs use a variety of habitats within barrier islands for foraging, including maritime forests, saltmarshes, and beaches. CONCLUSIONS: An observed shift to beach foraging during sea turtle nesting season suggests wild pigs have potential to hinder nesting success on islands without established management programs. These findings provide insight into the diverse diets of wild pigs on barrier islands and highlight the need for removal of wild pigs from sensitive island ecosystems because of their potential impacts to native plant and animal communities. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

While some established undergraduate summer programs are effective across many institutions, these programs may only be available to some principal investigators or may not fully address the diverse needs of incoming undergraduates. This article outlines a 10‐week science, technology, engineering, mathematics, and medicine (STEMM) education program designed to prepare undergraduate students for graduate school through a unique model incorporating mentoring dyads and triads, cultural exchanges, and diverse activities while emphasizing critical thinking, research skills, and cultural sensitivity. Specifically, we offer a straightforward and adaptable guide that we have used for mentoring undergraduate students in a laboratory focused on mitochondria and microscopy, but which may be customized for other disciplines. Key components include self‐guided projects, journal clubs, various weekly activities such as mindfulness training and laboratory techniques, and a focus on individual and cultural expression. Beyond this unique format, this 10‐week program also seeks to offer an intensive research program that emulates graduate‐level experiences, offering an immersive environment for personal and professional development, which has led to numerous achievements for past students, including publications and award‐winning posters. [ABSTRACT FROM AUTHOR]

This paper addresses the building of the Panama Canal (particularly from 1870‐1914) and looks at lessons that modern day Systems Engineers can apply from this significant infrastructure project. There were great successes and failures during the attempts to build a canal. The Systems issues include the importance of understanding the environment, recognizing the need to think beyond the physical object ‐ Panama Canal project had significant health issues, need for infrastructure / "realization systems", and even the need for a political revolution in Panama to enable it to be built. The importance of the organization building the system, and its leadership was also important. It is always instructive to look back at significant historical projects and learn the lessons (positive and negative). There is much to learn from a project and a system as big and important as the Panama Canal. [ABSTRACT FROM AUTHOR]

The INCOSE Complex Systems Working Group Heuristics Team has selected 67 Principles and Heuristics that are considered to be particularly relevant to Complex Systems. These have been incorporated into a Difficulty Assessment Tool that prioritizes the list of Principles and Heuristics based on scoring of a matrix of four Difficulty Elements and six System Elements (to characterize the nature of the complexity). The purpose of this paper is to describe an initial assessment of the effectiveness and usefulness of the Difficulty Assessment Tool. The Tool has been used to assess eight Case Studies by five assessment teams — one with three people working together, one with two people and the remaining three with individual assessments. The results of these assessments have been compared using four different correlation methods, using the total weighted Heuristic score, the maximum weighted Heuristic score, a Match / Mismatch analysis of the top fifteen and bottom seven Heuristics, and a difference ranking between pairs of assessors of all 67 Principles and Heuristics. The last two assessment methods are shown to be more insightful. The assessment teams then reviewed the relevance of the highest and lowest‐ranked Principles and Heuristics to the full Case Study definitions (Problem and Outcome). There is good agreement of relevance for the highest‐ranking Principles and Heuristics, less so for the lowest‐ranking ones. Based on this initial assessment, the DAT shows promise to help people develop complex systems. The paper concludes with recommendations for further assessment of the Difficulty Assessment Tool. [ABSTRACT FROM AUTHOR]

A first‐generation college student is typically defined as a student whose biological parent(s) or guardian(s) never attended college or who started but did not finish college. However, "first‐generation" can represent diverse family education situations. The first‐generation student community is a multifaceted, and intersectional group of individuals who frequently lack educational/financial resources to succeed and, consequently, require supportive environments with rigorous mentorship. However, first‐generation students often do not make their identity as first‐generation students known to others due to several psychosocial and academic factors. Therefore, they are often "invisible minorities" in higher education. In this paper, we describe the diverse family situations of first‐generation students, further define "first‐generation," and suggest five actions that first‐generation trainees at the undergraduate/graduate stages can engage in to succeed in an academic climate. We also provide suggestions for mentors to accommodate first‐generation students' unique experiences and equip them with tools to deliver intentional mentoring practices. We hope that this paper will help promote first‐generation student success throughout the academic pipeline. [ABSTRACT FROM AUTHOR]

Since 1901, the Nobel Prize in Physiology and Medicine has been awarded to numerous individuals for their outstanding contributions. This article presents a comprehensive analysis of the Nobel Prize recipients, focusing on gender, race, and nationality. We observe that an alarming disparity emerges when we examine the underrepresentation of Black scientists among Nobel laureates. Furthermore, trends in nationalities show how Americans make up the majority of Nobel Prize winners, while there is a noticeable lack of gender and racial minority winners of the Nobel Prize in Physiology and Medicine. Together, this highlights the importance of diversity and inclusion in scientific achievement. We offer suggestions and techniques, including funding opportunities and expanding nominators, to improve the gender, racial, and geographical diversity of Nobel Prizes. [ABSTRACT FROM AUTHOR]

Proper N fertilization and higher mowing heights are recommended to enhance rooting for greater turfgrass summer drought stress. To examine the effects of these primary cultural practices on centipedegrass [Eremochloa ophiuroides (Munro) Hack.] drought response in the mid‐Southern United States, a study was conducted to evaluate four mowing heights (1, 2, 3 and 4 inches) and N fertilization versus no fertilization. During the study, roots were periodically harvested at upper (0–3 inches) and lower (3–6 inches) soil depths, and roots were analyzed for architecture which included root length (RL) and surface area (SA), and root weight (RW). In July, plant‐soil cores were subjected to 36‐day drought simulation under greenhouse conditions. All turfgrass exhibited a pattern of decreasing leaf quality as drought progressed with unfertilized treatments maintaining acceptable leaf color (≥5) for 19 days at 5.9 compared to 4.8 for fertilized centipedegrass regardless of mowing height. In the field, root architecture and biomass across all mowing heights, fertilities, and soil depths peaked at 883.9 inches, 35.6 in2, and 5.8 grains for RL, SA, and RW, respectively, six weeks prior to drought simulation (WDPS) before declining to 740.5 inches, 29.6 in2, and 4.9 grains at the initiation of the drought simulation. The inability of N fertility and mowing height to enhance root growth particularly from spring into summer indicates soil temperatures may be a factor in centipedegrass root growth and thus drought stress avoidance. Plain Language Summary: Current practices suggest both raising the mowing height and proper nitrogen fertility of turfgrass will increase its drought tolerance. However, there is limited peer‐reviewed data to substantiate these claims for Louisiana or much of the deep South. The purpose of this study was to test this idea under Louisiana's subtropical growing conditions. After subjecting centipedegrass to varying mowing heights and levels of nitrogen fertilization, roots were analyzed from spring into summer with soil cores taken in summer and placed under drought simulation. Roots were measured for changes in length, mass, and surface area. The results of the study indicate that the roots did not benefit from either a raised mowing height, or higher nitrogen fertility, in terms of drought tolerance most likely due to increasing soil temperatures. This challenges the conventional wisdom and should encourage more research to be conducted in this area. [ABSTRACT FROM AUTHOR]

Model species (e.g., granivorous gamebirds, waterfowl, passerines, domesticated rodents) have been used for decades in guideline laboratory tests to generate survival, growth, and reproductive data for prospective ecological risk assessments (ERAs) for birds and mammals, while officially adopted risk assessment schemes for amphibians and reptiles do not exist. There are recognized shortcomings of current in vivo methods as well as uncertainty around the extent to which species with different life histories (e.g., terrestrial amphibians, reptiles, bats) than these commonly used models are protected by existing ERA frameworks. Approaches other than validating additional animal models for testing are being developed, but the incorporation of such new approach methodologies (NAMs) into risk assessment frameworks will require robust validations against in vivo responses. This takes time, and the ability to extrapolate findings from nonanimal studies to organism‐ and population‐level effects in terrestrial wildlife remains weak. Failure to adequately anticipate and predict hazards could have economic and potentially even legal consequences for regulators and product registrants. In order to be able to use fewer animals or replace them altogether in the long term, vertebrate use and whole organism data will be needed to provide data for NAM validation in the short term. Therefore, it is worth investing resources for potential updates to existing standard test guidelines used in the laboratory as well as addressing the need for clear guidance on the conduct of field studies. Herein, we review the potential for improving standard in vivo test methods and for advancing the use of field studies in wildlife risk assessment, as these tools will be needed in the foreseeable future. Integr Environ Assess Manag 2024;20:699–724. © 2023 His Majesty the King in Right of Canada and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. Key Points: Improving current approaches for laboratory animal and field effects assessment methods and simultaneously evaluating how to efficiently reduce the numbers of test subjects for the long term are worthy investments of resources.As in vivo animal testing will be required in some form in the near future, it is worth revisiting updates to standard test guidelines to address shortcomings.Clear regulatory guidance is required for field study design and conduct.It is important to fill critical knowledge gaps on the sensitivity of terrestrial amphibians, reptiles, and bats to environmental contaminants compared to current animal models and if necessary validate alternative methods for toxicological effects assesment pertaining to these taxa. [ABSTRACT FROM AUTHOR]

Despite advances in toxicity testing and the development of new approach methodologies (NAMs) for hazard assessment, the ecological risk assessment (ERA) framework for terrestrial wildlife (i.e., air‐breathing amphibians, reptiles, birds, and mammals) has remained unchanged for decades. While survival, growth, and reproductive endpoints derived from whole‐animal toxicity tests are central to hazard assessment, nonstandard measures of biological effects at multiple levels of biological organization (e.g., molecular, cellular, tissue, organ, organism, population, community, ecosystem) have the potential to enhance the relevance of prospective and retrospective wildlife ERAs. Other factors (e.g., indirect effects of contaminants on food supplies and infectious disease processes) are influenced by toxicants at individual, population, and community levels, and need to be factored into chemically based risk assessments to enhance the "eco" component of ERAs. Regulatory and logistical challenges often relegate such nonstandard endpoints and indirect effects to postregistration evaluations of pesticides and industrial chemicals and contaminated site evaluations. While NAMs are being developed, to date, their applications in ERAs focused on wildlife have been limited. No single magic tool or model will address all uncertainties in hazard assessment. Modernizing wildlife ERAs will likely entail combinations of laboratory‐ and field‐derived data at multiple levels of biological organization, knowledge collection solutions (e.g., systematic review, adverse outcome pathway frameworks), and inferential methods that facilitate integrations and risk estimations focused on species, populations, interspecific extrapolations, and ecosystem services modeling, with less dependence on whole‐animal data and simple hazard ratios. Integr Environ Assess Manag 2024;20:725–748. © 2023 His Majesty the King in Right of Canada and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Key Points: Characterizations of adverse effects in ecological risk assessments focused on wildlife have generally relied on toxicity data for survival, growth, and reproduction for new chemicals and pesticides.While exposure–response relationships for survival and reproduction will likely remain central to wildlife risk assessment in the near term, other endpoints at many levels of the biological organization have the potential to improve efficiency, reliability, and realism for the longer term.The value of new approach methodologies to ecotoxicological hazard assessment has been acknowledged for some time, but their development seems to have targeted aquatic species and phylogenetically lower forms, and applications for terrestrial wildlife are less apparent.We recommend increased attention to linkages of nonstandard molecular‐ to organism‐level endpoints to effects on wildlife at the population level, as well as to interactions at the community and ecosystem levels with a goal of preventing harmful effects of contaminants on wildlife populations. [ABSTRACT FROM AUTHOR]

Introduction/Aims: The CHAMPION MG study demonstrated that ravulizumab significantly improved Myasthenia Gravis‐Activities of Daily Living (MG‐ADL) and Quantitative Myasthenia Gravis (QMG) total scores versus placebo in adults with acetylcholine receptor antibody‐positive generalized myasthenia gravis (AChR+ gMG). This post hoc analysis aimed to assess these outcomes by time from MG diagnosis. Methods: Changes from baseline to week 26 in MG‐ADL and QMG total scores were analyzed by time from MG diagnosis to study entry (≤2 vs. >2 years). Within each subgroup, least‐squares (LS) mean changes for ravulizumab and placebo were compared using mixed models for repeated measures. Results: In ravulizumab‐treated patients, differences in LS mean (standard error of the mean) changes from baseline to week 26 were not statistically significant in the ≤2‐years subgroup versus the >2‐years subgroup for MG‐ADL (−4.3 [0.70] vs. −2.9 [0.37]; p =.0511) or QMG (−4.3 [0.94] vs. −2.5 [0.50]; p =.0822) scores. No clear trends were observed in the placebo group. LS mean changes from baseline were significantly greater for ravulizumab versus placebo in both the ≤2 and >2 years from diagnosis subgroups for MG‐ADL and QMG scores (all p <.05). The difference in treatment effect between the ≤2‐years and >2‐years subgroups was not statistically significant. No clinically meaningful between‐subgroup differences in treatment‐emergent adverse events were observed in ravulizumab‐treated patients. Discussion: Ravulizumab treatment improved clinical outcomes for patients with AChR+ gMG regardless of time from diagnosis. A numerical trend was observed favoring greater treatment effect with earlier versus later treatment after diagnosis. Further studies are required for confirmation. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 9-year-old Arabian gelding that was referred for hyporexia and pigmenturia after a trail ride. The horse exhibited severe azotemia and increased muscle enzyme activities. Cystoscopy revealed red filamentous material in the urine, and urine cytology showed acute renal tubular injury with neutrophilic inflammation. Despite treatment, the horse developed progressive azotemia and oliguria and was euthanized. Postmortem examination revealed acute renal tubular necrosis secondary to myoglobinuric nephropathy. The article discusses the unique gross and microscopic morphology of pigment-containing casts in horses with acute kidney injury. [Extracted from the article]

Aims: This paper explores Black women's perspectives on bladder health using a social‐ecological conceptual framework and life course perspective. Methods: We conducted a directed content analysis of data from the Study of Habits, Attitudes, Realities, and Experiences (SHARE), a focus group study by the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. Analysis was conducted on data from five focus groups and a member‐checking session where all participants self‐identified as Black or African American. Results: Forty‐two participants aged 11–14 or 45+ years reported life course experiences with their bladder. The intersection of race and gender was the lens through which participants viewed bladder health. Participants' accounts of their perspectives on bladder health explicitly and implicitly revealed structural racism as an explanatory overarching theme. Participants described (a) historically‐rooted and still pervasive practices of discrimination and segregation, engendering inequitable access to quality medical care and public facilities, (b) institutional barriers to toileting autonomy in educational and occupational settings, promoting unhealthy voiding habits, (c) internalized expectations of Black women's stereotyped role as family caregiver, compromising caregiver health, (d) lack of reliable information on bladder health, leading to unhealthy bladder behaviors, and (e) potentially stress‐related comorbid chronic conditions and associated medication use, causing or exacerbating bladder problems. Conclusions: Bladder health promotion interventions should address social‐ecological and life course factors shaping Black women's bladder health, including social and structural barriers to accessing equitable health information and medical care. [ABSTRACT FROM AUTHOR]

Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are protein‐ and lipid‐enriched hubs that mediate interorganellar communication by contributing to the dynamic transfer of Ca2+, lipid, and other metabolites between these organelles. Defective MERCs are associated with cellular oxidative stress, neurodegenerative disease, and cardiac and skeletal muscle pathology via mechanisms that are poorly understood. We previously demonstrated that skeletal muscle‐specific knockdown (KD) of the mitochondrial fusion mediator optic atrophy 1 (OPA1) induced ER stress and correlated with an induction of Mitofusin‐2, a known MERC protein. In the present study, we tested the hypothesis that Opa1 downregulation in skeletal muscle cells alters MERC formation by evaluating multiple myocyte systems, including from mice and Drosophila, and in primary myotubes. Our results revealed that OPA1 deficiency induced tighter and more frequent MERCs in concert with a greater abundance of MERC proteins involved in calcium exchange. Additionally, loss of OPA1 increased the expression of activating transcription factor 4 (ATF4), an integrated stress response (ISR) pathway effector. Reducing Atf4 expression prevented the OPA1‐loss‐induced tightening of MERC structures. OPA1 reduction was associated with decreased mitochondrial and sarcoplasmic reticulum, a specialized form of ER, calcium, which was reversed following ATF4 repression. These data suggest that mitochondrial stress, induced by OPA1 deficiency, regulates skeletal muscle MERC formation in an ATF4‐dependent manner. [ABSTRACT FROM AUTHOR]

Microbial symbioses have had profound impacts on the evolution of animals. Conversely, changes in host biology may impact the evolutionary trajectory of symbionts themselves. Blattabacterium cuenoti is present in almost all cockroach species and enables hosts to subsist on a nutrient‐poor diet. To investigate if host biology has impacted Blattabacterium at the genomic level, we sequenced and analyzed 25 genomes from Australian soil‐burrowing cockroaches (Blaberidae: Panesthiinae), which have undergone at least seven separate subterranean, subsocial transitions from above‐ground, wood‐feeding ancestors. We find at least three independent instances of genome erosion have occurred in Blattabacterium strains exclusive to Australian soil‐burrowing cockroaches. These shrinkages have involved the repeated inactivation of genes involved in amino acid biosynthesis and nitrogen recycling, the core role of Blattabacterium in the host‐symbiont relationship. The most drastic of these erosions have occurred in hosts thought to have transitioned underground the earliest relative to other lineages, further suggestive of a link between gene loss in Blattabacterium and the burrowing behavior of hosts. As Blattabacterium is unable to fulfill its core function in certain host lineages, these findings suggest soil‐burrowing cockroaches must acquire these nutrients from novel sources. Our study represents one of the first cases, to our knowledge, of parallel host adaptations leading to concomitant parallelism in their mutualistic symbionts, further underscoring the intimate relationship between these two partners. [ABSTRACT FROM AUTHOR]

Detection error can bias observations of ecological processes, especially when some species are never detected during sampling. In many communities, the probable identity of these missing species is known from previous research and natural history collections, but this information is rarely incorporated into subsequent models. Here, I present prior aggregation as a method for including information from external sources in Bayesian hierarchical detection models. Prior aggregation combines information from multiple prior distributions, in this case, an ecologically informative, species-level prior, and an uninformative community-level prior. This approach incorporates external information into the model without sacrificing the advantages of modeling species in the context of the community. Using simulated data supplied to a multispecies occupancy model, I demonstrated that prior aggregation improves estimates of (1) metacommunity richness and (2) environmental covariates were associated with species-specific occupancy probabilities. When applied to a dataset of small mammals in Vermont, prior aggregation allowed the model to estimate occupancy correlates of the Eastern cottontail Sylvilagus floridanus, a species observed at several sites in the region but never captured. Prior aggregation can be used to improve the analysis of several important metrics in population and community ecology, including abundance, survivorship, and diversity. [ABSTRACT FROM AUTHOR]

Two Ru(II)‐catalytic systems were developed for anti‐Markovnikov regioselective hydroacyloxylations of terminal alkynes to vinylic esters. [Ru(NCCH3)6][(BF4)2] favors (E)‐vinylic ester products with arylacetylenes and select carboxylic acids, whereas a Ru scorpionate complex with two electron‐withdrawing ligands favors (Z)‐vinylic ester isomers. [ABSTRACT FROM AUTHOR]

Objective: To assess pregnant Texans' decisions about where to obtain out‐of‐state abortion care following the September 2021 implementation of Senate Bill 8 (SB8), which prohibited abortions after detectable embryonic cardiac activity. Data Source: In‐depth telephone interviews with Texas residents ≥15 years of age who obtained out‐of‐state abortion care after SB8's implementation. Study Design: This qualitative study explored participants' experiences identifying and contacting abortion facilities and their concerns and considerations about traveling out of state. We used inductive and deductive codes in our thematic analysis describing people's decisions about where to obtain care and how they evaluated available options. Data Collection: Texas residents self‐referred to the study from flyers we provided to abortion facilities in Arkansas, Colorado, Kansas, Louisiana, Mississippi, New Mexico, and Oklahoma. We also enrolled participants from a concurrent online survey of Texans seeking abortion care. Principal Findings: Participants (n = 65) frequently obtained referral lists for out‐of‐state locations from health‐care providers, and a few received referrals to specific facilities; however, referrals rarely included the information people needed to decide where to obtain care. More than half of the participants prioritized getting the soonest appointment and often contacted multiple locations and traveled further to do so; others who could not travel further typically waited longer for an appointment. Although the participants rarely cited state abortion restrictions or cost of care as their main reason for choosing a location, they often made sacrifices to lessen the logistical and economic hardships that state restrictions and out‐of‐state travel costs created. Informative abortion facility websites and compassionate scheduling staff solidified some participants' facility choice. Conclusions: Pregnant Texans made difficult trade‐offs and experienced travel‐related burdens to obtain out‐of‐state abortion care. As abortion bans prohibit more people from obtaining in‐state care, efforts to strengthen patient navigation are needed to reduce care‐seeking burdens as this will support people's reproductive autonomy. [ABSTRACT FROM AUTHOR]

A fundamental challenge in the practical implementation of multistatic radar systems (MSRS) is the requirement for precise time and frequency synchronisation between the spatially separated radar nodes. The authors evaluate the performance of different classes of commercially available Global Navigation Satellite Systems (GNSS) timing receivers, Local Oscillators (LO) and GNSS Disciplined Oscillators (GNSSDOs) to determine the limitations of using one‐way GNSS Time and Frequency Transfer (TFT) in this application. From evaluating the performance of three pairs of GNSSDOs, it is concluded that one‐way GNSS TFT will likely be suitable only for the synchronisation of fully spatially coherent MSRS with carrier frequencies up to 100 MHz and waveform bandwidths up to 20 MHz. Whereas, in the case of short‐term spatially coherent MSRS, synchronisation of systems with carrier frequencies up to a few GHz and waveform bandwidths of over 100 MHz will likely be possible. The performance of the different classes of GNSSDOs during GNSS denial (holdover) are evaluated, where it is concluded that frequency offsets between LOs at the point of GNSS denial will often significantly contribute, or even dominate, the holdover performance. Analysis of two practical multistatic radar measurements verifies the function of using the GNSSDOs for wireless synchronisation of the ARESTOR MSRS. [ABSTRACT FROM AUTHOR]

Institutions of higher education (IHE) throughout the United States have a long history of acting out various levels of commitment to diversity advancement, equity, and inclusion (DEI). Despite decades of DEI "efforts," the academy is fraught with legacies of racism that uphold white supremacy and prevent marginalized populations from full participation. Furthermore, politicians have not only weaponized education but passed legislation to actively ban DEI programs and censor general education curricula (https://tinyurl.com/antiDEI). Ironically, systems of oppression are particularly apparent in the fields of Ecology, Evolution, and Conservation Biology (EECB), which recognize biological diversity as essential for ecological integrity and resilience. Yet, among EECB faculty, people who do not identify as cis‐heterosexual, nondisabled, affluent white males are poorly represented. Furthermore, IHE lacks metrics to quantify DEI as a priority. Here we show that only 30.3% of United States faculty positions advertised in EECB from Jan 2019 to May 2020 required a diversity statement; diversity statement requirements did not correspond with state‐level diversity metrics. Though many announcements "encourage women and minorities to apply," empirical evidence demonstrates that hiring committees at most institutions did not prioritize an applicant's DEI advancement potential. We suggest a model for change and call on administrators and faculty to implement SMART (i.e., Specific, Measurable, Achievable, Realistic, and Timely) strategies for DEI advancement across IHE throughout the United States. We anticipate our quantification of diversity statement requirements relative to other application materials will motivate institutional change in both policy and practice when evaluating a candidate's potential "fit." IHE must embrace a leadership role to not only shift the academic culture to one that upholds DEI but to educate and include people who represent the full diversity of our society. In the current context of political censure of education including book banning and backlash aimed at Critical Race Theory, which further reinforce systemic white supremacy, academic integrity and justice are more critical than ever. [ABSTRACT FROM AUTHOR]

This study examines the simulation of the heatwave events over Florida from the integration of two regional climate models (RCMs) at comparatively high resolution (at 10 km grid spacing) for two decades of the current climate (1986–2005) followed by their projection in the mid‐21st century (2041–2060). The two RCMs are coupled ocean–atmosphere (CRSM) and atmosphere only (URSM), which are forced at the lateral boundaries by the corresponding simulation of the Community Climate System Model v4 (CCSM4) for both the atmosphere and the ocean. The analysis reveals a reasonable simulation of the frequency, intensity and characteristic kinematic and thermodynamic features of the heatwave events over Florida from both the RCMs with the differences between URSM and CRSM being insignificant. The future projections (2041–2060) are presented only for URSM since the projected differences from CRSM were insignificant. We found the projected change of higher frequency ranging between 20 to over 50% increase relative to the late 20th‐century frequency of heatwave events. Similarly, the projections suggest a broadening of the season of their occurrence by over 2 months. These projected changes are associated with a projected increase in the mean surface temperature, a slight increase of surface humidity but with a mean reduction of surface relative humidity, and a westward dislocation of the North Atlantic Subtropical High. [ABSTRACT FROM AUTHOR]

The treatable traits approach is based on the recognition that the different clinical phenotypes of asthma and chronic obstructive airways disease (COPD) are a heterogeneous group of conditions with different underlying mechanisms and clinical manifestations, and that the identification and treatment of the specific clinical features or traits facilitates a personalised approach to management. Fundamentally, it recognises two important concepts. Firstly, that treatment for obstructive lung disease can achieve better outcomes if guided by specific clinical characteristics. Secondly, that in patients with a diagnosis of asthma, and/or COPD, poor respiratory health may also be due to numerous overlapping disorders that can present with symptoms that may be indistinguishable from asthma and/or COPD, comorbidities that might require treatment in their own right, and lifestyle or environmental factors that, if addressed, might lead to better control rather than simply increasing airways directed treatment. While these concepts are well accepted, how best to implement this personalised medicine approach in primary and secondary care within existing resource constraints remains uncertain. In this review, we consider the evidence base for this management approach and propose that the priority now is to assess different prototype templates for the identification and management of treatable traits in both asthma and COPD, in primary, secondary and tertiary care, to provide the evidence that will guide their use in clinical practice in different health care systems. [ABSTRACT FROM AUTHOR]

During aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized. We measured changes in mitochondrial morphology in aged murine gastrocnemius, soleus, and cardiac tissues using serial block‐face scanning electron microscopy and 3D reconstructions. We also used reverse transcriptase‐quantitative PCR, transmission electron microscopy quantification, Seahorse analysis, and metabolomics and lipidomics to measure changes in mitochondrial morphology and function after loss of mitochondria contact site and cristae organizing system (MICOS) complex genes, Chchd3, Chchd6, and Mitofilin. We identified significant changes in mitochondrial size in aged murine gastrocnemius, soleus, and cardiac tissues. We found that both age‐related loss of the MICOS complex and knockouts of MICOS genes in mice altered mitochondrial morphology. Given the critical role of mitochondria in maintaining cellular metabolism, we characterized the metabolomes and lipidomes of young and aged mouse tissues, which showed profound alterations consistent with changes in membrane integrity, supporting our observations of age‐related changes in muscle tissues. We found a relationship between changes in the MICOS complex and aging. Thus, it is important to understand the mechanisms that underlie the tissue‐dependent 3D mitochondrial phenotypic changes that occur in aging and the evolutionary conservation of these mechanisms between Drosophila and mammals. [ABSTRACT FROM AUTHOR]

BACKGROUND: As the population and range of wild pigs (Sus scrofa) continue to grow across North America, there has been an increase in environmental and economic damages caused by this invasive species, and control efforts to reduce damages have increased concomitantly. Despite the expanding impacts and costs associated with population control of wild pigs, the extent to which wild pig control reduces populations and diminishes environmental and agricultural damages are rarely quantified. The goal of this study is to quantify changes in wild pig relative abundance and subsequent changes in damages caused by invasive wild pigs in response to control. RESULTS: Using a combination of wild pig population surveys, agricultural damage assessments, and environmental rooting surveys across 19 mixed forest‐agricultural properties in South Carolina, USA, we quantified changes in wild pig relative abundance and associated damages over a 3‐year period following implementation of a professional control program. Following implementation of control efforts, both the number of wild pig detections and estimated abundance decreased markedly. Within 24 months relative abundance was reduced by an average of ~70%, which resulted in a corresponding decline in environmental rooting damage by ~99%. CONCLUSION: Our findings suggest that sustained wild pig control efforts can substantially reduce wild pig relative abundance, which in turn resulted in a reduction in environmental rooting damage by wild pigs. Ultimately this study will help fill critical knowledge gaps regarding the efficacy of wild pig control programs and the effort needed to reduce impacts to native ecosystems, livestock, and crops. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Raccoons (Procyon lotor) are the primary reservoir for rabies virus in eastern North America. Management of rabies in raccoons is achieved primarily with the use of oral rabies vaccination (ORV) and effective ORV bait densities are determined in part by the densities of raccoons. Decisions regarding ORV bait densities, however, are limited by an incomplete understanding of raccoon densities across the spectrum of landscapes they occupy. We carried out a mark‐recapture study of raccoons on the Savannah River Site in South Carolina, USA, from 2017–2019, to develop sex‐ and landscape‐specific raccoon density estimates across 4 rural land cover types in the southeastern United States: bottomland hardwood, riparian forest, isolated wetland, and upland pine (Pinus spp.). We captured 404 unique raccoons 773 times over the 3‐year trapping period. Estimated densities were 5.44 ± 0.37 (SE) animals/km2 in bottomland hardwood forest, 2.62 ± 0.32 animals/km2 in riparian forest, 2.19 ± 0.29 animals/km2 in isolated wetlands, and 2.14 ± 0.23 animals/km2 in upland pine. Densities were significantly higher in bottomland hardwood than all other land cover types, whereas densities among the remaining cover types were similar. These patterns are likely the result of landscape fragmentation and configuration, with riparian forests typically embedded in a matrix of less suitable cover types, leading to low densities despite presumably high resource availability. There were higher densities of males than females in every cover type except upland pine, where the sex ratio was balanced. Densities on our site were low compared to other rural areas, which likely results from the lack of human influence in terms of agriculture or development. The financial cost of baiting for ORV distribution may be reduced by considering the comparatively low densities of raccoons in these rural landscapes in the southeastern United States. [ABSTRACT FROM AUTHOR]

Summary: International recommendations encourage liberal administration of oxygen to patients having surgery under general anaesthesia, ostensibly to reduce surgical site infection. However, the optimal oxygen regimen to minimise postoperative complications and enhance recovery from surgery remains uncertain. The hospital operating theatre randomised oxygen (HOT‐ROX) trial is a multicentre, patient‐ and assessor‐blinded, parallel‐group, randomised clinical trial designed to assess the effect of a restricted, standard care, or liberal peri‐operative oxygen therapy regimen on days alive and at home after surgery in adults undergoing prolonged non‐cardiac surgery under general anaesthesia. Here, we report the findings of the internal vanguard feasibility phase of the trial undertaken in four large metropolitan hospitals in Australia and New Zealand that included the first 210 patients of a planned overall 2640 trial sample, with eight pre‐specified endpoints evaluating protocol implementation and safety. We screened a total of 956 participants between 1 September 2019 and 26 January 2021, with data from 210 participants included in the analysis. Median (IQR [range]) time‐weighted average intra‐operative FiO2 was 0.30 (0.26–0.35 [0.20–0.59]) and 0.47 (0.44–0.51 [0.37–0.68]) for restricted and standard care, respectively (mean difference (95%CI) 0.17 (0.14–0.20), p < 0.001). Median time‐weighted average intra‐operative FiO2 was 0.83 (0.80–0.85 [0.70–0.91]) for liberal oxygen therapy (mean difference (95%CI) compared with standard care 0.36 (0.33–0.39), p < 0.001). All feasibility endpoints were met. There were no significant patient adverse events. These data support the feasibility of proceeding with the HOT‐ROX trial without major protocol modifications. [ABSTRACT FROM AUTHOR]

Background: Identifying patients at high risk for colorectal cancer recurrence is essential for improving prognosis. In the postoperative period, circulating tumour DNA (ctDNA) has been demonstrated as a significant prognostic indicator of recurrence. These results have been obtained under the strict rigours of clinical trials, but not validated in a real‐world setting using in‐house testing. We report the outcomes of locally performed postoperative ctDNA testing conducted during routine clinical care and the association with the recurrence of colorectal cancer. Methods: We recruited 36 consecutive patients with newly diagnosed colorectal cancer between 2018 and 2020. Postoperative plasma samples were collected at the first outpatient review following resection. Tumour‐informed ctDNA analysis was performed using droplet digital polymerase chain reaction or targeted next‐generation sequencing. Results: At the time of surgery, there were 24 patients (66.7%) with localized cancer, nine (25%) with nodal spread, and three (8.3%) with metastatic disease. The median time from surgery to plasma sample donation was 22 days (IQR 20–28 days). At least one somatic mutation was identified in primary tumour tissue for 28 (77.8%) patients. Postoperative ctDNA was detected in five patients (13.9%). The median duration of follow‐up was 32.0 months (IQR 27.2–38.1 months). Two patients (5.56%) developed metastatic recurrence. However, neither had detectable postoperative ctDNA. There were no instances of loco‐regional recurrence. Conclusion: Analysis of postoperative ctDNA testing can be performed locally, however this study did not reproduce the adverse association between detectable postoperative ctDNA and the development of colorectal cancer recurrence seen in clinical trials. [ABSTRACT FROM AUTHOR]

Mitochondria respond to metabolic demands of the cell and to incremental damage, in part, through dynamic structural changes that include fission (fragmentation), fusion (merging of distinct mitochondria), autophagic degradation (mitophagy), and biogenic interactions with the endoplasmic reticulum (ER). High resolution study of mitochondrial structural and functional relationships requires rapid preservation of specimens to reduce technical artifacts coupled with quantitative assessment of mitochondrial architecture. A practical approach for assessing mitochondrial fine structure using two dimensional and three dimensional high‐resolution electron microscopy is presented, and a systematic approach to measure mitochondrial architecture, including volume, length, hyperbranching, cristae morphology, and the number and extent of interaction with the ER is described. These methods are used to assess mitochondrial architecture in cells and tissue with high energy demand, including skeletal muscle cells, mouse brain tissue, and Drosophila muscles. The accuracy of assessment is validated in cells and tissue with deletion of genes involved in mitochondrial dynamics. [ABSTRACT FROM AUTHOR]

Background: Data on the movement behavior of translocated wild pigs is needed to develop appropriate response strategies for containing and eliminating new source populations following translocation events. We conducted experimental trials to compare the home range establishment and space‐use metrics, including the number of days and distance traveled before becoming range residents, for wild pigs translocated with their social group and individually. Results: We found wild pigs translocated with their social group made less extensive movements away from the release location and established a stable home range ~5 days faster than those translocated individually. We also examined how habitat quality impacted the home range sizes of translocated wild pigs and found wild pigs maintained larger ranges in areas with higher proportion of low‐quality habitat. Conclusion: Collectively, our findings suggest translocations of invasive wild pigs have a greater probability of establishing a viable population near the release site when habitat quality is high and when released with members of their social unit compared to individuals moved independent of their social group or to low‐quality habitat. However, all wild pigs translocated in our study made extensive movements from their release location, highlighting the potential for single translocation events of either individuals or groups to have far‐reaching consequences within a much broader landscape beyond the location where they are released. These results highlight the challenges associated with containing populations in areas where illegal introduction of wild pigs occurs, and the need for rapid response once releases are identified. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The article discusses the use of inhaled corticosteroid (ICS)-formoterol maintenance and reliever therapy (MART) in adolescents and adults with asthma, highlighting its benefits in reducing severe exacerbation risk. Despite evidence supporting its efficacy, the uptake of ICS-formoterol MART has been low internationally, with some patients also being prescribed short-acting beta-agonist (SABA) alongside it. A survey conducted in New Zealand revealed that SABA co-prescribing with ICS-formoterol MART was relatively low at 16%, indicating that most patients can be reassured by their prescribing practitioner. The study also noted early adoption of ICS-formoterol reliever alone regimen with minimal SABA co-prescribing, suggesting a successful transition to this therapy in clinical practice. [Extracted from the article]

Serial block face scanning electron microscopy (SBF‐SEM), also referred to as serial block‐face electron microscopy, is an advanced ultrastructural imaging technique that enables three‐dimensional visualization that provides largerx‐ and y‐axis ranges than other volumetric EM techniques. While SEM is first introduced in the 1930s, SBF‐SEM is developed as a novel method to resolve the 3D architecture of neuronal networks across large volumes with nanometer resolution by Denk and Horstmann in 2004. Here, the authors provide an accessible overview of the advantages and challenges associated with SBF‐SEM. Beyond this, the applications of SBF‐SEM in biochemical domains as well as potential future clinical applications are briefly reviewed. Finally, the alternative forms of artificial intelligence‐based segmentation which may contribute to devising a feasible workflow involving SBF‐SEM, are also considered. [ABSTRACT FROM AUTHOR]

Machine learning has proven useful in analyzing complex biological data and has greatly influenced the course of research in structural biology and precision medicine. Deep neural network models oftentimes fail to predict the structure of complex proteins and are heavily dependent on experimentally determined structures for their training and validation. Single‐particle cryogenic electron microscopy (cryoEM) is also advancing the understanding of biology and will be needed to complement these models by continuously supplying high‐quality experimentally validated structures for improvements in prediction quality. In this perspective, the significance of structure prediction methods is highlighted, but the authors also ask, what if these programs cannot accurately predict a protein structure important for preventing disease? The role of cryoEM is discussed to help fill the gaps left by artificial intelligence predictive models in resolving targetable proteins and protein complexes that will pave the way for personalized therapeutics. [ABSTRACT FROM AUTHOR]

Purpose: To establish whether axial growth and refractive error can be modulated in anisohyperopic children by imposing relative peripheral hyperopic defocus (RPHD) using multifocal soft contact lenses. Methods: This study is a prospective, controlled paired‐eye study with anisohyperopic children. Axial growth and refractive error were observed without intervention for the first 6 months of the 3‐year trial with participants wearing single vision spectacles. Then, participants wore a centre‐near, multifocal, soft contact lens (+2.00 D add) in their more hyperopic eye for 2 years, with a single vision contact lens worn in the fellow eye if required. The 'centre‐near' portion of the contact lens in the more hyperopic eye corrected distance refractive error while the 'distance' portion imposed hyperopic defocus in the peripheral retina. Participants reverted to single vision spectacles for the final 6 months. Results: Eleven participants, mean age of 10.56 years (SD 1.43; range 8.25–13.42), completed the trial. No increase in axial length (AL) was found during the first 6 months in either eye (p > 0.99). Axial growth across the 2‐year intervention period was 0.11 mm (SEM 0.03; p = 0.06) in the test eye versus 0.15 mm (SEM 0.03; p = 0.003) in the control eye. AL was invariant during the final 6 months in both eyes (p > 0.99). Refractive error was stable during the first 6 months in both eyes (p = 0.71). Refractive error change across the 2‐year intervention period was −0.23 D (SEM 0.14; p = 0.32) in the test eye versus −0.30 D (SEM 0.14; p = 0.61) in the control eye. Neither eye demonstrated a change in refractive error during the final 6 months (p > 0.99). Conclusions: Imposing RPHD using the centre‐near, multifocal, contact lens specified here did not accelerate axial growth nor reduce refractive error in anisohyperopic children. [ABSTRACT FROM AUTHOR]

Background and Aim: Overt obscure gastrointestinal bleeding (OOGIB) is defined as continued bleeding with unknown source despite esophagogastroduodenoscopy (EGD) and colonoscopy evaluation. Small bowel evaluation through video capsule endoscopy (VCE) or double balloon enteroscopy (DBE) is often warranted. We studied the timing of DBE in hospitalized OOGIB patients regarding diagnostic yield, therapeutic yield, and GI rebleeding. Methods: We performed a retrospective review of DBEs performed at a tertiary medical center between November 2012 and December 2020. The inclusion criterion was first admission for OOGIB undergoing DBE. Those without previous EGD or colonoscopy were excluded. Patients were stratified into two groups: DBE performed within 72 h of OOGIB (emergent) and beyond 72 h of OOGIB (nonemergent). Propensity score matching was used to adjust for the difference in patients in the two groups. Logistic regression analysis was used to assess factors associated with diagnostic and therapeutic yield. Kaplan–Meir survival curve showed GI bleed‐free survival following initial bleed and was compared using the log rank test. Results: A total of 154 patients met the inclusion criterion, of which 62 had emergent DBE and 92 had nonemergent DBE. The propensity‐score‐matched sample consisted of 112 patients, with 56 patients each in the emergent and nonemergent groups. Univariate and multivariable logistic regression analysis showed a significant association between VCE and emergent DBE and diagnostic and therapeutic yield (P < 0.05). Emergent DBE patients had increased GI bleed‐free survival compared to those in the nonemergent group (P = 0.009). Conclusion: Our data demonstrate that emergent DBE during inpatient OOGIB can impact the overall diagnostic yield, therapeutic yield, and GI rebleeding post DBE. [ABSTRACT FROM AUTHOR]

Throughout the eastern United States, the National Rabies Management Program (NRMP) distributes oral rabies vaccine (ORV) baits to manage rabies virus circulation in raccoon (Procyon lotor) populations. The consumption of vaccine baits by non‐target species including Virginia opossums (Didelphis virginiana) may reduce the effectiveness of ORV programs, but competition for baits remains poorly quantified in many areas of the southeastern United States. We distributed placebo ORV baits injected with a biomarker across 4 land cover types (bottomland hardwood, upland pine, riparian, isolated wetland) on the Savannah River Site in South Carolina, USA, 2017–2019. We then trapped and collected whiskers from 247 raccoons and 78 opossums to assess biomarker presence using fluorescent microscopy. Our data revealed greater bait uptake probability by raccoons (estimated x̅ = 0.30, 95% CI = 0.19–0.44) compared to opossums (estimated x̅ = 0.11, 95% CI = 0.05–0.23) across all cover types surveyed. Probability of bait consumption was not affected by cover type or the abundance of raccoons or opossums. Among raccoons, males were more likely to consume baits than females (estimated x̅ = 0.28, 95% CI = 0.17–0.44 for males and 0.14, 95% CI = 0.05–0.31 for females) and probability of consumption increased by 0.08 with each additional day trapped during the 10‐day trapping session. Uptake rates for raccoons were relatively low compared to other studies and not influenced by competition with opossums. These low consumption rates indicate that additional research addressing the roles of baiting season, bait density, and resource selection will be important to maximize ORV bait uptake by target species in these southeastern landscapes. [ABSTRACT FROM AUTHOR]

Background: Limited recent data exists regarding discospondylitis in dogs. Hypothesis/Objectives: (i) Describe the signalment, clinical and imaging findings, etiologic agents, treatment, and outcome of dogs with discospondylitis, (ii) determine diagnostic agreement between radiographs, CT, and MRI with regard to the presence of discospondylitis and its location, and (iii) determine risk factors for relapse and progressive neurological deterioration. Animals: Three hundred eighty‐six dogs. Methods: Multi‐institutional retrospective study. Data extracted from medical records were: signalment, clinical and examination findings, diagnostic results, treatments, complications, and outcome. Potential risk factors were recorded. Breed distribution was compared to a control group. Agreement between imaging modalities was assessed via Cohen's kappa statistic. Other analyses were performed on categorical data, using cross tabulations with chi‐squared and Fisher's exact tests. Results: Male dogs were overrepresented (236/386 dogs). L7‐S1 (97/386 dogs) was the most common site. Staphylococcus species (23/38 positive blood cultures) were prevalent. There was a fair agreement (κ = 0.22) between radiographs and CT, but a poor agreement (κ = 0.05) between radiographs and MRI with regard to evidence of discospondylitis. There was good agreement between imaging modalities regarding location of disease. Trauma was associated with an increased risk of relapse (P =.01, OR: 9.0, 95% CI: 2.2‐37.0). Prior steroid therapy was associated with an increased risk of progressive neurological dysfunction (P =.04, OR: 4.7, 95% CI: 1.2‐18.6). Conclusions and Clinical Importance: Radiograph and MRI results could be discrepant in dogs with discospondylitis. Prior trauma and corticosteroids could be associated with relapse and progressive neurological dysfunction, respectively. [ABSTRACT FROM AUTHOR]

Information on freshwater mussel behavior in the sediment is scarce worldwide, especially in the Amazon. Laboratory experiments were used to measure the responses of the single mussel species Castalia ambigua in relation to combinations of two co‐occurring different morphotypes (Morphotype I with an elongated shell and Morphotype II with a rounded shell), and three different densities (four, eight, and 16 mussels). Horizontal movements (cm) were calculated by summing changes in the position of each specimen and the shell exposure at the sediment–water interface was obtained by measuring (mm) the exposed part of the shell. Castalia ambigua presented different patterns of shell exposure and horizontal movements linked with shell shape and density. Castalia ambigua Morphotype I remained less exposed with 4 mussels. In contrast, this morphotype was more exposed and tended to aggregate in treatments with 8 and 16 mussels, similar to observations of Morphotype II at all densities. Morphotype II is mainly found in low hydrodynamic energy habitats, suggesting that patches with high densities may stabilize the substrate around the shells of Morphotype I, which is associated with high hydrodynamic energy habitats. We suggest that these patterns may be associated with intrinsic factors of the species, such as reproduction, sexual dimorphism and feeding. Moreover, additional studies using other mussel species belonging to the families Hyriidae and Mycetopodidae are important, since the behavior of these mussels in the sediment may provide useful information on their functional roles in river ecosystems. [ABSTRACT FROM AUTHOR]

Introduction: Community engagement is increasingly recognized as a critical component of research, but few studies provide details on how to successfully incorporate community perspectives in urological research. This manuscript describes the community engagement strategy used by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS) to design RISE FOR HEALTH (RISE), a multicenter, population‐based, prospective cohort study to promote bladder health. Methods and Results: The PLUS Community Engagement Subcommittee, guided by a set of antiracist community engagement principles and practices, organized, implemented, and communicated findings for all RISE community engagement activities. Community engagement was conducted through a diverse network of community partners at PLUS clinical research centers called Rapid Assessment Partners (RAPs). Via online surveys (4), virtual discussion groups (14), and one‐on‐one interviews (12), RAPs provided input on RISE processes and materials, including in‐person visit procedures, specimen collection instructions, survey data collection instruments, recruitment materials, the study website, and the study name. This process resulted in significant changes to these aspects of the study design with reciprocal benefits for the community partners. Discussion: Meaningful community engagement improved the design and implementation of RISE. PLUS will continue to engage community partners to interpret the RISE study results, disseminate RISE findings, and inform other PLUS studies toward the development of interventions to promote bladder health. Future urological studies would also benefit from community participation in determining priority research questions to address. [ABSTRACT FROM AUTHOR]