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Restoration engineering measures, such as managed realignments or building groins, modify the environmental characteristics of coastal intertidal ecosystems. Creating physical modifications that are beneficial to an intertidal system's ecology necessitates an in‐depth understanding of the relationships between the abiotic and biotic components of a given intertidal habitat. In this study, we evaluate how hydrodynamics and sediment characteristics drive the development of the benthic macrofauna community during the first 5 years following engineering measures to enhance benthic macrofauna diversity at three locations. The creation of low‐energy habitats through groins (Knuitershoek and Baalhoek) and a managed realignment dike breach (Perkpolder) led to the accumulation of fine sediments in all three impact sites. Biomass of benthic macrofauna quickly increased between 2016 and 2020, with successional processes being more important in Perkpolder, where the habitat was started completely from scratch due to a managed realignment, than at Knuitershoek or Baalhoek, where habitat conditions were improved by adding groins. In addition, the density of benthos‐eating birds, especially oystercatchers, increased at some of the modified sites. While a low‐energy habitat may harbor more diverse assemblages of benthic macrofauna than a highly dynamic one, the extremely high silt content, which is typical for low‐energy habitats, may slow benthic community development. The observed increase of biomass at our impact sites highlights the value of the interventions, while the delays in the response of the benthic macrofauna community emphasizes the need for extensive monitoring both in time and space and the identification of underlying abiotic–biotic mechanisms. [ABSTRACT FROM AUTHOR]

Background: Although adult transplant centers are successfully transplanting organs from hepatitis C virus (HCV)‐infected donors with detectable viral load by nucleic acid testing (NAT+) into HCV‐negative recipients, this practice has not yet been adopted widely by the pediatric heart transplant community. Methods: We present a case series of four patients who received heart transplants from HCV NAT+ donors at a pediatric transplant center, including two pediatric patients < 18 years of age. Results: All recipients tolerated a 12‐week course of glecaprevir/pibrentasvir and achieved a sustained virologic response with no HCV or liver complications with over 1 year of follow‐up (range 1.4–2.5 years). All four have had good post‐heart transplant outcomes with normal graft function and good functional status without rejection or cardiac allograft vasculopathy at time of last follow‐up. Conclusions: This case series details the successful multidisciplinary implementation of a protocol to accept cardiac allografts from HCV NAT+ donors for transplantation into HCV negative recipients at our pediatric transplant center. With the limited donor pool in pediatrics and the morbidity associated with prolonged durations on the transplant waitlist, pediatric centers should consider utilizing organs from HCV NAT+ donors to broaden the donor pool. Future work should evaluate other organs beyond heart and optimal timing and duration of direct acting antiviral therapy. [ABSTRACT FROM AUTHOR]

Little is known about the extent of prior authorization requirements in otolaryngology. We performed a secondary analysis of data comparing prior authorization (PA) policies across 5 major Medicare Advantage insurers to estimate the counterfactual proportion of 2021 Medicare Part B fee‐for‐service spending and utilization for commonly performed otolaryngologic procedures that would have required PA. The counterfactual proportion of spending (range: 20.4%–27.6%) and utilization (range: 1.8%–4.5%) requiring PA was relatively consistent across insurers and largely attributable to rhinologic procedures. However, PA requirements for specific services varied widely among insurers. Among the 70 (of 196; 35.7%) services subject to PA by any insurer, nearly half were subject to PA by a single insurer (n = 34; 48.6%). Only 10 (14.3%) services were subject to PA by 4 (n = 6; 8.6%) or 5 (n = 4; 5.7%) insurers. These discrepancies illustrate the challenges of navigating discordant insurer policies for otolaryngologists and raise concerns about the validity of certain PA requirements. [ABSTRACT FROM AUTHOR]

Creating a plan for crisis prevention, intervention, and postvention procedures allows schools to prepare for the traumatic consequences when a crisis inevitably occurs. The comprehensive crisis plan checklist—second edition (CCPC‐2; McCleary & Aspiranti, 2020) is a 102‐item tool created for evaluating individual school and district crisis plans. The current study examined existing crisis plans from school districts across the United States to determine the amount and type of CCPC‐2 items that are present within school crisis plans. The number of CCPC‐2 items represented on the 73 plans evaluated ranged from 0 to 67 with a mean of 22.29 items. The average number of plans that included a single item on the CCPC‐2 was 16. There were no significant differences in the number of CCPC‐2 items represented across different geographic locations, urbanicity (urban, suburban, rural), or district/school‐level plan type. Discussion focuses on how crisis teams within the schools can use the CCPC‐2 when creating, reviewing, or revising their district‐ or school‐level crisis plan. Practitioner points: Crisis plans included an average of 22.29 comprehensive crisis plan checklist—second edition (CCPC‐2) items.There were no differences in the number of CCPC‐2 items included in a crisis plan across different geographic locations, urbanicity of district, or the type of plan.School crisis teams can use the CCPC‐2 to determine the types of crisis prevention, intervention, and postvention items needed within their school or district crisis plan. [ABSTRACT FROM AUTHOR]

Enfortumab vedotin (EV), a nectin‐4‐binding agent that affects microtubules, has become standard therapy for advanced urothelial carcinoma. The agent, now given in combination with pembrolizumab, frequently induces cutaneous reactions. Here, we report a severe EV‐induced cutaneous eruption. A 58‐year‐old woman with metastatic urothelial carcinoma developed a rash after receiving simultaneous first doses of EV and pembrolizumab. The eruption began on the flank and spread to involve her trunk and extremities with prominent involvement of folds, including the axillae and medial thighs. Skin biopsy revealed extensive vacuolar alteration of the basal epidermis and numerous epidermal keratinocytic mitotic figures, often suprabasilar, including ring and "starburst" forms. The findings supported a diagnosis of EV‐induced eruption. With EV cessation and systemic corticosteroids, the rash resolved over a few weeks. Pembrolizumab was restarted as monotherapy, and the patient's cancer showed a significant radiographic treatment response at 3 months. An emerging literature of small series and case reports, largely from oncologic literature, presents the histopathology of EV‐induced cutaneous eruption as a vacuolar interface dermatitis with the inconsistently reported feature of arrested mitotic figures. This case study demonstrates distinctive clinical and histopathologic features of EV‐induced eruption, which may inform dermatologic and oncologic management. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus (Mab) is highly drug resistant, and understanding regulation of antibiotic resistance is critical to future antibiotic development. Regulatory mechanisms controlling Mab's β‐lactamase (BlaMab) that mediates β‐lactam resistance remain unknown. S. aureus encodes a prototypical protease‐mediated two‐component system BlaRI regulating the β‐lactamase BlaZ. BlaR binds extracellular β‐lactams, activating an intracellular peptidase domain which cleaves BlaI to derepress blaZ. Mycobacterium tuberculosis (Mtb) encodes homologs of BlaRI (which we will denote as BlaIR to reflect the inverted gene order in mycobacteria) that regulate not only the Mtb β‐lactamase, blaC, but also additional genes related to respiration. We identified orthologs of blaIRMtb in Mab and hypothesized that they regulate blaMab. Surprisingly, neither deletion of blaIRMab nor overexpression of only blaIMab altered blaMab expression or β‐lactam susceptibility. However, BlaIMab did bind to conserved motifs upstream of several Mab genes involved in respiration, yielding a putative regulon that partially overlapped with BlaIMtb. Prompted by evidence that respiration inhibitors including clofazimine induce the BlaI regulon in Mtb, we found that clofazimine triggers induction of blaIRMab and its downstream regulon. Highlighting an important role for BlaIRMab in adapting to disruptions in energy metabolism, constitutive repression of the BlaIMab regulon rendered Mab highly susceptible to clofazimine. In addition to our unexpected findings that BlaIRMab does not regulate β−lactam resistance, this study highlights the novel role of mycobacterial BlaRI‐type regulators in regulating electron transport and respiration. [ABSTRACT FROM AUTHOR]

Over the last three decades, the technology that makes it possible to follow chemical processes in the solid state in real time has grown enormously. These studies have important implications for the design of new functional materials for applications in optoelectronics and sensors. Light–matter interactions are of particular importance, and photocrystallography has proved to be an important tool for studying these interactions. In this technique, the three‐dimensional structures of light‐activated molecules, in their excited states, are determined using single‐crystal X‐ray crystallography. With advances in the design of high‐power lasers, pulsed LEDs and time‐gated X‐ray detectors, the increased availability of synchrotron facilities, and most recently, the development of XFELs, it is now possible to determine the structures of molecules with lifetimes ranging from minutes down to picoseconds, within a single crystal, using the photocrystallographic technique. This review discusses the procedures for conducting successful photocrystallographic studies and outlines the different methodologies that have been developed to study structures with specific lifetime ranges. The complexity of the methods required increases considerably as the lifetime of the excited state shortens. The discussion is supported by examples of successful photocrystallographic studies across a range of timescales and emphasises the importance of the use of complementary analytical techniques in order to understand the solid‐state processes fully. [ABSTRACT FROM AUTHOR]

Phase 1 clinical drug trials critically depend on the participation of healthy volunteers to evaluate the safety and pharmacokinetics of new medicinal products. Current selection criteria and health definitions often overlook the unique health profiles of transgender and nonbinary individuals, potentially excluding them from participating in these essential early‐stage studies. This review aims to identify and discuss current knowledge gaps and considerations regarding the inclusion of transgender and nonbinary participants in phase 1 clinical drug trials. We highlight the need for research on how gender‐affirming hormone therapy may affect drug pharmacokinetics and call for the development of inclusive biological reference ranges that account for the physiological effects of hormone therapies. [ABSTRACT FROM AUTHOR]

In vivo estimation of cerebrospinal fluid (CSF) velocity is crucial for understanding the glymphatic system and its potential role in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Current cardiac or respiratory‐gated approaches, such as 4D flow magnetic resonance imaging (MRI), cannot capture CSF movement in real time because of limited temporal resolution and, in addition, deteriorate in accuracy at low fluid velocities. Other techniques like real‐time phase‐contrast‐MRI or time‐spatial labeling inversion pulse are not limited by temporal averaging but have limited availability, even in research settings. This study aims to quantify the inflow effect of dynamic CSF motion on functional MRI (fMRI) for in vivo, real‐time measurement of CSF flow velocity. We considered linear and nonlinear models of velocity waveforms and empirically fit them to fMRI data from a controlled flow experiment. To assess the utility of this methodology in human data, CSF flow velocities were computed from fMRI data acquired in eight healthy volunteers. Breath‐holding regimens were used to amplify CSF flow oscillations. Our experimental flow study revealed that CSF velocity is nonlinearly related to inflow effect‐mediated signal increase and well estimated using an extension of a previous nonlinear framework. Using this relationship, we recovered velocity from in vivo fMRI signal, demonstrating the potential of our approach for estimating CSF flow velocity in the human brain. This novel method could serve as an alternative approach to quantifying slow flow velocities in real time, such as CSF flow in the ventricular system, thereby providing valuable insights into the glymphatic system's function and its implications for neurological disorders. [ABSTRACT FROM AUTHOR]

Glaciers and ice sheets are an integral part of Earth's system, advancing and retreating in response to changes in climate. Clues about the past, present and future behaviour of these ice masses are found throughout current and former glaciated landscapes. In this commentary, we outline recent scientific advances from a collection of articles in which geomorphological evidence is used to inform us about the behaviour of glaciers and ice sheets across a range of spatial (landform to continent) and temporal (seasons to millennia) scales. Through a diversity of approaches including field measurements, remote sensing and numerical modelling, these studies build on an extensive background literature to deepen our understanding of how ice flows, how glaciers and ice sheets respond to climate change, and of the processes of ice advance and retreat and the stability of the system. Further integration of knowledge across the fields of geomorphology and glaciology will have tangible benefits for managing the societal and environmental impacts of glacier change and for improved projections of sea‐level rise over the coming decades to centuries. [ABSTRACT FROM AUTHOR]

The metabolic rate of a freely moving fish (routine metabolic rate) is tightly coupled with volitional movement (spontaneous activity), both of which commonly show strong daily cycles linked to the species‐specific diel activity pattern. Mummichog (Fundulus heteroclitus), an important estuarine fish in the north western Atlantic Ocean, are historically reported as diurnal (i.e., more active during daylight). Our recent laboratory studies on a Bay of Fundy population, however, showed a free‐running (i.e., similarly active daytime and night‐time) or even nocturnal (i.e., more active at night‐time) diel activity pattern. In the laboratory, near‐infrared (NIR) illumination is commonly used with a NIR‐sensitive camera to visualize fish activity across the light–dark periods of the day. Because NIR light is close to the visible light spectrum and certain fishes show sensitivity to NIR, the use of NIR with mummichog possibly could disturb the animals and obscure the identification of their true diel activity pattern. We aimed to determine if NIR illumination (940 nm wavelength) influences the diel activity pattern of mummichog. We used measurements of routine metabolic rate (oxygen consumption rate, MO2) as a proxy for activity, as evaluating the effect of NIR requires treatments where NIR lights are off, which precludes visualization and direct assessment of fish activity at night‐time. We measured routine MO2 of mummichogs over 6 days, exposed to either NIR off–on–off (2 days for each off or on period) or the opposite sequence of NIR on–off–on (to control for time‐dependent effects). NIR lights did not influence the diel cycle of routine MO2, and activity by proxy, in mummichog. Thus, NIR illumination is a suitable method to visualize mummichog during light–dark diel cycles. Routine MO2, and presumably activity, was similar or higher during night‐time periods compared to daytime periods, confirming a free‐running or nocturnal activity pattern for at least certain populations of mummichog. [ABSTRACT FROM AUTHOR]

Breast cancer survivors have an increased risk of developing second primary cancers, yet risks by race and ethnicity have not been comprehensively described. We evaluated second primary cancer risks among 717,335 women diagnosed with first primary breast cancer (aged 20–84 years and survived ≥1‐year) in the SEER registries using standardized incidence ratios (SIRs; observed/expected). SIRs were estimated by race and ethnicity compared with the racial‐ and ethnic‐matched general population, and further stratified by clinical characteristics of the index breast cancer. Poisson regression was used to test for heterogeneity by race and ethnicity. SIRs for second primary cancer differed by race and ethnicity with the highest risks observed among non‐Hispanic/Latina Asian American, Native Hawaiian, or other Pacific Islander (AANHPI), non‐Hispanic/Latina Black (Black), and Hispanic/Latina (Latina) survivors and attenuated risk among non‐Hispanic/Latina White (White) survivors (SIRAANHPI = 1.49, 95% CI = 1.44–1.54; SIRBlack = 1.41, 95% CI = 1.37–1.45; SIRLatina = 1.45, 95% CI = 1.41–1.49; SIRWhite = 1.09, 95% CI = 1.08–1.10; p‐heterogeneity<.001). SIRs were particularly elevated among AANHPI, Black, and Latina survivors diagnosed with an index breast cancer before age 50 (SIRs range = 1.88–2.19) or with estrogen receptor‐negative tumors (SIRs range = 1.60–1.94). Heterogeneity by race and ethnicity was observed for 16/27 site‐specific second cancers (all p‐heterogeneity's <.05) with markedly elevated risks among AANHPI, Black, and Latina survivors for acute myeloid and acute non‐lymphocytic leukemia (SIRs range = 2.68–3.15) and cancers of the contralateral breast (SIRs range = 2.60–3.01) and salivary gland (SIRs range = 2.03–3.96). We observed striking racial and ethnic differences in second cancer risk among breast cancer survivors. Additional research is needed to inform targeted approaches for early detection strategies and treatment to reduce these racial and ethnic disparities. [ABSTRACT FROM AUTHOR]

Older adults are persistently underrepresented in clinical drug trials worldwide, despite increasing multiple long‐term conditions and significant prescribing in this demographic. We discuss systemic challenges such as the exclusion of people with comorbid conditions and the lack of assessment for comorbidities as modifiers of treatment effects and highlight the rising trend of polypharmacy, especially among the oldest age groups, which is linked to a significant percentage of unplanned hospitalizations and medication errors. The consequences of these trends prompted the United Kingdom National Overprescribing review, culminating in a set of recommendations for drug development tailored to older adults. Building on this, two critical reports released in April 2023 by the International Longevity Centre (ILC) and the Nuffield Council on Bioethics (NCOB) are discussed. These reports emphasize the importance of diversity and inclusion in clinical trials, advocating for ethical frameworks and methodologies that cater to the complex needs of older adults. The development of inclusive criteria, innovative statistical methodologies, and the integration of patient‐reported outcomes are needed to address the persistent barriers to older adult participation in research, suggesting that pragmatic trials, exemplified by the UK's RECOVERY trial during the COVID‐19 pandemic, could pave the way for more inclusive research practices. [ABSTRACT FROM AUTHOR]

Background: The importance of prenatal care is undeniable, as pregnant persons who receive on‐time, adequate prenatal care have better maternal and infant health outcomes compared with those receiving late, less than adequate prenatal care. Previous studies assessing the relationship between neighborhood factors and maternal health outcomes have typically looked at singular neighborhood variables and their relationship with maternal health outcomes. In order to examine a greater number of place‐based risk factors simultaneously, our analysis used a unique neighborhood risk index to assess the association between cumulative risk and prenatal care utilization, which no other studies have done. Methods: Data from Rhode Island Vital Statistics for births between 2005 and 2014 were used to assess the relationship between neighborhood risk and prenatal care utilization using two established indices. We assessed neighborhood risk with an index composed of eight socioeconomic block‐group variables. A multivariate logistic regression model was used to examine the association between adequate use and neighborhood risk. Results: Individuals living in a high‐risk neighborhood were less likely to have adequate or better prenatal care utilization according to both the APNCU Index (adjusted odds ratio [aOR] 0.91, 95% confidence interval [CI] 0.87–0.95) and the R‐GINDEX (aOR 0.88, 95% CI 0.85–0.91) compared with those in low‐risk neighborhoods. Conclusion: Understanding the impact of neighborhood‐level factors on prenatal care use is a critical first step in ensuring that underserved neighborhoods are prioritized in interventions aimed at making access to prenatal care more equitable. [ABSTRACT FROM AUTHOR]

Dissolved oxygen (DO) is a critical water quality constituent that governs habitat suitability for aquatic biota, biogeochemical reactions and solubility of metals in streams. Recently introduced high‐frequency sensors have increased our ability to measure DO, but we still lack the capacity to understand and predict DO concentrations at high spatial resolutions or in unmonitored locations. Machine learning (ML) has been a commonly used approach for modelling DO, however, conventional ML models have no representation of the limnological processes governing DO dynamics. Here we implement and evaluate two process‐guided deep learning (PGDL) approaches for predicting daily minimum, mean and maximum DO concentrations in rivers from the Delaware River Basin, USA. In both cases, a multi‐task approach was taken in which the PGDL models predicted stream metabolism and gas exchange rates in addition to the DO concentrations themselves. Our results showed that for these sites, the PGDL approaches did not improve upon baseline predictions in temporal and spatially similar holdout experiments. One of the approaches did, however, improve predictions when applied to spatially dissimilar sites. Although this particular PGDL approach did not improve predictive accuracy in most cases, our results suggest that process guidance, perhaps a more constrained approach, could benefit a data‐driven DO model. [ABSTRACT FROM AUTHOR]

An exponential rise in the atmospheric vapour pressure deficit (VPD) is among the most consequential impacts of climate change in terrestrial ecosystems. Rising VPD has negative and cascading effects on nearly all aspects of plant function including photosynthesis, water status, growth and survival. These responses are exacerbated by land–atmosphere interactions that couple VPD to soil water and govern the evolution of drought, affecting a range of ecosystem services including carbon uptake, biodiversity, the provisioning of water resources and crop yields. However, despite the global nature of this phenomenon, research on how to incorporate these impacts into resilient management regimes is largely in its infancy, due in part to the entanglement of VPD trends with those of other co‐evolving climate drivers. Here, we review the mechanistic bases of VPD impacts at a range of spatial scales, paying particular attention to the independent and interactive influence of VPD in the context of other environmental changes. We then evaluate the consequences of these impacts within key management contexts, including water resources, croplands, wildfire risk mitigation and management of natural grasslands and forests. We conclude with recommendations describing how management regimes could be altered to mitigate the otherwise highly deleterious consequences of rising VPD. Summary statement: Rising atmospheric vapour pressure deficit (or VPD) is one of the most widespread and significant consequences of climate warming for terrestrial ecosystems. This article reviews the mechanistic bases of these usually deleterious impacts and synthesises that information into a set of management recommendations to mitigate them. [ABSTRACT FROM AUTHOR]

The International Union of Basic and Clinical Pharmacology (IUPHAR) Geriatric Committee aims to improve the use of drugs in older adults and develop new therapeutic approaches for the syndromes and diseases of old age through advocacy, education, and research. In the present paper, we propose strategies relevant to drug development and evaluation, spanning preclinical and the full range of clinical studies. Drugs for older adults need to consider not only age, but also other characteristics common in geriatric patients, such as multimorbidity, polypharmacy, falls, cognitive impairment, and frailty. The IUPHAR Geriatric Committee's position statement on 'Measurement of Frailty in Drug Development and Evaluation' is included, highlighting 12 key principles that cover the spectrum of translational research. We propose that where older adults are likely to be major users of a drug, that frailty is measured at baseline and as an outcome. Preclinical models that replicate the age, frailty, duration of exposure, comorbidities, and co‐medications of the proposed patients may improve translation. We highlight the potential application of recent technologies, such as physiologically based pharmacokinetic–pharmacodynamic modeling informed by frailty biology, and Artificial Intelligence, to inform personalized medicine for older patients. Considerations for the rapidly aging populations in low‐ and middle‐income countries related to health‐care and clinical trials are outlined. Involving older adults, their caregivers and health‐care providers in all phases of research should improve drug development, evaluation, and outcomes for older adults internationally. [ABSTRACT FROM AUTHOR]

Anthropogenically induced changes to the natural world are increasingly exposing organisms to stimuli and stress beyond that to which they are adapted. In aquatic systems, it is thought that certain life stages are more vulnerable than others, with embryos being flagged as highly susceptible to environmental stressors. Interestingly, evidence from across a wide range of taxa suggests that aquatic embryos can hatch prematurely, potentially as an adaptive response to external stressors, despite the potential for individual costs linked with underdeveloped behavioural and/or physiological functions. However, surprisingly little research has investigated the prevalence, causes and consequences of premature hatching, and no compilation of the literature exists. Here, we review what is known about premature hatching in aquatic embryos and discuss how this phenomenon is likely to become exacerbated with anthropogenically induced global change. Specifically, we (1) review the mechanisms of hatching, including triggers for premature hatching in experimental and natural systems; (2) discuss the potential implications of premature hatching at different levels of biological organisation from individuals to ecosystems; and (3) outline knowledge gaps and future research directions for understanding the drivers and consequences of premature hatching. We found evidence that aquatic embryos can hatch prematurely in response to a broad range of abiotic (i.e. temperature, oxygen, toxicants, light, pH, salinity) and biotic (i.e. predators, pathogens) stressors. We also provide empirical evidence that premature hatching appears to be a common response to rapid thermal ramping across fish species. We argue that premature hatching represents a fascinating yet untapped area of study, and the phenomenon may provide some additional resilience to aquatic communities in the face of ongoing global change. [ABSTRACT FROM AUTHOR]

Ponds, wetlands, and shallow lakes (collectively "shallow waterbodies") are among the most biogeochemically active freshwater ecosystems. Measurements of gross primary production (GPP), respiration (R), and net ecosystem production (NEP) are rare in shallow waterbodies compared to larger and deeper lakes, which can bias our understanding of lentic ecosystem processes. In this study, we calculated GPP, R, and NEP in 26 small, shallow waterbodies across temperate North America and Europe. We observed high rates of GPP (mean 8.4 g O2 m−3 d−1) and R (mean −9.1 g O2 m−3 d−1), while NEP varied from net heterotrophic to autotrophic. Metabolism rates were affected by depth and aquatic vegetation cover, and the shallowest waterbodies had the highest GPP, R, and the most variable NEP. The shallow waterbodies from this study had considerably higher metabolism rates compared to deeper lakes, stressing the importance of these systems as highly productive biogeochemical hotspots. Plain Language Summary: Ecosystem metabolism is an important metric for understanding how an ecosystem uses and transforms energy and materials. In aquatic ecosystems, ecosystem metabolism is most often calculated by measuring oxygen. Oxygen is produced by aquatic plants and algae through photosynthesis, and oxygen is consumed by bacteria and other organisms through aerobic respiration. Oxygen production and consumption (metabolism) indicate how organic matter is flowing through the ecosystem, and whether an aquatic system is predominantly respiring (indicating it is a carbon source), or photosynthesizing (indicating it is a carbon sink). Metabolism rates in freshwater lakes scale with surface area and depth, but there are few metabolism rates calculated from oxygen measurements in shallow waterbodies. Ponds, wetlands, and shallow lakes are the most abundant freshwater systems on Earth and may function differently from larger lakes. In this study, we show that shallow systems are incredibly productive, with some of the highest rates of metabolism among aquatic ecosystems, and that depth is one of the most important factors affecting metabolism rates. Key Points: Shallow and small waterbodies have high but variable rates of gross primary production and respirationDepth plays a large role in metabolism ratesShallow waterbodies are some of the most productive freshwater ecosystems, with implications for carbon cycling and ecosystem dynamics [ABSTRACT FROM AUTHOR]

Background: The use of potentially inappropriate medications (PIMs) is associated with increased risk of hospitalizations and emergency room visits and varies by racial and ethnic subgroups. Medicare's nationwide medication therapy management (MTM) program requires that Part D plans offer an annual comprehensive medication review (CMR) to all beneficiaries who qualify, and provides a platform to reduce PIM use. The objective of this study was to assess the impact of CMR on PIM discontinuation in Medicare beneficiaries and whether this differed by race or ethnicity. Methods: Retrospective cohort study of community‐dwelling Medicare Part D beneficiaries ≥66 years of age who were eligible for MTM from 2013 to 2019 based on 5% Medicare fee‐for‐service claims data linked to the 100% MTM data file. Among those using a PIM, MTM‐eligible CMR recipients were matched to non‐recipients via sequential stratification. The probability of PIM discontinuation was estimated using regression models that pooled yearly subcohorts accounting for within‐beneficiary correlations. The most common PIMs that were discontinued after CMR were reported. Results: We matched 24,368 CMR recipients to 24,368 CMR non‐recipients during the observation period. Median age was 74–75, 35% were males, most were White beneficiaries (86%–87%), and the median number of PIMs was 1. In adjusted analyses, CMR receipt was positively associated with PIM discontinuation (adjusted relative risk [aRR]: 1.26, 95% CI: 1.20–1.32). There was no evidence of differential impact of CMR by race or ethnicity. The PIMs most commonly discontinued after CMR were glimepiride, zolpidem, digoxin, amitriptyline, and nitrofurantoin. Conclusions: Among Medicare beneficiaries who are using a PIM, CMR receipt was associated with PIM discontinuation, suggesting that greater CMR use could facilitate PIM reduction for all racial and ethnic groups. [ABSTRACT FROM AUTHOR]

Objective: To investigate primary care practice ownership and specialist‐use patterns for commercially insured children with disabilities. Data Sources and Study Setting: A national commercial claims database and the Health Systems and Provider Database from 2012 to 2016 are the data sources for this study. Study Design: This cross‐sectional, descriptive study examines: (1) the most visited type of pediatric primary care physician and practice (independent or system‐owned); (2) pediatric and non‐pediatric specialist‐use patterns; and (3) how practice ownership relates to specialist‐use patterns. Data Collection/Extraction Methods: This study identifies 133,749 person‐years of commercially insured children with disabilities aged 0–18 years with at least 24 months of continuous insurance coverage by linking a national commercial claims data set with the Health Systems and Provider Database and applying the validated Children with Disabilities Algorithm. Principal Findings: Three‐quarters (75.9%) of children with disabilities received their pediatric primary care in independent practices. Nearly two thirds (59.6%) used at least one specialist with 45.1% using nonpediatric specialists, 28.8% using pediatric ones, and 17.0% using both. Specialist‐use patterns varied by both child age and specialist type. Children with disabilities in independent practices were as likely to see a specialist as those in system‐owned ones: 57.1% (95% confidence interval [95% CI] 56.7%–57.4%) versus 57.3% (95% CI 56.6%–58.0%), respectively (p = 0.635). The percent using two or more types of specialists was 46.1% (95% CI 45.4%–46.7%) in independent practices, comparable to that in systems 47.1% (95% CI 46.2%–48.0%) (p = 0.054). However, the mean number of specialist visits was significantly lower in independent practices than in systems—4.0 (95% CI 3.9%–4.0%) versus 4.4 (95% CI 4.3%–4.6%) respectively—reaching statistical significance with p < 0.0001. Conclusions: Recognizing how privately insured children with disabilities use pediatric primary care from pediatric and nonpediatric primary care specialists through both independent and system‐owned practices is important for improving care quality and value. [ABSTRACT FROM AUTHOR]

Purpose: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme‐inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. Methods: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE‐II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. Results: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long‐acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long‐acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long‐acting injectables and contraceptive implants. Conclusions: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long‐acting injectable contraceptives should be evidence‐based. [ABSTRACT FROM AUTHOR]

This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave‐reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points—Baseline (BL), following 10, 20, 30 and 40 km, 1 h post‐completion (1HP) and 24 h post‐completion (24HP). Flow‐mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P < 0.001 for both) and reactive hyperaemia was higher at 24HP (∼27%) compared with BL (P = 0.018). Compared to BL, both mean central systolic BP and mean central diastolic BP were 7% and 10% higher, respectively, following 10 km and 6% and 9% higher, respectively, following 20 km, and then decreased by 5% and 8%, respectively, at 24HP (P < 0.05 for all). AIx (%) decreased following 20 km and following 40 km compared with BL (P < 0.05 for both) but increased following 40 km when corrected for HR (AIx75) compared with BL (P = 0.02). Forward wave amplitude significantly increased at 10 km (15%) compared with BL (P = 0.049), whereas backward wave reflection and reflected magnitude were similar at all time points. FMD and baseline diameter remained similar. These data indicate preservation of macrovascular (endothelial) function, but not microvascular function resulting from the 50 km ultramarathon. What is the central question of this study?What are the acute effects of prolonged distance running (50 km race) on endothelial function, wave reflection and inflammation both during a distance race and within 24 h after completion of the race?What is the main finding and its importance?Even though macrovascular function remains unchanged after a 50 km ultramarathon, microvascular function is attenuated. However, the microvascular changes lasted less than 24 h post‐race suggesting the ultramarathon distance of 50 km has relatively short‐term effects in trained individuals. [ABSTRACT FROM AUTHOR]

Inclusivity in biomedical research provides many positive attributes, including increased productivity, higher creativity, and improved wellness for all. While marginalized individuals work tirelessly to achieve equity and inclusion, this task should not be left solely to those most affected by exclusionary tactics. These individuals and the organizations with whom they are affiliated would benefit from the support of an ally. An ally is defined as a person or organization that actively supports the rights of a marginalized group without being a member of it. Allies have a unique opportunity to play a pivotal role in promoting fairness, equity, and inclusion, and thus serve as positive change agents within an organizational setting. We summarize here the importance of being an effective and dynamic ally and offer guidance on how to achieve that goal. [ABSTRACT FROM AUTHOR]

Root production influences carbon and nutrient cycles and subsidizes soil biodiversity. However, the long‐term dynamics and drivers of belowground production are poorly understood for most ecosystems. In drylands, fire, eutrophication, and precipitation regimes could affect not only root production but also how roots track interannual variability in climate.We manipulated the intra‐annual precipitation regime, soil nitrogen, and fire in four common Chihuahuan Desert ecosystem types (three grasslands and one shrubland) in New Mexico, USA, where the 100‐year record indicates both long‐term drying and increasing interannual variability in aridity. First, we evaluated how root production tracked aridity over 10–17 years using climate sensitivity functions, which quantify long‐term, nonlinear relationships between biological processes and climate. Next, we determined the degree to which perturbations by fire, nitrogen addition or intra‐annual rainfall altered the sensitivity of root production to both mean and interannual variability in aridity.All ecosystems had nonlinear climate sensitivities that predicted declines in production with increases in the interannual variance of aridity. However, root production was the most sensitive to aridity in Chihuahuan Desert shrubland, with reduced production under drier and more variable aridity.Among the perturbations, only fire altered the sensitivity of root production to aridity. Root production was more than twice as sensitive to declines with aridity following prescribed fire than in unburned conditions. Neither the intra‐annual seasonal rainfall regime nor chronic nitrogen fertilization altered the sensitivity of roots to aridity.Synthesis. Our results yield new insight into how dryland plant roots respond to climate change. Our comparison of dryland ecosystems of the northern Chihuahuan Desert predicted that root production in shrublands would be more sensitive to future climates that are drier and more variable than root production in dry grasslands. Field manipulations revealed that fire could amplify the climate sensitivity of dry grassland root production, but in contrast, the climate sensitivity of root production was largely resistant to changes in the seasonal rainfall regime or increased soil fertilization. [ABSTRACT FROM AUTHOR]

While PhD programs prepare graduate students to perform biomedical research, a defined systematic training program for transferable skills is generally lacking. When provided, this training is often informal, unstructured, or inconsistent. Therefore, there is a need to provide critical skills in marketing, relationship building, project management, and budgeting to prepare trainees to navigate into a productive, engaging, and rewarding biomedical research career. To address this gap in training, the School of Graduate Studies at Meharry Medical College has developed the SHort Course In transFerable skills Training (SHIFT) Program, a 1‐year professional development program accessible to graduate students in the United States who are enrolled in graduate biomedical research related programs. The SHIFT Program has been launched to equip trainees with skills essential for success in all biomedical science careers. PhD students will be taught the primary constituents of career management through the use of four training modules. In Module I, students complete self‐assessments and are assigned to a small peer‐mentoring team with mentors. Module II consists of a 5‐day workshop that encompasses instruction on the transferable skills identified as essential for career success. Module III entails monthly interactive discussions over a 6‐month period involving case study review and mentor‐guided discussions to further reinforce skills learned. In Module IV, students compile the information learned from Modules I‐III to develop an Individual Development Plan that incorporates 3–5 specific, measurable, attainable, relevant, and time‐based career goals. Collectively, the SHIFT Program will allow participants to train, practice, and refresh skills, empowering them to navigate career transitions and obtain success in the career of their choice. [ABSTRACT FROM AUTHOR]

Objective: The primary objective of this study was to evaluate oncologic outcomes of all published cases of supracricoid partial laryngectomy (SCPL) performed in the United States. The secondary objective was to assess the functional outcomes associated with this procedure. Review Methods: A systematic review of PubMed, SCOPUS, and Embase for all English‐language studies pertaining to SCPL performed in the United States was conducted until August 2021. Primary outcomes included disease‐specific survival (DSS), overall survival, and local recurrence rate. Secondary outcomes included larynx preservation rate, gastrostromy tube dependency, days to gastrostomy tube removal, decannulation rate, and days to decannulation. Results: A total of six studies were included in the analysis. A total of 113 patients (58.5%) underwent SCPL surgery as a primary treatment method whereas 80 patients (41.5%) underwent SCPL as salvage surgery. The 5‐year DSS rates were 87.8% and 100% for primary and salvage procedures, respectively. Approximately 10.3% of patients undergoing a salvage SCPL procedure experienced a local recurrence whereas only 1.85% of primary SCPL procedures resulted in local recurrence. The rates of decannulation following primary and salvage SCPL were 92.7% and 88.1%, respectively. With regard to swallowing, primary and salvage SCPL procedures demonstrated comparably low postoperative gastrostomy tube dependency rates of 3.66% and 4.76%, respectively. Conclusions: SCPL performed in the United States is an effective surgical technique that produces excellent outcomes in qualifying patients, thus validating its viability as an organ‐preserving surgical alternative. Laryngoscope, 134:3003–3011, 2024 [ABSTRACT FROM AUTHOR]

Nitrate, the form of nitrogen often associated with kelp growth, is typically low in summer during periods of high macroalgal growth. More ephemeral, regenerated forms of nitrogen, such as ammonium and urea, are much less studied as sources of nitrogen for kelps, despite the relatively high concentrations of regenerated nitrogen found in the Southern California Bight, where kelps are common. To assess how nitrogen uptake by kelps varies by species and nitrogen form in southern California, USA, we measured uptake rates of nitrate, ammonium, and urea by Macrocystis pyrifera and Eisenia arborea individuals from four regions characterized by differences in nitrogen availability—Orange County, San Pedro, eastern Santa Catalina Island, and western Santa Catalina Island—during the summers of 2021 and 2022. Seawater samples collected at each location showed that overall nitrogen availability was low, but ammonium and urea were often more abundant than nitrate. We also quantified the internal %nitrogen of each kelp blade collected, which was positively associated with ambient environmental nitrogen concentrations at the time of collection. We observed that both kelp species readily took up nitrate, ammonium, and urea, with M. pyrifera taking up nitrate and ammonium more efficiently than E. arborea. Urea uptake efficiency for both species increased as internal percent nitrogen decreased. Our results indicate that lesser‐studied, more ephemeral forms of nitrogen can readily be taken up by these kelps, with possible upregulation of urea uptake as nitrogen availability declines. [ABSTRACT FROM AUTHOR]

A 9-year-old dog was presented with weight loss, respiratory effort, and an enlarged abdomen. Imaging studies and exploratory surgery showed pulmonary and splenic masses and bi-cavitary effusion, later classified as hemorrhage. Cytology of the peritoneal and pleural fluids also revealed several microfilariae. Immunologic and molecular analyses confirmed Dirofilaria immitis infection and histopathology of the spleen indicated a cavernous endothelial proliferation with undefined etiology (hemangiosarcoma vs reaction to parasite infestation). The nematode larvae are speculated to have entered body cavities via erratic migration or via hemorrhage and visceral lesions to be related to parasitism. Nematode infection should be considered as a differential diagnosis for internal bleeding of undetermined origin. [ABSTRACT FROM AUTHOR]

We aimed to determine the relative contribution of hypercapnia and hypoxia to the bradycardic response to apneas. We hypothesized that apneas with hypercapnia would cause greater bradycardia than normoxia, similar to the response seen with hypoxia, and that apneas with hypercapnic hypoxia would induce greater bradycardia than hypoxia or hypercapnia alone. Twenty‐six healthy participants (12 females; 23 ± 2 years; BMI 24 ± 3 kg/m2) underwent three gas challenges: hypercapnia (+5 torr end tidal partial pressure of CO2 [PETCO2]), hypoxia (50 torr end tidal partial pressure of O2 [PETO2]), and hypercapnic hypoxia (combined hypercapnia and hypoxia), with each condition interspersed with normocapnic normoxia. Heart rate and rhythm, blood pressure, PETCO2, PETO2, and oxygen saturation were measured continuously. Hypercapnic hypoxic apneas induced larger bradycardia (−19 ± 16 bpm) than normocapnic normoxic apneas (−11 ± 15 bpm; p = 0.002), but had a comparable response to hypoxic (−19 ± 15 bpm; p = 0.999) and hypercapnic apneas (−14 ± 14 bpm; p = 0.059). Hypercapnic apneas were not different from normocapnic normoxic apneas (p = 0.134). After removal of the normocapnic normoxic heart rate response, the change in heart rate during hypercapnic hypoxia (−11 ± 16 bpm) was similar to the summed change during hypercapnia+hypoxia (−9 ± 10 bpm; p = 0.485). Only hypoxia contributed to this bradycardic response. Under apneic conditions, the cardiac response is driven by hypoxia. [ABSTRACT FROM AUTHOR]

Objective(s): Despite advancements in imaging techniques and cytological analysis, plunging ranula remains a challenging surgical, radiologic, and pathologic phenomenon. Of the 18 patients we evaluated at our institution, we highlight three cases that illustrate the high rate of misleading imaging and cytological results when assessing plunging ranula. Methods: Imaging results, biopsy findings, operative techniques, and pathological reports were reviewed from patients who had either a preoperative or postoperative diagnosis of ranula and underwent surgery by a single head and neck surgeon at a tertiary care center. Results: Of the 18 identified patients, computed tomography was correct on preoperative imaging 73% of the time and magnetic resonance imaging was correct on preoperative imaging 71% of the time. Two patients underwent preoperative ultrasound and their ultrasound reports did not accurately diagnose the presence of a ranula. Two patients underwent preoperative fine needle aspiration biopsy due to inconclusive preoperative imaging, in which results suggested either a ranula or epidermal cyst. Both ultimately did not match the final pathology. Three of eighteen patients (17%) underwent an inappropriate initial surgery due to incorrect imaging diagnoses and/or biopsy findings. Conclusion: Despite use of preoperative modalities to distinguish plunging ranula from other cystic floor of mouth lesions, surgeons must be aware that no workup modality is fully precise. The potential for revision surgery must be included in all preoperative discussions for presumed plunging ranula. Level of Evidence: 4 Laryngoscope, 134:2689–2696, 2024 [ABSTRACT FROM AUTHOR]

This article describes a technique called robotic thyroidectomy via posterior neck approach (RT-PNA) using the Da Vinci single port (Sp) robotic system. The authors report their initial experience using this technique in a Western patient population. The RT-PNA approach allows for thyroid surgery without an anterior neck scar and appears to be safe and feasible. The authors suggest that this technique has potential advantages over other approaches, such as improved visualization and maneuverability, and may be suitable for patients who wish to avoid a visible scar. Further studies will explore the feasibility of performing total thyroidectomy using this approach. [Extracted from the article]

Coloboma, congenital heart disease, ichthyosiform dermatosis, intellectual disability, conductive hearing loss, and epilepsy (CHIME) syndrome is a rare autosomal recessive neuroectodermal disorder caused by PIGL gene mutations. There is emerging literature to support the use of interleukin‐17 (IL‐17) antagonists in the treatment of certain ichthyosiform dermatoses. Here, we report a case of severe ichthyosiform dermatosis in a child with CHIME syndrome who was recalcitrant to multiple topical medications and dupilumab. This is the first reported case of successful treatment of congenital ichthyosiform dermatosis in a CHIME syndrome patient with ixekizumab, an IL‐17A antagonist. [ABSTRACT FROM AUTHOR]

We examined how locally situated and transnationally circulated meanings of feminism interact forming implicit cultural meanings, and how these meanings about feminism appear in women's accounts of their own work and identifications. Using twenty‐four oral histories, we identified four implicit cultural meanings about feminism: (1) “Mainstream” feminism is/as white and middle‐class; (2) Feminists are lesbians; (3) Feminism is/as hostile to men; and (4) Feminism is/as a “western” ideology. In addition, we identified three strategies activists used to respond to these meanings: (1) distancing themselves from the word “feminist/feminism”; (2) explicitly embracing the term and clarifying its meaning; and (3) shifting from an individual to a structural level of analysis. Examining these discourses in a multinational sample with women of various racial‐ethnic and indigenous identities, we found that implicit cultural meanings often identified in the US or as western interact with locally found meanings affecting activists in the Majority World. Activists’ use of these implicit cultural meanings complicated prevalent, but often simplistic, narratives about feminists, feminism, and identity. [ABSTRACT FROM AUTHOR]

Psychostimulant use disorders (PSUD) are prevalent; however, no FDA‐approved medications have been made available for treatment. Previous studies have shown that dual inhibitors of the dopamine transporter (DAT) and sigma receptors significantly reduce the behavioral/reinforcing effects of cocaine, which have been associated with stimulation of extracellular dopamine (DA) levels resulting from DAT inhibition. Here, we employ microdialysis and fast scan cyclic voltammetry (FSCV) procedures to investigate the effects of dual inhibitors of DAT and sigma receptors in combination with cocaine on nucleus accumbens shell (NAS) DA dynamics in naïve male Sprague Dawley rats. In microdialysis studies, administration of rimcazole (3, 10 mg/kg; i.p.) or its structural analog SH 3‐24 (1, 3 mg/kg; i.p.), compounds that are dual inhibitors of DAT and sigma receptors, significantly reduced NAS DA efflux stimulated by increasing doses of cocaine (0.1, 0.3, 1.0 mg/kg; i.v.). Using the same experimental conditions, in FSCV tests, we show that rimcazole pretreatments attenuated cocaine‐induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Under the same conditions, JJC8‐091, a modafinil analog and dual inhibitor of DAT and sigma receptors, similarly attenuated cocaine‐induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Our results provide the neurochemical groundwork towards understanding actions of dual inhibitors of DAT and sigma receptors on DA dynamics that likely mediate the behavioral effects of psychostimulants like cocaine. [ABSTRACT FROM AUTHOR]

The switching behavior of the novel hybrid material (FA)Na[Fe(CN)5(NO)].H2O (1) in response to temperature (T), light irradiation and electric field (E) is studied using in situ X‐ray diffraction (XRD). Crystals of 1 display piezoelectricity, pyroelectricity, second and third harmonic generation. XRD shows that the FA+ are disordered at room‐temperature, but stepwise cooling from 273–100 K induces gradual ordering, while cooling under an applied field (E=+40 kVcm−1) induces a sudden phase change at 140 K. Structural‐dynamics calculations suggest the field pushes the system into a region of the structural potential‐energy surface that is otherwise inaccessible, demonstrating that application of T and E offers an effective route to manipulating the crystal chemistry of these materials. Photocrystallography also reveals photoinduced linkage isomerism, which coexists with but is not correlated to other switching behaviors. These experiments highlight a new approach to in situ studies of hybrid materials, providing insight into the structure–property relationships that underpin their functionality. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes. METHODS: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)‐related neurodegeneration were associated with identified trajectories. RESULTS: Five trajectories of depressive symptoms and dementia risk were identified. Compared to women with minimal symptoms, women who reported mild and stable and emerging depressive symptoms were at the highest risk of developing dementia and had more cerebrovascular disease and AD‐related neurodegeneration. DISCUSSION: There are heterogeneous profiles of depressive symptoms and dementia risk. Common neuropathological factors may contribute to both depression and dementia. Highlights: The progression of depressive symptoms and concurrent dementia risk is heterogeneous.Emerging depressive symptoms may be a prodromal symptom of dementia.Cerebrovascular disease and AD are potentially shared neuropathological factors. [ABSTRACT FROM AUTHOR]

Introduction: We sought to characterize social and structural drivers of HIV vulnerability for transgender women (TGW) in Zimbabwe, where TGW are not legally recognized, and explore differences in vulnerability by feminine presentation. Methods: A secondary analysis was conducted with a sub‐sample of participants recruited from a 2019 respondent‐driven sampling survey that comprised men who have sex with men, TGW and genderqueer individuals assigned male sex at birth, from two cities in Zimbabwe. Survey questionnaires captured information related to socio‐demographics, sexual and substance use behaviours, and social and structural barriers to HIV services. Secondary analyses were restricted to participants who identified as female, transfemale or transwomen (236/1538) and were unweighted. Descriptive statistics were used to calculate sample estimates and chi‐square and Fisher's exact tests were used to assess differences in vulnerability by feminine presentation. Results: Among 236 TGW, almost half (45.3%) presented as feminine in the 6 months preceding the survey and 8.5% had ever used hormones to affirm their gender identities. Median age among TGW was 23 years (interquartile range: 20–26). Feminine presenting TGW in our sample had higher prevalence of arrest (15.9% vs. 3.9%), rejection by family/friends (38.3% vs. 14.0%), employment termination (11.2% vs. 3.9%), employment refusal (14.0% vs. 3.9%), denial of healthcare (16.8% vs. 2.3%), physical, sexual or verbal harassment or abuse (59.8% vs. 34.1%), alcohol dependence (32.7% vs. 12.4%), recent transactional sex with a male or TGW partner (30.8% vs. 13.3%) and recent non‐injection drug use (38.3% vs. 20.2%) than non‐feminine presenting TGW (all p‐value <0.05). Conclusions: Findings suggest that TGW, particularly feminine presenting TGW, experience social and structural inequities which may contribute to HIV vulnerability. Interventions aimed at addressing inequities, including trans competency training for providers and gender‐affirming, psychosocial and legal support services for TGW, might mitigate risk. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of long COVID among Western Australian adults, a highly vaccinated population whose first major exposure to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was during the 2022 Omicron wave, and to assess its impact on health service use and return to work or study. Study design: Follow‐up survey (completed online or by telephone). Setting, participants: Adult Western Australians surveyed 90 days after positive SARS‐CoV‐2 test results (polymerase chain reaction or rapid antigen testing) during 16 July – 3 August 2022 who had consented to follow‐up contact for research purposes. Main outcome measures: Proportion of respondents with long COVID (ie, reporting new or ongoing symptoms or health problems, 90 days after positive SARS‐CoV‐2 test result); proportion with long COVID who sought health care for long COVID‐related symptoms two to three months after infection; proportion who reported not fully returning to previous work or study because of long COVID‐related symptoms. Results: Of the 70 876 adults with reported SARS‐CoV‐2 infections, 24 024 consented to contact (33.9%); after exclusions, 22 744 people were invited to complete the survey, of whom 11 697 (51.4%) provided complete responses. Our case definition for long COVID was satisfied by 2130 respondents (18.2%). The risk of long COVID was greater for women (v men: adjusted risk ratio [aRR], 1.5; 95% confidence interval [CI], 1.4–1.6) and for people aged 50–69 years (v 18–29 years: aRR, 1.6; 95% CI, 1.4–1.9) or with pre‐existing health conditions (aRR, 1.5; 95% CI, 1.4–1.7), as well as for people who had received two or fewer COVID–19 vaccine doses (v four or more: aRR, 1.4; 95% CI, 1.2–1.8) or three doses (aRR, 1.3; 95% CI, 1.1–1.5). The symptoms most frequently reported by people with long COVID were fatigue (1504, 70.6%) and concentration difficulties (1267, 59.5%). In the month preceding the survey, 814 people had consulted general practitioners (38.2%) and 34 reported being hospitalised (1.6%) with long COVID. Of 1779 respondents with long COVID who had worked or studied before the infection, 318 reported reducing or discontinuing this activity (17.8%). Conclusion: Ninety days after infection with the Omicron SARS‐CoV‐2 variant, 18.2% of survey respondents reported symptoms consistent with long COVID, of whom 38.7% (7.1% of all survey respondents) sought health care for related health concerns two to three months after the acute infection. [ABSTRACT FROM AUTHOR]

River networks play a crucial role in the global carbon cycle, as relevant sources of carbon dioxide (CO2) to the atmosphere. Advancements in high‐frequency monitoring in aquatic environments have enabled measurement of dissolved CO2 concentration at temporal resolutions essential for studying carbon variability and evasion from these dynamic ecosystems. Here, we describe the adaptation, deployment, and validation of an open‐source and relatively low‐cost in situ pCO2 sensor system for lotic ecosystems, the lotic‐SIPCO2. We tested the lotic‐SIPCO2 in 10 streams that spanned a range of land cover and basin size. Key system adaptations for lotic environments included prevention of biofouling, configuration for variable stage height, and reduction of headspace equilibration time. We then examined which input parameters contribute the most to uncertainty in estimating CO2 emission rates and found scaling factors related to the gas exchange velocity were the most influential when CO2 concentration was significantly above saturation. Near saturation, sensor measurement of pCO2 contributed most to uncertainty in estimating CO2 emissions. We also found high‐frequency measurements of pCO2 were not necessary to accurately estimate median emission rates given the CO2 regimes of our streams, but daily to weekly sampling was sufficient. High‐frequency measurements of pCO2 remain valuable for exploring in‐stream metabolic variability, source partitioning, and storm event dynamics. Our adaptations to the SIPCO2 offer a relatively affordable and robust means of monitoring dissolved CO2 in lotic ecosystems. Our findings demonstrate priorities and related considerations in the design of monitoring projects of dissolved CO2 and CO2 evasion dynamics more broadly. [ABSTRACT FROM AUTHOR]

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin disease characterized by defects in type VII collagen leading to a range of fibrotic pathologies resulting from skin fragility, aberrant wound healing, and altered dermal fibroblast physiology. Using a novel in vitro model of fibrosis based on endogenously produced extracellular matrix, we screened an FDA-approved compound library and identified antivirals as a class of drug not previously associated with anti-fibrotic action. Preclinical validation of our lead hit, daclatasvir, in a mouse model of RDEB demonstrated significant improvement in fibrosis as well as overall quality of life with increased survival, weight gain and activity, and a decrease in pruritus-induced hair loss. Immunohistochemical assessment of daclatasvir-treated RDEB mouse skin showed a reduction in fibrotic markers, which was supported by in vitro data demonstrating TGFβ pathway targeting and a reduction of total collagen retained in the extracellular matrix. Our data support the clinical development of antivirals for the treatment of patients with RDEB and potentially other fibrotic diseases. Synopsis: The antiviral daclatasvir was identified as an anti-fibrotic compound in a high throughput screen using a novel in vitro model of fibrosis. Daclatasvir improved life quality and survival in a mouse model of recessive dystrophic epidermolysis bullosa (RDEB). Endogenously-produced matrix from primary patient fibroblasts can be utilized as a detachment assay to screen compounds for anti-fibrotic repurposing. Antivirals are a novel class of fibrosis preventatives in RDEB as verified from two library screens. Daclatasvir was our repurposed hit of interest for preventing fibrosis in RDEB. Daclatasvir downregulated the TGFβ signaling pathway targets. Daclatasvir improved the life quality of RDEB mice. The antiviral daclatasvir was identified as an anti-fibrotic compound in a high throughput screen using a novel in vitro model of fibrosis. Daclatasvir improved life quality and survival in a mouse model of recessive dystrophic epidermolysis bullosa (RDEB). [ABSTRACT FROM AUTHOR]

African Americans (AA) have a higher risk for cardiovascular disease (CVD) as compared to their White (W) counterparts. CVD is characterized by increased blood pressure (BP), arterial stiffness and systemic inflammation. An acute inflammatory stimulus may explain physiological manifestations responsible for amplified CVD in AA that are not apparent at rest. The purpose of this study was to evaluate central and peripheral BP, central and local arterial stiffness, and indices of pulse wave morphology in young healthy AA and W participants in response to acute inflammation. Concentrations of the inflammatory cytokine interleukin‐6 (IL‐6) and measures of central and peripheral BP, central arterial stiffness (carotid–femoral pulse wave velocity (cfPWV)), local carotid arterial stiffness (β‐stiffness, elastic modulus (Ep)), and indices of pulse wave morphology were assessed in 28 participants (21 ± 2 years, AA: n = 11) at baseline (BL), 24 h and 48 h post‐inflammation. Changes in IL‐6 concentrations (ΔIL‐6) were significantly greater at 24 h as compared to 48 h post‐inflammation (0.652 ± 0.644 vs. −0.146 ± 0.532 pg/μl, P ≤ 0.0001). Among AA participants, central and peripheral diastolic BP were significantly decreased at 24 h post‐inflammation as compared to BL (aortic diastolic BP: −4 ± 4 mmHg, P = 0.016; brachial diastolic BP: −4 ± 4 mmHg, P = 0.014). AA participants also experienced a significant decrease in central and peripheral mean arterial BP at 48 h post‐inflammation as compared to BL (aortic mean arterial pressure: −4 ± 4 mmHg, P = 0.009; brachial mean arterial pressure: −4 ± 4 mmHg, P = 0.012). Despite haemodynamic changes, there were no differences in central or local carotid arterial stiffness or indices of pulse wave morphology. What is the central question of this study?Are there differences in interleukin‐6 concentrations, blood pressure, arterial stiffness and indices of pulse wave morphology between young healthy African American (AA) and White (W) individuals in response to an acute inflammatory stimulus?What is the main finding and its importance?While young healthy AA and W adults have similar interleukin‐6 concentrations, arterial stiffness and indices of pulse wave morphology in response to an acute inflammatory stimulus, only AA experience decreases in blood pressure within 48 h post‐stimulus. The findings could elucidate physiological manifestations responsible for amplified CVD in AA. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Genome‐wide association studies link susceptibility to late‐onset Alzheimer's disease (LOAD) with EphA1. Sequencing identified a non‐synonymous substitution P460L as a LOAD risk variant. Other Ephs regulate vascular permeability and immune cell recruitment. We hypothesized that P460L dysregulates EphA1 receptor activity and impacts neuroinflammation. METHODS: EphA1/P460L receptor activity was assayed in isogenic Human Embryonic Kidney (HEK) cells. Soluble EphA1/P460L (sEphA1/sP460L) reverse signaling in brain endothelial cells was assessed by T‐cell recruitment and barrier function assays. RESULTS: EphA1 and P460L were expressed in HEK cells, but membrane and soluble P460L were significantly reduced. Ligand engagement induced Y781 phosphorylation of EphA1 but not P460L. sEphA1 primed brain endothelial cells for increased T‐cell recruitment; however, sP460L was less effective. sEphA1 decreased the integrity of the brain endothelial barrier, while sP460L had no effect. DISCUSSION: These findings suggest that P460L alters EphA1‐dependent forward and reverse signaling, which may impact blood‐brain barrier function in LOAD. Highlights: EphA1‐dependent reverse signaling controls recruitment of T cells by brain endothelial cells.EphA1‐dependent reverse signaling remodels brain endothelial cell contacts.LOAD‐associated P460L variant of EphA1 shows reduced membrane expression and reduced ligand responses.LOAD‐associated P460L variant of EphA1 fails to reverse signal to brain endothelial cells. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of skeletal maturation on sodium (23Na) MRI relaxation parameters and the accuracy of tissue sodium concentration (TSC) quantification in human knee cartilage. Methods: Twelve pediatric knee specimens were imaged with whole‐body 10.5 T MRI using a density‐adapted 3D radial projection sequence to evaluate 23Na parameters: B1+, T1, biexponential T2*$$ {\mathrm{T}}_2^{\ast } $$, and TSC. Water, collagen, and sulfated glycosaminoglycan (sGAG) content were calculated from osteochondral biopsies. The TSC was corrected for B1+, relaxation, and water content. The literature‐based TSC (TSCLB) used previously published values for corrections, whereas the specimen‐specific TSC (TSCSP) used measurements from individual specimens. 23Na parameters were evaluated in eight cartilage compartments segmented on proton images. Associations between 23Na parameters, TSCLB − TSCSP difference, biochemical content, and age were determined. Results: From birth to 12 years, cartilage water content decreased by 18%; collagen increased by 59%; and sGAG decreased by 36% (all R2 ≥ 0.557). The short T2*$$ {\mathrm{T}}_2^{\ast } $$ (T2*S$$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$) decreased by 72%, and the signal fraction relaxing with T2*S$$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ (fT2*S$$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$) increased by 55% during the first 5 years but remained relatively stable after that. TSCSP was significantly correlated with sGAG content from biopsies (R2 = 0.739). Depending on age, TSCLB showed higher or lower values than TSCSP. The TSCLB − TSCSP difference was significantly correlated with T2*S$$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.850), fT2*S$$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.651), and water content (R2 = 0.738). Conclusion: TSC and relaxation parameters measured with 23Na MRI provide noninvasive information about changes in sGAG content and collagen matrix during cartilage maturation. Cartilage TSC quantification assuming fixed relaxation may be feasible in children older than 5 years. [ABSTRACT FROM AUTHOR]