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Abstract Wildfire is a growing concern as climate shifts. The hydrologic effects of wildfire, which include elevated hazards and changes in water quantity and quality, are increasingly assessed using numerical models. Post‐wildfire application of physically based distributed models provides unique insight into the underlying processes that affect water resources after wildfire. This work reviews and synthesizes post‐wildfire applications of physically based distributed models by examining the scales and geographic/ecohydrologic distribution of model applications, hydrologic response process representation, model parameterization, and model performance metrics. Highlighted gaps and opportunities for advancing physically based distributed hydrologic response modeling after wildfire include the following: (a) applying models in under‐represented geographic (S. America, Africa, Asia) and ecohydrologic regions (arid or dry subhumid climates), (b) incorporating all four major streamflow generation mechanisms (infiltration excess, saturation excess, subsurface storm flow, and groundwater flow), (c) representing integrated vadose zone and saturated zone processes to better capture subsurface streamflow generation, (d) building new remotely sensed model parameterization methods for precipitation interception, infiltration, and overland flow that account for burn severity and recovery, (e) incorporating distributed state variables (e.g., soil moisture, groundwater levels) in model performance assessment, (f) designing model intercomparison studies, including field datasets specifically for post‐wildfire model development and validation, (g) linking mechanistic vegetation regrowth models with hydrologic models to improve simulation of process shifts as ecosystems recover, and (h) creating a new community modeling framework to integrate modeling advances across the wildfire science community.

The incidence of knee injuries in sport, particularly involving the ACL, appears to be increasing yearly, especially in younger age athletes. Even more concerning is the frequency of ACL reinjury also appears to be increasing year after year. Improving the objective criteria and testing methods used to determine return to play (RTP) readiness following ACL surgery is one aspect of the rehabilitation process that can significantly help in reducing reinjury rates. Currently, the majority of clinicians are still using post operative time frames as their number one criterion for clearance to RTP. This flawed method demonstrates an inadequate reflection of the true unpredictable, dynamic environment athletes are returning to participate in. In our clinical experience, objective testing to allow for clearance to sport participation following an ACL injury should incorporate neurocognitive and reactive testing due to the nature of the injury typically occurs because of failed control of unanticipated reactive movements. The purpose of this manuscript is to share a neurocognitive testing sequence we currently employ consisting of 8 tests in 3 categories: Blazepod tests, reactive shuttle run tests, and reactive hop tests. The use of a more dynamic reactive testing battery may decrease the reinjury rates when an athlete is cleared for participation by measuring readiness in chaotic circumstances that are more truly reflective of the sporting environment the athlete is working to return to and in the process give them a greater sense of confidence.

Study region: Three watersheds in the Lake Champlain Basin of Vermont, USA. Study focus: Watershed models are essential for evaluating the impact of watershed management; however, they contain many parameters that are not directly measurable. These parameters are commonly estimated by calibration against observed data, often streamflow. Unfortunately, many areas lack long-term streamflow records, making parameter estimation in low data environments (LDE) challenging. A new calibration technique, simultaneous multi-basin calibration (MBC), was developed to estimate model parameters in LDE. Three Soil and Water Assessment Tool (SWAT) model initializations for USGS gages with ∼ 2-year records in the Lake Champlain Basin of Vermont, USA, were evaluated by comparing MBC and the commonly used similarity-based regionalization (SBR) approach, where calibrated parameters from a watershed with an extended data record are transferred to the LDE receptor watersheds. In MBC, each watershed is initialized, and observed flows from each initialization are aggregated to generate a combined streamflow record of sufficient length to calibrate using a differential evolution algorithm. New hydrological insights for the region: Using this new MBC method, we demonstrate improved model performance and more realistic model parameter values. This study demonstrates that short periods of hydrological measurement from multiple locations in a basin can represent a system similarly to long term measurements and that even short records taken at multiple locations significantly improve our hydrologic knowledge of a system as compared to relying on the similarity of a basin with a long record of flow. In addition, this study revealed that the hydrologic response is mediated by the interplay of very low soil-saturated hydraulic conductivity (Ksat) and cracking soils. As a result, even if Ksat is very low, cracking clays have a large impact on runoff production Garna et al. (2022).

Abstract BackgroundThere has been increasing demand for aesthetic surgery procedures in the United States, highlighting the critical importance of the competence of plastic surgery residents and rigorous methods of aesthetic surgery training. ObjectivesThe objective of this study was to review procedures and outcomes from our plastic surgery resident aesthetic clinic. Outcomes and costs were compared to national averages and reports from the literature. MethodsA retrospective chart review identified all adult patients who presented to the Resident Aesthetic Surgery Clinic at NYU Langone Health in 2021. Patient demographics, comorbidities, procedural data, postoperative complications, revisions, and surgeon fees were compiled. A brief confidence survey was distributed to participating residents before and after their clinic rotation. Data were analyzed using IBM SPSS software (Armonk, NY). ResultsIn 2021, 144/379 consultations led to an operation (38.0% conversion rate), resulting in 420 distinct surgical procedures. The majority (53.3%) of procedures involved the head and neck. Complication and revision rates were 5.5% and 1.0%, respectively, with surgeon fees consistently below the national average. Residents reported being significantly more confident performing face lifts, rhinoplasties, and aesthetic surgery in general following their clinic rotation. ConclusionsThese data represent the largest annual reported study of plastic surgery resident aesthetic procedures and outcomes, demonstrating the high volume and productivity of the NYU Resident Aesthetic Surgery Clinic. These results further support resident aesthetic clinics as a robust training modality. Level of Evidence: 4

IntroductionDominance relationships in which females dominate males are rare among mammals. Mechanistic hypotheses explaining the occurrence of female dominance suggest that females dominate males because (1) they are intrinsically more aggressive or less submissive than males, and/or (2) they have access to more social support than males.MethodsHere, we examine the determinants of female dominance across ontogenetic development in spotted hyenas (Crocuta crocuta) using 30 years of detailed behavioral observations from the Mara Hyena Project to evaluate these two hypotheses.ResultsAmong adult hyenas, we find that females spontaneously aggress at higher rates than males, whereas males spontaneously submit at higher rates than females. Once an aggressive interaction has been initiated, adult females are more likely than immigrant males to elicit submission from members of the opposite sex, and both adult natal and immigrant males are more likely than adult females to offer submission in response to an aggressive act. We also find that adult male aggressors are more likely to receive social support than are adult female aggressors, and that both adult natal and immigrant males are 2–3 times more likely to receive support when attacking a female than when attacking another male. Across all age classes, females are more likely than males to be targets of aggressive acts that occur with support. Further, receiving social support does slightly help immigrant males elicit submission from adult females compared to immigrant males acting alone, and it also helps females elicit submission from other females. However, adult females can dominate immigrant males with or without support far more often than immigrant males can dominate females, even when the immigrants are supported against females.DiscussionOverall, we find evidence for both mechanisms hypothesized to mediate female dominance in this species: (1) male and female hyenas clearly differ in their aggressive and submissive tendencies, and (2) realized social support plays an important role in shaping dominance relationships within a clan. Nevertheless, our results suggest that social support alone cannot explain sex-biased dominance in spotted hyenas. Although realized social support can certainly influence fight outcomes among females, adult females can easily dominate immigrant males without any support at all.

Muscle weakness is common in many neurological, neuromuscular, and musculoskeletal conditions. Muscle size only partially explains muscle strength as adaptions within the nervous system also contribute to strength. Brain-based biomarkers of neuromuscular function could provide diagnostic, prognostic, and predictive value in treating these disorders. Therefore, we sought to characterize and quantify the brain's contribution to strength by developing multimodal MRI pipelines to predict grip strength. However, the prediction of strength was not straightforward, and we present a case of sex being a clear confound in brain decoding analyses. While each MRI modality—structural MRI (i.e., gray matter morphometry), diffusion MRI (i.e., white matter fractional anisotropy), resting state functional MRI (i.e., functional connectivity), and task-evoked functional MRI (i.e., left or right hand motor task activation)—and a multimodal prediction pipeline demonstrated significant predictive power for strength (R2 = 0.108–0.536, p ≤ 0.001), after correcting for sex, the predictive power was substantially reduced (R2 = −0.038–0.075). Next, we flipped the analysis and demonstrated that each MRI modality and a multimodal prediction pipeline could significantly predict sex (accuracy = 68.0%−93.3%, AUC = 0.780–0.982, p < 0.001). However, correcting the brain features for strength reduced the accuracy for predicting sex (accuracy = 57.3%−69.3%, AUC = 0.615–0.780). Here we demonstrate the effects of sex-correlated confounds in brain-based predictive models across multiple brain MRI modalities for both regression and classification models. We discuss implications of confounds in predictive modeling and the development of brain-based MRI biomarkers, as well as possible strategies to overcome these barriers.

The last 2 years have been a period of unprecedented growth for the MOOSE community and the software itself. The number of monthly visitors to the website has grown from just over 3,000 to now averaging 5,000. In addition, over 1,800 pull requests have been merged since the beginning of 2020, and the new discussions forum has averaged 600 unique visitors per month. The previous publication has been cited over 200 times since it was published 2 years ago. This paper serves as an update on some of the key additions and changes to the code and ecosystem over the last 2 years, as well as recognizing contributions from the community.

Abstract Our society is experiencing more stress than ever before, leading to both negative psychiatric and physical outcomes. Chronic stress is linked to negative long-term health consequences, raising the possibility that stress is related to accelerated aging. In this study, we examine whether resilience factors affect stress-associated biological age acceleration. Recently developed “epigenetic clocks” such as GrimAge have shown utility in predicting biological age and mortality. Here, we assessed the impact of cumulative stress, stress physiology, and resilience on accelerated aging in a community sample (N = 444). Cumulative stress was associated with accelerated GrimAge (P = 0.0388) and stress-related physiologic measures of adrenal sensitivity (Cortisol/ACTH ratio) and insulin resistance (HOMA). After controlling for demographic and behavioral factors, HOMA correlated with accelerated GrimAge (P = 0.0186). Remarkably, psychological resilience factors of emotion regulation and self-control moderated these relationships. Emotion regulation moderated the association between stress and aging (P = 8.82e−4) such that with worse emotion regulation, there was greater stress-related age acceleration, while stronger emotion regulation prevented any significant effect of stress on GrimAge. Self-control moderated the relationship between stress and insulin resistance (P = 0.00732), with high self-control blunting this relationship. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge Acceleration even while accounting for demographic, physiologic, and behavioral covariates. These results demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.

Abstract Background Caregivers are invaluable sources of support for individuals recovering from head and neck cancer (HNC). Accordingly, minimizing caregiver distress is essential to promote the well-being of both caregivers and their patients. This study assessed if psychosocial distress (i.e., anxiety and depression) among HNC caregivers is associated with a difference in how caregivers and their patients perceive patients’ quality of life (QOL) after treatment completion. Methods Caregivers’ and patients’ perceptions of patient QOL were assessed using the University of Washington QOL Questionaire (UWQOL), a validated HNC-specific health-related QOL questionnaire. The survey is interpreted in terms of its two composite scores: a physical QOL score and a social-emotional QOL score with higher scores indicating better QOL. Caregiver anxiety was assessed using the Generalized Anxiety Questionaire-7 (GAD-7) and caregiver depression was assessed using the Patient Health Questionaire 8 (PHQ-8). Patients completed the UWQOL as part of clinic intake while caregivers were asked to complete the UWQOL for their patients in addition to the PHQ-8 and GAD-7 in private. Linear regression was used to analyze the association between differences in caregivers’ and patients’ QOL scores (both social-emotional and physical QOL subscale scores) and GAD-7 and PHQ-8 scores. Results Of 47 caregivers recruited, 42.6% (n = 20) viewed patients’ social-emotional QOL more negatively than patients themselves, while 31.9% viewed patients’ physical QOL more negatively. After controlling for covariates, differences in perception of social-emotional QOL (p = .01) and differences in perception of physical QOL (p = .007) were significantly associated with caregiver depression, but not anxiety. Caregivers who disagreed with patients regarding patients’ social-emotional QOL scored 6.80 points higher on the PHQ8 than agreeing caregivers. Caregivers who disagreed regarding patients’ physical QOL scored 6.09 points higher. Conclusion Caregivers commonly view patients’ QOL more negatively than patients themselves. These caregivers tend to have greater psychosocial distress than caregivers who agree with their patients. Interventions designed to identify and aid at-risk caregivers are critically needed. We propose screening for differences in perception of patient QOL as a way of identifying distressed caregivers as well as provider-facilitated communication between patients and caregivers as possible interventions that should be examined in future research.

Abstract The serine protease inhibitor (SERPIN) plasminogen activator inhibitor-1 (PAI-1) is a key regulator of the fibrinolytic system, inhibiting the serine proteases tissue- and urokinase-type plasminogen activator (tPA and uPA, respectively). Missense variants render PAI-1 non-functional through misfolding, leading to its turnover as a protease substrate, or to a more rapid transition to the latent/inactive state. Deep mutational scanning was performed to evaluate the impact of amino acid sequence variation on PAI-1 inhibition of uPA using an M13 filamentous phage display system. Error prone PCR was used to construct a mutagenized PAI-1 library encompassing ~ 70% of potential single amino acid substitutions. The relative effects of 27% of all possible missense variants on PAI-1 inhibition of uPA were determined using high-throughput DNA sequencing. 826 missense variants demonstrated conserved inhibitory activity while 1137 resulted in loss of PAI-1 inhibitory function. The least evolutionarily conserved regions of PAI-1 were also identified as being the most tolerant of missense mutations. The results of this screen confirm previous low-throughput mutational studies, including those of the reactive center loop. These data provide a powerful resource for explaining structure–function relationships for PAI-1 and for the interpretation of human genomic sequence variants.

Measles virus is highly contagious and outbreaks occur worldwide. Here the authors show that the orally bioavailable small-molecule polymerase inhibitor ERDRP-0519 prevents measles disease in squirrel monkeys and reduces virus shedding.

BackgroundChronic kidney disease (CKD) is a highly comorbid condition with significant effects on vascular health and remodeling. Upper extremity veins are important in end-stage kidney disease (ESKD) due to their potential use to create vascular accesses. However, unlike arteries, the contribution of CKD-associated factors to the chronic remodeling of veins has been barely studied.MethodsWe measured morphometric parameters in 315 upper extremity veins, 131 (85% basilic) from stage 5 CKD/ESKD patients and 184 (89% basilic) from non-CKD organ donors. Associations of demographic and clinical characteristics with intimal hyperplasia (IH) and medial fibrosis were evaluated using multivariate regression models.ResultsThe study cohort included 33% females, 30% blacks, 32% Hispanics, and 37% whites. Over 60% had hypertension, and 25% had diabetes independent of CKD status. Among kidney disease participants, 26% had stage 5 CKD, while 22 and 52% had ESKD with and without history of a previous arteriovenous fistula/graft (AVF/AVG), respectively. Intimal hyperplasia was associated with older age (β = 0.13 per year, confidence interval [CI] = 0.002–0.26), dialysis vintage > 12 months (β = 0.22, CI = 0.09–0.35), and previous AVF/AVG creation (β = 0.19, CI = 0.06–0.32). Upper quartile values of IH were significantly associated with diabetes (odds ratio [OR] = 2.02, CI = 1.08–3.80), which demonstrated an additive effect with previous AVF/AVG history and longer vintage in exacerbating IH. Medial fibrosis also increased as a function of age (β = 0.17, CI = 0.04–0.30) and among patients with diabetes (β = 0.15, CI = 0.03–0.28). Age was the predominant factor predicting upper quartile values of fibrosis (OR = 1.03 per year, CI = 1.01–1.05) independent of other comorbidities.ConclusionAge and diabetes are the most important risk factors for chronic development of venous IH and fibrosis independent of CKD status. Among kidney disease patients, longer dialysis vintage, and history of a previous AVF/AVG are strong predictors of IH.

Mineralocorticoid receptor antagonists (MRAs) slow cardiomyopathy in patients with Duchenne muscular dystrophy (DMD) and improve skeletal muscle pathology and function in dystrophic mice. However, glucocorticoids, known antiinflammatory drugs, remain a standard of care for DMD, despite substantial side effects. Exact mechanisms underlying mineralocorticoid receptor (MR) signaling contribution to dystrophy are unknown. Whether MRAs affect inflammation in dystrophic muscles and how they compare with glucocorticoids is unclear. The MRA spironolactone and glucocorticoid prednisolone were each administered for 1 week to dystrophic mdx mice during peak skeletal muscle necrosis to compare effects on inflammation. Both drugs reduced cytokine levels in mdx quadriceps, but prednisolone elevated diaphragm cytokines. Spironolactone did not alter myeloid populations in mdx quadriceps or diaphragms, but prednisolone increased F4/80hi macrophages. Both spironolactone and prednisolone reduced inflammatory gene expression in myeloid cells sorted from mdx quadriceps, while prednisolone additionally perturbed cell cycle genes. Spironolactone also repressed myeloid expression of the gene encoding fibronectin, while prednisolone increased its expression. Overall, spironolactone exhibits antiinflammatory properties without altering leukocyte distribution within skeletal muscles, while prednisolone suppresses quadriceps cytokines but increases diaphragm cytokines and pathology. Antiinflammatory properties of MRAs and different limb and respiratory muscle responses to glucocorticoids should be considered when optimizing treatments for patients with DMD.

Despite advances in treatment for multiple myeloma, the majority of patients ultimately develop relapsed disease marked by immune evasion and resistance to standard therapy. Immunotherapy has emerged as a powerful tool for tumor-directed cytotoxicity with the unique potential to induce immune memory to reduce the risk of relapse. Understanding the specific mechanisms of immune dysregulation and dysfunction in advanced myeloma is critical to the development of further therapies that produce a durable response. Adoptive cellular therapy, most strikingly CAR T cell therapy, has demonstrated dramatic responses in the setting of refractory disease. Understanding the factors that contribute to immune evasion and the mechanisms of response and resistance to therapy will be critical to developing the next generation of adoptive cellular therapies, informing novel combination therapy, and determining the optimal time to incorporate immune therapy in the treatment of myeloma.

In this work, akaganeite (β-FeO(OH)) impregnated maize cob biochar (Fe-MCB) was prepared by direct hydrolysis, and its adsorptive potential was tested against aqueous solutions of carbamazepine (CBZ), an emerging contaminant. The adsorbent was characterized by standard methods, namely XRD, SEM-EDX, FT-IR, BET surface area analysis, and VSM. Fe-MCB exhibited mesoporous textural structure with paramagnetic behavior at room temperature. The equilibrium data were modeled using the Langmuir, Freundlich, Fowler-Guggenheim and Sips isotherm models. The adsorption data were best described by Fowler-Guggenheim with an estimated maximum adsorption capacity of 81.80 mg g−1. The adsorption rate was described by the pseudo-first-order (PFO) model. The thermodynamic functions, namely enthalpy (ΔH = -6.88 kJ mol−1), negative Gibbs free energy (ΔG) values, entropy (ΔS = 26.33 J mol−1), indicated that the adsorption was exothermic, spontaneous, with the increased disorder at the solid-liquid interphase. The adsorption mechanism is thought to entail dispersive interactions. Modified maize cob biochar is a potentially techno-economic sorbent for CBZ adsorption.

Rib fractures still remain a common problem in blunt thoracic trauma, often resulting significant acute and/or chronic morbidity and mortality. The management of rib fractures has improved over the past two decades, resulting in overall improved patient outcomes. With advances in surgical stabilization of rib fractures (SSRF), improvements in regional analgesia, and the introduction of intercostal nerve cryoablation, patient outcomes from rib fractures have improved significantly over the past several years. This article explores the indications and technique for SSRF as well as discusses additional therapeutic modalities for rib fractures through regional anesthesia and intercostal nerve cryoablation.

Abstract Towards the larger goal of understanding factors relevant for improving visuo-motor control, we investigated the role of visual feedback for modulating the effectiveness of a simple hand-eye training protocol. The regimen comprised a series of curve tracing tasks undertaken over a period of one week by neurologically healthy individuals with their non-dominant hands. Our three subject groups differed in the training they experienced: those who received ‘Persistent’ visual-feedback by seeing their hand and trace evolve in real-time superimposed upon the reference patterns, those who received ‘Non-Persistent’ visual-feedback seeing their hand movement but not the emerging trace, and a ‘Control’ group that underwent no training. Improvements in performance were evaluated along two dimensions—accuracy and steadiness, to assess visuo-motor and motor skills, respectively. We found that persistent feedback leads to a significantly greater improvement in accuracy than non-persistent feedback. Steadiness, on the other hand, benefits from training irrespective of the persistence of feedback. Our results not only demonstrate the feasibility of rapid visuo-motor learning in adulthood, but more specifically, the influence of visual veridicality and a critical role for dynamically emergent visual information.

I argue in this paper that certain broad programmatic concerns offered by Norbert Wiener regarding the then-nascent field of cybernetics help us to see how the field has a certain kind of implicitly humanistic orientation. I take this orientation to be emergent or manifest in regard both to its interdisciplinarity and, in particular, to the way in which it highlights the need for not-just-scientific values to be at play in the evaluation and reception of its work. I marshal these points in response to some key recent varieties of scientism, namely those defended, respectively, by Alex Rosenberg and by James Ladyman, Don Ross, and David Spurrett, which have been philosophically resurgent of late. I contend that a humanistic approach to the sciences, following generally upon Wiener's cautionary points, escapes some obvious problems that ultimately beset varieties of scientism, particularly relating to the role that various values often play in and around scientific work.

Early social experience can alter epigenetic patterns and stress responses later in life. A study on wild spotted hyenas finds that maternal care and social connections after leaving the den influence DNA methylation and contribute to a developmentally plastic stress response.

The parasite causing toxoplasmosis can manipulate prey to behave in ways that promote transmission to the parasite’s definitive feline hosts. The first study consistent with this extended phenotype in the wild finds that infected hyena cubs approach lions more closely than uninfected peers and have higher rates of lion mortality.

ABSTRACT Group B Streptococcus (GBS) in the vaginal tract is a risk factor for preterm birth and adverse pregnancy outcomes. GBS colonization is also transient in nature, which likely reflects the contributions of pathogen determinants, interactions with commensal flora, and host factors, making this environment particularly challenging to understand. Additionally, dietary zinc deficiency is a health concern on the global scale that is known to be associated with recurrent bacterial infection and increased rate of preterm birth or stillbirth. However, the impact of zinc deficiency on vaginal health has not yet been studied. Here we use a murine model to assess the role of dietary zinc on GBS burden and the impact of GBS colonization on the vaginal microbiome. We show that GBS vaginal colonization is increased in a zinc-deficient host and that the presence of GBS significantly alters the microbial community structure of the vagina. Using machine learning approaches, we show that vaginal community turnover during GBS colonization is driven by computationally predictable changes in key taxa, including several organisms not previously described in the context of the vaginal microbiota, such as Akkermansia muciniphila. We observed that A. muciniphila increases GBS vaginal persistence and, in a cohort of human vaginal microbiome samples collected throughout pregnancy, we observed an increased prevalence of codetection of GBS and A. muciniphila in patients who delivered preterm compared to those who delivered at full term. These findings reveal the importance and complexity of both host zinc availability and native microbiome to GBS vaginal persistence. IMPORTANCE The presence of group B Streptococcus (GBS) in the vaginal tract, perturbations in the vaginal microbiota, and dietary zinc deficiency are three factors that are independently known to be associated with increased risk of adverse pregnancy outcomes. Here, we developed an experimental mouse model to assess the impact of dietary zinc deficiency on GBS vaginal burden and persistence and to determine how changes in GBS colonization impact vaginal microbial structure. We have employed unique animal, in silica metabolic, and machine learning models, paired with analyses of human cohort data, to identify taxonomic biomarkers that contribute to host susceptibility to GBS vaginal persistence. Collectively, the data reported here identify that both dietary zinc deficiency and the presence of A. muciniphila could perpetuate an increased GBS burden and prolonged exposure in the vaginal tract, which potentiate the risk of invasive infection in utero and in the newborn.

Abstract Evaluating historical simulations from global climate models (GCMs) remains an important exercise for better understanding future projections of climate change and variability in rapidly warming regions, such as the Arctic. As an alternative approach for comparing climate models and observations, we set up a machine learning classification task using a shallow artificial neural network (ANN). Specifically, we train an ANN on maps of annual mean near‐surface temperature in the Arctic from a multi‐model large ensemble archive in order to classify which GCM produced each temperature map. After training our ANN on data from the large ensembles, we input annual mean maps of Arctic temperature from observational reanalysis and sort the prediction output according to increasing values of the ANN's confidence for each GCM class. To attempt to understand how the ANN is classifying each temperature map with a GCM, we leverage a feature attribution method from explainable artificial intelligence. By comparing composites from the attribution method for every GCM classification, we find that the ANN is learning regional temperature patterns in the Arctic that are unique to each GCM relative to the multi‐model mean ensemble. In agreement with recent studies, we show that ANNs can be useful tools for extracting regional climate signals in GCMs and observations.

Traumatic brain injury (TBI) represents a major public health concern. Although the majority of individuals that suffer mild-moderate TBI recover relatively quickly, a substantial subset of individuals experiences prolonged and debilitating symptoms. An exacerbated response to physiological and psychological stressors after TBI may mediate poor functional recovery. Individuals with TBI can suffer from poor stress tolerance, impairments in the ability to evaluate stressors, and poor initiation (and cessation) of neuroendocrine stress responses, all of which can exacerbate TBI-mediated dysfunction. Here, we pay tribute to the pioneering neuroendocrinologist Dr. Bruce McEwen by discussing the ways in which his work on stress physiology and allostatic loading impacts the TBI patient population both before and after their injuries. Specifically, we will discuss the modulatory role of hypothalamic-pituitary-adrenal axis responses immediately after TBI and later in recovery. We will also consider the impact of stressors and stress responses in promoting post-concussive syndrome and post-traumatic stress disorders, two common sequelae of TBI. Finally, we will explore the role of early life stressors, prior to brain injuries, as modulators of injury outcomes.

Purpose To describe the cornea and keratorefractive surgeries experience of U.S. ophthalmology residents. Methods Deidentified case logs of residents graduating in 2018 were collected from ophthalmology residency program directors in the United States. Using Current Procedure Terminology codes, case logs were reviewed in the categories of cornea and keratorefractive surgeries. Accreditation Council for Graduate Medical Education national graduating resident surgical case logs on cornea procedures published from 2010 to 2020 were also analyzed. Results Case logs were received for 152/488 (31.1%) residents from 36/115 (31.3%) ophthalmology residency programs. The most common procedures logged by residents as primary surgeons were pterygium removal (4.3 ± 4.2) and keratorefractive surgeries (3.6 ± 6.2). Residents logged an average of 2.4 keratoplasties as primary surgeon, performing an average of 1.4 penetrating keratoplasties (PKs) and 0.8 endothelial keratoplasties (EKs). As assistants, the most common procedures logged were keratorefractive surgeries (6.1 ± 4.9), EKs (3.8 ± 3.3), and PKs (3.5 ± 2.3). Medium or large residency class size was associated with higher cornea procedural volumes (odds ratio: 8.9; 95% confidence interval: 1.1–75.6; p

Duchenne muscular dystrophy (DMD) is a striated muscle degenerative disease due to loss of functional dystrophin protein. Loss of dystrophin results in susceptibility of muscle membranes to damage, leading to muscle degeneration and continuous inflammation and fibrosis that further exacerbate pathology. Long-term glucocorticoid receptor (GR) agonist treatment, the current standard-of-care for DMD, modestly improves prognosis but has serious side effects. The mineralocorticoid receptor (MR), a ligand-activated transcription factor present in many cell types, has been implicated as a therapeutic target for DMD. MR antagonists (MRAs) have fewer side effects than GR agonists and are used clinically for heart failure. MRA efficacy has recently been demonstrated for DMD cardiomyopathy and in preclinical studies, MRAs also alleviate dystrophic skeletal muscle pathology. MRAs lead to improvements in muscle force and membrane stability and reductions in degeneration, inflammation, and fibrosis in dystrophic muscles. Myofiber-specific MR knockout leads to most of these improvements, supporting an MR-dependent mechanism of action, but MRAs additionally stabilize myofiber membranes in an MR-independent manner. Immune cell MR signaling in dystrophic and acutely injured normal muscle contributes to wound healing, and myeloid-specific MR knockout is detrimental. More research is needed to fully elucidate MR signaling in striated muscle microenvironments. Direct comparisons of genomic and non-genomic effects of glucocorticoids and MRAs on skeletal muscles and heart will contribute to optimal temporal use of these drugs, since they compete for binding conserved receptors. Despite the advent of genetic medicines, therapies targeting inflammation and fibrosis will be necessary to achieve optimal patient outcomes.

Intoxication is a leading risk factor for injury, and TBI increases the risk for later alcohol misuse, especially when the injury is sustained in childhood. Previously, we modeled this pattern in mice, wherein females injured at postnatal day 21 drank significantly more than uninjured females, while we did not see this effect in males. However, the biological underpinnings of this sex difference have remained elusive. In this study, we utilize this preclinical model and traditional endocrine manipulations to assess the effect of perinatal sex steroids on post-injury ethanol response. We found that perinatal androgen administration and adult ovariectomy prevented the development of conditioned place preference to ethanol in females, while there was not an effect of gonadectomy either developmental time point on the severity of axonal degeneration. Finally, although TBI increased the number of microglia in males, there was no corresponding effect of gonadectomy, which suggests that males exhibit prolonged neuroinflammation after brain injury irrespective of circulating sex steroids. Taken together, our results indicate a potential role for ovarian sex steroids in the development of greater alcohol preference after a juvenile TBI in female mice.

Exposure to alcohol has multiple effects on nervous system function, and organisms have evolved mechanisms to optimally respond to the presence of ethanol. Sex differences in ethanol-induced behaviors have been observed in several organisms, ranging from humans to invertebrates. However, the molecular mechanisms underlying the dimorphic regulation of ethanol-induced behaviors remain incompletely understood. Here, we observed sex differences in ethanol sedation sensitivity in Drosophila Genome Reference Panel (DGRP) lines of Drosophila melanogaster compared to the absence of dimorphism in standard laboratory wildtype and control lines. However, in dose response experiments, we were able to unmask dimorphic responses for the control mutant line w1118 by lowering the testing ethanol concentration. Notably, feminization of the small population of Corazonin (Crz) neurons in males was sufficient to induce female-like sedation sensitivity. We also tested the role of the transcription factor apontic (apt) based on its known expression in Crz neurons and its regulation of sedation responses. Interestingly, loss of function apt mutations increased sedation times in both males and females as compared to controls. No significant difference between male and female apt mutants was observed, suggesting a possible role of apt in the regulation of dimorphic ethanol-induced responses. Thus, our results shed light into the mechanisms regulating sex-differences in ethanol-induced behaviors at the cellular and molecular level, suggesting that the genetic sex in a small neuronal population plays an important role in modulating sex differences in behavioral responses to ethanol.

Background The neutrophil‐to‐lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow‐up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5–24.9) and was evaluated as continuous variable and categorical tertiles (low: NLR ≤2.70, n=1963; intermediate: NLR 2.70–4.20, n=1958; high: NLR ≥4.20, n=1960). No patients had known baseline infection. High baseline NLR was associated with increased risk of death or rehospitalization at 3 years (58.4% versus 41.0%; adjusted hazard ratio [aHR], 1.39; 95% CI, 1.18–1.63; P

Abstract. There is great interest in expanding the use of ultrasound (US), but new challenges exist with its application to lumbar facet–targeted procedures. The primary aim of this systematic review and meta-analysis was to determine the risk of incorrect needle placement associated with US–guided lumbar medial branch blocks (MBB) and facet joint injections (FJI) as confirmed by fluoroscopy or computerized tomography (CT). An a priori protocol was registered, and a database search was conducted. Inclusion criteria included all study types. Risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials and the National Heart, Lung, and Blood tool for assessing risk bias for observational cohort studies. Pooled analysis of the risk difference (RD) of incorrect needle placement was calculated. Pooled analysis of 7 studies demonstrated an 11% RD (P < 0.0009) of incorrect needle placement for US-guided MBB confirmed using fluoroscopy with and without contrast. Pooled analysis of 3 studies demonstrated a 13% RD (P < 0.0001) of incorrect needle placement for US-guided FJI confirmed using CT. The time to complete a single-level MBB ranged from 2.6 to 5.0 minutes. The certainty of evidence was low to very low. Ultrasound-guided lumbar MBB and FJI are associated with a significant risk of incorrect needle placement when confirmed by fluoroscopy or CT. The technical limitations of US and individual patient factors could contribute to the risk of incorrect needle placement.

Abstract Network analyses rarely include fitness components, such as germination, to tie invasive plants to population‐level effects on the natives. We address this limitation in a previously studied network of flower visitors around a suite of native and invasive plants that includes an endemic plant at Badlands National Park, South Dakota, USA. Eriogonum visheri coflowers with two abundant invasive plants, Salsola tragus and Melilotus officinalis, as well as a common congener, E. pauciflorum. Network analyses had suggested strong linkages between E. visheri and S. tragus and E. pauciflorum, with a weaker link to M. officinalis. We measured visitation, pollen deposited on stigmas, achene weight and germination over three field seasons (two for germination) in four populations (two in the final season) of E. visheri and applied in situ pollen treatments to E. visheri, adding pollen from other flowers on the same plant; flowers on other E. visheri plants; S. tragus, M. officinalis, or E. pauciflorum; open pollination; or excluding pollinators. Insect visitation to E. visheri was not affected by floral abundance of any of the focal species. Most visitors were halictid bees; one of these (Lasioglossum packeri) was the only identified species to visit E. visheri all three years. Ninety‐seven percent of pollen on collected E. visheri stigmas was conspecific, but 22% of flowers had >1 grain of E. pauciflorum pollen on stigmas and 7% had >1 grain of S. tragus pollen;

Abstract Background Focused cardiac ultrasound (FOCUS) can aid in evaluation and management of patients with cardiac arrest, but image quality in this population has been questioned. Our goal was to determine how often adequate imaging can be obtained in cardiac arrest patients. Methods We conducted a prospective cohort study to examine the utility of FOCUS in cardiac arrest. All patients who presented to the Emergency Department (ED) in cardiac arrest or who had cardiac arrest while in the ED over 6 months were prospectively identified. FOCUS images were obtained as part of routine clinical care. Patients with images obtained were paired with age- and gender-matched controls who underwent FOCUS for another indication during the study period. Image quality was scored by two blinded reviewers using a 0–4 scale, with a score of ≥ 2 considered adequate. Results There were 137 consecutive cardiac arrests, 121 out-of-hospital and 16 in-hospital, during the study period. FOCUS images were recorded in 126 (92%), who were included in the analysis. The average age was 58 years, and 45% were female. Ninety-seven studies (77%) were obtained during advanced cardiac life support while 29 (23%) were obtained after return of spontaneous circulation. The controls were appropriately matched. Of the cardiac arrest studies, 106 (84%) were rated adequate, compared to 116 (92%) in controls (p = 0.08). When compared to control FOCUS studies, the scores given to studies of cardiac arrest patients were lower (p = 0.001). Conclusions FOCUS can reliably be used during cardiac arrest to obtain images adequate to answer clinical questions and guide therapies.

Background: Total hip arthroplasty (THA) performed for displaced femoral neck fractures (FNF) is becoming a more frequent treatment in the active elderly population. The complication profiles associated with THA surgical approaches in the fracture setting are unclear. The purpose of this study was to compare a series of THA for FNF performed via the direct anterior (DA) approach vs alternative approaches (anterolateral and posterolateral). Methods: A retrospective review identified 52 patients who underwent primary THA for FNF between 2009 and 2018, including 20 via the DA approach and 32 by alternative approaches. All procedures were exclusively performed by high-volume arthroplasty surgeons. Perioperative results, complications, and clinical outcomes were compared with those of routine statistical methods. Mean follow-up duration was 3 years (range, 1-8). Results: The average age was 74 years (range, 57-92) with similar baseline characteristics between the 2 groups (P = .09). The DA cohort demonstrated significantly shorter length of stay (3 days vs 5 days, P < .01) and discharge to home vs skilled nursing facility (40.0% vs 9.4% P = .014). There was a trend toward decreased complications (0% vs 16%, P = .08). There were no dislocations or fractures in either cohort. Final Harris Hip Scores (94 vs 81, P = .07) and return to community ambulation (96%) were similar between DA and alternative approach groups. Conclusion: The DA approach to THA performed for FNF appears safe with improved outcomes compared with alternative approaches. Larger studies are needed to verify these results.

Nature is highly efficient at producing chiral compounds that are enantiomerically pure. The inherent chirality of naturally occurring biomolecules means that many have the potential to be used as chiral dopants for cholesteric liquid crystal (CLC) systems. Though many biomolecules have been identified as chiral dopants, many remain yet to be probed for their ability to function as chiral dopants. Here, 10 naturally occurring biomolecules comprised of steroids and bile acids were tested as chiral dopants for CLCs. Progesterone was identified as having high miscibility with nematic liquid crystals and was used in responsive liquid crystal devices. Progesterone-doped CLC devices were fabricated to exhibit either normal mode or reverse mode switchable behavior. Polymer stabilized CLCs (PSCLC) devices exhibiting dynamic electro-optic red- and blue-tuning behaviors were also fabricated. Furthermore, immiscible lithocholic acid was synthetically modified to afford two derivatives that were miscible at 10 wt. % in nematic liquid crystals. The two lithocholic acid derivatives were used as chiral dopants and incorporated into polymer stabilized CLCs which exhibited blue tuning behavior.

Pseudomonas aeruginosa (PsA) is an opportunistic bacterial pathogen that causes life-threatening infections in individuals with compromised immune systems and exacerbates health concerns for those with cystic fibrosis (CF). PsA rapidly develops antibiotic resistance; thus, novel therapeutics are urgently needed to effectively combat this pathogen. Previously, we have shown that a novel cationic Zinc (II) porphyrin (ZnPor) has potent bactericidal activity against planktonic and biofilm-associated PsA cells, and disassembles the biofilm matrix via interactions with eDNA In the present study, we report that ZnPor caused a significant decrease in PsA populations in mouse lungs within an in vivo model of PsA pulmonary infection. Additionally, when combined with an obligately lytic phage PEV2, ZnPor at its minimum inhibitory concentration (MIC) displayed synergy against PsA in an established in vitro lung model resulting in greater protection of H441 lung cells versus either treatment alone. Concentrations above the minimum bactericidal concentration (MBC) of ZnPor were not toxic to H441 cells; however, no synergy was observed. This dose-dependent response is likely due to ZnPor’s antiviral activity, reported herein. Together, these findings show the utility of ZnPor alone, and its synergy with PEV2, which could be a tunable combination used in the treatment of antibiotic-resistant infections.

Cholesteric liquid crystals (CLC) are molecules that can self-assemble into helicoidal superstructures exhibiting circularly polarized reflection. The facile self-assembly and resulting optical properties makes CLCs a promising technology for an array of industrial applications, including reflective displays, tunable mirror-less lasers, optical storage, tunable color filters, and smart windows. The helicoidal structure of CLC can be stabilized via in situ photopolymerization of liquid crystal monomers in a CLC mixture, resulting in polymer-stabilized CLCs (PSCLCs). PSCLCs exhibit a dynamic optical response that can be induced by external stimuli, including electric fields, heat, and light. In this review, we discuss the electro-optic response and potential mechanism of PSCLCs reported over the past decade. Multiple electro-optic responses in PSCLCs with negative or positive dielectric anisotropy have been identified, including bandwidth broadening, red and blue tuning, and switching the reflection notch when an electric field is applied. The reconfigurable optical response of PSCLCs with positive dielectric anisotropy is also discussed. That is, red tuning (or broadening) by applying a DC field and switching by applying an AC field were both observed for the first time in a PSCLC sample. Finally, we discuss the potential mechanism for the dynamic response in PSCLCs.

Abstract The Nobel Prize in Physiology or Medicine is a prestigious award given every year for ostensibly the most important discovery in the field. Prizes in Medicine have typically gone to honor foundational knowledge rather than measurable impact. Two recent examples from global health (a rotavirus vaccine, child growth standards) offer alternatives for what might be lauded in medicine. These two examples and historical achievements regarding cholera and smallpox are worthy but do not fall within the scope of Nobel awards for Peace or Economics. The COVID-19 pandemic gives a new context for the idea that discovery and implementation are both keys to medicine. New patterns that redefine achievement in medicine could emerge by Nobel Prize precedent to promote greater health equity and international collaboration.

The complexity of cirrhosis requires patients and their caregivers to be well educated to improve outcomes. Data are lacking regarding how to best educate patients and their caregivers in the setting of cirrhosis. Our aim is to understand (both through existing literature and by asking patients and their caregivers) how patients learn about their disease, barriers in their education and disease management, and self‐management strategies. We performed a structured search of published articles in PubMed (1973 to 2020) using keywords “cirrhosis” plus “barriers”, “education”, “self‐management”, or “self‐care”. Additionally, we conducted a focus group of a representative sample of patients and their caregivers to understand how knowledge about cirrhosis is found and incorporated into self‐management. Of 504 returned manuscripts, 11 pertained to barriers in cirrhosis, interventions, or educational management. Barriers are well documented and include disease complexity, medication challenges, comorbid conditions, and lack of effective education. However, data regarding addressing these barriers, especially effective educational interventions, are scarce. Current strategies include booklets and videos, patient empowerment, and in‐person lectures. Without widespread use of these interventions, patients are left with suboptimal knowledge about their disease, a sentiment unanimously echoed by our focus group. Despite linkage to subspecialty care and consistent follow‐up, patients remain uncertain about their disease origin, prognosis, and therapies to manage symptoms. It is clear that more data are needed to assess effective strategies to address unmet educational needs. Existing strategies need to be blended and improved, their effectiveness evaluated, and the results distributed widely.

Background: Permanent Supportive Housing (PSH), which provides subsidies for independent housing and supportive services, is an evidence-based practice that improves health and housing for homeless experienced persons. Though most PSH is scattered-site, that is, housing dispersed throughout the mainstream rental market, project-based PSH offers housing and supportive services in dedicated facilities with on-site services. In 2013, the Veterans Health Administration (VA) at Greater Los Angeles opened a novel project-based PSH program located on a VA campus. To inform plans to expand project-based PSH at this VA, we examined participants’ experiences in this program. We aimed to identify participant characteristics that suggested they were well suited for the planned PSH expansion; to characterize services that participants found valuable in this setting; and to highlight gaps between participants’ needs and PSH services provided. Methods: We performed semi-structured interviews with a convenience sample (n = 24) of participants who had engaged in this project-based PSH program. Interviews asked why participants selected housing on a VA campus and explored valued program characteristics, designs, and services. Using rapid analysis methods, we generated templated summaries of each participant’s responses across the domains of our interview guide, then used matrix analyses to identify salient themes across the interviews. Key Findings: Participants appreciated the ease of access to medical and mental health services; however, as services were assumed to be optimized by virtue of co-location with VA healthcare, their PSH providers often did not link them with non-VA social services as assertively as desired. Many participants raised concerns about building safety and on-site substance use. A lack of participant engagement in program oversight, often leading to conflicts with staff and building management, was also highlighted in our interviews. Discussion: Given the value placed on ease of access to healthcare, these data suggest the value of this PSH model for persons with healthcare vulnerabilities. Specific recommendations for the planned PSH expansion include: (1) continuation of proximate, open-access healthcare; (2) clear tenant policies; (3) tenant councils for each development; (4) staff knowledgeable of non-VA resources and social services; (5) Veteran-preferred hiring practices by Property/Service management; (6) gender-specific accommodations; and (7) robust 24/7 security on-site.

In mid-1930, the Yiddish novelist, playwright, poet, journalist, and world traveller Leib Malach visited Montreal to attend the dedication of a new home for the Jewish Public Library. He then sent the Buenos Aires Yiddish daily Di Prese a three-part travelogue devoted to: Social, cultural, and linguistic conditions in Montreal and the Province of Quebec; the Jewish School Question in Montreal; and Yiddish culture in Montreal. By making implicit comparisons between the two deeply Catholic, but very different societies of Argentina and Quebec, Malach’s travelogue held up a mirror to his intended readership in South America. Quebec’s proximity to the United States and Canada’s status as a British Dominion suggested one point of contrast with Argentina. The long-festering Jewish School Question crystallized the colliding issues of religious confession, public policy, and provincial and internal Jewish community politics in Quebec, which lacked obvious parallels in Argentina. Descriptions of the Yiddish cultural milieu of Montreal offered oblique comparisons with conditions prevailing in the larger Yiddish-speaking community of Buenos Aires. This essay thus attempts to situate Malach’s Montreal travelogue within the frameworks of Canadian and Latin American Jewish Studies, along with transnational Yiddish Studies. En 1930, le romancier, dramaturge, poète, journaliste et globe-trotter yiddish Leib Malach s’est rendu à Montréal pour assister à l’inauguration de la nouvelle bibliothèque publique juive. Il a ensuite envoyé au quotidien yiddish Di Prese de Buenos Aires un récit de voyage en trois parties consacrées aux conditions sociales, culturelles et linguistiques à Montréal et dans la province de Québec, à la question des écoles juives à Montréal, et à la culture yiddish à Montréal. En établissant des comparaisons implicites entre les deux sociétés profondément catholiques, mais très différentes, de l’Argentine et du Québec, le carnet de voyage de Malach tendait un miroir à ses lecteurs d’Amérique du Sud. La proximité du Québec avec les ÉtatsUnis et le statut du Canada en tant que dominion britannique suggèrent un point de contraste avec l’Argentine. La question de l’éducation juive, qui perdure depuis longtemps, cristallise les enjeux de la confession religieuse, de la politique publique et de la politique provinciale et interne de la communauté juive au Québec, qui n’ont pas de parallèles évidents en Argentine. Les descriptions du milieu culturel yiddish de Montréal offraient des comparaisons indirectes avec les conditions prévalant dans la grande communauté yiddishophone de Buenos Aires. Cet essai tente donc de situer le récit de voyage de Malach à Montréal dans le cadre des études juives canadiennes et latino-américaines, ainsi que des études yiddish transnationales.

Abstract An increase in heavy precipitation associated with climate change has exacerbated flooding in the Eastern U.S. To assess regional flood risk with changing climatic conditions, we demonstrate the application of a novel hydrologic modeling framework that integrates climate projections with a coupled Noah‐MP land surface model and a two‐dimensional HEC‐RAS hydrodynamic model. We employ this framework along a 41 km reach of the Susquehanna River near Harrisburg, Pennsylvania, where recent flood damages exceeded $2 billion (2011 Irene and Lee floods). Historical and future 30‐year and 100‐year peak‐discharge estimates were compared to assess how flood risk might be altered due to climate change. Results indicate that precipitation increases from climate change do not always lead to increases in flood risk, because interplay of hydrological components in the watershed, which are considered by Noah‐MP, largely controls flooding severity. However, climate change is expected to increase the severity of extreme events; if a 50‐year flood (the recurrence interval of Tropical Storm Lee) occurred toward the end of the 21st century in the worst‐case emission scenario, then flood volume would increase by 40% and flood extent by 15%, due to an increase in soil moisture from a wetter overall climate.