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Abstract Depression is the leading cause of disability worldwide, exerting a profound negative impact on quality of life in those who experience it. Depression is associated with disruptions to several closely related neural and cognitive processes, including dopamine transmission, fronto-striatal brain activity and connectivity, reward processing and motivation. Physical activity, especially aerobic exercise, reduces depressive symptoms, but the mechanisms driving its antidepressant effects are poorly understood. Here we propose a novel hypothesis for understanding the antidepressant effects of exercise, centred on motivation, across different levels of explanation. There is robust evidence that aerobic exercise decreases systemic inflammation. Inflammation is known to reduce dopamine transmission, which in turn is strongly implicated in effort-based decision making for reward. Drawing on a broad range of research in humans and animals, we propose that by reducing inflammation and boosting dopamine transmission, with consequent effects on effort-based decision making for reward, exercise initially specifically improves ‘interest-activity’ symptoms of depression—namely anhedonia, fatigue and subjective cognitive impairment - by increasing propensity to exert effort. Extending this framework to the topic of cognitive control, we explain how cognitive impairment in depression may also be conceptualised through an effort-based decision-making framework, which may help to explain the impact of exercise on cognitive impairment. Understanding the mechanisms underlying the antidepressant effects of exercise could inform the development of novel intervention strategies, in particular personalised interventions and boost social prescribing.

Aerosol particle number concentration measurements are a crucial part of aerosol research. Vertical profile measurements and high-altitude/low-pressure performance of the respective instruments become more important for remote sensing validation and a vital tool for the observation of climate variables. This study tests the new, commercially available water condensation particle counter (MAGIC 210-LP) for the deployment at aircraft cruising pressure levels that the European research infrastructure IAGOS (In-service Aircraft for a Global Observing System; http://www.iagos.org, last access: 2 May 2023) is aiming for by operating measurement instrumentation onboard passenger aircraft. We conducted laboratory experiments for conditions to simulate passenger aircraft flight altitude at operation pressure. We demonstrate that this type of water condensation particle counter shows excellent agreement with a butanol-based instrument used in parallel. A Faraday cup aerosol electrometer serves as the reference instrument. Experiments are performed with test aerosol ammonium sulfate and fresh combustion soot at pressure levels ranging from 700 to 200 hPa. For soluble particles like ammonium sulfate, the 50 % detection efficiency cut-off diameter (D50) is around 5 nm and does not differ significantly for all performed experiments. For non-soluble fresh soot particles, the D50 cut-off diameter of approximately 10 nm does not vary substantially as a function of pressure, whereas the 90 % detection efficiency cut-off diameter D90 increases from 19 nm at 700 hPa to 37 nm at 200 hPa. The overall counting efficiency for particles larger than 40 nm reaches 100 % for working pressures of 200 hPa and higher.

ABSTRACT: The effect of ethanol on milk has been shown to be temperature-dependent, with higher ethanol concentrations and temperatures reversibly dissociating casein micelles. This work looked to expand on this knowledge, while also demonstrating the efficiency and precision of a custom-made continuous monitoring unit that combines solutions at defined concentrations and temperatures while measuring various parameters (i.e., absorbance, fluorescence, pressure). Caseins were found to self-associate at moderate ethanol concentrations (i.e., 12–36% vol/vol ethanol); however, they dissociated and remained in the serum at higher ethanol concentrations (≥48% vol/vol) and temperatures (24 and 34°C). Although serum casein content was found to be positively correlated with protein hydrophobicity, the addition of ethanol only increased protein hydrophobicity when the sample was held at high temperatures (34–64°C). Overall, the greatest dissociation of casein micelles was found between 40 and 60% (vol/vol) ethanol concentration at elevated temperatures (≥34°C). At these ethanol concentrations and temperatures, skim milk absorbance was minimized, serum casein content (including β-casein content) was maximized, and protein hydrophobicity reached a relative maximum.

ABSTRACT: High-pressure-jet (HPJ) processing of various dairy systems has been shown to disrupt fat droplets and casein micelles and cause a strong association between fat and casein proteins. The present work seeks to better describe this association between fat and casein using a model milk formulated from confectionary coating fat (3.6% wt/wt), micellar casein (3.4% wt/wt), and water (93% wt/wt), which was then pasteurized, homogenized, and then either HPJ-treated (400 MPa) or not (non-HPJ-treated, control). Upon ultracentrifugation, fat in the non-HPJ-treated model milk creamed due to its low density. In the HPJ-treated model milk, fat precipitated with protein into a thick bottom layer upon ultracentrifugation, reflecting a strong association between protein and fat. Differential scanning calorimetry (DSC) and time-domain nuclear magnetic resonance of the non-HPJ-treated model milk revealed fat in 2 physical states: (1) fat that is physically similar to the bulk fat and (2) fat that was in smaller droplets (i.e., homogenized) and crystallized at a lower temperature than the bulk fat. In contrast, DSC of HPJ-treated model milks supported the presence of fat in 3 states: (1) fat that is physically similar to the bulk fat, (2) fat in small droplets that required substantial supercooling beyond the non-HPJ-treated model milk to crystallize, and (3) fat in such small domains that it crystallizes in a less stable polymorphic form than the non-HPJ-treated model milk (or does not crystallize at all). The state of fat within the HPJ-treated model milk changed minimally with acidification, indicating that the association is not dependent on the charge on the casein. Cryogenic transmission electron microscopy (Cryo-TEM) of the non-HPJ-treated model milk revealed uniform casein micelles, which likely adsorbed to the surface of fat globules post-homogenization. In contrast, Cryo-TEM of the HPJ-treated model milk revealed a porous protein aggregate that likely had dispersed fat throughout. Together, these results suggest that HPJ treatment causes fat to be entrapped by casein proteins in very small domains.

Capturing the vertical profiles and horizontal variations of atmospheric aerosols often requires accurate airborne measurements. With the advantage of avoiding health and safety concerns related to the use of butanol or other chemicals, water-based condensation particle counters have emerged to provide measurements under various environments. However, airborne deployments are relatively rare due to the lack of instrument characterization under reduced pressure at flight altitudes. This study investigates the performance of a commercial “versatile” water-based condensation particle counter (vWCPC, model 3789, TSI, Shoreview, MN, USA) under various ambient pressure conditions (500–920 hPa) with a wide range of particle total number concentrations (1500–70 000 cm−3). The effect of conditioner temperature on vWCPC 3789 performance at low pressure is examined through numerical simulation and laboratory experiments. We show that the default instrument temperature setting of 30 ∘C for the conditioner is not suitable for airborne measurement and that the optimal conditioner temperature for low-pressure operation is 27∘. Under the optimal conditioner temperature (27∘), the 7 nm cut-off size is also maintained. Additionally, we show that insufficient droplet growth becomes more significant under the low-pressure operation. The counting efficiency of the vWCPC 3789 can vary up to 20 % for particles of different chemical compositions (e.g., ammonium sulfate and sucrose particles). However, such variation is independent of pressure.

Abstract Background Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes. Method Individual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators. Results Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms. Conclusion The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.

Introduction Clinicians often do not have experience assessing perinatal patients unless they work as part of a perinatal team. Informal feedback points to a lack of confidence in performing perinatal assessments. Objectives The aim of the project was to assess clinicians’ confidence in performing perinatal assessments in outpatient and inpatient settings including the Emergency Department. Additionally, we wanted to assess whether access to a perinatal assessment tool was beneficial. We hypothesise that clinicians lack confidence in performing perinatal assessments and would benefit from using a perinatal assessment tool. Methods We designed a survey of 10 questions assessing the above. The survey was sent out to psychiatric trainees and nurses at South London & Maudsley NHS Foundation Trust. The participant’s confidence in completing perinatal assessments in various settings was assessed using a 5 point Likert scale. Results 52 responses were received. 50% of participants felt not so confident in performing perinatal assessments in the outpatient setting. 40.38%(n=21) of participants felt not so confident in exploring the mother and foetal relationship. 71.15% (n=37) of participants felt that they would benefit from additional teaching with 48.1% of participants citing that they would benefit from access to an assessment tool. Conclusions As predicted, the results of the survey show that clinicians lack confidence in performing perinatal assessments. Therefore, we have commenced work on modifying the existing Stafford Interview. This is a structured interview that explores the obstetric and psycho-social background and psychiatric complications of pregnancy. The survey is due to be replicated in other project locations to allow transcultural comparison. Disclosure No significant relationships.

The mass balance of the Greenland Ice Sheet (GrIS) in a warming climate is of critical interest in the context of future sea level rise. Increased melting in the GrIS percolation zone due to atmospheric warming over the past several decades has led to increased mass loss at lower elevations. Previous studies have hypothesized that this warming is accompanied by a precipitation increase, as would be expected from the Clausius–Clapeyron relationship, compensating for some of the melt-induced mass loss throughout the western GrIS. This study tests that hypothesis by calculating snow accumulation rates and trends across the western GrIS percolation zone, providing new accumulation rate estimates in regions with sparse in situ data or data that do not span the recent accelerating surface melt. We present accumulation records from sixteen 22–32 m long firn cores and 4436 km of ground-penetrating radar, covering the past 20–60 years of accumulation, collected across the western GrIS percolation zone as part of the Greenland Traverse for Accumulation and Climate Studies (GreenTrACS) project. Trends from both radar and firn cores, as well as commonly used regional climate models, show decreasing accumulation rates of 2.4±1.5 % a−1 over the 1996–2016 period, which we attribute to shifting storm tracks related to stronger atmospheric summer blocking over Greenland. Changes in atmospheric circulation over the past 20 years, specifically anomalously strong summertime blocking, have reduced GrIS surface mass balance through both an increase in surface melting and a decrease in accumulation rates.

Drawing on feminist and critical theories of politics and emotions, this paper attends to the hegemony of Social Emotional Learning (SEL) for multiply-marginalized students and explores what exemplary Young Adult (YA) novels can teach scholars, educators, and students about the productive use of anger in the face of injustice. Two acclaimed young adult novels are examined using Critical Content Analysis to illustrate the potential for using such books to critically discuss what anger "does" in the face of injustice related to race and gender.

In this study we characterized the performance of three new particle counters able to detect particles smaller than 3 nm during the Helsinki condensation particle counter (CPC) workshop in summer 2016: the Aerosol Dynamics Inc. (ADI; Berkeley, USA) versatile water condensation particle counter (vWCPC), TSI 3777 nano enhancer (TSI Inc., Shoreview, USA) and modified and boosted TSI 3010-type CPC from Université Blaise Pascal called a B3010. The performance of all CPCs was first measured with charged tungsten oxide test particles at temperature settings which resulted in supersaturation low enough to not detect any ions produced by a radioactive source. Due to similar measured detection efficiencies, additional comparison between the 3777 and vWCPC were conducted using electrically neutral tungsten oxide test particles and with positively charged tetradodecylammonium bromide. Furthermore, the detection efficiencies of the 3777 and vWCPC were measured with boosted temperature settings yielding supersaturation which was at the onset of homogeneous nucleation for the 3777 or confined within the range of liquid water for the ADI vWCPC. Finally, CPC-specific tests were conducted to probe the response of the 3777 to various inlet flow relative humidities, of the B3010 to various inlet flow rates and of the vWCPC to various particle concentrations. For the 3777 and vWCPC the measured 50 % detection diameters (d50s) were in the range of 1.3–2.4 nm for the tungsten oxide particles, depending on the particle charging state and CPC temperature settings, between 2.5 and 3.3 nm for the organic test aerosol, and in the range of 3.2–3.4 nm for tungsten oxide for the B3010.

The mass balance of the Greenland Ice Sheet (GrIS) in a warming climate is of critical interest to scientists and the general public in the context of future sea-level rise. An improved understanding of temporal and spatial variability of snow accumulation will reduce uncertainties in GrIS mass balance models and improve projections of Greenland's contribution to sea-level rise, currently estimated at 0.089 ± 0.03 m by 2100. Here we analyze 25 NASA Operation IceBridge accumulation radar flights totaling > 17 700 km from 2013 to 2014 to determine snow accumulation in the GrIS dry snow and percolation zones over the past 100–300 years. IceBridge accumulation rates are calculated and used to validate accumulation rates from three regional climate models. Averaged over all 25 flights, the RMS difference between the models and IceBridge accumulation is between 0.023 ± 0.019 and 0.043 ± 0.029 m w.e. a−1, although each model shows significantly larger differences from IceBridge accumulation on a regional basis. In the southeast region, for example, the Modèle Atmosphérique Régional (MARv3.5.2) overestimates by an average of 20.89 ± 6.75 % across the drainage basin. Our results indicate that these regional differences between model and IceBridge accumulation are large enough to significantly alter GrIS surface mass balance estimates. Empirical orthogonal function analysis suggests that the first two principal components account for 33 and 19 % of the variance, and correlate with the Atlantic Multidecadal Oscillation (AMO) and wintertime North Atlantic Oscillation (NAO), respectively. Regions that disagree strongest with climate models are those in which we have the fewest IceBridge data points, requiring additional in situ measurements to verify model uncertainties.

Abstract SARS-CoV-2 has the capacity to evolve mutations that escape vaccine- and infection-acquired immunity and antiviral drugs. A variant-agnostic therapeutic agent that protects against severe disease without putting selective pressure on the virus would thus be a valuable biomedical tool that would maintain its efficacy despite the ongoing emergence of new variants. Here, we challenge male rhesus macaques with SARS-CoV-2 Delta—the most pathogenic variant in a highly susceptible animal model. At the time of challenge, we also treat the macaques with aerosolized RBD-62, a protein developed through multiple rounds of in vitro evolution of SARS-CoV-2 RBD to acquire 1000-fold enhanced ACE2 binding affinity. RBD-62 treatment equivalently suppresses virus replication in both upper and lower airways, a phenomenon not previously observed with clinically approved vaccines. Importantly, RBD-62 does not block the development of virus-specific T- and B-cell responses and does not elicit anti-drug immunity. These data provide proof-of-concept that RBD-62 can prevent severe disease from a highly virulent variant.

Alkaline based fuel cells are among the most efficient due to the enhanced kinetics of oxygen reduction in alkaline media. In space applications, they have demonstrated efficiencies near 60%, with the potential to generate electricity with efficiencies at nearly 70%. One of the largest hurdles to overcome in the general uptake of hydrogen fuel cells is the ability to store hydrogen fuel in a form with sufficient energy density to allow for mobile systems to be truly viable. This often means that hydrogen has to be stored at very high pressure (around 70 MPa) in bulky tanks to provide sufficient capacity. Clearly this is not suitable for smaller vehicles or portable systems. Partly to address this, there has been considerable interest in direct oxidation liquid fuelled cells due to the very high specific energy density of liquid fuels. A very compact variant of the liquid fuelled cell which has received little attention is the alkaline dissolved fuel cell where the fuel is dissolved in the electrolyte and the system relies on a selective cathode for efficient operation. Borohydrides present a particularly good option for an alkaline dissolved fuel system, having high energy densities, a low standard potential for the oxidation to borax (an 8 electron process) and good stability in alkaline conditions. A key area in the success of a fuel cell utilizing borohydride is the development of an anode which can make use of the full 8 electron oxidation to borax directly oxidising the borohydride with as little of the hydrolysis reaction occurring as possible. This is in addition to common requirements of high activity, high stability, good electronic conductivity and transport of reactants and products. Here we present investigations into the oxidation of borohydride in alkaline media under various conditions for a selection of candidate materials in different forms using an RDE (rotating disc electrode) based procedure. Results demonstrate that hydrolysis or an indirect oxidation mechanism reduces the coulombic efficiency of the oxidation reaction observed for the materials investigated so far. There is also a significant difference in behaviour between candidate materials. The best performing materials from the RDE studies will be used to develop suitably active and durable functional fuel cell electrodes using scalable processes such as screen printing.

The extent to which plasma HDL concentration regulates reverse cholesterol transport (RCT) is not known. The principal acceptors of unesterified cholesterol (UC) from cultured cells are small pre-β-HDL, which we have shown increase in plasma during intravenous infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) discs in humans. We have now examined the effects on tissue fluid HDL and RCT. ApoA-I/PC or proapoA-I/PC discs were infused into 16 healthy males. Eleven had been given intravenous radiocholesterol to label tissue pools; in 12 prenodal leg lymph was collected throughout; and in 8 all feces were collected. The rise in small pre-β-HDL in plasma was associated with increases in 1) pre-β-HDL concentration in lymph (all subjects), 2) the size of other lymph HDL (four of four subjects), 3) the cholesterol content of lymph lipoproteins relative to plasma lipoproteins (P < 0.01, n = 4), 4) cholesterol-specific radioactivity in lymph (five of nine subjects), 5) plasma lathosterol (P < 0.004, n = 4), 6) plasma cholesterol esterification rate (P < 0.001, n = 4), and 7) fecal bile acid excretion (P < 0.001, n = 8).These results support the hypothesis that small pre-β-HDL generated in plasma readily cross endothelium into tissue fluid, and thereby promote efflux of UC from peripheral cells. After delivery to the liver, peripheral cholesterol appears to be utilized more for bile acid synthesis than for biliary cholesterol secretion in humans.

Objective There are no globally agreed on strategies on early detection and first response management of postpartum haemorrhage (PPH) during and after caesarean birth. Our study aimed to develop an international expert’s consensus on evidence-based approaches for early detection and obstetric first response management of PPH intraoperatively and postoperatively in caesarean birth.Design Systematic review and three-stage modified Delphi expert consensus.Setting International.Population Panel of 22 global experts in PPH with diverse backgrounds, and gender, professional and geographic balance.Outcome measures Agreement or disagreement on strategies for early detection and first response management of PPH at caesarean birth.Results Experts agreed that the same PPH definition should apply to both vaginal and caesarean birth. For the intraoperative phase, the experts agreed that early detection should be accomplished via quantitative blood loss measurement, complemented by monitoring the woman’s haemodynamic status; and that first response should be triggered once the woman loses at least 500 mL of blood with continued bleeding or when she exhibits clinical signs of haemodynamic instability, whichever occurs first. For the first response, experts agreed on immediate administration of uterotonics and tranexamic acid, examination to determine aetiology and rapid initiation of cause-specific responses. In the postoperative phase, the experts agreed that caesarean birth-related PPH should be detected primarily via frequently monitoring the woman’s haemodynamic status and clinical signs and symptoms of internal bleeding, supplemented by cumulative blood loss assessment performed quantitatively or by visual estimation. Postoperative first response was determined to require an individualised approach.Conclusion These agreed on proposed approaches could help improve the detection of PPH in the intraoperative and postoperative phases of caesarean birth and the first response management of intraoperative PPH. Determining how best to implement these strategies is a critical next step.

Wildlife-human relations in the United States are predominantly influenced by Euro-American sociocultural dynamics and (neo)colonial legacies. Humans dominate nonhuman animals through violence, suffering, and death. Wildlife management as a practice is becoming increasingly criticized. Disagreement emerges from epistemological and ontological foundations and remains contentious in theory and practice. Environmental education reinforces the subjugation of nonhumans and particular individuals that are governed by human decision-making, and power assemblages. However, public values have shifted to a mutualism orientation where management practices are challenged by shifting moral standards of society that value the intrinsic rights, welfare, and agency of individual beings. We present two related case studies that showcase posthuman pedagogy and illustrate how 'real-world' field experiences can shape students' ontologies and cosmologies. This work draws from the first author's fieldwork on salmon-sea lion-human relations in the Columbia River Basin of the Pacific Northwest US. This includes over 120 semi-structured interviews, two deployments of the Vertically Integrated Project (VIP) model, participant observation, and archival data. We focus on four specific fieldwork moments captured by student reflection. Posthuman pedagogy allows educators and scholars to rest with the material relations that dictate the lives of nonhuman participants and provides pragmatic openings for more-than-human worlds.

Abstract Developing an intervention that results in virologic control following discontinuation of antiretroviral therapy (ART) is a major objective of HIV-1 cure research. In this study, we investigated the therapeutic efficacy of a vaccine consisting of adenovirus serotype 26 (Ad26) and modified vaccinia Ankara (MVA) with or without an SIV Envelope (Env) gp140 protein with alum adjuvant in combination with the TLR7 agonist vesatolimod (GS-9620) in 36 ART-suppressed, SIVmac251-infected rhesus macaques. Ad26/MVA therapeutic vaccination led to robust humoral and cellular immune responses, and the Env protein boost increased antibody responses. Following discontinuation of ART, virologic control was observed in 5/12 animals in each vaccine group, compared with 0/12 animals in the sham control group. These data demonstrate therapeutic efficacy of Ad26/MVA vaccination with vesatolimod but no clear additional benefit of adding an Env protein boost. SIV-specific cellular immune responses correlated with virologic control. Our findings show partial efficacy of therapeutic vaccination following ART discontinuation in SIV-infected rhesus macaques.

ABSTRACT HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in human V2-apex bNAb heavy-chain precursor-expressing knock-in mice and as chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) in rhesus macaques (RMs). Trimer immunization of knock-in mice induced V2-directed NAbs, indicating activation of V2-apex bNAb precursor-expressing mouse B cells. SCIV infection of RMs elicited high-titer viremia, potent autologous tier 2 neutralizing antibodies, and rapid sequence escape in the canonical V2-apex epitope. Six of seven animals also developed low-titer heterologous plasma breadth that mapped to the V2-apex. Antibody cloning from two of these animals identified multiple expanded lineages with long heavy chain third complementarity determining regions that cross-neutralized as many as 7 of 19 primary HIV-1 strains, but with low potency. Negative stain electron microscopy (NSEM) of members of the two most cross-reactive lineages confirmed V2 targeting but identified an angle of approach distinct from prototypical V2-apex bNAbs, with antibody binding either requiring or inducing an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. IMPORTANCE An effective HIV-1 vaccination strategy will need to stimulate rare precursor B cells of multiple bNAb lineages and affinity mature them along desired pathways. Here, we searched for V2-apex germ line-targeting Envs among a large set of diverse primate lentiviruses and identified minimally modified versions of one chimpanzee SIV Env that bound several human V2-apex bNAb precursors and stimulated one of these in a V2-apex bNAb precursor-expressing knock-in mouse. We also generated chimeric simian-chimpanzee immunodeficiency viruses and showed that they elicit low-titer V2-directed heterologous plasma breadth in six of seven infected rhesus macaques. Characterization of this antibody response identified a new class of weakly cross-reactive neutralizing antibodies that target the V2-apex, but only in occluded-open Env trimers. The existence of this cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design.

Purpose: Gun violence is a serious public health crisis in the United States, with firearm-related violence accounting for as many deaths annually as traffic accidents. Gunshot wounds cause an array of musculoskeletal injuries, especially in the extremities, making them an important consideration for orthopedic trauma providers. Recently, there has been a decrease in gun violence mortality but an increase in gun violence incidence. This has coincided with high economic costs secondary to non-fatal gunshot wound treatment. Results: This review highlights the ramifications of gun violence, the financial instability it causes, its contribution to the closure of orthopedic trauma centers, and its disproportionate effects on racial minorities and rural populations due to trauma care inaccessibility. Trauma centers are reimbursed at low rates for treatment of orthopedic injuries caused by gunshot wounds, resulting in the loss of millions of dollars annually. Economic pressure has forced the closure of many orthopedic trauma centers, ultimately limiting access of minority groups to trauma care given the disparately high gun violence incidence in these communities. Additionally, rural Americans face severe access inequities, and due to a lack of appropriate research funding, the effects of gun violence on rural communities are not fully understood. Conclusion: It is imperative that orthopedic surgeons advocate for increased funding to facilitate research of gun violence through the lens of public health. Funding for orthopedic trauma centers should be increased to redirect hospital system resources to better treat high risk patient populations, improve rural access to appropriate orthopedic trauma care, and mitigate gun violence incidence.

Despite the rapid creation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines, the precise correlates of immunity against severe Coronavirus Disease 2019 (COVID-19) are still unknown. Neutralizing antibodies represent a robust surrogate of protection in early Phase III studies, but vaccines provide protection prior to the evolution of neutralization, vaccines provide protection against variants that evade neutralization, and vaccines continue to provide protection against disease severity in the setting of waning neutralizing titers. Thus, in this study, using an Ad26.CoV2.S dose-down approach in nonhuman primates (NHPs), the role of neutralization, Fc effector function, and T-cell immunity were collectively probed against infection as well as against viral control. While dosing-down minimally impacted neutralizing and binding antibody titers, Fc receptor binding and functional antibody levels were induced in a highly dose-dependent manner. Neutralizing antibody and Fc receptor binding titers, but minimally T cells, were linked to the prevention of transmission. Conversely, Fc receptor binding/function and T cells were linked to antiviral control, with a minimal role for neutralization. These data point to dichotomous roles of neutralization and T-cell function in protection against transmission and disease severity and a continuous role for Fc effector function as a correlate of immunity key to halting and controlling SARS-CoV-2 and emerging variants.

New Findings What is the central question of this study? To what extent cardiorespiratory fitness is impaired in patients with abdominal aortic aneurysmal (AAA) disease and corresponding implications for postoperative survival requires further investigation. What is the main finding and its importance? Cardiorespiratory fitness is impaired in patients with AAA disease. Patients with peak oxygen uptake of