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Background The optimal thresholds for the initiation of invasive ventilation in patients with hypoxemic respiratory failure are unknown. Using the saturation-to-inspired oxygen ratio (SF), we compared lower versus higher hypoxemia severity thresholds for initiating invasive ventilation. Methods This target trial emulation included patients from the Medical Information Mart for Intensive Care (MIMIC-IV, 2008–2019) and the Amsterdam University Medical Centers (AmsterdamUMCdb, 2003–2016) databases admitted to intensive care and receiving inspired oxygen fraction ≥ 0.4 via non-rebreather mask, noninvasive ventilation, or high-flow nasal cannula. We compared the effect of using invasive ventilation initiation thresholds of SF Results We studied 3,357 patients in the primary analysis. For invasive ventilation initiation thresholds SF Conclusion Initiating invasive ventilation at lower hypoxemia severity will increase the rate of invasive ventilation, but this can either increase or decrease the expected mortality, with the direction of effect likely depending on baseline mortality risk and clinical context.

Introduction Leadership development is a cornerstone aspect of military medical education. Operation Bushmaster, a medical field practicum (MFP) conducted by the USU, tests fourth-year medical students’ clinical skills and leadership acumen in an operational environment. No studies have examined students’ perceptions of their own leadership development during this MFP. Therefore, this study explored leadership development from the students’ perspectives. Materials and Methods Using a qualitative phenomenological design, we analyzed the reflection papers of 166 military medical students who participated in Operation Bushmaster during the fall of 2021. Our research team coded and categorized the data. Once defined, these categories served as the themes in this study. Results Three central themes were expressed: (1) the importance of direct and decisive communication, (2) unit cohesion and interpersonal relationships enhance the team’s ability to adapt, and (3) followership quality determines leadership outcomes. The students’ leadership ability was maximized by established relationships within their unit and well-practiced communication, and a decreased propensity for followership negatively affected leadership. Overall, Operation Bushmaster increased students’ appreciation of the importance of leadership development and overall enhanced their leadership outlook as a future military medical officer. Conclusions This study provided an introspective vantage from military medical students pertaining to their own leadership development, as participants described how the challenging environment of a military MFP challenged them to hone and develop their leadership skills. As a result, the participants gained a greater appreciation of continued leadership development and realization of their future roles and responsibilities within the military health care system.

Introduction Developing physicians as leaders has gained attention across the United States. Undergraduate medical education (UME) and graduate medical education (GME) leader development programs have increased. During postgraduate years (PGY), graduates bring their leadership education to the bedside; however, associations between leader performance in medical school and GME is largely unknown. It is important to find experiences that can assess leader performance that may be useful to predict future performance. The purpose of this study was to determine if (1) there is a correlation between leader performance during the fourth year of medical school versus leader performance in PGY1 and 3, and (2) leader performance during the fourth year of medical school is associated with military leadership performance in PGY1 and 3s while taking previous academic performance markers into account. Methods This study examined overall leader performance of learners (classes of 2016-2018) during the fourth year of medical school and their graduate leader performance post-medical school. Leader performance was assessed by faculty during a medical field practicum (UME leader performance) and graduate leader performance was assessed by program directors at the end of PGY1 (N = 297; 58.3%) and 3 (N = 142; 28.1%). Pearson correlation analysis examined relationships among UME leader performance and between the PGY leader performance items. In addition, stepwise multiple linear regression analyses were conducted to examine the relationship between leader performance at the end of medical school with military leadership performance in PGY1 and 3, while taking into account the academic performance markers. Results Pearson correlation analyses revealed that the UME leader performance was correlated with 3 of 10 variables at PGY1, and was correlated at PGY3 with 10 out of 10 variables. Results of the stepwise multiple linear regression analysis indicated that leader performance during the fourth year of medical school explained an additional 3.5% of the variance of PGY1 leader performance after controlling for the previous academic performance markers (MCAT total score, USMLE Step 1 score and Step 2 CK score). In contrast, leader performance during the fourth year of medical school alone accounted for an additional 10.9% of the variance of PGY3 leader performance above and beyond the set of academic performance markers. Overall, UME leader performance has more predictive power in PGY leader performance than the MCAT or USMLE Step exams. Conclusions The findings of this study indicate that a positive relationship exists between leader performance at the end of medical school and leader performance in PGY1 and 3 years of residency. These correlations were stronger in PGY3 compared to PGY1. During PGY1, learners may be more focused on being a physician and an effective team member compared to PGY3 where they have a deeper understanding of their roles and responsibilities and can take on more leadership roles. Additionally, this study also found that MCAT and USMLE Step exams performance was not predictive of PGY1 or PGY3 leader performance. These findings provide evidence of the power of continued leader development in UME and beyond.

Perioperative cefazolin administration for total joint arthroplasty is a first-line antibiotic recommended by the American Academy of Orthopaedic Surgeons (AAOS) guidelines for the prevention of periprosthetic joint infections (PJIs). We aim to analyze the clinical viability of giving patients with a documented penicillin allergy (PA) a perioperative full-strength cefazolin "test dose" under anesthesia.This is a retrospective chart review of 2,451 total joint arthroplasties from a high-volume arthroplasty orthopaedic surgeon over a 5-year period from January 2013 through December 2017. This surgeon routinely gave patients with a documented PA a full-strength cefazolin test dose while under anesthesia instead of administrating a second-line antibiotic. The primary outcomes examined were allergic reaction and postoperative infection.Cefazolin was given to 87.1% of all patients (1,990) and 46.0% of patients with a PA (143). The total rate of allergic reactions among all patients was 0.5% (11). Only one patient with a documented PA who received cefazolin had an allergic reaction. The reaction was not severe and did not require any additional treatment. In patients who had no reported allergies and received cefazolin, 0.3% (6) had an allergic reaction. There was no statistically significant difference in the rate of allergic reaction when comparing patients with and without a PA (P = 0.95). Patients receiving cefazolin had an overall PJI rate of 2.9% (57) versus those patients receiving antibiotics other than cefazolin who sustained a 5.5% PJI rate (16), which was statistically significant (P = 0.02).This study found that utilization of a full-strength test dose of cefazolin in patients with a documented PA is a feasible, safe, and effective way of increasing the rate of cefazolin administration and thus mitigating the risk of PJIs.

Two novel dinuclear Pt(ii) complexes featuring 8-hydroxyquinoline bridges were synthesized and found to have photophysical properties dominated by ligand-centered transitions mirroring that of a mononuclear model system, [Pt(8HQ)2].

African elephants (Loxodonta africana) are increasingly exposed to high levels of human disturbance and are threatened by poaching and human–elephant conflict. As anthropogenic pressures continue to increase, both inside and outside protected areas, understanding elephant behavioural responses to human activity is required for future conservation management. Here, we use bycatch data from camera trap surveys to provide inferences on elephant habitat use and temporal activity in Kasungu National Park (KNP), Malawi. The KNP elephant population has declined by ~ 95% since the late 1970s, primarily because of intensive poaching, and information on elephant ecology and behaviour can assist in the species’ recovery. Using occupancy modelling, we show that proximity to water is the primary driver of elephant habitat use in KNP, with sites closer to water having a positive effect on elephant site use. Our occupancy results suggest that elephants do not avoid sites of higher human activity, while results from temporal activity models show that elephants avoid peak times of human activity and exhibit primarily nocturnal behaviour when using the KNP road network. As key park infrastructure is located near permanent water sources, elephant spatiotemporal behaviour may represent a trade-off between resource utilisation and anthropogenic-risk factors, with temporal partitioning used to reduce encounter rates. Increased law enforcement activity around permanent water sources could help to protect the KNP elephant population during the dry season. Our findings highlight that camera trap bycatch data can be a useful tool for the conservation management of threatened species beyond the initial scope of research.

Musculoskeletal injuries have been reported to be the main contributor to the interruption or dismissal of a horse’s athletic career. The muscles are responsible for the production of forces involved in movement, yet the muscles are often overlooked with regards to pre/rehabilitation. The use of massage therapy as part of a training programme is becoming increasingly popular. The beneficial effects of massage have been widely researched, though much of the research is on the immediate effects, and consistency between studies is lacking. This study was a preliminary investigation into the effects of a short-term massage programme on the gait parameters of riding school horses. 15 clinically sound riding school horses of different breed, age and height were used in a controlled, blind study. The horses were divided in to three groups of five ensuring a mixture of height, breed and age. Group Massage received a 10 min massage at each side on the proximal hindlimb, once a week for three weeks. Group Sham received 10 min groom at each side on the proximal hindlimb, once a week for three weeks; and the Control Group has received no treatment. Gait analysis was conducted on days 1 and 28. In walk, a significant improvement in stride length symmetry index (SI) (P=0.043) and protraction SI (P=0.0043) was found for the Massage Group, with hock flexion SI significantly better for the Massage Group at day 28 (P=0.03). At trot and canter, hock flexion SI was improved in Group Massage (P=0.003 and P=0.024, respectively). A short-term massage programme to the proximal hindlimb improved gait symmetry, particularly hock flexion SI, within riding school horses. An appropriate dosage level for particular results needs to be determined in order to effectively utilise massage within a training programme. Further studies analysing kinetic parameters alongside kinematic parameters will enable further conclusions to be drawn.

Basic ecological knowledge on African small carnivores and how they interact with the wider carnivore guild are lacking for many species. The caracal (Caracal caracal) has a widespread distribution across Africa, yet there is a paucity of information on this species outside of savannah and agricultural landscapes. Using camera trap data from Kasungu National Park, Malawi, we provide novel information on caracal habitat use in a miombo woodland and compare the spatiotemporal dynamics between caracal and members of the large carnivore guild (leopard, Panthera pardus and spotted hyaena, Crocuta crocuta). We found that caracal were more likely to use sites with higher grass cover and further away from permanent water sources. Caracal site use increased in areas with lower spotted hyaena abundance and caracal exhibited different temporal activity patterns to spotted hyaena. In contrast, caracal did not exhibit spatial or temporal avoidance of leopard at the scale investigated here. However, the probability of detecting caracal at sites of higher leopard abundance was significantly lower, suggesting possible behavioural mechanisms to avoid interaction. Our study provides an insight into caracal ecology in a miombo woodland and improves our understanding of community dynamics between a lesser-studied small carnivore and the large carnivore guild.

There is wide variation in mortality among patients hospitalized with COVID-19. Whether this is related to patient or hospital factors is unknown.To compare the risk of mortality for patients hospitalized with COVID-19 and to determine whether the majority of that variation was explained by differences in patient characteristics across sites.An international multicenter cohort study of hospitalized adults with laboratory-confirmed COVID-19 enrolled from 10 hospitals in Ontario, Canada and 8 hospitals in Copenhagen, Denmark between January 1, 2020 and November 11, 2020.Inpatient mortality. We used a multivariable multilevel regression model to compare the in-hospital mortality risk across hospitals and quantify the variation attributable to patient-level factors.There were 1364 adults hospitalized with COVID-19 in Ontario (n = 1149) and in Denmark (n = 215). In Ontario, the absolute risk of in-hospital mortality ranged from 12.0% to 39.8% across hospitals. Ninety-eight percent of the variation in mortality in Ontario was explained by differences in the characteristics of the patients. In Denmark, the absolute risk of inpatients ranged from 13.8% to 20.6%. One hundred percent of the variation in mortality in Denmark was explained by differences in the characteristics of the inpatients.There was wide variation in inpatient COVID-19 mortality across hospitals, which was largely explained by patient-level factors, such as age and severity of presenting illness. However, hospital-level factors that could have affected care, including resource availability and capacity, were not taken into account. These findings highlight potential limitations in comparing crude mortality rates across hospitals for the purposes of reporting on the quality of care.

ObjectiveTo estimate costs, quality-adjusted life-years, and the value of undertaking a future randomized controlled trial for different oxygenation thresholds used to initiate invasive ventilation in hypoxemic respiratory failure.DesignModel-based cost-utility estimation with individual-level simulation and value-of-information analysis.SettingCritical care units.ParticipantsAdults admitted to critical care receiving non-invasive oxygen.InterventionsWe compared four strategies: initiation of invasive ventilation at thresholds of saturation-to-inspired oxygen fraction ratio (SF) < 110, < 98, or < 88, and usual care.Main resultsAn invasive ventilation initiation threshold of SF < 110, compared to usual care, resulted in more predicted invasive ventilation (62% vs 31%), hospital survival (78.4% vs 75.5%), quality-adjusted life years (QALYs) (8.48 vs 8.34), and lifetime costs (86,700 Canadian dollars (CAD) vs 75,600 CAD). Among the four strategies, threshold SF < 110 had the highest expected net monetary benefit (761,000 CAD), but there was significant uncertainty, because all four strategies had similar probability (range: 23.5% to 27.5%) of having the best net monetary benefit. The expected value to society over the next 10 years of a 400-person randomized trial of oxygenation thresholds was 4.27 billion CAD, and remained high (2.64 billion CAD) in a scenario analysis considering a hypothetical threshold that resulted in less invasive ventilation and similar survival compared to usual care.ConclusionThe preferred threshold to initiate invasive ventilation in hypoxemic respiratory failure is uncertain. It would be highly valuable to society to identify thresholds that, in comparison to usual care, either improve survival or reduce invasive ventilation without reducing survival.Key pointsQuestionWhat are the costs and quality-adjusted life-years associated with different oxygenation thresholds for initiating invasive ventilation, and what is the expected value to society of a randomized controlled trial?FindingsIn this health economic evaluation comparing usual care to three different thresholds for initiating invasive ventilation in hypoxemic respiratory failure based on the saturation-to-inspired oxygen fraction ratio (SF), we found that threshold SF < 110 had the highest expected quality-adjusted life-years and net monetary benefit, despite increased predicted invasive ventilation use. However, there was significant residual uncertainty, and the expected value to society of a 400-person randomized trial to compare thresholds for initiating invasive ventilation was greater than 2.5 billion Canadian dollars.MeaningThe preferred threshold to initiate invasive ventilation in hypoxemic respiratory failure is uncertain and further study would be valuable to society.Social media summaryWhen should we intubate and start invasive ventilation for people with hypoxemic respiratory failure? Our health economic evaluation shows that the preferred threshold is uncertain, but that a clinical trial to determine such a threshold would be immensely valuable to patients and society

IntroductionRecent advancements in big data analytics and the formation of large-scale clinical data repositories provide a unique opportunity to determine the current state of pediatric hearing health care for children who have developmental disabilities. Before answering unresolved questions about diagnostic practice, it is paramount to determine a standard and reliable method for identifying children who have reduced hearing because clinical management is affected by hearing status. The purpose of this study was to compare 5 different methods for identifying cases of reduced hearing from pure-tone thresholds based on developmental disability status.MethodsUsing retrospective clinical data from 100,960 children (0–18 years), hearing status was determined for a total of 226,580 encounters from three clinical sites. 9% of the children had a diagnosis of intellectual disability, autism spectrum disorder, Down syndrome, or cerebral palsy.ResultsResults revealed that encounters from children who have developmental disabilities were more likely to have insufficient data to allow hearing status to be determined. Moreover, methods with higher data demands (i.e., number of thresholds and ear-specific thresholds) resulted in fewer classifiable encounters. The average child age when hearing status was classified for the first time was older for children who have developmental disabilities than for children in the comparison group. Allowing thresholds to build up over multiple test sessions did result in more children who have developmental disabilities being classified than for single-encounter methods, but a meaningful decrease in child age at the time of classification was not seen for this strategy. Compared to the comparison group, children who have developmental disabilities were more likely to have reduced hearing that was stable over time, yet their hearing status was determined at older ages.DiscussionResults provide key guidance to researchers for how to determine hearing status in children for big data applications using electronic health records. Furthermore, several assessment disparities are spotlighted for children who have developmental disabilities that warrant further investigation.

Introduction: Chediak-Higashi syndrome (CHS) is rare autosomal recessive disorder caused by bi-allelic variants in the Lysosomal Trafficking Regulator (LYST) gene. Diagnosis is established by the detection of pathogenic variants in LYST in combination with clinical evidence of disease. Conventional molecular genetic testing of LYST by genomic DNA (gDNA) Sanger sequencing detects the majority of pathogenic variants, but some remain undetected for several individuals clinically diagnosed with CHS. In this study, cDNA Sanger sequencing was pursued as a complementary method to identify variant alleles that are undetected by gDNA Sanger sequencing and to increase molecular diagnostic yield.Methods: Six unrelated individuals with CHS were clinically evaluated and included in this study. gDNA Sanger sequencing and cDNA Sanger sequencing were performed to identify pathogenic LYST variants.Results: Ten novel LYST alleles were identified, including eight nonsense or frameshift variants and two in-frame deletions. Six of these were identified by conventional gDNA Sanger sequencing; cDNA Sanger sequencing was required to identify the remaining variant alleles.Conclusion: By utilizing cDNA sequencing as a complementary technique to identify LYST variants, a complete molecular diagnosis was obtained for all six CHS patients. In this small CHS cohort, the molecular diagnostic yield was increased, and canonical splice site variants identified from gDNA Sanger sequencing were validated by cDNA sequencing. The identification of novel LYST alleles will aid in diagnosing patients and these molecular diagnoses will also lead to genetic counseling, access to services and treatments and clinical trials in the future.

The global demand for renewable energy has placed added pressure on communities to increase hydropower development in rivers. While hydropower provides the opportunity for sustainable electricity generation, it is not without environmental impacts and adverse effects to river processes. Increased understanding of the characteristics of hydropeaking flow regimes and the associated interactions and impacts on stream functions and native biota will help to facilitate improved mitigation measures downstream of hydropower facilities. This presentation provides an overview of several studies that quantify the characteristics of hydropeaks, assess hydropeak attenuation, and evaluate impacts of hydropeaking regimes on benthic communities and native riverine biota. Building on these studies and examples of hydropeaking impacts on native aquatic species in California, USA, the presentation concludes with recommendations for improved hydropeaking flow management via a Functional Flows approach.

Funder: Nottingham Trent University; Id: http://dx.doi.org/10.13039/100010016, Funder: People's Trust for Endangered Species; Id: http://dx.doi.org/10.13039/100018690, In light of rapidly expanding road networks worldwide, there is increasing global awareness of the growing amount of mammalian roadkill. However, the ways in which road mortality affects the population dynamics of different species remains largely unclear. We aimed to categorise the demographic parameters in mammalian populations around the world that are directly or indirectly affected by road mortality, as well as identify the most effective study designs for quantifying population-level consequences of road mortality. We conducted a comprehensive systematic review to synthesise literature published between 2000 and 2021 and out of 11,238 unique studies returned, 83 studies were retained comprising 69 mammalian species and 150 populations. A bias towards research-intensive countries and larger mammals was apparent. Although searches were conducted in five languages, all studies meeting the inclusion criteria were in English. Relatively few studies (13.3%) provided relevant demographic context to roadkill figures, hampering understanding of the impacts on population persistence. We categorised five direct demographic parameters affected by road mortality: sex- and age-biased mortality, the percentage of a population killed on roads per year (values up to 50% were reported), the contribution of roadkill to total mortality rates (up to 80%), and roadkill during inter-patch or long-distance movements. Female-biased mortality may be more prevalent than previously recognised and is likely to be critical to population dynamics. Roadkill was the greatest source of mortality for 28% of studied populations and both additive and compensatory mechanisms to roadkill were found to occur, bringing varied challenges to conservation around roads. In addition, intra-specific population differences in demographic effects of road mortality were common. This highlights that the relative importance of road mortality is likely to be context specific as the road configuration and habitat quality surrounding a population can vary. Road ecology studies that collect data on key life parameters, such as age/stage/sex-specific survival and dispersal success, and that use a combination of methods are critical in understanding long-term impacts. Quantifying the demographic impacts of road mortality is an important yet complex consideration for proactive road management.

Rationale: Invasive ventilation is a significant event for patients with respiratory failure. Physiologic thresholds standardize the use of invasive ventilation in clinical trials, but it is unknown whether thresholds prompt invasive ventilation in clinical practice. Objectives: To measure, in patients with hypoxemic respiratory failure, the probability of invasive ventilation within 3 hours after meeting physiologic thresholds. Methods: We studied patients admitted to intensive care receiving FiO2 of 0.4 or more via nonrebreather mask, noninvasive positive pressure ventilation, or high-flow nasal cannula, using data from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019) and the Amsterdam University Medical Centers Database (AmsterdamUMCdb) (2003-2016). We evaluated 17 thresholds, including the ratio of arterial to inspired oxygen, the ratio of saturation to inspired oxygen ratio, composite scores, and criteria from randomized trials. We report the probability of invasive ventilation within 3 hours of meeting each threshold and its association with covariates using odds ratios (ORs) and 95% credible intervals (CrIs). Measurements and Main Results: We studied 4,726 patients (3,365 from MIMIC, 1,361 from AmsterdamUMCdb). Invasive ventilation occurred in 28% (1,320). In MIMIC, the highest probability of invasive ventilation within 3 hours of meeting a threshold was 20%, after meeting prespecified neurologic or respiratory criteria while on vasopressors, and 19%, after a ratio of arterial to inspired oxygen of

SummaryAnimals moving through landscapes need to strike a balance between finding sufficient resources to grow and reproduce while minimizing encounters with predators1,2. Because encounter rates are determined by the average distance over which directed motion persists1,3–5, this trade-off should be apparent in individuals’ movement. Using GPS data from 1,396 individuals across 62 species of terrestrial mammals, we show how predators maintained directed motion ~7 times longer than for similarly-sized prey, revealing how prey species must trade off search efficiency against predator encounter rates. Individual search strategies were also modulated by resource abundance, with prey species forced to risk higher predator encounter rates when resources were scarce. These findings highlight the interplay between encounter rates and resource availability in shaping broad patterns mammalian movement strategies.

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Connecting rivers, people, & science through immersive field-based education

The consequences of poor breed management and inbreeding can range from gradual declines in individual productivity to more serious fertility and mortality concerns. However, many small and closed groups, as well as larger unmanaged populations, are plagued by genetic regression, often due to a dearth in breeding support tools which are accessible and easy to use in supporting decision‐making. To address this, we have developed a population management tool (BCAS, Breed Conservation and Management System) based on individual relatedness assessed using pedigree‐based kinship, which offers breeding recommendations for such populations. Moreover, we demonstrate the success of this tool in 16 years of employment in a closed equine population native to the UK, most notably, the rate of inbreeding reducing from more than 3% per generation, to less than 0.5%, or that attributed to genetic drift, as assessed over the last 16 years of implementation. Furthermore, with adherence to this program, the long‐term impact of poor management has been reversed and the genetic resource within the breed has grown from an effective population size of 20 in 1994 to more than 140 in 2020. The development and availability of our BCAS for breed management and selection establish a new paradigm for the successful maintenance of genetic resources in animal populations., Across the last 16 years, a genetic breed management program has led to the British population of the Cleveland Bay transitioning from an effective population size well below the UN FAO limit of concern of 50, to a stratified breeding system with N e now over 145.

Emerging research suggests an association between exposure to violence, specifically indirect forms, and substance use among youth involved in the child welfare (CW) system. However, this has only been recently and tentatively explored. This study examined the associations among various forms of indirect violence exposure and substance use among subgroups of youth involved in the CW system. The analytic sample consisted of participants (aged 11 years or older) in the baseline year of the second National Survey of Child and Adolescent Well-Being (2008–2012), including youth and their caregivers. Latent class analysis was used to examine associations among distinct forms of indirect violence exposure and substance use and the potential identification of unique at-risk groups. Models for the overall sample suggested two classes of at-risk youth, with the higher-risk class having higher probabilities of alcohol, marijuana, and hard drug use, which coincided with higher probabilities of exposure to arrests, stealing, drug deals, and weapon use. However, stratified models suggested unique results for youth aged 13–14 and 15–17, suggesting that the confluence of these risks appears to differ developmentally. Prevention and intervention services for CW-involved youth should assess and address violence exposure types among youth as a potential opportunity to mitigate substance use and subsequent high-risk behavior.

Colletotrichum lentis is an important pathogen of lentils in Canada causing the disease anthracnose. Fungicide applications are an important tool for the control of this disease and, historically, ...

Military and law enforcement breachers are exposed to many low-level blasts during their training and occupational experiences in which they detonate explosives to force entry into secured structures. There is a concern that exposure to these repetitive blast events in career breachers could result in cumulative neurological effects. This study aimed to determine concentrations of neurofilament light (NF-L), tau, and amyloid-beta 42 (Aβ42) in serum and in neuronal-derived extracellular vesicles (EVs) in an experienced breacher population, and to examine biomarker associations with neurobehavioral symptoms. Thirty-four participants enrolled in the study: 20 experienced breachers and 14 matched military or civilian law enforcement controls. EV tau concentrations were significantly elevated in experienced breachers (0.3301 ± 0.5225) compared to controls (−0.4279 ± 0.7557; F = 10.43, p = 0.003). No statistically significant changes were observed in EV levels of NF-L or Aβ42 or in serum levels of NF-L, tau, or Aβ42 (p’s > 0.05). Elevated EV tau concentrations correlated with increased Neurobehavioral Symptom Inventory (NSI) score in experienced breachers (r = 0.596, p = 0.015) and predicted higher NSI score (F(1,14) = 7.702, p = 0.015, R2 = 0.355). These findings show that neuronal-derived EV concentrations of tau are significantly elevated and associated with neurobehavioral symptoms in this sample of experienced breachers who have a history of many low-level blast exposures.

ImportanceDifferential use of therapies for respiratory failure according to patient race/ethnicity may represent health inequity and could impact patient survival.ObjectiveMeasure the association between patient race/ethnicity and the use of invasive ventilation, and the impact of any association on survival.DesignRetrospective cohort analysis using a Bayesian multistate model that adjusted for baseline covariates and time-varying severity.SettingMulticenter study using the Medical Information Mart for Intensive Care IV (MIMIC-IV) and Phillips eICU (eICU) databases from the USA.ParticipantsNon-intubated adults receiving oxygen within the first 24 hours of ICU admission.ExposurePatient race/ethnicity (Asian, Black, Hispanic, white).Main outcomes and measuresPrimary output was the cause-specific hazard ratio (HR) of invasive ventilation for patient race/ethnicity. Secondary output was change in 28-day survival mediated by differences in invasive ventilation rate. We reported posterior means and 95% credible intervals (CrI).ResultsWe studied 38,263 patients, 52% (20,033) from MIMIC-IV and 48% (18,230) from eICU, 2% Asian (892), 11% Black (4,289), 5% Hispanic (1,964), and 81% white (31,923). Invasive ventilation occurred in 3,511 (9.2%), and 2,869 (7.5%) died. The rate of invasive ventilation was lower in Asian (HR 0.82, CrI 0.70 to 0.95), Black (HR 0.78, CrI 0.71 to 0.86), and Hispanic (HR 0.70, CrI 0.61 to 0.79) patients as compared to white patients. For the average patient, lower rates of invasive ventilation did not mediate differences in survival. For a reference patient with inspired oxygen (FiO2) varied from 0.5 to 1.0, the change in survival mediated by lower rates of invasive ventilation ranged from probable benefit (probability 0.82 for Asian patients, 0.91 for Black patients, and 0.93 for Hispanic patients) at FiO2 0.5 to probable harm (probability 0.87 for Asian patients, 0.92 for Black patients, and 0.97 for Hispanic patients) at FiO2 1.0, although the mean absolute changes in mortality were all less than 1.5%.ConclusionsAsian, Black, and Hispanic patients had a lower rate of invasive ventilation than white patients. The changes in 28-day survival mediated by this difference ranged from slight benefit at lower inspired oxygen fractions to slight harm at inspired oxygen fraction of 1.0, and there was no difference in survival for the average patient.Key PointsQuestionWhat is the association between patient race/ethnicity and the use of invasive ventilation in hypoxemic respiratory failure, and what is the impact of any differences on survival?FindingsWe studied 38,263 patients from two US databases, who were 2% Asian (892), 11% Black (4,289), 5% Hispanic (1,964), and 81% white (31,118). Invasive ventilation occurred in 3,511 (9.2%), and 2,869 (7.5%) died. The hazard ratio (HR) for invasive ventilation was lower in Asian (HR 0.82, CrI 0.70 to 0.95), Black (HR 0.78, CrI 0.71 to 0.86), and Hispanic (HR 0.70, CrI 0.61 to 0.79) patients as compared to white patients. For the average patient, race/ethnicity differences in invasive ventilation rates did not mediate differences in 28-day survival. For the reference patient, at inspired oxygen fractions up to 0.9, lower invasive ventilation rates mediated a modest survival benefit, whereas at inspired oxygen fraction of 1.0, the lower invasive ventilation rates mediated a modest survival decrease, although the absolute changes were all less than 1.5%.MeaningAsian, Black, and Hispanic patients had a lower rate of invasive ventilation than white patients. Although this difference had no impact on 28-day survival for the average patient, the change in survival mediated by lower rates of invasive ventilation could range from slight benefit at lower inspired oxygen fractions to slight harm at inspired oxygen fraction of 1.0.

While water resource managers and river scientists recognize the inherent interconnections among hydrology, river structure, biophysical processes and ecological patterns, management of environmental flows still pays insufficient attention to the ecological and geomorphological functionality of particular aspects of the flow regime. Implementation of more natural flow regimes has improved habitat conditions for native species in many moderately impaired rivers but mimicking a natural flow regime in heavily modified riverine landscapes cannot be expected to yield successful ecological outcomes unless such flows trigger functional processes. For example, the restoration of peak flows may not regenerate habitats if the river is starved of sediment or if the river channel is highly confined. High biodiversity is supported when variable flow regimes interact with spatially variable (heterogeneous) river channel and floodplain forms. In contrast, as rivers become homogeneous, biodiversity decreases when these dynamic spatiotemporal interactions are limited by flow alterations, blocked by channel levees, or perturbed by sediment deficit or surplus. Thus, the design of a more natural environmental flow regime without consideration of the implications for sediment transport and implicit recognition of channel–floodplain geomorphology is likely to have limited success in river management and restoration. To enhance the functionality of environmental flows, considerations of physical, biogeochemical, and ecological processes and the inherent heterogeneity of the riverine landscape must be included. A Functional Flows approach enhances the benefits from limited environmental flow allocations by focusing on the ecological and geomorphological functionality of particular aspects of the flow regime, considering geomorphic context, and emphasizing spatiotemporal diversity at key locations in the riverscape, such as adjacent floodplains or tributary junctions. In this paper, we outline and illustrate the concept of Functional Flows using a flow-chain model and provide two case study examples from Australia and the United States, where improvements in channel habitat and reconnection with the floodplain help to achieve the desired functionality of environmental flows.

Openness in research can lead to greater reproducibility, an accelerated pace of discovery, and decreased redundancy of effort. In addition, open research ensures equitable access to knowledge and the ability for any community to assess, interrogate, and build upon prior work. In order for research to succeed, openness and reproducibility are required. In turn, this requires open infrastructure and distributed access; but few institutions can provide all of these services alone. Providing a trustworthy network for perpetual availability of research data is critical to ensuring reproducibility, transparency, and ongoing inquiry. There is increased attention on the importance of open research and data sharing, leading to a proliferation of platforms to store data, materials, etc. These platforms exist in a fragmented environment that lacks technical integration and coordination with local library expertise and services, hampering curation and long-term stewardship. For example, the open source OSF enables researchers to directly create and manage research projects and integrates with other tools researchers use (Google Drive, Dropbox, Box, etc.), but lacks the ability to archive that materialle locally at a researcher’s institution. Long-term stewardship and preservation requires multiple copies of data archived in different locations, and creating archives seamlessly would be ideal. COS and IA propose to address the preservation and stewardship challenges by providing open, cooperative infrastructure to ensure long-term access and connection to research data, and by supporting and promoting adoption of open science practices to enhance research reproducibility as well as data sharing and reuse. In this workshop, participants will gain skills to implement reproducible research practices using OSF and other tools, and then curate and preserve research artifacts on Internet Archive. We will further demonstrate the possibilities to preserve such content in local institutional repositories or other distributed networks, uses community-developed standards and protocols.

Over the past 30 years, much has been learned from strategies used around the world to establish and implement environmental flow programs. Approaches vary from highly prescriptive regulatory requirements to largely voluntary programs. These examples have shown that allocating water to the environment does not necessarily constrain human uses and can have benefits for both agriculture and ecosystems. Some efforts attempt to reduce conflict between agriculture and the environment by limiting water allocations spatially, while others attempt to reconcile competing water demands through comprehensive, regional allocation schemes that vary with climate conditions over time. Here we summarize strategies for water allocation planning and implementation that can be used to balance environmental and agricultural water needs. Effective strategies incorporate: a holistic environmental water allocation approach that focuses on protecting overall ecological structure and functions; environmental flow protections at broad spatial and temporal scales; consideration of surface-ground water interactions and the relationships between flow, sediment, temperature, and water quality. From an implementation perspective, approaches that establish a volumetric water budget for the environment based on interannual variation in water availability, integrate across programs in a transparent manner, are broadly inclusive, and incorporate traditional values and perspectives have the highest likelihood of success. Environmental flow strategies that consider technical solutions, establish clear objectives and anticipate how environmental water will be allocated under different water year types, and are sensitive to social issues and concerns will increase certainty in how much water is allocated for agriculture and the environment. Beyond reconciling conflicts between competing demands, emerging technical and institutional approaches to environmental flows can improve resiliency of water management programs to climate change by preventing the over-exploitation of water supplies, enhancing flexibility, and providing a framework for adaptation.

Nature's contribution to people (i.e. ecosystem services) is becoming integral to conservation science and policy, yet our knowledge is restricted to only a few services and taxa. Vultures (family: Accipitridae and Cathartidae), most of which are threatened with extinction, have been touted for delivering regulation and maintenance services via their capacity to rapidly consume organic matter. As such, their appellation as "nature's clean-up crew" has become very popular. However, a comprehensive evaluation of the supporting evidence for such appellation was absent from the published literature. We performed a systematic review and evidence assessment to quantify the global contribution of vultures towards over 20 ecosystem services and disservices. Our analysis determined a critical imbalance in the scope and focus of published research. In contrast to the birds' popularised image as cleaners of the environment, we found only weak evidence to support any regulation and maintenance services for vultures. Moreover, studies on regulation and maintenance disservices were prominent. The only ecosystem services supported by strong evidence were cultural, although even these were evidenced by a limited number of studies. Finally, we unveil major knowledge gaps in the ecosystem service and disservice literature on a taxonomic and spatial scale related to vultures. Our analysis highlights the urgent need to quantify the net contribution of vultures to people.

Response-adaptive randomization is being used in COVID-19 trials, but it is unknown whether outcome rate changes during surges of COVID-19 will lead to bias in trial results. In response-adaptive randomization, allocation ratios are adjusted according to interim analyses to assign more patients to promising interventions. Although it is known that response-adaptive randomization may give biased estimates if outcome rates drift over time, observed mortality fluctuations in the COVID-19 pandemic are more extreme than any previously tested in simulation. We hypothesized that pandemic surges induce bias in trials using response-adaptive randomization, and that adjustment for time will alleviate that bias. Bayesian 4-arm superiority trials with a mortality outcome were simulated to investigate bias in treatment effect, comparing complete and response-adaptive randomization under different pandemic scenarios based on data from New York, Spain, and Italy. Relative bias in the odds ratio associated with treatment ranged from 0.3% to 11% and was largest in trials with a surge and an effective intervention that did not adjust for time. Bias was attenuated by adjustment for time without compromising the false-positive rate. Trials using response-adaptive randomization were more likely to identify effective interventions but were slower to drop ineffective interventions. Even with variation in outcome rates similar to observed pandemic surges, COVID-19 trials using response-adaptive randomization that adjust for time can provide accurate estimates of treatment effects.

ImportanceDiabetes has been reported to be associated with an increased risk of death among patients with COVID-19. However, available studies lack detail on COVID illness severity and measurement of relevant comorbidities.Design, Setting, and ParticipantsWe conducted a multicenter, retrospective cohort study of patients over the age of 18 years who were hospitalized with COVID-19 between January 1, 2020 and November 30, 2020 in Ontario, Canada and Copenhagen, Denmark. Chart abstraction emphasizing co-morbidities and disease severity was performed by trained research personnel. The association between diabetes and death was measured using Poissson regression.Main Outcomes and Measureswithin hospital 30-day risk of death.ResultsOur study included 1018 hospitalized patients with COVID-19 in Ontario and 305 in Denmark, of whom 405 and 75 patients respectively had pre-existing diabetes. In both Ontario and Denmark, patients with diabetes were more likely to be older, have chronic kidney disease, cardiovascular disease, higher troponin levels, and to receive antibiotics compared with adults who did not have diabetes. In Ontario, the crude mortality rate ratio among patients with diabetes was 1.60 [1.24 – 2.07 95% CI] and in the adjusted regression model was 1.19 [0.86 – 1.66 95% CI]. In Denmark, the crude mortality rate ratio among patients with diabetes was 1.27 (0.68 – 2.36 95% CI) and in the adjusted model was 0.87 (0.49 – 1.54 95% CI)]. Meta-analyzing the two rate ratios from each region resulted in a crude mortality rate ratio of 1.55 (95% CI 1.22,1.96) and an adjusted mortality rate ratio of 1.11 (95% CI 0.84, 1.47).ConclusionsPresence of diabetes was not strongly associated with in-hospital COVID mortality independent of illness severity and other comorbidities.

Environmental flow management in watersheds with multi-objective reservoirs is often presented as an additional constraint to an already strained and over-allocated stream system. Nevertheless, environmental flow legislation and regulatory policies are increasingly being developed and implemented globally. In California, USA, recent legislative and regulatory policies place environmental flows at the forefront of the state’s water management objectives; however, the increased reliance on hydropower to support climate change mitigation goals may complicate efforts on both issues. This study modelled alternative environmental flow strategies in the major tributaries to the San Joaquin River in California. Strategies included detailed water management rules for hydropower production, flood control, and water deliveries, and three methodological approaches to environmental flow releases: minimum instream flows (“baseline”) year-round, 40% of full natural flow (FNF) during the spring runoff season and minimum releases the remainder of the year, and functional flows year-round. Results show that environmental flow strategies affect downstream flow releases in each of the San Joaquin’s four sub-basins differently depending on infrastructure capacity, water management objectives, and hydrologic year types. While hydropower production was comparable or declined in the Stanislaus, Tuolumne, and Merced basins, functional flow and 40% FNF strategies increased hydropower production in the Upper San Joaquin basin by 11%. Uncontrolled spill of high flow events decreased when high flow releases were based on hydrologic cues rather than exclusively on flood storage capacity. Water deliveries were reduced in all years regardless of environmental flow strategy. The 40% FNF and functional flow strategies both increased water released to the river relative to baseline, but in different ways. The functional flow strategy allocated water in a holistic approach that enhanced ecological functions in all years, but particularly in moderate and wet years. In contrast, the 40% FNF strategy provided increased flows relative to baseline and some ecological benefit in dry years, but less ecological benefit in other years. This study shows that alternative environmental flow strategies will have different and important trade-offs for integrated water management, and may mutually benefit seemingly conflicting objectives.

OBJECTIVES On the basis of the data from school-aged children, there is consistent evidence that there is a prolonged course of auditory development for perceiving speech embedded in competing background sounds. Furthermore, age-related differences are prolonged and pronounced for a two-talker speech masker compared to a speech-shaped noise masker. However, little is known about the course of development during the toddler and preschool years because it is difficult to collect reliable behavioral data from this age range. The goal of this study was to extend our lower age limit to include toddlers and preschoolers to characterize the developmental trajectory for masked speech detection thresholds across childhood. DESIGN Participants were 2- to 15-year-old children (n = 67) and adults (n = 17), all with normal hearing. Thresholds (71%) were measured for detecting a two-syllable word embedded in one of two maskers: speech-shaped noise or two-talker speech. The masker was presented at 55 dB SPL throughout testing. Stimuli were presented to the left ear via a lightweight headphone. Data were collected using an observer-based testing method in which the participant's behavior was judged by an experimenter using a two-interval, two-alternative testing paradigm. The participant's response to the stimulus was shaped by training him/her to perform a conditioned play-based response to the sound. For children, receptive vocabulary and working memory were measured. Data were fitted with a linear regression model to establish the course of development for each masker condition. Appropriateness of the test method was also evaluated by determining if there were age-related differences in training data, inter-rater reliability, or slope or upper asymptote estimates from pooled psychometric functions across different age groups. RESULTS Child and adult speech detection thresholds were poorer in the two-talker masker than in the speech-shaped noise masker, but different developmental trajectories were seen for the two masker conditions. For the speech-shaped noise masker, threshold improved by about 5 dB across the age span tested, with adult-like performance being reached around 10 years of age. For the two-talker masker condition, thresholds improved by about 7 dB between 2.5 and 15 years. However, the linear fit for this condition failed to achieve adult-like performance because of limited data from teenagers. No significant age-related differences were seen in training data, probe hit rate, or inter-rater reliability. Furthermore, slope and upper asymptote estimates from pooled psychometric functions were similar across different child age groups. CONCLUSIONS Different developmental patterns were seen across the two maskers, with more pronounced child-adult differences and prolonged immaturity during childhood for the two-talker masker relative to the speech-shaped noise masker. Our data do not support the idea that there is rapid improvement of masked speech detection thresholds between 2.5 and 5 years of age. This study also highlights that our observer-based method can be used to collect reliable behavioral data from toddlers and preschoolers-a time period where we know little about auditory development.

Despite being found guilty of egregious acts, crimes against humanity and war crimes, 54 of the 90 perpetrators sentenced by the International Criminal Tribunal for the Former Yugoslavia (icty) were granted unconditional early release (uer). This article argues that uer did a disservice to two principal expressive purposes of punishment - moral condemnation of the crimes and the overall norm projected by the icty, the ‘universal repugnance of group-based killing’. Fundamentally, punishment of perpetrators signifies the inherent worth of victims. Interviews with key stakeholders in Bosnia and Herzegovina revealed that the interviewees largely concurred with authors who posit that punitive justice conveys valuable messages to audiences. This article complements expressivist theories by demonstrating the extent to which expressivism was negated as perpetrators were granted uer. Finally, it proposes how early release in future tribunals and courts might be tailored to counter the negation of international criminal justice’s expressive value.