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We developed and validated the Influenza Severity Scale (ISS), a standardized risk assessment for influenza, to estimate and predict the probability of major clinical events in patients with laboratory-confirmed infection. Data from the Canadian Immunization Research Network’s Serious Outcomes Surveillance Network (2011/2012–2018/2019 influenza seasons) enabled the selecting of all laboratory-confirmed influenza patients. A machine learning-based approach then identified variables, generated weighted scores, and evaluated model performance. This study included 12,954 patients with laboratory-confirmed influenza infections. The optimal scale encompassed ten variables: demographic (age and sex), health history (smoking status, chronic pulmonary disease, diabetes mellitus, and influenza vaccination status), clinical presentation (cough, sputum production, and shortness of breath), and function (need for regular support for activities of daily living). As a continuous variable, the scale had an AU-ROC of 0.73 (95% CI, 0.71–0.74). Aggregated scores classified participants into three risk categories: low (ISS < 30; 79.9% sensitivity, 51% specificity), moderate (ISS ≥ 30 but < 50; 54.5% sensitivity, 55.9% specificity), and high (ISS ≥ 50; 51.4% sensitivity, 80.5% specificity). ISS demonstrated a solid ability to identify patients with hospitalized laboratory-confirmed influenza at increased risk for Major Clinical Events, potentially impacting clinical practice and research. [ABSTRACT FROM AUTHOR]

Polycystin-1 (PC-1) and PC-2 form a heteromeric ion channel complex that is abundantly expressed in primary cilia of renal epithelial cells. This complex functions as a non-selective cation channel, and mutations within the polycystin complex cause autosomal dominant polycystic kidney disease (ADPKD). The spatial and temporal regulation of the polycystin complex within the ciliary membrane remains poorly understood. Using both whole-cell and ciliary patch-clamp recordings, we identify a cilia-enriched oxysterol, 7β,27-dihydroxycholesterol (DHC), that serves as a necessary activator of the polycystin complex. We further identify an oxysterol-binding pocket within PC-2 and showed that mutations within this binding pocket disrupt 7β,27-DHC–dependent polycystin activation. Pharmacologic and genetic inhibition of oxysterol synthesis reduces channel activity in primary cilia. In summary, our findings reveal a regulator of the polycystin complex. This oxysterol-binding pocket in PC-2 may provide a specific target for potential ADPKD therapeutics. It is currently unknown how environmental cues regulate ciliary Polycystin ion channels on renal epithelial cells. Here authors identify a cilia-enriched oxysterol, 7β,27- dihydroxycholesterol (DHC), as a necessary activator of the polycystin complex [ABSTRACT FROM AUTHOR]

Deep learning (DL) has shown potential to provide powerful representations of bulk RNA-seq data in cancer research. However, there is no consensus regarding the impact of design choices of DL approaches on the performance of the learned representation, including the model architecture, the training methodology and the various hyperparameters. To address this problem, we evaluate the performance of various design choices of DL representation learning methods using TCGA and DepMap pan-cancer datasets and assess their predictive power for survival and gene essentiality predictions. We demonstrate that baseline methods achieve comparable or superior performance compared to more complex models on survival predictions tasks. DL representation methods, however, are the most efficient to predict the gene essentiality of cell lines. We show that auto-encoders (AE) are consistently improved by techniques such as masking and multi-head training. Our results suggest that the impact of DL representations and of pretraining are highly task- and architecture-dependent, highlighting the need for adopting rigorous evaluation guidelines. These guidelines for robust evaluation are implemented in a pipeline made available to the research community. [ABSTRACT FROM AUTHOR]

The mechanism by which subarachnoid hemorrhage (SAH) leads to chronic neurologic deficits is unclear. One possibility is that blood activates microglia to drive inflammation that leads to synaptic loss and impaired brain function. Using the endovascular perforation model of SAH in rats, we investigated short-term effects on microglia together with long-term effects on EEG and neurologic function for up to 3 months. Within the first week, microglia were increased both at the site of injury and diffusely across the cortex (2.5-fold increase in SAH compared to controls, p = 0.012). Concomitantly, EEGs from SAH animals showed focal increases in slow wave activity and diffuse reduction in fast activity. When expressed as a fast-slow spectral ratio, there were significant interactions between group and time (p < 0.001) with less ipsilateral recovery over time. EEG changes were most pronounced during the first week and correlated with neurobehavioral impairment. In vitro, the blood product hemin was sufficient to increase microglia phagocytosis nearly six-fold (p = 0.032). Immunomodulatory treatment with fingolimod after SAH reduced microglia, improved neurological function, and increased survival. These findings, which parallel many of the EEG changes seen in patients, suggest that targeting neuroinflammation could reduce long-term neurologic dysfunction following SAH. [ABSTRACT FROM AUTHOR]

At this Dutch festival, scientists learn about participants' sex, drugs and rock-and-roll habits. [ABSTRACT FROM AUTHOR]

Auditory stimuli that are relevant to a listener have the potential to capture focal attention even when unattended, the listener's own name being a particularly effective stimulus. We report two experiments to test the attention-capturing potential of the listener's own name in normal speech and time-compressed speech. In Experiment 1, 39 participants were tested with a visual word categorization task with uncompressed spoken names as background auditory distractors. Participants' word categorization performance was slower when hearing their own name rather than other names, and in a final test, they were faster at detecting their own name than other names. Experiment 2 used the same task paradigm, but the auditory distractors were time-compressed names. Three compression levels were tested with 25 participants in each condition. Participants' word categorization performance was again slower when hearing their own name than when hearing other names; the slowing was strongest with slight compression and weakest with intense compression. Personally relevant time-compressed speech has the potential to capture attention, but the degree of capture depends on the level of compression. Attention capture by time-compressed speech has practical significance and provides partial evidence for the duplex-mechanism account of auditory distraction. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are the preferred treatment for venous thromboembolism (VTE). However, DOAC use in patients with a BMI greater than 40 kg/m2 has not been well studied despite the growing prevalence of obesity, and current literature is often underpowered. Methods: This multicenter, retrospective, observational study evaluated patients 18 years and older who received DOACs for acute VTE treatment. Patients receiving DOACs for recurrent VTE or for failure of another agent were excluded. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding within 12 months (or one month after stopping anticoagulation therapy). A propensity score analysis was performed to balance patient characteristics and evaluate the primary endpoints by BMI group. Time-to-event outcomes were analyzed using weighted Kaplan-Meier curves. Results: There were 165 patients with a BMI of at least 40 kg/m2 and 320 patients with a BMI less than 40 kg/m2. The majority received apixaban (373, 77%). Recurrent VTE occurred in 5 (3.0%) and 13 (4.1%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 0.66; 95% CI: 0.16–2.69). Major bleeding occurred in 5 (3.0%) and 15 (4.7%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 1.19; 95% CI: 0.36–3.92). Conclusion: There was no significant difference in VTE recurrence or major bleeding related to BMI among patients treated with DOACs. This study showed that DOACs may be a safe and effective VTE treatment option in patients with obesity. Key points: Data supporting the use of direct oral anticoagulants (DOACs) for the treatment of venous thromboembolism (VTE) in patients with obesity are limited. This multicenter analysis aimed to evaluate the effectiveness and safety of DOACs in patients with and without obesity. The majority of patients received apixaban. VTE recurrence and rates of major bleeding were not different between patients with a BMI of at least 40 kg/m2 compared to a BMI less than 40 kg/m2. This study adds to the growing body of evidence supporting the use of DOACs, particularly apixaban, in patients with obesity, although future prospective trials and additional data in patients at extremes of body weight will be useful. [ABSTRACT FROM AUTHOR]

Many researchers describe public outreach as a labour of love, often carried out in their spare time. But some funders reward these activities. [ABSTRACT FROM AUTHOR]

In 2020, the COVID-19 pandemic forced unprecedented disruptions in higher education operations. While the adverse mental health effects experienced by college students due to these changes are well documented, less is known about the impact on their sexual and reproductive health (SRH), and the reciprocal relationships between SRH and mental health among adolescents and emerging adults. This position paper reviews existing literature on the effects of the COVID-19 pandemic on SRH, sexual violence, unintended pregnancy, sexually transmitted illness and human immunodeficiency virus rates and highlights issues specific to college-aged males, females, racial/ethnic and sexual minorities, and individuals with disabilities. The need to conceptualize SRH as an integral component of normal development, overall health, and well-being in the context of COVID-19 is discussed. The need to prioritize the design and implementation of developmentally appropriate, evidence-based SRH interventions specifically targeting college students is identified. Furthermore, an intergenerational approach to SRH that includes parents/caregivers and/or college faculty and staff (e.g., coaches, trainers) could facilitate comprehensive SRH prevention programming that enhances sexual violence prevention training programs currently mandated by many colleges. Policies and programs designed to mitigate adverse pandemic-related exacerbations in negative SRH outcomes are urgently needed and should be included in mainstream clinical psychology, not only focused on preventing unwanted outcomes but also in promoting rewarding interpersonal relationships and overall well-being. Recommendations for clinical psychologists and mental health researchers are made. [ABSTRACT FROM AUTHOR]

As X wanes, researchers are turning to Reddit for insights and data, and to better connect with the public. [ABSTRACT FROM AUTHOR]

Hemorrhagic diseases caused by epizootic hemorrhagic disease virus or by bluetongue virus (BTV) are the most important orbivirus diseases affecting ruminants, including white-tailed deer (WTD). Bluetongue virus is of particular concern for farmed WTD in Florida, given its lethality and its wide distribution throughout the state. This study reports the clinical findings, ancillary diagnostics, and genomic characterization of two BTV serotype 1 strains isolated from two farmed WTD, from two different farms in Florida in 2019 and 2022. Phylogenetic and genetic analyses indicated that these two novel BTV-1 strains were reassortants. In addition, our analyses reveal that most genome segments of these strains were acquired from BTVs previously detected in ruminants in Florida, substantiating their endemism in the Southeastern U.S. Our findings underscore the need for additional research to determine the genetic diversity of BTV strains in Florida, their prevalence, and the potential risk of new BTV strains to WTD and other ruminants. [ABSTRACT FROM AUTHOR]

Introduction: There is an increasing movement to suggest the practice of newborn circumcision causes significant physical and emotional harm. Previous studies have provided evidence that circumcision can decrease the transmission of certain sexually transmitted infections, though there is limited research on satisfaction and regret pertaining to circumcision status. We aim to examine personal comfort, regret, overall, and sexual satisfaction of males based on their circumcision status. Methods: We utilized Amazon.com "Mechanical Turk" survey marketplace on July 2018 to survey men age > 17 years regarding their circumcision status. We then analyzed the data using bivariate statistics and linear logistic regression models. The outcomes of this survey were regret towards circumcision status, the desire to change one's status, perceived sexual pleasure and satisfaction, medical complications related to one's status, and comfort with others seeing one's penis. Results: A total of 406 men were surveyed, and 332 were circumcised. No significant difference between circumcised and uncircumcised men pertaining to regret, desire to change their status, and sexual satisfaction was identified. On average, uncircumcised men believed their status conferred a mild increase in sexual pleasure, and circumcised men felt more comfortable with sexual partners and others seeing their penis. There was no difference in medical complications between the groups. Conclusions: This study provides objective data to incorporate into counseling parents regarding circumcision to facilitate shared decision-making. This is the first study to look closely at attitudes towards circumcision status in men circumcised before adulthood in the USA. Policy Implications: These findings should be incorporated into shared decision-making between parents and health care providers, as well as taken into consideration when developing professional guidance regarding circumcision in newborn males. [ABSTRACT FROM AUTHOR]

Planets with short orbital periods (roughly under 10 days) are common around stars like the Sun1,2. Stars expand as they evolve and thus we expect their close planetary companions to be engulfed, possibly powering luminous mass ejections from the host star3–5. However, this phase has never been directly observed. Here we report observations of ZTF SLRN-2020, a short-lived optical outburst in the Galactic disk accompanied by bright and long-lived infrared emission. The resulting light curve and spectra share striking similarities with those of red novae6,7—a class of eruptions now confirmed8 to arise from mergers of binary stars. Its exceptionally low optical luminosity (approximately 1035 erg s−1) and radiated energy (approximately 6.5 × 1041 erg) point to the engulfment of a planet of fewer than roughly ten Jupiter masses by its Sun-like host star. We estimate the Galactic rate of such subluminous red novae to be roughly between 0.1 and several per year. Future Galactic plane surveys should routinely identify these, showing the demographics of planetary engulfment and the ultimate fate of planets in the inner Solar System.Observations of ZTF SLRN-2020, a short-lived optical outburst in the Galactic disk accompanied by bright, long-lived infrared emission, show that the resulting light curve and spectra are consistent with the signatures of a planet being engulfed by its host star. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to determine the learning curve of tracheal−esophageal ultrasound by prehospital medical and paramedical staff. Methods: A single-center prospective study was carried out at a French EMS (SAMU 92). Volunteer participants first received a short theoretical training through e-learning, followed by two separate hands-on workshops on healthy volunteers, spaced one to two months apart. Learners were timed to obtain the tracheal–esophageal ultrasound target image 10 consecutive times. The first workshop was intended to perform a learning curve, and the second was to assess unlearning. The secondary objectives were to compare performance by profession and by previous ultrasound experience. Results: We included 32 participants with a mean age of 38 (± 10) years, consisting of 56% men. During the first workshop, the target image acquisition time was 20.4 [IQR: 10.6;41] seconds on the first try and 5.02 [3.72;7.5] seconds on the 10th (p < 0.0001). The image acquisition time during the second workshop was shorter compared to the first one (p = 0.016). In subgroup analyses, we found no significant difference between physicians and nurses (p = 0.055 at the first workshop and p = 0.164 at the second) or according to previous ultrasound experience (p = 0.054 at the first workshop and p = 0.176), counter to multivariate analysis (p = 0.02). Conclusions: A short web-based learning completed by a hands-on workshop made it possible to obtain the ultrasound image in less than 10 s, regardless of the profession or previous experience in ultrasound. [ABSTRACT FROM AUTHOR]

Purpose of Review: Direct-to-consumer telemedicine has vastly expanded in recent years, and urologic conditions are a common target for these companies. We aim to identify the urologic conditions being treated by direct-to-consumer telemedicine platforms and review the feasibility of adherence to evidence-based practice guidelines via this relatively new healthcare model. Recent Findings: Erectile dysfunction, premature ejaculation, testosterone deficiency, and male infertility are being treated with direct-to-consumer telemedicine. Such platforms treating erectile dysfunction perform modestly in practice guideline adherence. Guidelines-based treatment of other urologic conditions via telemedicine is feasible, however, the treatment of these conditions through popular direct-to-consumer telemedicine platforms is largely unstudied. Summary: The impact of direct-to-consumer telemedicine on the field of urology is vast and likely to continue to grow. Future studies should inspect direct-to-consumer telemedicine companies' practice patterns and treatment outcomes to ensure the field's standards of care are being met. Guidelines specific to the treatment of various urologic conditions via telemedicine are needed. [ABSTRACT FROM AUTHOR]

Disaster exposure is a strong predictor of survivor mental health following large-scale disasters. However, there is continued debate regarding how disaster exposure should be measured and quantified, as well as whether specific types of disaster exposure are more likely to influence certain mental health outcomes like psychological distress or post-traumatic stress disorder (PTSD). In this article, we propose the Disaster Exposure Matrix to explain how specific types and levels of disaster exposure are associated with particular mental health outcomes. We use data from the Sandy Child and Family Health study—an observational cohort study of 1000 randomly selected New Jersey residents who were living in the nine counties most-affected by Hurricane Sandy (2012)—to examine how direct and indirect disaster exposure at both the individual and community levels influence the likelihood of experiencing psychological distress and probable PTSD in the two years after Hurricane Sandy. Weighted logistic regression models demonstrate that particular measures of individual-level direct and indirect exposure uniquely influence probable PTSD and psychological distress, respectively. Community-level indirect exposure is significantly associated with psychological distress but not with probable PTSD. Findings highlight the importance of specificity when measuring the effects of disaster exposure on mental health, including separating exposures that occur at the individual and community level, as well as distinguishing those that are experienced directly from the event from those that are indirect and experienced after the meteorological or geophysical event has passed. [ABSTRACT FROM AUTHOR]

Wastewater-based epidemiology (WBE) has emerged as a valuable epidemiologic tool to detect the presence of pathogens and track disease trends within a community. WBE overcomes some limitations of traditional clinical disease surveillance as it uses pooled samples from the entire community, irrespective of health-seeking behaviors and symptomatic status of infected individuals. WBE has the potential to estimate the number of infections within a community by using a mass balance equation, however, it has yet to be assessed for accuracy. We hypothesized that the mass balance equation-based approach using measured SARS-CoV-2 wastewater concentrations can generate accurate prevalence estimates of COVID-19 within a community. This study encompassed wastewater sampling over a 53-week period during the COVID-19 pandemic in Gainesville, Florida, to assess the ability of the mass balance equation to generate accurate COVID-19 prevalence estimates. The SARS-CoV-2 wastewater concentration showed a significant linear association (Parameter estimate = 39.43, P value < 0.0001) with clinically reported COVID-19 cases. Overall, the mass balance equation produced accurate COVID-19 prevalence estimates with a median absolute error of 1.28%, as compared to the clinical reference group. Therefore, the mass balance equation applied to WBE is an effective tool for generating accurate community-level prevalence estimates of COVID-19 to improve community surveillance. [ABSTRACT FROM AUTHOR]

Understanding whether and how the absence of positive relationships may predict longer-term physical health outcomes is central to building a working conceptual model of the interplay of social and physical development across the lifespan. This study sought to examine the extent to which difficulties establishing positive social relationships from adolescence onward serve as long-term predictors of low adult vagal tone, which in turn has been linked to numerous long-term health problems. A diverse community sample of 141 individuals was followed via multiple methods and reporters from age 13 to 29. Across this span, social relationship quality was assessed via close friend and peer reports, observations of romantic interactions, and self-reported romantic relationship satisfaction. A range of potential personality and functional covariates was also considered. Vagal tone while at rest was assessed at age 29. Adult vagal tone was predicted across periods as long as 16 years by: adolescents' difficulty establishing themselves as desirable companions among peers; early adults' inability to establish strong close friendships; and lack of warmth in romantic relationships as an adult. Poor early adult friendship quality statistically mediated the link from adolescent peer difficulties to adult vagal tone. A range of potential confounding factors was examined but was not linked to vagal tone. Within the limits of the correlational design of the study, robust connections between adult vagal tone and social relationship quality from adolescence onward suggest at least a possible mechanism by which relationship difficulties may get 'under the skin' to influence future physiological functioning. [ABSTRACT FROM AUTHOR]

Background: We report dose-escalation results from an open-label, phase 1/2 trial evaluating avelumab (anti-PD-L1) in paediatric patients with refractory/relapsed solid tumours. Methods: In phase 1, patients aged < 18 years with solid (including central nervous system [CNS]) tumours for which standard therapy did not exist or had failed were enrolled in sequential cohorts of 3–6 patients. Patients received avelumab 10 or 20 mg/kg intravenously every 2 weeks. Primary endpoints were dose-limiting toxicities (DLTs) and grade ≥ 3 treatment-emergent adverse events (AEs). Results: At data cut-off (27 July 2021), 21 patients aged 3–17 years had received avelumab 10 mg/kg (n = 6) or 20 mg/kg (n = 15). One patient had three events that were classified as a DLT (fatigue with hemiparesis and muscular weakness associated with pseudoprogression; 20 mg/kg cohort). Grade ≥ 3 AEs occurred in five (83%) and 11 (73%) patients in the 10 and 20 mg/kg cohorts, respectively, and were treatment-related in one patient (7%; grade 3 [DLT]) in the 20 mg/kg cohort. Avelumab exposure in paediatric patients receiving 20 mg/kg dosing, but not 10 mg/kg, was comparable or higher compared with approved adult dosing (10 mg/kg or 800 mg flat dose). No objective responses were observed. Four patients with CNS tumours (20 mg/kg cohort) achieved stable disease, which was ongoing in two patients with astrocytoma at cut-off (for 24.7 and 30.3 months). Conclusion: In paediatric patients with refractory/relapsed solid tumours, avelumab monotherapy showed a safety profile consistent with previous adult studies, but clinical benefits were limited. [ABSTRACT FROM AUTHOR]

Purpose: The neutrophil-to-lymphocyte ratio (NLR) is the most widely biomarker used to assess the inflammatory system in various solid cancers. An elevated NLR has been reported to be associated with worse outcomes in head and neck squamous cell cancers (HNSCC). However, questions remain about the prognostic value of these findings in HNSCC patients with lung metastasis. This study aims to quantify the prognostic impact of NLR on HNSCC patients with lung metastasis. Methods: A retrospective chart review of 169 HNSCC patients was performed at the Otorhinolaryngology and the Stomatology and Maxillofacial Surgery Department (Saint-Pierre Hospital), between 2000 and 2017. All patients were divided into two subgroups. Patients who developed lung involvement were assigned to the lung-metastasis-group (LM-group) in contrast to no-lung-metastasis-group patients (NLM-group). The prognostic significance of NLR was evaluated using multivariable analysis adjusting for overall-survival (OS) and lung-metastasis-free-survival (LMFS). Results: 95 patients were enrolled in the NLM-group while 74 were in the LM-group. Multivariable analysis highlights that patients with a higher NLR value had shortened OS in the NLM subgroup (HR 1.3; p = 0.024). However, this association was not found in the LM subgroup. When considering both subgroups, an elevated NLR was reported as a prognostic factor of poor LMFS (HR 1.65; p = 0.047). Conclusion: Our data revealed that pretreatment NLR is an independent prognostic factor of mortality and lung metastasis development. However, the prognostic value of NLR is not confirmed in patients who suffered from lung metastasis. Physicians should integrate these findings in their treatment algorithm approach. Level of evidence: 4 [ABSTRACT FROM AUTHOR]

New marking methods for studying small biocontrol agents (especially predatory mites) are needed because many current techniques are expensive, ineffective or not applicable to small organisms. The objective of this study was to determine whether SmartWater, a liquid and permanent fluorescent dye, can be used to mark Phytoseiulus persimilis for experimentation without any deleterious effects on its dispersal, behavior, reproduction, and biocontrol efficacy. Our results show that there were no significant differences in movement, inter-plant dispersal, feeding behavior, survivability, and reproduction between marked P. persimilis and control individuals sprayed with water. We also found that the SmartWater mark lasted for the duration of the mites' life, indicating strong durability over time. Marking efficacy may be reduced, due to a trade-off between batch marking efficacy and the possibility of drowning study organisms. However, we feel future research could improve liquid marking techniques that would reduce this risk. Overall, this study concludes that SmartWater could be a useful marking tool for predatory mites in both laboratory and field studies. [ABSTRACT FROM AUTHOR]

Purpose of Review: Techniques for phalloplasty and penile prosthesis implantation have been associated with a high rate of complications, but recent advances in surgical options and penile implant technology may mark a paradigm shift in the approach to female-to-male genital gender-affirming surgery. This review aims to highlight the current state of research on phalloplasty and penile prosthesis implantation and explores the newest innovations for improving outcomes. Recent Findings: Multiple techniques for phalloplasty have been described with variable outcomes, complications, and strengths. In addition, the majority of penile prosthesis implants have been designed for cis-male anatomy, and rates of complications have been markedly higher in neophallus implantation. The introduction of two new models specifically designed for the neophallus by Zephyr Surgical Implants in recent years may signal a new horizon for penile prostheses tailored for the neophallus. Summary: The steady rise in the number of transgender individuals seeking surgical treatment options for female-to-male genital gender-affirming surgery has driven the evolution of techniques for phalloplasty and penile prosthesis implantation. Complications remain stubbornly elevated when compared to cis-male outcomes, but the first penile prosthesis designed for the neophallus offers hope that additional breakthroughs may be forthcoming. Additional studies with standardized outcomes are needed to further evaluate superiority between different techniques and penile prostheses. [ABSTRACT FROM AUTHOR]

The derived graph of a voltage graph consisting of a single vertex and two loops of different voltages is a circulant graph with two generators. We characterize the automorphism groups of connected, two-generator circulant graphs, and give their determining and distinguishing number, and when relevant, their cost of 2-distinguishing. We do the same for the subdivisions of connected, two-generator circulant graphs obtained by replacing one loop in the voltage graph with a directed cycle. [ABSTRACT FROM AUTHOR]

We illustrate the observability of the end stages of the earliest (Population III) stars at high redshifts z ≳ 10 , using the recently observed transient, GN-z11-flash as an example. We find that the observed spectrum of this transient is consistent with its originating from a shock-breakout in a Population III supernova occurring in the GN-z11 galaxy at z ∼ 11 . The energetics of the explosion indicate a progenitor star of mass ∼ 300 M ⊙ in that galaxy, with of order unity such events expected over an observing timescale of a few years. We forecast the expected number of such transients from z > 10 galaxies as a function of their host stellar mass and star formation rate. Our findings are important in the context of future searches to detect and identify the signatures of galaxies at Cosmic Dawn. [ABSTRACT FROM AUTHOR]

Purpose: Whether epinephrine or norepinephrine is preferable as the continuous intravenous vasopressor used to treat post-resuscitation shock is unclear. We assessed outcomes of patients with post-resuscitation shock after out-of-hospital cardiac arrest according to whether the continuous intravenous vasopressor used was epinephrine or norepinephrine. Methods: We conducted an observational multicenter study of consecutive patients managed in 2011–2018 for post-resuscitation shock. The primary outcome was all-cause hospital mortality, and secondary outcomes were cardiovascular hospital mortality and unfavorable neurological outcome (Cerebral Performance Category 3–5). A multivariate regression analysis and a propensity score analysis were performed, as well as several sensitivity analyses. Results: Of the 766 patients included in five hospitals, 285 (37%) received epinephrine and 481 (63%) norepinephrine. All-cause hospital mortality was significantly higher in the epinephrine group (OR 2.6; 95%CI 1.4–4.7; P = 0.002). Cardiovascular hospital mortality was also higher with epinephrine (aOR 5.5; 95%CI 3.0–10.3; P < 0.001), as was the proportion of patients with CPC of 3–5 at hospital discharge. Sensitivity analyses produced consistent results. The analysis involving adjustment on a propensity score to control for confounders showed similar findings (aOR 2.1; 95%CI 1.1–4.0; P = 0.02). Conclusion: Among patients with post-resuscitation shock after out-of-hospital cardiac arrest, use of epinephrine was associated with higher all-cause and cardiovascular-specific mortality, compared with norepinephrine infusion. Until additional data become available, intensivists may want to choose norepinephrine rather than epinephrine for the treatment of post-resuscitation shock after OHCA. [ABSTRACT FROM AUTHOR]

Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, the emergence of coronavirus in our species has been associated with zoonotic transmissions from animal reservoirs1,2, underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae, human infections reported so far have been limited to alphacoronaviruses and betacoronaviruses3–5. Here we identify porcine deltacoronavirus strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the genes encoding Nsp15 and the spike glycoprotein. In particular, structural analysis predicts that one of the changes in the spike S1 subunit, which contains the receptor-binding domain, may affect the flexibility of the protein and its binding to the host cell receptor. Our findings highlight the potential for evolutionary change and adaptation leading to human infections by coronaviruses outside of the previously recognized human-associated coronavirus groups, particularly in settings where there may be close human–animal contact.The presence of porcine deltacoronavirus has been detected in three children from Haiti that could have originated from zoonotic spillover. [ABSTRACT FROM AUTHOR]

Background: Bats are important components of forested ecosystems and are found in forests worldwide. Consequently, they often interact with fire. Previous reviews of the effects of fire on bats have focused on prescribed fire effects, in part due to the limited number of studies on bat responses to wildfire. However, over the past several years, studies on bat responses to wildfire and prescribed fire have increased considerably. We reviewed this rapidly expanding body of literature to determine whether bats respond differently to prescribed fire and wildfire, and the important factors driving those differences. We also examined regional similarities and differences in bat response to prescribed fire and wildfire and identified areas in need of further research. Results: Our review included 52 studies (29 prescribed fire, 23 wildfire) from North and South America, Europe, Australia, and Africa, although studies from Europe, South America, and Africa were limited. In general, we found that bats show positive or neutral responses to prescribed fire, whereas a greater proportion of negative responses were reported for wildfire. However, some of the negative responses to wildfire are short-lived or local, suggesting that bats may be resilient to the effects of fire. Factors such as fire severity, fire frequency, time since last burn, burn extent, season of burn, and pyrodiversity were all found to be important drivers of bats’ responses to both prescribed fire and wildfire. Conclusions: The importance of the spatial and temporal aspects of fire suggests that these factors need to be considered when designing future studies and interpreting results. Pyrodiversity may be a particularly important concept to further our understanding of bats’ responses to fire. We found several gaps in our knowledge including lack of information on direct effects of fire (e.g., mortality), regional and taxonomic biases, effects of wildfire on roosting habitat, and the effects of climate change. Although current studies suggest that fire may be an important management tool for improving bat habitat, the threat of more frequent, extensive, and severe wildfires may put additional stress on some bat populations, particularly those being impacted by disease, habitat loss and fragmentation, and climate change. [ABSTRACT FROM AUTHOR]

It is commonly argued that an undesirable feature of a theoretical or phenomenological model is that salient observables are sensitive to values of parameters in the model. But in what sense is it undesirable to have such ‘fine-tuning’ of observables (and hence of the underlying model)? In this paper, we argue that the fine-tuning can be interpreted as a shortcoming of the explanatory capacity of the model: in particular it signals a lack of a particular type of explanatory depth. The aspect of depth that we probe relates most closely to a lack of sensitivity to changes in parameters associated with such models. In support of this argument, we develop a schema—for (a certain class of) models that arise broadly in physical settings—that quantitatively relates fine-tuning of observables to a lack of depth of explanations based on these models. We apply our schema in two different settings in which, within each setting, we compare the depth of two competing explanations. The first setting involves explanations for the Euclidean nature of spatial slices of the universe today: in particular, we compare an explanation provided by the big-bang model of the early 1970s (where no inflationary period is included) with an explanation provided by a general model of cosmic inflation. The second setting has a more phenomenological character, where the goal is to infer from a limited sequence of data points, using maximum entropy techniques, the underlying probability distribution from which these data are drawn. In both of these settings we find that our analysis favors the model that intuitively provides the deeper explanation of the observable(s) of interest. We thus provide an account that relates two ‘theoretical virtues’ of models used broadly in physical settings—namely, a lack of fine-tuning and explanatory depth—and argue that finely tuned models sacrifice explanatory depth. [ABSTRACT FROM AUTHOR]

To develop and validate a brief, structured, behavioral health module for use by local public health practitioners to rapidly assess behavioral health needs in disaster settings. Data were collected through in-person, telephone, and web-based interviews of 101 individuals affected by Hurricanes Katrina (n = 44) and Sandy (n = 57) in New Orleans and New Jersey in April and May 2018, respectively. Questions included in the core module were selected based on convergent validity, internal consistency reliability, test–retest reliability across administration modes, principal component analysis (PCA), question comprehension, efficiency, accessibility, and use in population-based surveys. Almost all scales showed excellent internal consistency reliability (Cronbach's alpha, 0.79–0.92), convergent validity (r > 0.61), and test–retest reliability (in-person vs. telephone, intra-class coefficient, ICC, 0.75–1.00; in-person vs. web-based ICC, 0.73–0.97). PCA of the behavioral health scales yielded two components to include in the module—mental health and substance use. The core module has 26 questions—including self-reported general health (1 question); symptoms of posttraumatic stress disorder, depression, and anxiety (Primary Care PTSD Screen, Patient Health Questionnaire-4; 8 questions); drinking and other substance use (Alcohol Use Disorders Identification Test-Concise, AUDIT-C; Drug Abuse Screening Test, DAST-10; stand-alone question regarding increased substance use since disaster; 14 questions); prior mental health conditions, treatment, and treatment disruption (3 questions)—and can be administered in 5–10 minutes through any mode. This flexible module allows practitioners to quickly evaluate behavioral health needs, effectively allocate resources, and appropriately target interventions to help promote recovery of disaster-affected communities. [ABSTRACT FROM AUTHOR]

Background: The use of personal protective equipment (PPE) by emergency medical services (EMS) providers requires specific attention, as it takes place in out-of-hospital unsecured settings. The aim of this study was to evaluate which PPE gown was less contaminating during doffing procedures in an EMS setting. Six well-trained healthcare worker (HCW) subjects tested 4 different gowns: (1) surgical gowns (SG), (2) full body coveralls (FBC), (3) self-made alternative PPEs (SMP), and (4) non-surgical isolation gowns (NSIG). An invisible tracer was sprayed on the gown after donning each subject. After doffing, each HCW was photographed under UV lights to show areas of fluorescent "contamination" on their clothes. The number, size, and intensity level of contaminated areas were noted, as well as observational deviation from the procedure and doffing time. In addition, the subjects were asked to take a questionnaire about their perception of the level of comfort, ease of doffing, and overall safety for each gown. Results: Despite a well-trained team of HCW subjects, contamination while doffing was observed with every type of PPE gown, and with each HCW subject. All body areas were contaminated at least once, except the face. Contamination was more frequent while doffing FBCs. On the other hand, the removal of SG was found to be the least contaminating. The mean doffing time was significantly shorter with SG 1:29 and longer with FBC 2:26 (p=0.005). Conclusion: Results of this study converge towards the selection of surgical gowns over other types of PPE gowns, which met both contamination criteria as well as staff appreciation in this context. Specific attention should be paid to the legs and abdomino-pelvic areas. Additional protection such as protective trousers or aprons could be added. [ABSTRACT FROM AUTHOR]

The spotted-wing drosophila, Drosophila suzukii Matsumura, is an invasive pest causing significant damage to soft skinned fruits. Control of D. suzukii is critical since there is no tolerance for infested fruit in the market. While most insecticides control one or more D. suzukii life-stages (e.g., egg, larvae, and adult), the impact of insecticides that are toxic to immature stages is unclear on the subsequent generation of a field population. Insecticides were applied at field recommended rates on cherries and blueberries in the laboratory to determine immature D. suzukii mortality. Spinetoram, cyantraniliprole, malathion, methomyl, spinosad, and phosmet resulted in relatively high mortality of all immature life stages. Zeta-cypermethrin, cyclaniliprole, and fenpropathrin resulted in lower mortality of egg and all larval instars. Malathion was also applied to lowbush blueberries with different fruit sizes (small, medium, and large) in the laboratory and there was no statistical difference in mortality rates depending on fruit sizes. Mortality data from the laboratory experiments were used to parameterize a refined D. suzukii population model. The model revealed that the timing and order of different insecticide classes are important to control D. suzukii population. Model runs that included early applications of more effective insecticides resulted in high immature mortality and greater reduction of D. suzukii populations compared to treatments applied later. [ABSTRACT FROM AUTHOR]

Satellite observations from the Clouds and the Earth’s Radiant Energy System show that Earth’s energy imbalance has doubled from 0.5 ± 0.2 Wm−2 during the first 10 years of this century to 1.0 ± 0.2 Wm−2 during the past decade. The increase is the result of a 0.9 ± 0.3 Wm−2 increase absorbed solar radiation (ASR) that is partially offset by a 0.4 ± 0.25 Wm−2 increase in outgoing longwave radiation (OLR). Despite marked differences in ASR and OLR trends during the hiatus (2000–2010), transition-to-El Niño (2010–2016) and post-El Niño (2016–2022) periods, trends in net top-of-atmosphere flux (NET) remain within 0.1 Wm−2 per decade of one another, implying a steady acceleration of climate warming. Northern and southern hemisphere trends in NET are consistent to 0.06 ± 0.31 Wm−2 per decade due to a compensation between weak ASR and OLR hemispheric trend differences of opposite sign. We find that large decreases in stratocumulus and middle clouds over the sub-tropics and decreases in low and middle clouds at mid-latitudes are the primary reasons for increasing ASR trends in the northern hemisphere (NH). These changes are especially large over the eastern and northern Pacific Ocean, and coincide with large increases in sea-surface temperature (SST). The decrease in cloud fraction and higher SSTs over the NH sub-tropics lead to a significant increase in OLR from cloud-free regions, which partially compensate for the NH ASR increase. Decreases in middle cloud reflection and a weaker reduction in low-cloud reflection account for the increase in ASR in the southern hemisphere, while OLR changes are weak. Changes in cloud cover in response to SST increases imply a feedback to climate change yet a contribution from radiative forcing or internal variability cannot be ruled out. [ABSTRACT FROM AUTHOR]

Carbonaceous chondrite compositions could be an order of magnitude more abundant in comets than in asteroids; future observations of comets will calibrate this proportion. Even adopting the full reduction factor of HT ht associated with the value of I N i from Desch et al.[1], a cometary Chicxulub impactor would be up to HT ht times more likely than an asteroid Chicxulub impactor[2]. A cometary Chicxulub impactor remains more likely than an asteroid Chicxulub impactor if the fraction of CC-like comets is HT ht . [Extracted from the article]

Background: Hypoglycemia usually includes various neurological symptoms, which are the consequence of neuroglycopenia. When it is severe, it is associated with altered mental status, even coma. Case presentation: We report the case of a patient with severe hypoglycemia, completely asymptomatic, due to the increase of lactate production in response to tissue hypoperfusion following a hemorrhagic shock. This illustrates that lactate can substitute glucose as an energy substrate for the brain. It is also a reminder that this metabolite, despite its bad reputation maintained by its role as a marker of severity in critical care patients, has a fundamental role in our metabolism. Conclusions: Following the example of the "happy hypoxemia" recently reported in the literature describing asymptomatic hypoxemia in COVID-19 patients, we describe a case of "happy hypoglycemia." [ABSTRACT FROM AUTHOR]

Understanding the major determinants of crash fatalities continues to be an important topic of investigation for safety researchers. Regression models using a vast number of explanatory variables are often used which result in a huge array of specifications. Results often vary among studies based on size of estimated coefficients and significance levels. To address this, we explore both significance and model sturdiness in regression models using Leamer's s-values. This Bayesian technique allows us to address estimation uncertainty and model ambiguity over all possible subset regressions so as to evaluate the effect of key variables which we focus on as contributors to crash fatalities. These include cell phone use, fleet modernization, suicidal behavior, alcohol use, and speed limits. [ABSTRACT FROM AUTHOR]

Collaborative monitoring over broad scales and levels of ecological organization can inform conservation efforts necessary to address the contemporary biodiversity crisis. An important challenge to collaborative monitoring is motivating local engagement with enough buy-in from stakeholders while providing adequate top-down direction for scientific rigor, quality control, and coordination. Collaborative monitoring must reconcile this inherent tension between top-down control and bottom-up engagement. Highly mobile and cryptic taxa, such as bats, present a particularly acute challenge. Given their scale of movement, complex life histories, and rapidly expanding threats, understanding population trends of bats requires coordinated broad-scale collaborative monitoring. The North American Bat Monitoring Program (NABat) reconciles top-down, bottom-up tension with a hierarchical master sample survey design, integrated data analysis, dynamic data curation, regional monitoring hubs, and knowledge delivery through web-based infrastructure. NABat supports collaborative monitoring across spatial and organizational scales and the full annual lifecycle of bats. [ABSTRACT FROM AUTHOR]

As a means to understand human neuropsychiatric disorders from human brain samples, we compared the transcription patterns and histological features of postmortem brain to fresh human neocortex isolated immediately following surgical removal. Compared to a number of neuropsychiatric disease-associated postmortem transcriptomes, the fresh human brain transcriptome had an entirely unique transcriptional pattern. To understand this difference, we measured genome-wide transcription as a function of time after fresh tissue removal to mimic the postmortem interval. Within a few hours, a selective reduction in the number of neuronal activity-dependent transcripts occurred with relative preservation of housekeeping genes commonly used as a reference for RNA normalization. Gene clustering indicated a rapid reduction in neuronal gene expression with a reciprocal time-dependent increase in astroglial and microglial gene expression that continued to increase for at least 24 h after tissue resection. Predicted transcriptional changes were confirmed histologically on the same tissue demonstrating that while neurons were degenerating, glial cells underwent an outgrowth of their processes. The rapid loss of neuronal genes and reciprocal expression of glial genes highlights highly dynamic transcriptional and cellular changes that occur during the postmortem interval. Understanding these time-dependent changes in gene expression in post mortem brain samples is critical for the interpretation of research studies on human brain disorders. [ABSTRACT FROM AUTHOR]

Influenza is an acute respiratory infection for which vaccination is our best prevention strategy. Small seasonal changes in circulating influenza viruses (antigenic drift) result in the need for annual influenza vaccination, in which the vaccine formulation is updated to better match the predominant circulating influenza viruses that have undergone important antigenic changes. Although the burden of influenza infection and its complications is the highest in older adults, vaccine effectiveness is the lowest in this vulnerable population. This is largely due to waning of the immune response with age known as "immune senescence", and presents an important, unmet challenge. Possible strategies to tackle this include adjuvant and high-dose vaccines, and herd immunity induced by greater vaccine uptake. [ABSTRACT FROM AUTHOR]

The origin of the Chicxulub impactor, which is attributed as the cause of the K/T mass extinction event, is an unsolved puzzle. The background impact rates of main-belt asteroids and long-period comets have been previously dismissed as being too low to explain the Chicxulub impact event. Here, we show that a fraction of long-period comets are tidally disrupted after passing close to the Sun, each producing a collection of smaller fragments that cross the orbit of Earth. This population could increase the impact rate of long-period comets capable of producing Chicxulub impact events by an order of magnitude. This new rate would be consistent with the age of the Chicxulub impact crater, thereby providing a satisfactory explanation for the origin of the impactor. Our hypothesis explains the composition of the largest confirmed impact crater in Earth's history as well as the largest one within the last million years. It predicts a larger proportion of impactors with carbonaceous chondritic compositions than would be expected from meteorite falls of main-belt asteroids. [ABSTRACT FROM AUTHOR]

The concept of "robust dynamics" describes the incorporation of mechanically interlocked molecules (MIMs) into metal-organic framework (MOF) materials such that large amplitude motions (e.g., rotation or translation of a macrocycle) can occur inside the free volume pore of the MOF. To aid in the preparation of such materials, reticular synthesis was used herein to design rigid molecular building blocks with predetermined ordered structures starting from the well-known MOF NOTT-101. New linkers were synthesized that have a T-shape, based on a triphenylene tetra-carboxylate strut, and their incorporation into Cu(II)-based MOFs was investigated. The single-crystal structures of three new MOFs, UWCM-12 (fof), β-UWCM-13 (loz), UWCM-14 (lil), with naked T-shaped linkers were determined; β-UWCM-13 is the first reported example of the loz topology. A fourth MOF, UWDM-14 (lil) is analogous to UWCM-14 (lil) but contains a [2]rotaxane linker. Variable-temperature, 2H solid-state NMR was used to probe the dynamics of a 24-membered macrocycle threaded onto the MOF skeleton. [ABSTRACT FROM AUTHOR]

Purpose of Review: To highlight and review encouraging preliminary studies behind several alternative products and interventions for erectile dysfunction (ED). Recent Findings: Alternative treatments for ED are becoming more prevalent with increased consumer interest. "Natural" products are sold online, and numerous clinics offer various off-label and investigational interventions. These alternative treatments have demonstrated varying degrees of efficacy in randomized trials and meta-analyses, but none of these interventions has robust enough evidence to be considered first-line therapy. These treatments may find a role in combination with guideline treatments or may be used in novel penile rehabilitation research protocols. Summary: With growing interest in alternative treatment for men's health, an awareness of the literature is imperative for patient counsel. Alternative treatments, like l-arginine, have a growing body of evidence for efficacy in combination with PDE5i, and low-intensity shock wave therapy and stem cell therapy continue to demonstrate encouraging outcomes in ED trials. [ABSTRACT FROM AUTHOR]

In mammals, telomere protection is mediated by the essential protein TRF2, which binds chromosome ends and ensures genome integrity1,2. TRF2 depletion results in end-to-end chromosome fusions in all cell types that have been tested so far. Here we find that TRF2 is dispensable for the proliferation and survival of mouse embryonic stem (ES) cells. Trf2−/− (also known as Terf2) ES cells do not exhibit telomere fusions and can be expanded indefinitely. In response to the deletion of TRF2, ES cells exhibit a muted DNA damage response that is characterized by the recruitment of γH2AX—but not 53BP1—to telomeres. To define the mechanisms that control this unique DNA damage response in ES cells, we performed a CRISPR–Cas9-knockout screen. We found a strong dependency of TRF2-null ES cells on the telomere-associated protein POT1B and on the chromatin remodelling factor BRD2. Co-depletion of POT1B or BRD2 with TRF2 restores a canonical DNA damage response at telomeres, resulting in frequent telomere fusions. We found that TRF2 depletion in ES cells activates a totipotent-like two-cell-stage transcriptional program that includes high levels of ZSCAN4. We show that the upregulation of ZSCAN4 contributes to telomere protection in the absence of TRF2. Together, our results uncover a unique response to telomere deprotection during early development. Depletion of TRF2—an essential mediator of telomere protection in most mammalian cells—in mouse embryonic stem cells activates a compensatory transcriptional program that renders TRF2 dispensable for their survival and proliferation. [ABSTRACT FROM AUTHOR]

The olfactory cues used by various animals to detect and identify food items often include volatile organic compounds (VOCs) produced by food-associated microorganisms. Microbial VOCs have potential as lures to trap animal pests, including insect crop pests. This study investigated microorganisms whose VOCs are attractive to natural populations of the spotted wing drosophila (SWD), an invasive insect pest of ripening fruits. The microorganisms readily cultured from wild SWD and SWD-infested fruits included yeasts, especially Hanseniaspora species, and various bacteria, including Proteobacteria (especially Acetobacteraceae and Enterobacteriaceae) and Actinobacteria. Traps in a raspberry planting that were baited with cultures of Hanseniaspora uvarum, H. opuntiae and the commercial lure Scentry trapped relatively high numbers of both SWD and non-target drosophilids. The VOCs associated with these baits were dominated by ethyl acetate and, for yeasts, other esters. By contrast, Gluconobacter species (Acetobacteraceae), whose VOCs were dominated by acetic acid and acetoin and lacked detectable ethyl acetate, trapped 60–75% fewer SWD but with very high selectivity for SWD. VOCs of two other taxa tested, the yeast Pichia sp. and Curtobacterium sp. (Actinobacteria), trapped very few SWD or other insects. Our demonstration of among-microbial variation in VOCs and their attractiveness to SWD and non-pest insects under field conditions provides the basis for improved design of lures for SWD management. Further research is required to establish how different microbial VOC profiles may function as reliable cues of habitat suitability for fly feeding and oviposition, and how this variation maps onto among-insect species differences in habitat preference. [ABSTRACT FROM AUTHOR]

The learning of stimulus-outcome associations allows for predictions about the environment. Ventral striatum and dopaminergic midbrain neurons form a larger network for generating reward prediction signals from sensory cues. Yet, the network plasticity mechanisms to generate predictive signals in these distributed circuits have not been entirely clarified. Also, direct evidence of the underlying interregional assembly formation and information transfer is still missing. Here we show that phasic dopamine is sufficient to reinforce the distinctness of stimulus representations in the ventral striatum even in the absence of reward. Upon such reinforcement, striatal stimulus encoding gives rise to interregional assemblies that drive dopaminergic neurons during stimulus-outcome learning. These assemblies dynamically encode the predicted reward value of conditioned stimuli. Together, our data reveal that ventral striatal and midbrain reward networks form a reinforcing loop to generate reward prediction coding. It is not entirely understood how network plasticity produces the coding of predicted value during stimulus-outcome learning. Here, the authors reveal a reinforcing loop in distributed limbic circuits, transforming sensory stimuli into reward prediction coding broadcasted by dopamine neurons to the brain. [ABSTRACT FROM AUTHOR]