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Background: The primary objective of this study was to investigate the relative contributions of factors from multiple social-ecological levels in explaining outdoor play changes in childcare centers during the COVID-19 pandemic. Methods: In Alberta, Canada, licensed childcare center directors (n = 160) completed an online questionnaire. For outcomes, changes in the frequency and duration of outdoor play in childcare centers during COVID-19 compared to before COVID-19 were measured. For exposures, center demographic, director, parental, social, environmental, and policy-level factors were measured. Hierarchical regression analyses were conducted separately for winter (December–March) and nonwinter months (April–November). Results: In most instances, factors at each social-ecological level explained a statistically significant amount of unique variance in changes in outdoor play in childcare centers during COVID-19. Full models accounted for more than 26% of the variance in the outcomes. Changes in parental interest in outdoor play was the most consistent correlate of changes in the frequency and duration of outdoor play in both winter and nonwinter months during COVID-19. In terms of changes in the duration of outdoor play, social support from the provincial government, health authority, and licensing, and changes in the number of play areas in licensed outdoor play spaces were also consistent correlates in both winter and nonwinter months during COVID-19. Conclusions: Factors from multiple social-ecological levels uniquely contributed to changes in outdoor play in childcare centers during the COVID-19 pandemic. Findings can help inform interventions and public health initiatives related to outdoor play in childcare centers during and after the ongoing pandemic.

Many have begun to despair that climate justice will prevail even in a minimal form. The affective dimensions of such despair, we suggest, threaten to make climate action appear too demanding. Thus, despair constitutes a moral challenge to individual climate action that has not yet received adequate attention. In response, we defend a duty to act in hope for a more just (climate) future. However, as we see it, this duty falls differentially upon the shoulders of more and less advantaged agents in society. From arguments by Black thinkers like Derrick Bell, we draw a set of distinctions between two types of hope: one for ideal justice, and one for more modest change; and between two types of hopeful actions, those undertaken through formal political channels and those we call 'extra-political' actions; and between two sites of differential moral burdens, those of the privileged and those of the oppressed. Ours is a case for facing even bleak realities, demanding otherwise, and acting in hope to achieve a better future.

This study examines the influence of in-group identity between supervisors and subordinates and the clarity of the bonus determination criteria on supervisors’ discretionary adjustments of subordinates’ bonus compensation through the lens of social identity theory. Using field data from a multinational manufacturing company’s subsidiary in China, we find that in-group sales agents receive higher bonus awards and that this effect is more pronounced when there is high clarity of the bonus determination criteria. Additional analysis shows that these effects hold for higher-tenured sales agents and in regions characterized by lower sales agent turnover. Finally, we find that higher bonus awards are positively (negatively) associated with in-group sales agents’ future performance when there is low (high) clarity of the bonus determination criteria. Our findings hold potential implications for management practices in corporations operating in countries that have strong relationship-based cultures. Data Availability: Data used in this study are provided by a proprietary source.

Purpose: Despite promising preclinical studies, toxicities have precluded combinations of chemotherapy and DNA damage response (DDR) inhibitors. We hypothesized that tumor-targeted chemotherapy delivery might enable clinical translation of such combinations. Patients and Methods: In a phase I trial, we combined sacituzumab govitecan, antibody–drug conjugate (ADC) that delivers topoisomerase-1 inhibitor SN-38 to tumors expressing Trop-2, with ataxia telangiectasia and Rad3-related (ATR) inhibitor berzosertib. Twelve patients were enrolled across three dose levels. Results: Treatment was well tolerated, with improved safety over conventional chemotherapy-based combinations, allowing escalation to the highest dose. No dose-limiting toxicities or clinically relevant ≥grade 4 adverse events occurred. Tumor regressions were observed in 2 patients with neuroendocrine prostate cancer, and a patient with small cell lung cancer transformed from EGFR-mutant non–small cell lung cancer. Conclusions: ADC-based delivery of cytotoxic payloads represents a new paradigm to increase efficacy of DDR inhibitors.

The previously published index of relative abundance of the northeastern offshore stock of spotted dolphins, the species most affected by the purse-seine fishery for tunas in the eastern Pacific Ocean, shows a decreasing trend in the last two decades despite dramatic reductions in incidental mortality since the early 1970s. To better understand the behaviour of this index, the effects of changes in data quality and methods of searching on estimation of relative abundance using current methodologies have been studied here. Changes in data quality since the late 1980s have led to a dramatic reduction in the proportion of sightings that are reported on or near the trackline. The decreasing trend in the index in the late 1970s and through the 1980s is strongly influenced by the fit of the detection function to the high proportion of sightings near the trackline that was present in the data during that time period. If this excess of sightings near the trackline is spurious, then much of the decreasing trend in the index over this time period is likely spurious. In addition, part of the decrease in the index in the late 1980s to mid-1990s is probably due to changes in data-collection biases that result from a dramatic increase in the amount of searching that is currently being carried out using helicopters as compared to high-powered binoculars. The results suggest that trends in bias associated with changes in data quality and fishery operations may have contributed to a trend in the index on the order of 1.0-1.5% per year, or approximately 25-33% of the maximum growth rate of the northeastern stock of offshore spotted dolphin. The pervasive nature of these sources of bias, and their potential magnitude relative to the maximum growth rates of the dolphin species involved, make use of this index in population growth models ill-advised. Fishery-derived indices such as these may be most useful for comparing trends in relative abundance between species, when the sources of biases are unlikely to be species-specific.

Exacerbated food insecurity has been among the many challenges presented by the emergence of the novel coronavirus 2019 in the United States. In the wake of the pandemic, expanded focus has turned to the capacities of established federal nutrition assistance programs and emergent nutrition access models to address these challenges. Supplemental Nutrition Assistance Program-based incentive pro­grams, or nutrition incentive programs, are an emergent model designed to provide financial incentives (additional funds) to limited-resource, Supplemental Nutrition Assistance Program (SNAP)-enrolled shoppers to improve the afforda­bility of fresh fruits and vegetables at farm-direct and other retail outlets. While policymakers, researchers, and other stakeholders have advanced efforts to evaluate the overall impact and efficacy of nutrition incentive programs, much remains to be understood about how these programs operate under pandemic conditions and how effective they have been at mitigating the associated increase in food hardship for limited-resource families. To examine the salient factors influencing nutrition incentive program operations during the pandemic, we applied a three-round, online Delphi process with an expert panel (N=15) of nutrition incentive practitioners between May and October 2021, analyzing the data using thematic analysis and descriptive statistics. The panelists reached consen­sus on several barriers, opportunities, and innova­tive adaptations in incentive programming opera­tions, both in the early stages of the pandemic outbreak and that may persist long-term. The find­ings—which include barriers such as “staff burnout and/or turnover,” opportunities such as “increased collaboration and networking between stakehold­ers,” and innovative adaptions such as “targeted expansion of SNAP/EBT eligibility”—have impli­cations for the operational and adaptive capacities of SNAP-based incentive program practitioners over the next several years. We provide recommen­dations for both researchers and nutrition incentive practitioners with an emphasis on further explor­ing and operationalizing the long-term barrier, oppor­tunity, and innovative adaptation findings to aid the continued development of nutrition incen­tive pro­gram resilience in preparation for future pandemic events or comparable food system shocks.

Ethylene epoxidation is an important reaction to form ethylene oxide (EO), which is a precursor to many other critical chemicals. This study links short-term EO production to the effects on the microstructure of Ag/yttria-stabilized zirconia cells with and without an electrochemically promoted catalyst (EPOC). Nano scale features called striations were observed using a Scanning Electron Microscope (SEM) on the silver under all reaction conditions tested. While appearing in both cases, the striations for the EPOC case are finer in size (~150 to 250 nm) compared to the no current case (~400 to 500 nm). These features did not appear when epoxidation conditions were not present. Striation formation was further linked to the epoxidation reaction through electrochemical impedance spectroscopy (EIS) and gas chromatography (GC). Ethylene conversion to EO declines over the course of hours as striations form, indicating that striations have a negative influence on the reaction. Striation formation further effected the electrochemical performance of the cells, resulting in the low frequency depressions observed in EIS to shrink in both cases after 10 hours of epoxidation.

Mixed fisheries occur when multiple species are caught together and harvested by multiple fleets. The biological and technical interactions in mixed fisheries distinguish them from single-species fisheries, which makes them challenging for their assessment and management. The present knowledge synthesis reviewed pertinent policy documents and academic databases for twenty-three mixed fisheries worldwide; aiming to characterize attributes of mixed fisheries, provide overviews on their assessment and management, assess current research progress, and identify key factors that impact management effectiveness. Mixed fisheries were found to exhibit varying characteristics worldwide, rendering the implementation of universal management solutions unlikely. While mixed fisheries stock assessment and management are mostly based on single-species approaches, additional mixed fisheries considerations were incorporated at various scales, including multispecies, sector-specific, fishery, and ecosystem levels. Ecosystem-wide management considerations were the most significant contributor to improved management performance in terms of conserving stock biomass and preventing overfishing, underscoring the merits of the Ecosystem-based Fisheries Management (EBFM) principle. Mixed fisheries research demonstrated regional and thematic variations, with the most popular topics addressing immediate and practical management concerns, and the less frequently discussed topics offering valuable insights related to climate change and socio-ecological perspectives. The synthesis identified the available management approaches for mixed fisheries from different jurisdictions, yet their diversity highlighted a lack of global consensus on best management practices. Future mixed fisheries will benefit from balancing tradeoffs between ecological and socio-economic needs, implementing EBFM, adopting diverse and harmonized management tools, and prioritizing monitoring efforts.

Summary The production of in vitro embryos has sped up the dissemination of superior genetic material. However, the variation among the cattle response to oocyte and embryo production is a challenging factor. This variation is even higher in the Wagyu cattle as the breed has a small effective population size. The identification of an effective marker related to reproductive efficiency would allow the selection of more responsive females to reproductive protocols. The objective of this study was to evaluate the blood levels of anti-Müllerian hormone and associate it with oocyte recovery and blastocyst rate of embryos produced in vitro in Wagyu cows, as well as observe the hormone circulating levels in males. Serum samples from 29 females with seven follicular aspirations and four bulls were used. AMH measurements were performed using the bovine AMH ELISA kit. A positive correlation was identified between oocyte production and blastocyst rate (r = 0.84, P = 9 × 10−9), and AMH levels with oocyte (r = 0.49, P = 0.006) and embryo (r = 0.39, P = 0.03) production. The mean levels of AMH were different between animals with low (11.06 ± 3.01) and high (20.75 ± 4.46) oocyte production (P = 0.01). Males showed high serological levels of AMH (3829 ± 2328 pg/ml) compared with other breeds. It is possible to use the serological measurement of AMH as a method to select Wagyu females with greater capacity for oocyte and embryo production. Further studies correlating AMH serological levels with Sertoli cell function in bulls are needed.

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

Perspectives on past climate using lake sediments are critical for assessing modern and future climate change. These perspectives are especially important for water-stressed regions such as the western United States. One such region is northwestern California (CA), where Holocene-length hydroclimatic records are scarce. Here, we present a 9000-year, relative lake level record from Maddox Lake (CA) using a multi-indicator approach. The Early Holocene is characterized by variably low lake levels with a brief excursion to wetter climates/relative highstand ca. 8.4–8.06 cal ka BP, possibly related to the 8.2 ka cold event and changing Atlantic Meridional Overturning Circulation (AMOC). From 5.2–0.55 cal ka BP, Maddox Lake experienced a long-term regression, tracking changes in summer-winter insolation, tropical and northeast Pacific SSTs, and the southward migration of the ITCZ. This gradual regression culminated in a pronounced relative lowstand during the Medieval Climatic Anomaly (MCA). A marked relative highstand followed the MCA, correlative to the Little Ice Age. The latter reflects a far-field response to North Atlantic volcanism, solar variability, and possibly changes in AMOC and Arctic sea ice extent. Our results further confirm the hydroclimatic sensitivity of northwest California to various forcings including those emanating from the North Atlantic.

Reulceration is a common complication following ray amputations of the foot. The primary aim of this study was to evaluate the incidence of re-ulceration following isolated and combined central ray amputations. This was a retrospective review of 55 consecutive limbs that underwent central ray amputations at Wake Forest Baptist Medical Centers. Procedures were performed at the 3 central rays or a combination of central rays. Incidence of postoperative ulceration was evaluated on the ipsilateral foot. We hypothesized there would not be an association between which ray was resected and development of reulceration. 24 patients (43%) experienced repeat ulceration following a central ray amputation. Median follow up time was 17.4 months (range 4 days to 99 months). The estimated ulcer recurrence rate at 1 year was 41.8%. There was no statistical difference based on location of amputation (second, third, 4 rays) with regards to reulceration, further amputation, transmetatarsal amputation, or below knee amputations. However, reulceration seemed to be much quicker in those patients undergoing a third ray amputation. Like the medial and lateral rays, central ray amputations can be a good initial salvage procedure to clear devitalized tissue and prevent the spreading of infection. The results of the present study suggest that there is no detectable difference between location of central ray amputations and development of re-ulceration, more proximal amputations, or death among this cohort.

In this paper, we present a variational theory of lift that, unlike Kutta’s theory, is derived from first principles in mechanics: Hertz’s principle of least curvature. In this theory, the unique value of circulation is determined by minimizing the Appellian of the flowfield. Interestingly, it recovers the Kutta condition in the special case of an airfoil with a sharp trailing edge. In this paper, we apply such a theory to the classical problem of the flow over a flat plate. The resulting ideal flow does not match Kutta’s solution in this case; it results in a nonlifting solution for any uncambered, fore-aft symmetric shape, confirming experimental findings in superfluids. This result provides necessary conditions for lift generation in an ideal fluid. For a real fluid over a flat plate with a sharp leading edge, viscosity plays an important role, leading to a flow separation at the leading edge, even at small angles of attack. This separation bubble creates asymmetry in the outer inviscid flowfield (outside the bubble), which enables lift. This problem is discussed in the light of the developed variational theory of lift and some historical details about the development of Kutta’s theory.

Trauma-exposed youth often experience impairing externalizing problems (EXTs), yet the relationship between EXTs, trauma exposure, and posttraumatic stress symptoms (PTSS) are not well understood. To examine the extent of their co-occurrence, we report the rates and correlates of youth EXTs relative to clinically elevated PTSS in a sample of youth referred to a trauma and grief specialty clinic.Self- and caregiver-report measures were obtained from 260 youth ages 7-19 years (The 4 groups were comorbid PTSS and EXTs (18%); EXTs-only group (36%); PTSS-only group (13%), and subclinical symptom group (34%). The comorbid PTSS and EXTs group had the highest scores on all other child and caregiver symptom measures. Compared to the subclinical group, youth in the PTSS-only group had increased depressive symptoms and suicidal ideation, whereas youth in the EXTs-only group had elevated levels of caregiver strain.Co-occurring PTSS and EXTs is a common presentation among trauma-exposed youth referred to treatment. These youth are also likely to suffer from other problems of clinical concern, including suicidal ideation, and their problems are associated with caregiver distress. More research is needed to examine unique risk and resiliency factors related to the development of youth EXTs in response to trauma exposure. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Advances in time-resolved structural techniques, mainly in macromolecular crystallography and small-angle X-ray scattering (SAXS), allow for a detailed view of the dynamics of biological macromolecules and reactions between binding partners. Of particular promise, are mix-and-inject techniques, which offer a wide range of experimental possibility as microfluidic mixers are used to rapidly combine two species just prior to data collection. Most mix-and-inject approaches rely on diffusive mixers, which have been effectively used within crystallography and SAXS for a variety of systems, but their success is dependent on a specific set of conditions to facilitate fast diffusion for mixing. The use of a new chaotic advection mixer designed for microfluidic applications helps to further broaden the types of systems compatible with time-resolved mixing experiments. The chaotic advection mixer can create ultra-thin, alternating layers of liquid, enabling faster diffusion so that even more slowly diffusing molecules, like proteins or nucleic acids, can achieve fast mixing on timescales relevant to biological reactions. This mixer was first used in UV–vis absorbance and SAXS experiments with systems of a variety of molecular weights, and thus diffusion speeds. Careful effort was also dedicated to making a loop-loading sample-delivery system that consumes as little sample as possible, enabling the study of precious, laboratory-purified samples. The combination of the versatile mixer with low sample consumption opens the door to many new applications for mix-and-inject studies.

A boundless spectrum of chronic lung diseases is said to effect over 500 million persons globally. Lung transplantation is a well-established therapeutic option for patients suffering from end-stage lung diseases, however waitlist mortality and primary graft failure remain major determinants as post-transplantation 5-year survival is just above 50 percent. Recent innovations in lung transplantation have been aimed at increasing organ availability, improving allograft quality, function, and longevity. Ex-vivo Lung Perfusion (EVLP) is an exciting modality responsible for multiple paths of lung allograft reconditioning as well as significantly extending preservation times. Mechanical circulatory support (MCS), specifically extracorporeal membrane oxygenation (ECMO) has consistently gained popularity not only for its use as a bridge to transplantation, but also its intraoperative role. In tandem, EVLP and ECMO have shown promising results in increasing the number of lung transplantations performed, therefore decreasing waitlist mortality. Primary graft dysfunction (PGD) and chronic lung allograft rejection (CLAD) continue to be the most feared predictors of poor outcomes. In this review we will highlight the historical progression of lung transplantation, its encumbrance, and the most recent advancements in promising techniques for long-term allograft protection and patient survival.