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A community of practice (COP) can offer learning and support as a group of people who come together to share concerns, best practices, or new knowledge about some shared interest or passion. However, creating or joining a COP may present challenges, especially for those whose networks are relatively undeveloped. In this article, we define a COP and share how vicarious learning and crowdsourcing, as pragmatic, relational, and information-gathering processes, offer important benefits to teaching and learning COPs. After discussing how vicarious learning and crowdsourcing can be extended within a COP, we offer specific theory-to-practice learning ideas and suggestions. We end the article with brief insights for other management educators about our own COP experiences.

Using a randomized controlled trial, we investigated changes in both sexual harassment (SH) perpetration and victimization of 2104 middle school students in New York City who received divergent saturation and dosage levels of "Shifting Boundaries," an SH prevention program, which was represented by the length of the program. We assessed the saturation effect of the program by comparing the outcomes across respondents from 26 schools in which there were varying percentages of students enrolled in the program. The data suggested that, overall, the program was effective in reducing sexual harassment victimization but achieved a null effect against respondents' SH perpetration and that neither the length nor the school-saturation level of the program exerted a significant effect on SH perpetration. Although the data indicated a significant difference in SH victimization between the treatment and control group, when comparing subgroups who received treatment with divergent saturation and dosage levels, no statistically significant difference was identified. Our results suggested that the program effect was not contingent on the portion of students in a school who enrolled in the program, nor was it contingent on the dosage.

Abstract Background Tackling poor mental health in university students has been identified as a priority in higher education. However, there are few evidence-based prevention initiatives designed for students. Repetitive Negative Thought (RNT, e.g. worry, rumination) is elevated in university students and is a well-established vulnerability factor for anxiety and depression. Furthermore, there are now evidence-based cognitive-behavioural interventions to tackle RNT. A mobile self-help cognitive-behavioural app targeting RNT, adapted for students may therefore be an effective, scalable, and acceptable way to improve prevention in students. Methods An online single blind, two-arm parallel-group Randomised Controlled Trial (RCT) to examine the incidence of major depression and symptoms of anxiety and depression across 12 months in university students aged over 16 who screen into the study with self-reported high levels of worry and/or rumination and no current diagnosis of major depression. Eligible participants will be randomised to the active intervention arm (usual practice plus using a self-guided mobile app targeting RNT) or to the control arm (usual practice). In total, 648 participants aged over 16, with no current major depression, bipolar disorder or psychosis will be recruited from UK universities. Assessments will take place at baseline (pre-randomisation), 3 months and 12 months post- randomisation. Primary endpoint and outcome is incidence of major depression as determined by self-reported diagnostic criteria at 12-month follow-up. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and academic outcomes are secondary outcomes. Compliance, adverse events, and potentially mediating variables will be carefully monitored. Discussion The trial aims to provide a better understanding of the causal role of tackling RNT (worry, rumination) using a self-help mobile app with respect to preventing depression in university students. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective mobile-health public health strategies for preventing common mental health problems. Trial registration https://www.isrctn.com/ISRCTN86795807 Date of registration: 27 October 2022

Groundwater recharge is a key hydrogeological variable that informs the renewability of groundwater resources. Long-term average (LTA) groundwater recharge provides a measure of replenishment under the prevailing climatic and land-use conditions and is therefore of considerable interest in assessing the sustainability of groundwater withdrawals globally. This study builds on the modelling results by MacDonald et al. (2021), who produced the first LTA groundwater recharge map across Africa using a linear mixed model (LMM) rooted in 134 ground-based studies. Here, continent-wide predictions of groundwater recharge were generated using random forest (RF) regression employing five variables (precipitation, potential evapotranspiration, soil moisture, normalised difference vegetation index (NDVI) and aridity index) at a higher spatial resolution (0.1° resolution) to explore whether an improved model might be achieved through machine learning. Through the development of a series of RF models, we confirm that a RF model is able to generate maps of higher spatial variability than a LMM; the performance of final RF models in terms of the goodness of fit (R2=0.83; 0.88 with residual kriging) is comparable to the LMM (R2=0.86). The higher spatial scale of the predictor data (0.1°) in RF models better preserves small-scale variability from predictor data than the values provided via interpolated LMMs; these may prove useful in testing global- to local-scale models. The RF model remains, nevertheless, constrained by its representation of focused recharge and by the limited range of recharge studies in humid, equatorial Africa, especially in the areas of high precipitation. This confers substantial uncertainty in model estimates.

Abstract Climate change poses a massive and growing threat to wildlife. Calls are growing for coordinated and collaborative responses to conserve species threatened by climate change, but how this works in practice remains largely unexplored. Focusing on seabirds in North‐West Europe, we carried out 32 semi‐structured stakeholder interviews to (1) explore existing conservation work linked to climate change, (2) identify barriers to work on climate change among conservation actors, and (3) identify key conservation actors and characterize their interactions. Interviewees identified a range of research, policy, and practical conservation work for seabirds related—directly or indirectly—to climate change. They highlighted the importance of general conservation work to facilitate seabird adaptation to climate change, and global mitigation of climate change (e.g., through decarbonization and ecosystem restoration). Interviewees identified several barriers to conservation work explicitly addressing climate change, pertaining to information, leadership, resources, and values/beliefs. We discovered that seabird conservation networks are generally well‐established and harmonious, but not tension‐free. There are also some misunderstandings over actor responsibilities that could lead to bystander effects. We present suggestions to increase the effectiveness and efficiency of seabird conservation in response to climate change.

Abstract The immunomodulatory effects of omega-3 and omega-6 fatty acids are a crucial subject of investigation for sustainable fish aquaculture, as fish oil is increasingly replaced by terrestrial vegetable oils in aquafeeds. Unlike previous research focusing on fish oil replacement with vegetable alternatives, our study explored how the omega-6 to omega-3 polyunsaturated fatty acid (PUFA) ratio in low-fish oil aquafeeds influences Atlantic salmon's antiviral and antibacterial immune responses. Atlantic salmon were fed aquafeeds rich in soy oil (high in omega-6) or linseed oil (high in omega-3) for 12 weeks and then challenged with bacterial (formalin-killed Aeromonas salmonicida) or viral-like (polyriboinosinic polyribocytidylic acid) antigens. The head kidneys of salmon fed high dietary omega-3 levels exhibited a more anti-inflammatory fatty acid profile and a restrained induction of pro-inflammatory and neutrophil-related genes during the immune challenges. The high-omega-3 diet also promoted a higher expression of genes associated with the interferon-mediated signaling pathway, potentially enhancing antiviral immunity. This research highlights the capacity of vegetable oils with different omega-6 to omega-3 PUFA ratios to modulate specific components of fish immune responses, offering insights for future research on the intricate lipid nutrition-immunity interplay and the development of novel sustainable low-fish oil clinical aquaculture feeds.

Due to the nature of open-pen farming, salmon are exposed to numerous pathogens shared by other farms and their wild counterparts. Industry must manage these outbreaks through vaccination, oral or bath treatments, and more recently through functional feed administration. Globally, the most important pathogens of salmon are sea lice (Lepeophtheirus salmonis, and Caligus rogercresseyi) not only due to their direct impacts on the host, but indirectly by enhancing host susceptibility to co-infection. This study aims to characterize molecular responses during a co-infection of L. salmonis and a salmon orthomyxovirus (infectious salmon anemia virus; ISAv) under administration of four functional feed diets: a control feed with a low 0.3 % EPA/DHA + high-ω6 (Ctrl), an EPA/DHA enriched pro-inflammatory diet 1 % EPA/DHA + high-ω6; FA + I), an EPA/DHA enriched anti-inflammatory diet (1 % EPA/DHA+high-ω3; FA-I), and a low EPA/DHA feed (0.3 %) with an immunostimulant added (0.3 % EPA/DHA + high-ω6 + immunostimulant (IS); Ctrl + IS). Atlantic salmon (40 fish per tank; 8 tanks per feed) were acclimated to one of the four experimental diets. Sea lice copepodids were introduced to all experimental tanks and 10 fish sampled from each tank at each time point (prior to infection [−3], and 11, 33, 47 days post infection). A high virulence ISAv isolate (ISAV-HPR4) was intraperitoneally injected into donor fish 6 days prior to their transfer into the experimental tanks for cohabitation (ca. 10–15 % of tank density; 4 tanks per feed group) to achieve peak shedding rates at time of stocking. Fatty acid enriched (FA + I and FA-I) diets had a significant impact on sea lice abundance on fish infected with lice only. Gene expression profiles measured by reverse transcriptase-qPCR showed significant upregulation in several antiviral genes (irf7b and mxb) associated with the interferon system in all but the fish fed the immunostimulating diet. An increase in transcript levels (irf7b, isg15a, mmp-9, mxb) accounted for high lice and high viral loads in diets FA + I and Ctrl + IS. As feeds successful at reducing lice were the least successful in survival of co-infected fish, there appears to be a trade-off for better anti-parasitic responses, which is enhanced through dietary supplementation. This will require further research to ensure careful selection of feed combinations and expected co-infection challenges.

The COVID-19 pandemic, polarized politics, and heightened stigma and discrimination are salient drivers for negative mental health outcomes, particularly among marginalized racial and ethnic minoritized groups. Intersectionality of race, ethnicity, foreign-born status, and educational attainment may distinctively shape an individual's experience of discrimination and mental health during such unprecedented time. The present study examines the differential associations of racial discrimination and mental health based on an individual's race, ethnicity, foreign-born status, and educational attainment during the COVID-19 pandemic. Analyses were based on a nationally representative sample of U.S. adults collected between October and November 2021 (n = 6276). We utilized multivariable linear regressions to identify the multiplicative effects of race, ethnic, foreign-born status and self-reported racial discrimination on mental health, stratified by educational attainment. Among individuals with lower educational attainment, associations between racial discrimination and poor mental health were stronger among Asians (US-born: β = −2.07, p = 0.03; foreign-born: β = −3.18, p = 0.02) and US-born multiracial individuals (β = −1.96, p = 0.02) than their White counterparts. Among individuals with higher educational attainment, foreign-born Hispanics (β = − 3.66, p

Abstract Background A collective trauma like COVID-19 impacts individuals differently due to socio-contextual and individual characteristics. Younger adults, minorities, affiliates of certain political parties, and residents of some regions of the United States reported experiencing poorer mental health during the pandemic. Being diagnosed with COVID-19, or losing a friend/family to it, was related to more adverse mental health symptoms. While the negative impact of COVID-19 on health outcomes has been studied, mental health changes during this pandemic need further exploration. Methods In a study of 8,612 U.S. households, using three surveys collected from a nationally representative panel between May 2020 and October 2021, using a repeated cross-sectional design, a linear mixed effect regression model was performed to investigate factors associated with the mental health status, based on the Mental Health Inventory-5, of individuals throughout different phases of the COVID-19 pandemic, and whether an improvement over time, especially after vaccines became available, was observed. Results An overall improvement in mental health was observed after vaccines became available. Individuals with no COVID-related death in their household, those not wearing masks, those identifying as members of the Republican Party, race/ethnicities other than Asian, men, older adults, and residents of the South were less likely than others to report mental health challenges. Conclusions Our results highlight the need for widespread mental health interventions and health promotion to address challenges during the COVID-19 pandemic and beyond. Due to the worse mental health observed among Asians, younger adults, women, low-income families, those with a higher level of concern for COVID-19, people who lost someone to COVID-19, and/or individuals with histories of opioid use disorder and criminal legal involvement, over the period of this study, targeted attention needs to be given to the mental health of these groups.

As most disease causing pathogens require transmission from an infectious individual to a susceptible individual, continued persistence of the pathogen within the population requires the replenishment of susceptibles through births, immigration, or waning immunity.Consider the introduction of an unknown infectious disease into a fully susceptible population where it is not known how long immunity is conferred once an individual recovers from infection. If, initially, the prevalence of disease increases (that is, the infection takes off), the number of infectives will usually decrease to a low level after the first major outbreak. During this post-outbreak period, the disease dynamics may be influenced by stochastic effects and there is a non-zero probability that the epidemic will die out. Die out in this period following the first major outbreak is known as an epidemic fade-out. If the disease does not die out, the susceptible population may be replenished by the waning of immunity, and a second wave may start.In this study, we investigate if the rate of waning immunity (and other epidemiological parameters) can be reliably estimated from multiple outbreak data, in which some outbreaks display epidemic fade-out and others do not. We generated synthetic outbreak data from independent simulations of stochastic SIRS models in multiple communities. Some outbreaks faded-out and some did not. We conducted Bayesian parameter estimation under two alternative approaches: independently on each outbreak and under a hierarchical framework. When conducting independent estimation, the waning immunity rate was poorly estimated and biased towards zero when an epidemic fade-out was observed. However, under a hierarchical approach, we obtained more accurate and precise posterior estimates for the rate of waning immunity and other epidemiological parameters. The greatest improvement in estimates was obtained for those communities in which epidemic fade-out was observed.Our findings demonstrate the feasibility and value of adopting a Bayesian hierarchical approach for parameter inference for stochastic epidemic models.

There is widespread recognition of the need for new homes to feature only low or zero-carbon (LZC) heating. However, residential developers continue to choose conventional high-carbon options such as natural gas boilers over net-zero compatible alternatives. This study explores how UK local authorities (LAs) within the English planning system can encourage residential developers to deploy LZC heating systems within their projects. We adopt an embedded case study design and analyse 30 residential project proposals within two LA areas. Our study examines local planning policies and interactions between developers and LA officers, along with the resultant outcomes, through documentary analysis and expert interviews with local stakeholders. We find that LAs can encourage developers to adopt LZC heating technologies above and beyond what is required nationally. The conditions for this to occur are (1) a planning policy which restricts allowable heating technology options, (2) empowering LA officers to enforce policies, (3) advice and support for developers to consider alternatives, and where necessary, (4) political backing to challenge unwilling developers. Study findings highlight the important role of LAs in creating the conditions for the transition to LZC heating, which show how they can use powers within the planning system to encourage developers to make low carbon choices without the need for direct investment.

The salinisation of freshwater resources is a priority concern in Asian mega-deltas including the Bengal Basin of Bangladesh where the livelihoods, ecosystem services and health of coastal populations are increasingly under threat. Understanding trends and variations in surface water salinity is required to inform sustainable use of freshwater supplies in the face of hydrological regimes intensified by global environmental change. We interrogate 86 time series of fortnightly records of in situ surface water salinity between 1990 and 2019. Statistical and geospatial techniques were employed to characterise spatiotemporal distributions and trends in surface water salinity and identify key drivers of change in the coastal region of Bangladesh. The observed spatiotemporal structure in surface water salinity is primarily controlled by the magnitude and seasonality of river discharge entering the delta. In the moribund delta north of the Sundarbans, the contour between fresh and brackish water migrates seasonally between ~20 and ~40 km northward during the dry season. Abrupt increases in surface water salinity are observed throughout the coastal region in response to variations in upstream river discharge; the prominence of these events highlights their importance in driving salinity increases. Areas which are better connected to more voluminous seasonal river discharge (active delta), show greater recovery to these episodic inundations by cyclones than those less-well flushed by river discharge (moribund delta). Our reported observations provide a baseline for understanding the consequences of global environmental change and informing more climate-resilient adaptation strategies in coastal environments of Bangladesh and other Asian mega-deltas.

Given the rapid expansion of offshore wind development in the United States (US), the accurate mapping of benthic habitats, specifically surficial sediments, is essential for mitigating potential impacts on these valuable ecosystems. However, offshore wind development has outpaced results from environmental monitoring efforts, compelling stakeholders to rely on a limited set of public geospatial data for conducting impact assessments. The present study therefore sought to develop and evaluate a systematic workflow for generating regional-scale sediment maps using public geospatial data that may pose integration and modeling challenges. To demonstrate this approach, sediment distributions were characterized on the northeastern US continental shelf where offshore wind development has occurred since 2016. Publicly available sediment and bathymetric data in the region were processed using national classification standards and spatial tools, respectively, and integrated using a machine learning algorithm to predict sediment occurrence. Overall, this approach and the generated sediment composite effectively predicted sediment distributions in coastal areas but underperformed in offshore areas where data were either scarce or of poor quality. Despite these shortcomings, this study builds on benthic habitat mapping efforts and highlights the need for regional collaboration to standardize seafloor data collection and sharing activities for supporting offshore wind energy decisions.

Abstract Previous immunological studies in the eastern USA have failed to establish a direct connection between Paleoamericans and extinct megafauna species. The lack of physical evidence for the presence of extinct megafauna begs the question, did early Paleoamericans regularly hunt or scavenge these animals, or were some megafauna already extinct? In this study of 120 Paleoamerican stone tools from across North and South Carolina, we investigate this question using crossover immunoelectrophoresis (CIEP). We find immunological support for the exploitation of extant and extinct megafauna, including Proboscidea, Equidae, and Bovidae (possibly Bison antiquus), on Clovis points and scrapers, as well as possible early Paleoamerican Haw River points. Post-Clovis points tested positive for Equidae and Bovidae but not Proboscidea. Microwear results are consistent with projectile usage, butchery, fresh- and dry hide scraping, the use of ochre-coated dry hides for hafting, and dry hide sheath wear. This study represents the first direct evidence of the exploitation of extinct megafauna by Clovis and other Paleoamerican cultures in the Carolinas and more broadly, across the eastern United States, where there is generally poor to non-existent faunal preservation. Future CIEP analysis of stone tools may provide evidence on the timing and demography of megafaunal collapse leading to eventual extinction.

Abstract The head‐to‐head oriented pair of melon resistance genes, Fom‐1 and Prv, control resistance to Fusarium oxysporum races 0 and 2 and papaya ringspot virus (PRSV), respectively. They encode, via several RNA splice variants, TIR‐NBS‐LRR proteins, and Prv has a C‐terminal extra domain with a second NBS homologous sequence. In other systems, paired R‐proteins were shown to operate by “labor division,” with one protein having an extra integrated domain that directly binds the pathogen's Avr factor, and the second protein executing the defense response. We report that the expression of the two genes in two pairs of near‐isogenic lines was higher in the resistant isoline and inducible by F. oxysporum race 2 but not by PRSV. The intergenic DNA region separating the coding sequences of the two genes acted as a bi‐directional promoter and drove GUS expression in transgenic melon roots and transgenic tobacco plants. Expression of both genes was strong in melon root tips, around the root vascular cylinder, and the phloem and xylem parenchyma of tobacco stems and petioles. The pattern of GUS expression suggests coordinated expression of the two genes. In agreement with the above model, Prv's extra domain was shown to interact with the cylindrical inclusion protein of PRSV both in yeast cells and in planta.

Summary: Sickle cell disease (SCD) is characterized by hemolysis, vaso-occlusion, and ischemia. HIV-1 infection was previously shown to be suppressed in SCD PBMCs. Here, we report that HIV-1 suppression is attributed to the increased expression of iron, hypoxia, and interferon-induced innate antiviral factors. Inhibition of upregulated antiviral genes, HMOX-1, CDKN1A, and CH25H, increased HIV-1 replication in SCD PBMCs, suggesting their critical role in HIV-1 suppression. Levels of IFN-β were elevated in SCD patients. Sickle cell hemoglobin (HbS) treatment of THP-1-derived and primary monocyte-derived macrophages induced production of IFN-β, upregulated antiviral gene expression, and suppressed HIV-1 infection. Infection with mouse-adapted EcoHIV was suppressed in the SCD mice that also exhibited elevated levels of antiviral restriction factors. Our findings suggest that hemolysis and release of HbS leads to the induction of IFN-β production, induction of cellular antiviral state by the expression of iron and IFN-driven factors, and suppression of HIV-1 infection.

We present cosmological constraints from the sample of Type Ia supernovae (SNe Ia) discovered and measured during the full 5 yr of the Dark Energy Survey (DES) SN program. In contrast to most previous cosmological samples, in which SNe are classified based on their spectra, we classify the DES SNe using a machine learning algorithm applied to their light curves in four photometric bands. Spectroscopic redshifts are acquired from a dedicated follow-up survey of the host galaxies. After accounting for the likelihood of each SN being an SN Ia, we find 1635 DES SNe in the redshift range 0.10 < z < 1.13 that pass quality selection criteria sufficient to constrain cosmological parameters. This quintuples the number of high-quality z > 0.5 SNe compared to the previous leading compilation of Pantheon+ and results in the tightest cosmological constraints achieved by any SN data set to date. To derive cosmological constraints, we combine the DES SN data with a high-quality external low-redshift sample consisting of 194 SNe Ia spanning 0.025 < z < 0.10. Using SN data alone and including systematic uncertainties, we find Ω _M = 0.352 ± 0.017 in flat ΛCDM. SN data alone now require acceleration ( q _0 < 0 in ΛCDM) with over 5 σ confidence. We find $({{\rm{\Omega }}}_{{\rm{M}}},w)=({0.264}_{-0.096}^{+0.074},-{0.80}_{-0.16}^{+0.14})$ in flat w CDM. For flat w _0 w _a CDM, we find $({{\rm{\Omega }}}_{{\rm{M}}},{w}_{0},{w}_{a})=({0.495}_{-0.043}^{+0.033},-{0.36}_{-0.30}^{+0.36},-{8.8}_{-4.5}^{+3.7})$ , consistent with a constant equation of state to within ∼2 σ . Including Planck cosmic microwave background, Sloan Digital Sky Survey baryon acoustic oscillation, and DES 3 × 2pt data gives (Ω _M , w ) = (0.321 ± 0.007, −0.941 ± 0.026). In all cases, dark energy is consistent with a cosmological constant to within ∼2 σ . Systematic errors on cosmological parameters are subdominant compared to statistical errors; these results thus pave the way for future photometrically classified SN analyses.

Criminal legal system involvement (CLI) is a critical social determinant of health that lies at the intersection of multiple sources of health disparities. The COVID-19 pandemic exacerbates many of these disparities, and specific vulnerabilities faced by the CLI population. This study investigated the prevalence of COVID-19-related misinformation, as well as its relationship with COVID-19 information sources used among Americans experiencing CLI. A nationally representative sample of American adults aged 18+ (N = 1,161), including a subsample of CLI individuals (n = 168), were surveyed in February-March 2021. On a 10-item test, CLI participants endorsed a greater number of misinformation statements (M = 1.88 vs. 1.27) than non-CLI participants, p < .001. CLI participants reported less use of government and scientific sources (p = .017) and less use of personal sources (p = .003) for COVID-19 information than non-CLI participants. Poisson models showed that use of government and scientific sources was negatively associated with misinformation endorsement for non-CLI participants (IRR = .841, p < .001), but not for CLI participants (IRR = .957, p = .619). These findings suggest that building and leveraging trust in important information sources are critical to the containment and mitigation of COVID-19-related misinformation in the CLI population.

Objectives Aspirin could be offered for colorectal cancer prevention for the UK general population. To ensure the views of the general population are considered in future guidance, we explored public perceptions of aspirin for preventive therapy.Design We conducted an online survey to investigate aspirin use, and awareness of aspirin for cancer prevention among the UK general population. We conducted semistructured interviews with a subsample of survey respondents to explore participants’ acceptability towards aspirin for cancer preventive therapy. We analysed the interview data using reflexive thematic analysis and mapped the themes onto the Theoretical Domains Framework, and the Necessity and Concerns Framework.Setting Online survey and remote interviews.Participants We recruited 400 UK respondents aged 50–70 years through a market research company to the survey. We purposefully sampled, recruited and interviewed 20 survey respondents.Results In the survey, 19.0% (76/400) of respondents were aware that aspirin can be used to prevent cancer. Among those who had previously taken aspirin, 1.9% (4/216) had taken it for cancer prevention. The interviews generated three themes: (1) perceived necessity of aspirin; (2) concerns about side effects; and (3) preferred information sources. Participants with a personal or family history of cancer were more likely to perceive aspirin as necessary for cancer prevention. Concerns about taking aspirin at higher doses and its side effects, such as gastrointestinal bleeding, were common. Many described wanting guidance and advice on aspirin to be communicated from sources perceived as trustworthy, such as healthcare professionals.Conclusions Among the general population, those with a personal or family history of cancer may be more receptive towards taking aspirin for preventive therapy. Future policies and campaigns recommending aspirin may be of particular interest to these groups. Multiple considerations about the benefits and risks of aspirin highlight the need to support informed decisions on the medication.

Abstract Rare-earth and actinide complexes are critical for a wealth of clean-energy applications. Three-dimensional (3D) structural generation and prediction for these organometallic systems remains a challenge, limiting opportunities for computational chemical discovery. Here, we introduce Architector, a high-throughput in-silico synthesis code for s-, p-, d-, and f-block mononuclear organometallic complexes capable of capturing nearly the full diversity of the known experimental chemical space. Beyond known chemical space, Architector performs in-silico design of new complexes including any chemically accessible metal-ligand combinations. Architector leverages metal-center symmetry, interatomic force fields, and tight binding methods to build many possible 3D conformers from minimal 2D inputs including metal oxidation and spin state. Over a set of more than 6,000 x-ray diffraction (XRD)-determined complexes spanning the periodic table, we demonstrate quantitative agreement between Architector-predicted and experimentally observed structures. Further, we demonstrate out-of-the box conformer generation and energetic rankings of non-minimum energy conformers produced from Architector, which are critical for exploring potential energy surfaces and training force fields. Overall, Architector represents a transformative step towards cross-periodic table computational design of metal complex chemistry.

The shift of proton pump inhibitors (PPIs) from prescription to nonprescription (nonRx) status in Canada has altered pharmacist treatment options for heartburn. This report examines pharmacist approaches to therapy based on case severity; pharmacist confidence and consult duration were also explored. A 2022 online survey gathered data from Ontario and Québec pharmacists regarding their therapeutic approaches for two hypothetical heartburn cases. A total of 715 pharmacists participated, with most having 1–10 years of experience. In Ontario, common choices for the milder case included a solo histamine-2 receptor antagonist (H2RA) (21.2%), combination H2RA + antacid (29.4%), and nonRx PPI (22.3%). For the more severe case, common choices for Québec were switches to nonRx H2RA (22.1%), combination H2RA + antacid (13.4%), a nonRx PPI (24.9%), or prescription PPI (22.5%). Pharmacists often recommended switching medications or referring patients with recurring symptoms after seven days. The approaches varied significantly between cases and provinces. The Ontario pharmacists favoured a combination H2RA + antacid for the milder case, while the Québec pharmacists preferred a solo H2RA. For the more severe case, both groups often chose nonRx H2RA followed by nonRx PPI. Despite the differences, the pharmacists demonstrated confidence in managing these situations. These findings highlight potential debates regarding optimal therapeutic approaches and the impact of drug scheduling on patient care.

Reported herein is the development of assays for the spectrophotometric quantification of biocatalytic silicon−oxygen bond hydrolysis. Central to these assays are a series of chromogenic substrates that release highly absorbing phenoxy anions upon cleavage of the sessile bond. These substrates were tested with silicatein, an enzyme from a marine sponge that is known to catalyse the hydrolysis and condensation of silyl ethers. It was found that, of the substrates tested, tert-butyldimethyl(2-methyl-4-nitrophenoxy)silane provided the best assay performance, as evidenced by the highest ratio of enzyme catalysed reaction rate compared with the background (uncatalysed) reaction. These substrates were also found to be suitable for detailed enzyme kinetics measurements, as demonstrated by their use to determine the Michaelis−Menten kinetic parameters for silicatein.

The influenza pandemic of 1918-19 was the most devastating pandemic of the 20th century. It killed an estimated 50-100 million people worldwide. In late 1918, when the severity of the disease was apparent, the Australian Quarantine Service was established. Vessels returning from overseas and inter-state were intercepted, and people were examined for signs of illness and quarantined. Some of these vessels carried the infection throughout their voyage and cases were prevalent by the time the ship arrived at a Quarantine Station. We study four outbreaks that took place on board the Medic, Boonah, Devon, and Manuka in late 1918. These ships had returned from overseas and some of them were carrying troops that served in the First World War. By analysing these outbreaks under a stochastic Bayesian hierarchical modeling framework, we estimate the transmission rates among crew and passengers aboard these ships. Furthermore, we ask whether the removal of infectious, convalescent, and healthy individuals after arriving at a Quarantine Station in Australia was an effective public health response.

Clinical trials often collect intermediate or surrogate endpoints other than their true endpoint of interest. It is important that the treatment effect on the surrogate endpoint accurately predicts the treatment effect on the true endpoint. There are settings in which the proposed surrogate endpoint is positively correlated with the true endpoint, but the treatment has opposite effects on the surrogate and true endpoints, a phenomenon labeled “surrogate paradox”. Covariate information may be useful in predicting an individual’s risk of surrogate paradox. In this work, we propose methods for incorporating covariates into measures of assessing the risk of surrogate paradox using the meta-analytic causal association framework. The measures calculate the probability that a treatment will have opposite effects on the surrogate and true endpoints and determine the size of a positive treatment effect on the surrogate endpoint that would reduce the risk of a negative treatment effect on the true endpoint as a function of covariates, allowing the effects of covariates on the surrogate and true endpoint to vary across trials.

There are limitations with current protein sensing methods. Here the authors report DigitISA, a digital immunosensor assay based on microchip electrophoretic separation and single-molecule detection that enables quantitation of protein biomarkers in a single, solution-phase step.

It is often difficult to compile and synthesise evidence across multiple studies to inform policy and practice because different outcomes have been measured in different ways or datasets and models have not been fully or consistently reported. In the case of peatlands, a critical terrestrial carbon store, this lack of consistency hampers the evidence-based decisions in policy and practice that are needed to support effective restoration and conservation. This study adapted methods pioneered in the medical community to reach consensus over peatland outcomes that could be consistently measured and reported to improve the synthesis of data and reduce research waste. Here we report on a methodological framework for identifying, evaluating and prioritising the outcomes that should be measured. We discuss the subsequent steps to standardise methods for measuring and reporting outcomes in peatland research and monitoring. The framework was used to identify and prioritise sets of key variables (known as core domain sets) for UK blanket and raised bogs, and for tropical peat swamps. Peatland experts took part in a structured elicitation and prioritisation process, comprising two workshops and questionnaires, that focused on climate (32 and 18 unique outcomes for UK and tropical peats, respectively), hydrology (26 UK and 16 tropical outcomes), biodiversity (8 UK and 22 tropical outcomes) and fire-related outcomes (13, for tropical peatlands only). Future research is needed to tackle the challenges of standardising methods for data collection, management, analysis, reporting and re-use, and to extend the approach to other types of peatland. The process reported here is a first step towards creating datasets that can be synthesised to inform evidence-based policy and practice, and contribute towards the conservation, restoration and sustainable management of this globally significant carbon store.

An individual tagging model was implemented within the spatial, seasonal, multi-stock, multi-fleet operating models of the peer-reviewed Management Strategy Evaluation (MSE) framework for Atlantic bluefin tuna to evaluate the benefits of a harvest strategy that utilizes conventional gene tagging. A multi-year Brownie estimator was developed to test the accuracy and precision of exploitation rate estimates arising from gene tagging programs with various scenarios for spatial release distribution, release numbers and fishery exploitation rates. Harvest strategies that used the Brownie estimator were tested to evaluate yield and resource conservation performance relative to idealized management using perfect information. For the eastern stock, releasing 1,000 fish throughout the Atlantic and genotyping 27% of all landed fish at an estimated cost of US$2M was sufficient to obtain estimates of exploitation rate with a coefficient of variation of 20%. For the western stock, the same precision in exploitation rate estimates required the release of 1,300 fish and genotyping rate of 35% at an estimated cost of US$2.5M. Harvest strategies using the gene tagging data provided expected yield and resource conservation performance that was not substantially lower than a harvest strategy assuming using perfect information regarding vulnerable biomass. Reducing the number of releases most strongly affected the worst-case ‘lower-tail’ outcomes for West area yield and eastern stock biomass. Conventional gene tagging harvest strategies offer a promising basis for calculating management advice for Atlantic bluefin tuna that may be cheaper, simpler, and more robust than the current conventional stock assessment paradigm.

Abstract Conservation guidance—an authoritative source of information and recommendations explicitly supporting decision‐making and action regarding nature conservation—represents an important tool to communicate evidence‐based advice to conservation actors. Given the rapidly increasing pressure that climate change poses to biodiversity, producing accessible, well‐informed guidance on how to best manage the impacts and risks of changing climatic conditions is particularly urgent. Guidance documents should ideally be produced with multistage input from stakeholders who are likely to use and implement such advice; however, this step can be complicated and costly, and remains largely unformalized. Moreover, there is currently little direct evidence synthesized for actions that specifically target climate change and guidance remains largely absent. Here, we introduce a process for co‐developing guidance for species conservation in the face of climate change, using seabirds in the North‐East Atlantic as a case study. Specifically, we collated evidence on climate change vulnerability and possible conservation actions using literature synthesis, stakeholder surveys, and ecological modeling. This evidence base was then discussed, refined, and expanded using structured stakeholder workshops. We summarize the knowledge gained through stakeholder engagement and provide recommendations for future international efforts to co‐produce conservation guidance for managing wildlife, in the context of a rapidly changing climate.

Background: In recent years, interest in prognostic calculators for predicting patient health outcomes has grown with the popularity of personalized medicine. These calculators, which can inform treatment decisions, employ many different methods, each of which has advantages and disadvantages. Methods: We present a comparison of a multistate model (MSM) and a random survival forest (RSF) through a case study of prognostic predictions for patients with oropharyngeal squamous cell carcinoma. The MSM is highly structured and takes into account some aspects of the clinical context and knowledge about oropharyngeal cancer, while the RSF can be thought of as a black-box non-parametric approach. Key in this comparison are the high rate of missing values within these data and the different approaches used by the MSM and RSF to handle missingness. Results: We compare the accuracy (discrimination and calibration) of survival probabilities predicted by both approaches and use simulation studies to better understand how predictive accuracy is influenced by the approach to (1) handling missing data and (2) modeling structural/disease progression information present in the data. We conclude that both approaches have similar predictive accuracy, with a slight advantage going to the MSM. Conclusions: Although the MSM shows slightly better predictive ability than the RSF, consideration of other differences are key when selecting the best approach for addressing a specific research question. These key differences include the methods’ ability to incorporate domain knowledge, and their ability to handle missing data as well as their interpretability, and ease of implementation. Ultimately, selecting the statistical method that has the most potential to aid in clinical decisions requires thoughtful consideration of the specific goals.

Truncating mutations in filamin C (FLNC) are associated with dilated cardiomyopathy and arrhythmogenic cardiomyopathy. FLNC is an actin-binding protein and is known to interact with transmembrane and structural proteins; hence, the ablation of FLNC in cardiomyocytes is expected to dysregulate cell adhesion, cytoskeletal organization, sarcomere structural integrity, and likely nuclear function. Our previous study showed that the transcriptional profiles of FLNC homozygous deletions in human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are highly comparable to the transcriptome profiles of hiPSC-CMs from patients with FLNC truncating mutations. Therefore, in this study, we used CRISPR-Cas-engineered hiPSC-derived FLNC knockout cardiac myocytes as a model of FLNC cardiomyopathy to determine pathogenic mechanisms and to examine structural changes caused by FLNC deficiency. RNA sequencing data indicated the significant upregulation of focal adhesion signaling and the dysregulation of thin filament genes in FLNC-knockout (FLNCKO) hiPSC-CMs compared to isogenic hiPSC-CMs. Furthermore, our findings suggest that the complete loss of FLNC in cardiomyocytes led to cytoskeletal defects and the activation of focal adhesion kinase. Pharmacological inhibition of PDGFRA signaling using crenolanib (an FDA-approved drug) reduced focal adhesion kinase activation and partially normalized the focal adhesion signaling pathway. The findings from this study suggest the opportunity in repurposing FDA-approved drug as a therapeutic strategy to treat FLNC cardiomyopathy.

Nongravitational accelerations in the absence of observed activity have recently been identified on near-Earth objects (NEOs), opening the question of the prevalence of anisotropic mass loss in the near-Earth environment. Motivated by the necessity of nongravitational accelerations to identify 2010 VL _65 and 2021 UA _12 as a single object, we investigate the problem of linking separate apparitions in the presence of nongravitational perturbations. We find that nongravitational accelerations on the order of 1 × 10 ^–9 au day ^−2 can lead to a change in plane-of-sky positions of ∼1 × 10 ^3 arcsec between apparitions. Moreover, we inject synthetic tracklets of hypothetical nongravitationally accelerating NEOs into the Minor Planet Center orbit identification algorithms. We find that at large nongravitational accelerations (∣ A _i ∣ ≥ 1 × 10 ^−8 au day ^−2 ) these algorithms fail to link a significant fraction of these tracklets. We further show that if orbits can be determined for both apparitions, the tracklets will be linked regardless of nongravitational accelerations, although they may be linked to multiple objects. In order to aid in the identification and linkage of nongravitationally accelerating objects, we propose and test a new methodology to search for unlinked pairs. When applied to the current census of NEOs, we recover the previously identified case but identify no new linkages. We conclude that current linking algorithms are generally robust to nongravitational accelerations, but objects with large nongravitational accelerations may potentially be missed. While current algorithms are well-positioned for the anticipated increase in the census population from future survey missions, it may be possible to find objects with large nongravitational accelerations hidden in isolated tracklet pairs.

We present the full Hubble diagram of photometrically classified Type Ia supernovae (SNe Ia) from the Dark Energy Survey supernova program (DES-SN). DES-SN discovered more than 20,000 SN candidates and obtained spectroscopic redshifts of 7000 host galaxies. Based on the light-curve quality, we select 1635 photometrically identified SNe Ia with spectroscopic redshift 0.10 < z < 1.13, which is the largest sample of supernovae from any single survey and increases the number of known z > 0.5 supernovae by a factor of 5. In a companion paper, we present cosmological results of the DES-SN sample combined with 194 spectroscopically classified SNe Ia at low redshift as an anchor for cosmological fits. Here we present extensive modeling of this combined sample and validate the entire analysis pipeline used to derive distances. We show that the statistical and systematic uncertainties on cosmological parameters are ${\sigma }_{{{\rm{\Omega }}}_{M},\mathrm{stat}+\mathrm{sys}}^{{\rm{\Lambda }}\mathrm{CDM}}=$ 0.017 in a flat ΛCDM model, and $({\sigma }_{{{\rm{\Omega }}}_{M}},{\sigma }_{w}{)}_{\mathrm{stat}+\mathrm{sys}}^{w\mathrm{CDM}}$ = (0.082, 0.152) in a flat w CDM model. Combining the DES SN data with the highly complementary cosmic microwave background measurements by Planck Collaboration reduces by a factor of 4 uncertainties on cosmological parameters. In all cases, statistical uncertainties dominate over systematics. We show that uncertainties due to photometric classification make up less than 10% of the total systematic uncertainty budget. This result sets the stage for the next generation of SN cosmology surveys such as the Vera C. Rubin Observatory's Legacy Survey of Space and Time.

The classical Neumann boundary value problem of an isotropic, homogeneous elastic half-plane under plane strain conditions is readdressed as the limiting case of the fully three-dimensional problem. Analytical solutions of the stress and strain tensors are obtained by taking the limit from known three-dimensional solutions. It is shown that the displacement fields for the plane strain problem are not well defined. A small number of simple expressions are developed, which provide a general solution for linearly-varying traction over arbitrary regions on the boundary. A simple, efficient, and rapidly convergent algorithm is developed which uses these solutions as analytic elements and provides a solution approach to the general boundary value problem. The method is verified against known solutions for Hertzian contact between parallel cylinders. Two numerical examples are presented for the analysis of shallow foundation systems. In the first, the boundary conditions are informed by analytical elastoplastic calculations and a strain influence analysis is performed and compared with the Schmertmann method. Subsequently, empirical laboratory contact traction distributions measured by Bauer et al., in both the normal and tangential directions are employed as boundary conditions for an analysis of the underlying stress field.

Abstract Background The National Institute for Health and Care Excellence (NG151) recommends considering daily aspirin for people with Lynch syndrome to reduce colorectal cancer risk. However, deciding whether to initiate aspirin could be a complex decision for patients and their healthcare providers, as both the potential benefits and harms need to be considered. Methods We conducted semi-structured interviews to explore the barriers and facilitators to using aspirin for preventive therapy. We recruited 15 people with Lynch syndrome, and 23 healthcare providers across multiple professions in primary, and specialist care (e.g. clinical genetics) in the United Kingdom. Interview schedules were informed by the Theoretical Domains Framework. Results There were three themes: 1) Considering potential harms and benefits; 2) Healthcare pathway; 3) Patients’ level of interest in aspirin. All healthcare providers, across primary and specialist care, viewed general practitioners (GPs) as being responsible for prescribing and overseeing the use of aspirin. However, GPs were unfamiliar with aspirin for preventive therapy, and concerned about prescribing at higher doses (300-600 mg). To support decision-making, GPs wanted clarification from specialist clinicians on the evidence and dose to prescribe. Not all participants with Lynch syndrome received information on aspirin from their healthcare provider, and several were unsure who to discuss aspirin with. GPs were more inclined to prescribe aspirin for patients with expressed preferences for the medication, however several patients were uncertain and wanted further guidance. Conclusions Coordinated and multilevel strategies are needed, addressing the needs of both GPs and people with Lynch syndrome, to ensure consistent implementation of national guidance on aspirin for preventive therapy.

Abstract In low‐income urban areas of major cities in Africa, sanitation provision derives primarily from onsite systems often comprising septic tanks and pit latrines. Such systems rely upon the ability of the surrounding soil and substratum to attenuate contaminants like nitrate and pathogenic microorganisms in wastewater. Here, we assess soil–water and solute dynamics in Quaternary aeolian sands underlying a densely populated suburb (Keur Massar) of Dakar (Senegal) using high‐frequency monitoring and vadose zone modeling (Hydrus‐1D). Observations of rainfall intensity, soil moisture content, and shallow groundwater‐level fluctuations and nitrate concentrations were carried out at an experimental site adjacent to a septic tank supplied by toilets used by a primary school. Rapid rises in soil moisture content and episodic recharge contributions observed in groundwater levels caused by heavy (>10 mm h−1) and extreme (>20 mm h−1) rainfall are well modeled (R2 = .79–.83; RMSE = 0.012–0.019) by pore‐matrix flow in the unsaturated zone by the Darcy–Richards equation. Spot sampling around the most intense rainfall of 2020 (45 mm h−1) reveals a fivefold rise and fall in the concentration of nitrate in soil moisture (∼500 to ∼2,500 mg L−1). These measurements provide new insight into the hydrological dynamics by which shallow groundwater is grossly contaminated (>500 mg L−1) by nitrate through episodic flushing by heavy rainfall of wastewater from a vast estimated network of over 250,000 septic tanks underlying this suburb of Dakar.

Background: Monocytes play a large role in chronic inflammatory conditions such as obesity, atherosclerosis and infection. Marine-derived omega-3 fatty acids such as docosahexaenoic acid (DHA) beneficially alter immune function and attenuate chronic inflammation in part by modifying gene expression. Comparisons with plant-derived omega-3 α-linolenic acid (ALA) on immune cell gene expression and function are limited. Methods: Transcriptome analysis was performed on THP-1 human monocytes treated with ALA, DHA or vehicle for 48 hr using fold change analysis, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), variable importance analysis (VIP), and ingenuity pathway analysis (IPA). Candidate genes were validated by qPCR. Functional assays evaluated the transcriptomic predictions. Expression of candidate transcripts identified in THP-1 cells were examined in PBMC from clinical trial (OXBIO; NCT 03583281) participants consuming ALA- or DHA-rich oil supplements. Findings: ALA and DHA-treated monocytes presented distinct transcriptomic profiles as per VIP and PLS-DA. Both fatty acids were predicted to reduce cellular cholesterol content, while ALA would uniquely increase response to infection and chemotactic signals. Functional assays revealed ALA and DHA decreased cholesterol content. DHA significantly decreased the response to infection and chemotaxis, but ALA had no effect. Candidate transcripts responded similarly in PBMC from n-3 PUFA supplemented women with obesity. Conclusion: ALA and DHA differentially alter the transcription profiles and functions associated with the response to infection, chemotaxis, and cholesterol metabolism in mononuclear immune cells. Thus, they may uniquely affect related disease processes contributing to obesity, atherosclerosis, and the response to infection.

Leiomyomas are a common type of benign soft tissue tumor arising from smooth muscle, most often occurring within females’ genitourinary and gastrointestinal tract. However, primary leiomyomas of the chest wall residing in the extra-pleural space are an extremely rare subset of leiomyomatous lesion presentation. We present a case of a fifty-two-year-old male who initially presented complaining of dyspnea worsening with exertion. Computed tomography imaging was performed showing an extra-pleural mass residing under the left sixth rib. Subsequent core needle biopsy and immunohistochemical staining were performed, and the definitive diagnosis of primary leiomyoma of the posterior mediastinal chest wall. Although extremely rare, this neoplastic condition should be included in your differential diagnosis when diagnostic imaging reveals a benign mass residing in the extra-pleural space, and subsequent biopsy specimens consist of smooth muscle fibers.

Bacteria from the genus Pseudomonas have been extensively studied for their capacity to act as biological control agents of disease and pests and for their ability to enhance and promote crop production in agricultural systems. While initial research primarily focused on the human pathogenic bacteria Pseudomonas aeruginosa, recent studies indicate the significance of type VI secretion (T6SS) in other Pseudomonas strains for biocontrol purposes. This system possibly plays a pivotal role in restricting the biological activity of target microorganisms and may also contribute to the bolstering of the survival capabilities of the bacteria within their applied environment. The type VI secretion system is a phage-like structure used to translocate effectors into both prokaryotic and eukaryotic target cells. T6SSs are involved in a myriad of interactions, some of which have direct implications in the success of Pseudomonas as biocontrol agents. The prevalence of T6SSs in the genomes of Pseudomonas species is notably greater than the estimated 25% occurrence rate found in Gram-negative bacteria. This observation implies that T6SS likely plays a pivotal role in the survival and fitness of Pseudomonas. This review provides a brief overview of T6SS, its role in Pseudomonas with biocontrol applications, and future avenues of research within this subject matter.