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Abstract Mucopolysaccharidosis type IIIA (MPS IIIA) is a rare paediatric lysosomal storage disorder, caused by the progressive accumulation of heparan sulphate, resulting in neurocognitive decline and behavioural abnormalities. Anecdotal reports from paediatricians indicate a more severe neurodegeneration in MPS IIIA patients, following infection, suggesting inflammation as a potential driver of neuropathology. To test this hypothesis, we performed acute studies in which WT and MPS IIIA mice were challenged with the TLR3-dependent viral mimetic poly(I:C). The challenge with an acute high poly(I:C) dose exacerbated systemic and brain cytokine expression, especially IL-1β in the hippocampus. This was accompanied by an increase in caspase-1 activity within the brain of MPS IIIA mice with concomitant loss of hippocampal GFAP and NeuN expression. Similar levels of cell damage, together with exacerbation of gliosis, were also observed in MPS IIIA mice following low chronic poly(I:C) dosing. While further investigation is warranted to fully understand the extent of IL-1β involvement in MPS IIIA exacerbated neurodegeneration, our data robustly reinforces our previous findings, indicating IL-1β as a pivotal catalyst for neuropathological processes in MPS IIIA.

Abstract Host country language acquisition is widely considered an important factor to prevent the social and economic exclusion of immigrants. High-income countries invest considerably in language courses for new immigrants, yet hitherto our understanding of when participation in such courses seems to stimulate language acquisition remains limited. As a result, this article addresses whether the timing of language course enrolment is related to course outcomes in terms of credentialed language proficiency. This study benefits from longitudinal population data including all new migrants entering Flanders (Belgium) in 2009–2021, to assess whether associations between language course timing and outcomes persist, for different legal categories of immigrants, when controlling for compositional factors. Findings indicate that for most immigrant categories, negative associations between course postponement and host country language attainment are explained by migration background and human capital. However, amongst family and humanitarian migrants, a negative association between course timing and outcomes persists. This persistent negative linkage suggests a stronger vulnerability to less effective (informal) learning trajectories and downward spiralling opportunities and motivation in the case of language course postponement, but also highlights the need for future research using causal estimation strategies. As such, research on language course timing and outcomes contributes to the literature highlighting that timing – e.g. regarding asylum procedures, housing, but also language programmes – matters in immigrants’ trajectories of integration in host countries.

Abstract Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality. The advent of approved treatments for this devastating condition has significantly changed SMA patients' life expectancy and quality of life. Nevertheless, these are not without limitations, and research efforts are underway to develop new approaches for improved and long‐lasting benefits for patients. Protein arginine methyltransferases (PRMTs) are emerging as druggable epigenetic targets, with several small‐molecule PRMT inhibitors already in clinical trials. From a screen of epigenetic molecules, we have identified MS023, a potent and selective type I PRMT inhibitor able to promote SMN2 exon 7 inclusion in preclinical SMA models. Treatment of SMA mice with MS023 results in amelioration of the disease phenotype, with strong synergistic amplification of the positive effect when delivered in combination with the antisense oligonucleotide nusinersen. Moreover, transcriptomic analysis revealed that MS023 treatment has minimal off‐target effects, and the added benefit is mainly due to targeting neuroinflammation. Our study warrants further clinical investigation of PRMT inhibition both as a stand‐alone and add‐on therapy for SMA.

We present 4k video and whole transcriptome data for seven deep-sea invertebrate animals collected in the Eastern Pacific Ocean during a research expedition onboard the Schmidt Ocean Institute's R/V Falkor in August of 2021. The animals include one jellyfish (Atolla sp.), three siphonophores (Apolemia sp., Praya sp., and Halistemma sp.), one larvacean (Bathochordaeus mcnutti), one tunicate (Pyrosomatidae sp.), and one ctenophore (Lampocteis sp.). Four of the animals were sequenced with long-read RNA sequencing technology, such that the reads themselves define a reference assembly for those animals. The larvacean tissues were successfully preserved in situ and has paired long-read reference data and short read quantitative transcriptomic data for within-specimen analyses of gene expression. Additionally, for three animals we provide quantitative image data, and a 3D model for one siphonophore. The paired image and transcriptomic data can be used for species identification, species description, and reference genetic data for these deep-sea animals. [ABSTRACT FROM AUTHOR]

Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0–37.5 mg of Dox/mL of beads) is reported. Up to 400 microbubbles were bound to Dox-loaded beads (70–150 microns). This facilitated ultrasound imaging of the beads and increased the release rate of Dox upon exposure to high intensity focused ultrasound (HIFU). Furthermore, ultrasound exposure (1 MPa peak negative pressure) increased the distance at which Dox could be detected from beads embedded in a tissue-mimicking phantom, compared with a no ultrasound control. [ABSTRACT FROM AUTHOR]

Colorectal carcinoma (CRC) is a common cause of mortality1, but a comprehensive description of its genomic landscape is lacking2–9. Here we perform whole-genome sequencing of 2,023 CRC samples from participants in the UK 100,000 Genomes Project, thereby providing a highly detailed somatic mutational landscape of this cancer. Integrated analyses identify more than 250 putative CRC driver genes, many not previously implicated in CRC or other cancers, including several recurrent changes outside the coding genome. We extend the molecular pathways involved in CRC development, define four new common subgroups of microsatellite-stable CRC based on genomic features and show that these groups have independent prognostic associations. We also characterize several rare molecular CRC subgroups, some with potential clinical relevance, including cancers with both microsatellite and chromosomal instability. We demonstrate a spectrum of mutational profiles across the colorectum, which reflect aetiological differences. These include the role of Escherichiacolipks+ colibactin in rectal cancers10 and the importance of the SBS93 signature11–13, which suggests that diet or smoking is a risk factor. Immune-escape driver mutations14 are near-ubiquitous in hypermutant tumours and occur in about half of microsatellite-stable CRCs, often in the form of HLA copy number changes. Many driver mutations are actionable, including those associated with rare subgroups (for example, BRCA1 and IDH1), highlighting the role of whole-genome sequencing in optimizing patient care.Whole-genome sequencing of more than 2,000 colorectal carcinoma samples provides a highly detailed view of the genomic landscape of this cancer and identifies new driver mutations. [ABSTRACT FROM AUTHOR]

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery. [ABSTRACT FROM AUTHOR]

Effective recruitment strategies are pivotal for informatics-based intervention trials success, particularly for people living with HIV (PLWH), where engagement can be challenging. Although informatics interventions are recognized for improving health outcomes, the effectiveness of their recruitment strategies remains unclear. We investigated the application of a social marketing framework in navigating the nuances of recruitment for informatics-based intervention trials for PLWH by examining participant experiences and perceptions. We used qualitative descriptive methodology to conduct semi-structured interviews with 90 research participants from four informatics-based intervention trials. Directed inductive and deductive content analyses were guided by Howcutt et al.'s social marketing framework on applying the decision-making process to research recruitment. The majority were male (86.7%), living in the Northeast United States (56%), and identified as Black (32%) or White (32%). Most participants (60%) completed the interview remotely. Sixteen subthemes emerged from five themes: motivation, perception, attitude formation, integration, and learning. Findings from our interview data suggest that concepts from Howcutt et al.'s framework informed participants' decisions to participate in an informatics-based intervention trial. We found that the participants' perceptions of trust in the research process were integral to the participants across the four trials. However, the recruitment approach and communication medium preferences varied between older and younger age groups. Social marketing framework can provide insight into improving the research recruitment process. Future work should delve into the complex interplay between the type of informatics-based interventions, trust in the research process, and communication preferences, and how these factors collectively influence participants' willingness to engage. [ABSTRACT FROM AUTHOR]

Air pollution is arguably the most pressing human health concern today, accounting for approximately 7–9 million premature deaths worldwide. In the United States, more than 40% of early deaths caused by air pollution are assessed to be caused by emissions produced by neighboring states. This article examines one of the governance mechanisms used by the U.S. to address this issue: section 126 of the Clean Air Act. Critical factors including case length, evidence used, and case outcome are compiled for the population of section 126 petitions submitted from 2000–2022. This evidence is assessed using comparative case analysis. The findings reinforce two issues with the petition process already identified in the literature–the use of cost as a proxy for significance and the excessive and unclear burden of proof placed on downwind states–adding texture to the latter issue by examining the modeling techniques used by downwind states. This analysis identifies lengthy response timelines as an additional issue and calls to attention the infrequency with which the EPA has formally accepted petitions. Collectively, these issues increase the cost, complexity, and unpredictability of filing a section 126 petition. [ABSTRACT FROM AUTHOR]

Purpose: With over 100,000 procedures completed per year, hip and knee arthroplasty are two of the most common surgical procedures performed in Canada. There has been literature indicating that patient reported outcome measures (PROM) will start to plateau between six and 12 months. The purpose of this paper was to analyze the trajectory of PROMs following total hip and knee arthroplasty (THA and TKA), as well as assess the impact of any potential confounders on this trajectory. The central research question was: At what point do PROMS plateau among patients that undergo elective THA and TKA? Methods: This study was a retrospective analysis of data from a prospective database. Patients were eligible if they had undergone an elective, primary THA/TKA with Oxford Scores recorded pre-operatively, and at least at two of the following four time points: six weeks, six months, one year, and two years. Results: Mean pre-operative Oxford scores were 18.0 (7.8) for THA, and 20.1 (7.5) for TKA. For both THA and TKA, there were statistically significant interval improvements in Oxford scores from six weeks [THA: 33.8 (7.9)/TKA: 28.7 (7.8)] to six months [THA: 40.2 (7.3)/TKA: 35.9 (8.3)], and from six months to one year [THA: 41.0 (7.3)/TKA: 37.3 (8.4)], but not from one to two years [THA: 40.0 (8.5)/TKA: 36.4 (9.6)]. Conclusions: Patients undergoing either primary THA or TKA can expect clinically meaningful improvements in the first six months after surgery. Beyond this time point, there is a plateau in PROMs. These findings are important for both setting patient expectations in pre-operative discussions, and allowing surgeons to have a realistic understanding of their patients' expected post-operative course. [ABSTRACT FROM AUTHOR]

Large language models (LLMs) such as ChatGPT present immense opportunities, but without proper training for users (and potentially oversight), they carry risks of misuse as well. We argue that current approaches focusing predominantly on transparency and explainability fall short in addressing the diverse needs and concerns of various user groups. We highlight the limitations of existing methodologies and propose a framework anchored on user-centric guidelines. In particular, we argue that LLM users should be given guidelines on what tasks LLMs can do well and which they cannot, which tasks require further guidance or refinement by the user, and context-specific heuristics. We further argue that (some) users should be taught to refine and elaborate adequate prompts, be provided with good procedures for prompt iteration, and be taught efficient ways to verify outputs. We suggest that for users, shifting away from looking at the technology itself, but rather looking at the usage of it within contextualized sociotechnical systems, can help solve many issues related to LLMs. We further emphasize the role of real-world case studies in shaping these guidelines, ensuring they are grounded in practical, applicable strategies. Like any technology, risks of misuse can be managed through education, regulation, and responsible development. [ABSTRACT FROM AUTHOR]

First impressions can influence rater-based judgments but their contribution to rater bias is unclear. Research suggests raters can overcome first impressions in experimental exam contexts with explicit first impressions, but these findings may not generalize to a workplace context with implicit first impressions. The study had two aims. First, to assess if first impressions affect raters' judgments when workplace performance changes. Second, whether explicitly stating these impressions affects subsequent ratings compared to implicitly-formed first impressions. Physician raters viewed six videos where learner performance either changed (Strong to Weak or Weak to Strong) or remained consistent. Raters were assigned two groups. Group one (n = 23, Explicit) made a first impression global rating (FIGR), then scored learners using the Mini-CEX. Group two (n = 22, Implicit) scored learners at the end of the video solely with the Mini-CEX. For the Explicit group, in the Strong to Weak condition, the FIGR (M = 5.94) was higher than the Mini-CEX Global rating (GR) (M = 3.02, p <.001). In the Weak to Strong condition, the FIGR (M = 2.44) was lower than the Mini-CEX GR (M = 3.96 p <.001). There was no difference between the FIGR and the Mini-CEX GR in the consistent condition (M = 6.61, M = 6.65 respectively, p =.84). There were no statistically significant differences in any of the conditions when comparing both groups' Mini-CEX GR. Therefore, raters adjusted their judgments based on the learners' performances. Furthermore, raters who made their first impressions explicit showed similar rater bias to raters who followed a more naturalistic process. [ABSTRACT FROM AUTHOR]

ChatGPT frequently appears in the media, with many predicting significant disruptions, especially in the fields of accounting and auditing. Yet research has demonstrated relatively poor performance of ChatGPT on student assessment questions. We extend this research to examine whether more recent ChatGPT models and capabilities can pass major accounting certification exams including the Certified Public Accountant (CPA), Certified Management Accountant (CMA), Certified Internal Auditor (CIA), and Enrolled Agent (EA) certification exams. We find that the ChatGPT 3.5 model cannot pass any exam (average score across all assessments of 53.1%). However, with additional enhancements, ChatGPT can pass all sections of each tested exam: moving to the ChatGPT 4 model improved scores by an average of 16.5%, providing 10-shot training improved scores an additional 6.6%, and allowing the model to use reasoning and acting (e.g., allow ChatGPT to use a calculator and other resources) improved scores an additional 8.9%. After all these improvements, ChatGPT passed all exams with an average score of 85.1%. This high performance indicates that ChatGPT has sufficient capabilities to disrupt the accounting and auditing industries, which we discuss in detail. This research provides practical insights for accounting professionals, investors, and stakeholders on how to adapt and mitigate the potential harms of this technology in accounting and auditing firms. [ABSTRACT FROM AUTHOR]

Introduction: Synthetic cannabinoid receptor agonists (SCRAs) are associated with significant toxicity and are increasingly used in electronic vaping devices. We assessed the availability of SCRA vaping products to UK purchasers on the surface web. Methods: An internet snapshot survey was performed between October 2022 and January 2023 on 'google.com' using the search terms "buy c-liquid vape", "buy herbal incense vape liquid", "buy cannabis vape liquid", "buy hashish vape liquid", "buy K2 vape liquid". Results: 62 websites selling 128 SCRA vaping brands were identified. Most were purportedly based in the USA (41 websites, 66%) and most sold other controlled substances. Purchase incentives offered included discreet packaging (38, 61%), discounts for bulk purchase (34, 55%) and tracked delivery (30, 48%). Many websites stated SCRA products were: not for human consumption (41, 66%), for research purposes only (15, 24%), or legal (28, 45%). Websites sold a median (IQR) of 16 (7–25) SCRA vaping brands. Almost all were bottles of vaping liquid (1220/1225, 99.6%). The most common bottle size was 5mL (60%), the median (IQR) total volume of SCRA liquid per sale was 50mL (10–200mL). Median (IQR) price was £3.39/mL (£2.01/mL– £5.29/mL). Price decreased with increasing volume purchased (£6.58/mL for ≤ 5mL, £1.60/mL for > 200mL). Conclusion: SCRA vaping products are easily obtainable online, in both small and bulk quantities. Information provided to purchasers on safety and legality is lacking or misleading. Further studies are needed to confirm the chemistry of these products. Policymakers should consider steps to limit the potential harm caused by the purchase and use of these products. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the impact of human gut microbiota on the immune pathways in the respiratory tract using a gnotobiotic (Gn) piglet model. We humanized piglets with rural and urban infant fecal microbiota (RIFM and UIFM, respectively) and then infected them with a H1N1 swine influenza virus. We analyzed the microbial diversity and structure of the intestinal and respiratory tracts of the piglets before and after the influenza virus infection and measured the viral load and immune responses. We found that the viral load in the upper respiratory tract of UIFM transplanted piglets was higher than their rural cohorts (RIFM), while virus-specific antibody responses were comparable. The relative cytokine gene expression in the tracheobronchial (respiratory tract) and mesenteric (gastrointestinal) lymph nodes, lungs, blood, and spleen of RIFM and UIFM piglets revealed a trend in reciprocal regulation of proinflammatory, innate, and adaptive immune-associated cytokines as well as the frequency of T-helper/memory cells, cytotoxic T cells, and myeloid immune cell subsets. We also observed different phylum-level shifts of the fecal microbiota in response to influenza virus infection between the two piglet groups, suggesting the potential impact of the gut microbiota on the immune responses to influenza virus infection and lung microbiota. In conclusion, Gn piglets humanized with diverse infant fecal microbiota had differential immune regulation, with UIFM favoring the activation of proinflammatory immune mediators following an influenza virus infection compared to their rural RIFM cohorts. Furthermore, Gn piglets can be a useful model in investigating the impact of diverse human microbiota of the gastrointestinal tract, probably also the respiratory tract, on respiratory health and testing specific probiotic- or prebiotic-based therapeutics. [ABSTRACT FROM AUTHOR]

The studied oilfield in the Zagros folded belt accommodates hydrocarbons in the Cretaceous carbonate rocks of the Ilam and Sarvak Formations. The compressional tectonic regime of the study area is reflected in the presence of the NW-SE trending active Ch.1 and Ch.2 thrust fault-related anticlines and associated NW-SE trending reverse faults. The NW-SE trending reverse faults have formed a pop-up structure in the crest of the Ch.2 anticline dividing it into 3 sectors (A, B, and C) with different geomechanical characteristics. Sector B as the high-strain central part of the pop-up structure despite Sectors A and B as the low-strain parts (in the footwall of the reverse faults forming the pop-up structure), is considered a high-risk region for performing acid fracturing stimulation of the reservoirs. In seismic time slices at the Gachsaran level, ChF.1 and ChF.2 faults with NE-SW trend display sinistral and dextral displacement respectively, representing tear faults related to the basal thrust of the Zagros Fore-dip Fault. Horizontal and vertical stress magnitudes for the study area were derived from well-log data. The horizontal stress orientations were established from the dominant directions of the induced fractures and breakouts observed from the FMI log data and are in ~ 030° (NE-SW) and ~ 120° (NW-SE), respectively. Based on these determined horizontal stress orientations, the expected induced fracture propagation direction is ~ 030° and their opening would likely occur in the direction ~ 120°. Based on this deduced stress information, the optimal azimuthal perforation would be from 000° to 060° for acid-fracture stimulation of Ilam and Sarvak reservoirs. [ABSTRACT FROM AUTHOR]

T-lineage acute lymphoblastic leukaemia (T-ALL) is a high-risk tumour1 that has eluded comprehensive genomic characterization, which is partly due to the high frequency of noncoding genomic alterations that result in oncogene deregulation2,3. Here we report an integrated analysis of genome and transcriptome sequencing of tumour and remission samples from more than 1,300 uniformly treated children with T-ALL, coupled with epigenomic and single-cell analyses of malignant and normal T cell precursors. This approach identified 15 subtypes with distinct genomic drivers, gene expression patterns, developmental states and outcomes. Analyses of chromatin topology revealed multiple mechanisms of enhancer deregulation that involve enhancers and genes in a subtype-specific manner, thereby demonstrating widespread involvement of the noncoding genome. We show that the immunophenotypically described, high-risk entity of early T cell precursor ALL is superseded by a broader category of ‘early T cell precursor-like’ leukaemia. This category has a variable immunophenotype and diverse genomic alterations of a core set of genes that encode regulators of hematopoietic stem cell development. Using multivariable outcome models, we show that genetic subtypes, driver and concomitant genetic alterations independently predict treatment failure and survival. These findings provide a roadmap for the classification, risk stratification and mechanistic understanding of this disease.Comprehensive genomic and transcriptomics analyses of more than 1,300 cases of childhood T-lineage acute lymphoblastic leukaemia identify 15 distinct subtypes that are associated with specific outcomes. [ABSTRACT FROM AUTHOR]

Test subjects were assessed in a partial gravity environment during parabolic flight while they performed mission-critical activities that challenged their balance and locomotion. These functional activities included rising from a seated position and walking, jumping down, recovering from falls, and maintaining an upright stance. Twelve volunteers were tested during 10 parabolas that produced 0.25×g, 0.5×g, or 0.75×g, and at 1×g during level flight intervals between parabolas. Additionally, 14 other subjects were tested using identical procedures in a 1×g laboratory setting. Partial gravity altered the performance of settling after standing and navigating around obstacles. As gravity levels decreased, the time required to stand up, settle, walk, and negotiate obstacles, and the number of falls increased. Information obtained from these tests will allow space agencies to assess the vestibular, sensorimotor, and cardiovascular risks associated with different levels of partial gravity. [ABSTRACT FROM AUTHOR]

Propagule dispersal is a crucial aspect of the survival and reproduction of sessile organisms, such as plants and fungi. As such, the colours of fleshy fruits serve as a visual cue for animal dispersers. However, little is known about how, or whether, specific traits of fungal fruiting bodies, such as colour or shape, attract animal dispersers, and additionally the identities of fungal dispersers are poorly understood. Globally, most truffle-like fungi are dull-coloured, subterranean, and likely have scents that are attractive to mammalian dispersers. In Aotearoa-New Zealand, however, brightly coloured truffle-like fungi that emerge from the forest floor have seemingly proliferated. This proliferation has prompted the hypothesis that they are adapted to dispersal by a bird-dominated fauna. In our study, we used the literature and citizen science data (GBIF) to explore whether colourful species occur at a higher proportion of the total truffle-like fungi flora in Aotearoa-New Zealand than elsewhere in the world. In addition, we tested for a relationship between biotic factors (avian frugivory and forest cover) and abiotic factors (precipitation, radiation, and temperature) and the prevalence of brightly coloured truffle-like fungi across the world. The most colourful truffle-like fungi are in three defined regions: Australia, South and Central America and the Caribbean, and Aotearoa-NZ. Potential dispersers and the environment both relate to the distribution of truffle-like fungi: we found that increasing levels of frugivory were associated with higher proportions of colourful truffle-like fungi. This finding provides new insights into drivers of certain fungal traits, and their interactions between birds and fungi. Unique ecosystems, such as Aotearoa-NZ's bird-dominated biota, provide fascinating opportunities to explore how plants and fungi interact with the sensory systems of animals. [ABSTRACT FROM AUTHOR]

Grain boundaries (GBs) profoundly influence the properties and performance of materials, emphasizing the importance of understanding the GB structure and phase behavior. As recent computational studies have demonstrated the existence of multiple GB phases associated with varying the atomic density at the interface, we introduce a validated, open-source GRand canonical Interface Predictor (GRIP) tool that automates high-throughput, grand canonical optimization of GB structures. While previous studies of GB phases have almost exclusively focused on cubic systems, we demonstrate the utility of GRIP in an application to hexagonal close-packed titanium. We perform a systematic high-throughput exploration of tilt GBs in titanium and discover previously unreported structures and phase transitions. In low-angle boundaries, we demonstrate a coupling between point defect absorption and the change in the GB dislocation network topology due to GB phase transformations, which has important implications for the accommodation of radiation-induced defects. Grain boundaries strongly influence the properties of crystalline materials, but identifying their multiple phases remains difficult. Here, authors show a new tool for automated grain boundary structure prediction with an application to Ti. [ABSTRACT FROM AUTHOR]

Attentional biases to negative information are often observed in emotional disorders such as anxiety and depression. Recently, Fergus et al. (Cognitive Therapy and Research 37:735-741, 2013) demonstrated that participants scoring high in Intolerance of Uncertainty (IU), a transdiagnostic risk factor for emotional disorders, were faster at identifying targets with uncertainty-based information (e.g., word stimuli such as 'maybe'), relative to neutral information (e.g. word stimuli related to household items). Moreover, this effect was specific to IU over other anxious traits such as worry. This report aimed to conceptually replicate the results of Fergus et al. (Cognitive Therapy and Research 37:735-741, 2013). The current experiment was conducted with a student sample (n = 126). As in the original study, a visual search task with uncertainty-based and neutral information (e.g., word stimuli) was used. Reaction times were collected. IU and trait anxiety was measured via self-report. We partially replicated the results of Fergus et al. (Cognitive Therapy and Research 37:735-741, 2013). We found that higher IU was significantly associated with faster identification of uncertainty-based information, relative to neutral information. However, we also observed a similar pattern of results for trait anxiety. Additionally, we observed no specificity of IU or trait anxiety in predicting faster identification of uncertainty-based information, relative to neutral information. Despite the lack of specificity of IU or trait anxiety in predicting attentional bias to uncertainty-based information, these findings highlight that negative emotionality may be generally associated with attentional biases to uncertainty-based information in the absence of direct threat. [ABSTRACT FROM AUTHOR]

Powerful associations that link drugs of abuse with cues in the drug-paired environment often serve as prepotent relapse triggers. Drug-associated contexts and cues activate ensembles of nucleus accumbens (NAc) neurons, including D1-class medium spiny neurons (MSNs) that typically promote, and D2-class MSNs that typically oppose, drug seeking. We found that in mice, cocaine conditioning upregulated transiently the activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), in a small subset of NAc neurons. The NPAS4+ NAc ensemble was required for cocaine conditioned place preference. We also observed that NPAS4 functions within NAc D2-, but not D1-, MSNs to support cocaine-context associations and cue-induced cocaine, but not sucrose, seeking. Together, our data show that the NPAS4+ ensemble of NAc neurons is essential for cocaine-context associations in mice, and that NPAS4 itself functions in NAc D2-MSNs to support cocaine-context associations by suppressing drug-induced counteradaptations that oppose relapse-related behaviour. Neuronal PAS domain protein 4 (NPAS4) is an immediate early gene, but its role in striatal circuits in drug seeking behaviour is not understood. Here the authors show that exposure to cocaine in mice results in induction of NPAS4 in a subset of nucleus accumbens (NAc) neurons, and in D2-neurons of the NAc it contributes to cocaine-associations and cocaine seeking behaviour. [ABSTRACT FROM AUTHOR]

Analysis of the liver using imaging for persons with cystic fibrosis (CF) continues to evolve as new medical therapies are developed improving and extending life. In the 2010s, therapies targeted at modulating protein folding became available to those with CF. Therapeutic options have continued to expand, now providing both correction of protein folding and stabilization for most gene mutations that code for the CF transmembrane receptor protein (CFTR). Today, approximately 80% of persons with CF are eligible for highly effective modulator therapy. With these advancements, the impact of CF on the liver has become more complex, adding metabolism of CFTR modulators to intrinsic CF hepatobiliary involvement (CFHBI) and adding not previously appreciated vascular changes within the liver due to increased longevity in persons with CF. A combination of serum biomarkers and imaging is needed to add clarity to the diagnosis and monitoring of the severity of liver disease. A substantial portion of persons with CF will develop at least CFHBI and a subset will develop advanced cystic fibrosis-associated liver disease (aCFLD); therefore, diagnosis and monitoring need to begin in childhood. In this review, we cover the use of and need for imaging, including elastography, ultrasound, and magnetic resonance imaging (MRI), in diagnosing and monitoring CFHBI and its associated complications. [ABSTRACT FROM AUTHOR]

Studying the nervous system underlying animal motor control can shed light on how animals can adapt flexibly to a changing environment. We focus on the neural basis of feeding control in Aplysia californica. Using the Synthetic Nervous System framework, we developed a model of Aplysia feeding neural circuitry that balances neurophysiological plausibility and computational complexity. The circuitry includes neurons, synapses, and feedback pathways identified in existing literature. We organized the neurons into three layers and five subnetworks according to their functional roles. Simulation results demonstrate that the circuitry model can capture the intrinsic dynamics at neuronal and network levels. When combined with a simplified peripheral biomechanical model, it is sufficient to mediate three animal-like feeding behaviors (biting, swallowing, and rejection). The kinematic, dynamic, and neural responses of the model also share similar features with animal data. These results emphasize the functional roles of sensory feedback during feeding. [ABSTRACT FROM AUTHOR]

Donald L. Morton, MD, epitomized one of America's dream scenarios: a person evolving from the humblest of origins to become an international celebrity in his profession, leading the world in the discipline of surgical oncology. His pioneering accomplishments in various roles have been well documented. Scientists, clinicians, students, and patients benefited from his contributions to the management of malignant diseases, particularly melanoma. His many attributes in pursuing the goal to cure malignant diseases are well known. Browsing the scientific literature reveals an almost unmatched publication record and continuous National Institutes of Health funding. He revealed dozens of original concealed ideas, not least of which is the tumor-draining regional lymph node, now called the sentinel lymph node (SLN). When others gave up on the original promise of immunotherapy, he saw the future, the clinical promise which has lately materialized in the control of previously untreatable malignancies. He regarded the fellowship-training of more than 100 surgical oncologists as one of his biggest achievements. In this article, we celebrate the human side of a man with creative courage and far-reaching insight. [ABSTRACT FROM AUTHOR]

Objective: To assess impact of image quality on prostate cancer extraprostatic extension (EPE) detection on MRI using a deep learning-based AI algorithm. Materials and methods: This retrospective, single institution study included patients who were imaged with mpMRI and subsequently underwent radical prostatectomy from June 2007 to August 2022. One genitourinary radiologist prospectively evaluated each patient using the NCI EPE grading system. Each T2WI was classified as low- or high-quality by a previously developed AI algorithm. Fisher's exact tests were performed to compare EPE detection metrics between low- and high-quality images. Univariable and multivariable analyses were conducted to assess the predictive value of image quality for pathological EPE. Results: A total of 773 consecutive patients (median age 61 [IQR 56–67] years) were evaluated. At radical prostatectomy, 23% (180/773) of patients had EPE at pathology, and 41% (131/318) of positive EPE calls on mpMRI were confirmed to have EPE. The AI algorithm classified 36% (280/773) of T2WIs as low-quality and 64% (493/773) as high-quality. For EPE grade ≥ 1, high-quality T2WI significantly improved specificity for EPE detection (72% [95% CI 67–76%] vs. 63% [95% CI 56–69%], P = 0.03), but did not significantly affect sensitivity (72% [95% CI 62–80%] vs. 75% [95% CI 63–85%]), positive predictive value (44% [95% CI 39–49%] vs. 38% [95% CI 32–43%]), or negative predictive value (89% [95% CI 86–92%] vs. 89% [95% CI 85–93%]). Sensitivity, specificity, PPV, and NPV for EPE grades ≥ 2 and ≥ 3 did not show significant differences attributable to imaging quality. For NCI EPE grade 1, high-quality images (OR 3.05, 95% CI 1.54–5.86; P < 0.001) demonstrated a stronger association with pathologic EPE than low-quality images (OR 1.76, 95% CI 0.63–4.24; P = 0.24). Conclusion: Our study successfully employed a deep learning-based AI algorithm to classify image quality of prostate MRI and demonstrated that better quality T2WI was associated with more accurate prediction of EPE at final pathology. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the various factors that may contribute to the academic self-concept of autistic college students, including the potential influence of academic success. Methods: A sample of autistic participants (n = 12) were interviewed regarding autistic college students' experiences. Transcripts were analyzed using a modified grounded theory approach. Results: Most students had a positive academic self-concept due to factors like major selection based on passion and interest, following family values, personal motivation to do well, proving someone wrong, and striving for high academic achievement. Although accommodations were not the main focus of the study, they were found to affect student academic self-concept as well. Conclusion: Post-secondary institutions should consider incorporating intervention and support programs that assist in improving neurodiverse students' self motivation and self regulation skills to encourage these students to be academically successful while maintaining their well-being. They should also provide professional development initiatives aimed at enhancing the capacity of faculty and staff to address the unique needs of autistic students and ensure the successful implementation of accommodations. This approach will contribute to a more inclusive and supportive learning environment for autistic college students, promoting their academic success and well-being. [ABSTRACT FROM AUTHOR]

Water retaining structures are critical elements of civil infrastructure. Internal erosion of soils forming the containment structures may occur progressively and lead to expensive maintenance costs or failures. The strength, stress–strain behavior and critical state of soils which have eroded, as well as the characteristics of the erosion, may be affected by hydraulic gradient, confining stress and relative density of the soil at the start of the erosion. Here, erosion and triaxial tests have been conducted on gap-graded soil samples. The tests and results are novel as the samples were prepared to be homogenous post-erosion and prior to triaxial testing by adopting a new sample formation procedure. The post-erosion homogeneity was evaluated in terms of particle size distribution and void ratio along a sample's length. The erosion-induced mechanical property changes can then be linked to a measure of initial state, more reliably than when erosion causes samples to be heterogeneous. The results show that erosion causes the critical state line in the compression plane to move upwards. The movement is lesser than the increase in void ratio caused by erosion. The state parameter is therefore reduced, consistent with the soil's reduced peak strength and its less dilative response. Regarding the erosion characteristics, the flow rate decreases with the increase in initial relative density or effective stress, but increases with the increase in the hydraulic gradient being applied. The cumulative eroded soil mass increases with the increase in hydraulic gradient and decreases with the increase in initial density and effective confining stress. [ABSTRACT FROM AUTHOR]

Effective seabird conservation requires understanding their marine spatial ecology. Tracking can reveal details of their foraging ecology and habitat use, as well as the suitability of marine protected areas for at-sea conservation, but results are often regionally specific. Here we characterised the foraging behaviour of tropical breeding brown boobies Sula leucogaster in the Chagos Archipelago, Western Indian Ocean, and tested habitat requirements. GPS tracking of thirteen individuals from two colonies, located 142 km apart on the same atoll (Great Chagos Bank), showed similar foraging effort and habitat preferences despite differences in season and breeding stage. Brown boobies from both tracked populations foraged close to the colony along the atoll shelf edge, avoiding deep oceanic areas and shallow waters of the Great Chagos Bank atoll, but within the Chagos Archipelago Marine Protected Area. Sea-level height anomaly and sea surface temperature were important foraging predictors at both sites, although birds experienced distinct environmental conditions between colonies. These results suggest that while brown boobies have colony-specific at-sea foraging areas, similarities in habitat drivers of distribution and foraging behaviour can inform predictions of distributions at other colonies within the archipelago, with important benefits for at-sea conservation efforts. [ABSTRACT FROM AUTHOR]

Administrators and faculty at many colleges and universities are dedicated to making the faculty hiring process fair and equitable. One program that has shown promise is to train and appoint a Diversity Advocate (DA) to serve on each faculty search and screen committee. In this study, we created and examined the early stages of a DA program at a single institution. After undergoing special training, the DA works on the search committee to encourage best practices and to discourage schemas and stereotypes from interfering with the process. Our DA program differs from some in that efforts are made to train DAs who are demographically in the majority, work in the area where the search is taking place, and have earned tenure or promotion. Training those who are demographically in the majority helps meet our goal of broadening the responsibility for evidence-based and equitable hiring practices across faculty members. While reliable data on hiring outcomes is not yet available, we developed a survey to evaluate the DA training and conducted focus groups to understand the DA experience better. Our results highlight how DAs intervened in the search process to make it more equitable. The interventions included encouraging the use of best practices, such as leading the committee in creating a rubric for evaluating candidates and intervening when bias was present. Our study provides evidence that a DA program is one way to expand the pool of faculty committed to inclusive excellence. [ABSTRACT FROM AUTHOR]

The freshwater zooplankton of New Zealand-Aotearoa are species-poor with only two indigenous Daphnia species: D. thomsoni, and D. tewaipounamu. Over the last two decades, two species of invasive non-indigenous Daphnia, D. pulicaria/pulex and D. galeata, have become well established in many lakes in New Zealand-Aotearoa and their distribution appears to be rapidly increasing. We report the current distribution of these two invasive species in approximately 300 lakes throughout New Zealand-Aotearoa and test the hypothesis that the distribution and establishment of these invaders is more closely related to human access to a lake than to any environmental attributes of a lake's water or biota and consider potential implications of our findings for lake management. Boosted regression tree analysis identified total nitrogen and distance from the coast (D. pulicaria) and annual lake temperature (D. galeata) as key variables explaining current distributions. Inclusion of spatial autocorrelation overwhelmed other explanatory variables, highlighting the greater likelihood of spread from known source locations. Proximity to a road was an important predictor for D. pulicaria, and when tested separately both invasive Daphnia occurred significantly more often in lakes within 200 m of a road. Critically, D. galeata's realised niche completely envelopes D. thomsoni's, which could force the native species to become extinct through competitive exclusion. These results suggest that the spread of D. pulicaria and D. galeata to lakes where they do not yet occur is unlikely to be prevented unless public access to these waterways is denied or strictly controlled. [ABSTRACT FROM AUTHOR]

The coordination of complex behavior requires knowledge of both neural dynamics and the mechanics of the periphery. The feeding system of Aplysia californica is an excellent model for investigating questions in soft body systems' neuromechanics because of its experimental tractability. Prior work has attempted to elucidate the mechanical properties of the periphery by using a Hill-type muscle model to characterize the force generation capabilities of the key protractor muscle responsible for moving Aplysia's grasper anteriorly, the I2 muscle. However, the I1/I3 muscle, which is the main driver of retractions of Aplysia's grasper, has not been characterized. Because of the importance of the musculature's properties in generating functional behavior, understanding the properties of muscles like the I1/I3 complex may help to create more realistic simulations of the feeding behavior of Aplysia, which can aid in greater understanding of the neuromechanics of soft-bodied systems. To bridge this gap, in this work, the I1/I3 muscle complex was characterized using force-frequency, length-tension, and force-velocity experiments and showed that a Hill-type model can accurately predict its force-generation properties. Furthermore, the muscle's peak isometric force and stiffness were found to exceed those of the I2 muscle, and these results were analyzed in the context of prior studies on the I1/I3 complex's kinematics in vivo. [ABSTRACT FROM AUTHOR]

We prove a central limit theorem (CLT) for the Fréchet mean of independent and identically distributed observations in a compact Riemannian manifold assuming that the population Fréchet mean is unique. Previous general CLT results in this setting have assumed that the cut locus of the Fréchet mean lies outside the support of the population distribution. In this paper we present a CLT under some mild technical conditions on the manifold plus the following assumption on the population distribution: in a neighbourhood of the cut locus of the population Fréchet mean, the population distribution is absolutely continuous with respect to the volume measure on the manifold and in this neighhbourhood the Radon–Nikodym derivative has a version that is continuous. So far as we are aware, the CLT given here is the first which allows the cut locus to have co-dimension one or two when it is included in the support of the distribution. A key part of the proof is establishing an asymptotic approximation for the parallel transport of a certain vector field. Whether or not a non-standard term arises in the CLT depends on whether the co-dimension of the cut locus is one or greater than one: in the former case a non-standard term appears but not in the latter case. This is the first paper to give a general and explicit expression for the non-standard term which arises when the co-dimension of the cut locus is one. [ABSTRACT FROM AUTHOR]

The first dose of COVID-19 vaccines led to an overall reduction in cardiovascular events, and in rare cases, cardiovascular complications. There is less information about the effect of second and booster doses on cardiovascular diseases. Using longitudinal health records from 45.7 million adults in England between December 2020 and January 2022, our study compared the incidence of thrombotic and cardiovascular complications up to 26 weeks after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273). These findings support the wide uptake of future COVID-19 vaccination programs. COVID-19 vaccines have been associated with rare cardiovascular and thrombotic complications. Here, the authors use population-based longitudinal electronic health record data from ~46 million adults in England to quantify these outcomes following different vaccine doses and schedules. [ABSTRACT FROM AUTHOR]

Finding alloys with specific design properties is challenging due to the large number of possible compositions and the complex interactions between elements. This study introduces a multi-objective Bayesian optimization approach guiding molecular dynamics simulations for discovering high-performance refractory alloys with both targeted intrinsic static thermomechanical properties and also deformation mechanisms occurring during dynamic loading. The objective functions are aiming for excellent thermomechanical stability via a high bulk modulus, a low thermal expansion, a high heat capacity, and for a resilient deformation mechanism maximizing the retention of the BCC phase after shock loading. Contrasting two optimization procedures, we show that the Pareto-optimal solutions are confined to a small performance space when the property objectives display a cooperative relationship. Conversely, the Pareto front is much broader in the performance space when these properties have antagonistic relationships. Density functional theory simulations validate these findings and unveil underlying atomic-bond changes driving property improvements. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to evaluate contrasting approaches for handling excess demand through the lens of a retailer (newsvendor) whose risk attitude (risk-neutral versus risk-averse) is modeled explicitly. We employ representative newsvendor models and provide comparison between two well-established stockout policies when demand exceeds supply. The "while supplies last" policy avoids the need for a secondary production order to satisfy the excess demand but faces potential opportunity cost through lost sales. Conversely, the "accepting backorders" policy relies on recourse production availability which is potentially costly but meets all levels of realized demand. Across distinct parameter classes, we incorporate comparison between the two policies in terms of financial metrics including expected profit and conditional value-at-risk criteria as well as metrics that relate to inventory availability and, hence, customer service, e.g., stockout probabilities and expected excess inventory. Powerful analytical results encompass both financial and inventory metrics and reveal that the outperforming policy is simply determined through relative underage cost values. That is, our insights indicate general advantages of accepting backorders when profit margins are sufficiently large and advantages of ignoring excess demand when profit margins are smaller. Although these extensive analytical takeaways hold in general, our numerical study reveals mean order quantity deviations (decision bias) in addition to which modeling approaches and counterpart optimal solutions maintain outperformance (resiliency) or lead to underperformance (sensitivity) when evaluated across all objective function criteria. [ABSTRACT FROM AUTHOR]

Introduction: Women born with anorectal malformation (ARM) or Hirschsprung disease (HD) may have impaired urologic function resulting in sequelae in adulthood. This study assessed and compared self-reported urinary outcomes in adult females born with ARM or HD to a reference population. Methods: This was an IRB approved, cross-sectional study of female-born patients with ARM or HD, who completed surveys between November 2021 and August 2022. Female patients between the ages of 18 and 80 years were included. Lower Urinary Tract Symptom Questionnaires were administered through REDCap and the responses were compared to a reference population using Chi-squared or Fisher's exact tests. Results: Sixty-six born female patients answered the questionnaires, two of them identified as non-binary. The response rate was 76%. Median age was 31.6 years. The majority were born with cloaca (56.3%), followed by other type of ARMs (28.1%), complex malformation (9.4%), and HD (6.3%). A history of bladder reconstruction was present for 26.6%. Catheterization through a channel or native urethra was present in 18.8%. Two had ureterostomies and were excluded from the analysis. Seven had chronic kidney disease or end-stage renal disease, three with a history of kidney transplantation. Patients with cloaca had significantly higher rates of urinary incontinence, urinary tract infection, and social problems due to impaired urological functioning, when compared to an age-matched reference population (Table 3). Conclusion: This study emphasizes the need for a multi-disciplinary team that includes urology and nephrology following patients with ARM long term, especially within the subgroup of cloaca. Level of Evidence: III. [ABSTRACT FROM AUTHOR]

Machine learning tools capable of identifying animals by sound have proliferated, making the challenge of interpreting their outputs much more prevalent. These tools, like their predecessors, quantify prediction uncertainty with scores that tend to resemble probabilities but are actually unitless scores that are (generally) positively related to prediction accuracy in species-specific ways. BirdNET is one such tool, a freely available animal sound identification algorithm capable of identifying > 6,000 species, most of them birds. We describe two ways in which BirdNET "confidence scores"—and the output scores of other detector tools—can be used appropriately to interpret BirdNET results (reviewing them down to a user-defined threshold or converting them to probabilities), and provide a step-by-step tutorial to follow these suggestions. These suggestions are complementary to common performance metrics like precision, recall, and receiver operating characteristic. BirdNET can be a powerful tool for acoustic-based biodiversity research, but its utility depends on the careful use and interpretation of its outputs. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to understand bisexual women's lived experiences and meaning-making with regard to same-sex performativity (SSP)– that is, heterosexual women's engagement in public same-sex behavior such as kissing. Cisgender bisexual women (N = 187) provided qualitative descriptions of their perceptions of SSP. Two research questions guided this feminist phenomenological study: (a) How do bisexual women perceive and make sense of SSP, including women who engage in SSP? and (b) What factors influence bisexual women's perceptions and meaning making of SSP? We found that bisexual women made sense of SSP by situating their perceptions and experiences of SSP in a heteropatriarchal context. Bisexual women perceived the link between SSP and the male gaze as challenging bisexual legitimacy and reinforcing negative stereotypes about bisexuality; nevertheless, many bisexual women were resistant to decrying SSP. Our findings reveal bisexual women's complex interpretive work and negotiation with tensions that underpin their sense of SSP— they perceive heterosexual women's engagement in male-oriented SSP behavior as potentially harmful, yet are reluctant to condemn this behavior and limit women's opportunities for sexual expression. These findings highlight the need to recognize the impact of heteronormativity and gendered power dynamics on bisexual and heterosexual women's experiences, embodiment, and expressions of sexuality. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s00222-024-01257-1The publication of this article unfortunately contained mistakes. The style of the references was not correct. The corrected reference list is given below.The original article has been corrected.Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.By Yuan Liu; Melanie Matchett Wood and David Zureick-BrownReported by Author; Author; Author [Extracted from the article]

For G and H 1 , ... , H n finite groups, does there exist a 3-manifold group with G as a quotient but no H i as a quotient? We answer all such questions in terms of the group cohomology of finite groups. We prove non-existence with topological results generalizing the theory of semicharacteristics. To prove existence of 3-manifolds with certain finite quotients but not others, we use a probabilistic method, by first proving a formula for the distribution of the (profinite completion of) the fundamental group of a random 3-manifold in the Dunfield-Thurston model of random Heegaard splittings as the genus goes to infinity. We believe this is the first construction of a new distribution of random groups from its moments. [ABSTRACT FROM AUTHOR]

We consider the distribution of the Galois groups Gal (K un / K) of maximal unramified extensions as K ranges over Γ -extensions of ℚ or F q (t) . We prove two properties of Gal (K un / K) coming from number theory, which we use as motivation to build a probability distribution on profinite groups with these properties. In Part I, we build such a distribution as a limit of distributions on n -generated profinite groups. In Part II, we prove as q → ∞ , agreement of Gal (K un / K) as K varies over totally real Γ -extensions of F q (t) with our distribution from Part I, in the moments that are relatively prime to q (q − 1) | Γ | . In particular, we prove for every finite group Γ , in the q → ∞ limit, the prime-to- q (q − 1) | Γ | -moments of the distribution of class groups of totally real Γ -extensions of F q (t) agree with the prediction of the Cohen–Lenstra–Martinet heuristics. [ABSTRACT FROM AUTHOR]

Artisanal and small-scale gold mining (ASGM) is crucial to the livelihoods of close to 20 million people in over 80 countries, including 4-5 million women, mainly in rural areas with limited alternative economic prospects, particularly in developing countries. ASGM is largely informal, which can add to the challenge of addressing negative social and environmental effects including impacts on biodiversity. However, with proper guidance, ASGM can operate in a responsible manner, using cleaner production methods that minimize impacts on human health and the environment. This study presents and analyzes the interactions between ASGM and biodiversity based on new findings from 27 ASGM National Action Plans (NAPs) developed within the framework of Article 7 and Annex C of the Minamata Convention on Mercury, as well as a global literature review of more than 100 publications. In terms of key findings according to the literature reviewed, alongside other human occupation such as agriculture and industrial activities, ASGM also has an impact on the environment and biodiversity. The interrelationship between ASGM and biodiversity, including protected areas, is pervasive at every stage of ASGM operations, from extraction to mine closure, and generates significant impacts on the surrounding ecosystems. These impacts include, in descending order of most reported impacts: deforestation, soil degradation, chemical contamination of aquatic and terrestrial systems, and changes to the turbidity of watercourses. Tropical regions and key species such as amphibians and freshwater fish are among the most affected. Singly or combined, these environmental stressors lead to loss or deterioration of habitat and, by extension, indigenous biodiversity and ecosystem services. In addition, legal, institutional, and regulatory frameworks and related measures, inadequate or non-existent in some cases, may not necessarily support sustainable practices, often resulting in exploited sites abandoned without remediation, reclamation, rehabilitation, or restoration measures. To mitigate such impacts a key recommendation arising from the literature review is to strengthen the integration of the interrelationship between ASGM and biodiversity in the implementation of existing relevant national strategies, including those developed under the NAPs. The global literature review also highlights the importance of a multi-stakeholder, systemic approach combining the use of geospatial analysis, scientific and local knowledge, as well as the adaptation of the relevant frameworks, capacity building, and awareness raising. This approach can inform decision making with a view to developing sustainable initiatives that prevent and reduce the impacts of artisanal and small-scale gold mining on ecosystems, and that preserve biodiversity. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to identify prognostic risk factors for prolonged opioid use at 2 and 6 weeks after hip arthroscopy using data from the Femoroacetabular Impingement RandomiSed controlled Trial and its external validation cohort study. Methods: Opioids were prescribed for postoperative pain management at the surgeon's discretion, with a majority being prescribed a combination of oxycodone and paracetamol (5/325 mg). Prolonged opioid use was defined as the ongoing use of any dosage of opioids reported at either 2 or 6 weeks after surgery to treat femoroacetabular impingement, as recorded in the patient's study medication log. Multivariable logistic regressions were performed to evaluate patient and surgical characteristics, such as preoperative opioid use, type of surgical procedure and intraoperative cartilage state that may be associated with prolonged opioid use at either 2 and 6 weeks postoperatively. Results: A total of 265 and 231 patients were included for analysis at 2 and 6 weeks postoperatively, respectively. The median age of participants was 35 years (interquartile range [IQR]: 27–42) and 33% were female. At 2 weeks postoperatively, female sex (odds ratio [OR]: 2.56; 95% confidence interval: [CI] 1.34–4.98, p = 0.005), higher body mass index (BMI) (OR: 1.10; 95% CI: 1.02–1.18, p = 0.009), active tobacco use (OR: 4.06; 95% CI: 1.90–8.97, p < 0.001), preoperative opioid use (OR: 10.1; 95% CI: 3.25–39.1, p < 0.001) and an Outerbridge classification of ≥3 (OR: 2.33; 95% CI: 1.25–4.43, p = 0.009) were significantly associated with prolonged opioid use. At 6 weeks postoperatively, only preoperative opioid use was significantly associated with prolonged opioid consumption (OR: 10.6; 95% CI: 3.60–32.6, p < 0.001). Conclusion: Preoperative opioid use was significantly associated with continued opioid use at 2 and 6 weeks postoperatively. Specific patient factors including female sex, higher BMI, active tobacco use and more severe cartilage damage should be considered in developing targeted strategies to limit opioid use after surgery. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

Purpose: Moral distress (MD) refers to the psychological disequilibrium that emerges when institutional policies and/or practices conflict with an individual's professional values and ethics. MD has been interrogated frequently in health care and ancillary medical settings, and has been identified as a critical barrier to enhanced organizational climate and patient care. However, little work has investigated experiences of MD among members of the intimate partner violence (IPV) and sexual violence (SV) workforce. Methods: This study investigates MD in a sample of IPV and SV service providers via secondary analysis of 33 qualitative interviews conducted with service providers in the summer and fall of 2020 as the COVID-19 pandemic response was unfolding. Results: Qualitative content analysis revealed multiple overlapping vectors of MD experienced by IPV and SV service providers related to institutional resource constraints, providers working beyond their capacity and/or competency, shifting responsibilities within service agencies creating burdens among staff; and breakdowns in communication. Impacts of these experiences at individual, organizational, and client levels were identified by participants. Conculsions: The study uncovers the need for further investigation of MD as a framework within the IPV/SV field, as well as potential lessons from similar service settings which could support IPV and SV agencies in addressing staff experiences of MD. [ABSTRACT FROM AUTHOR]