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In response to unwaveringly high attrition from STEM pathways, STEM Intervention Programs (SIPs) support STEM students in effort to increase retention. Using mixed methods (survey and focus groups), we studied students at one university who were either supported or unsupported by SIPs to understand how students may differ in experiences believed to contribute to STEM persistence. We evaluated: sense of belonging, scientific self-efficacy, scientific community values, scientific identity, and STEM involvement. The enrollment status of students two and a half years postsurvey was also tracked. SIP students reported significantly higher science identity and sense of belonging and were more involved in STEM-related activities than counterparts unsupported by SIPs. Differences in these measures were correlated with race/ethnicity, college generation status, and age. Notably, SIP students had higher odds of persisting in STEM than students not supported by SIPs. Focus group data provide additional meaning to the measured survey constructs and revealed nuanced qualitative differences between SIP and non-SIP student experiences. Overall, being involved in a SIP at our institution trends positively with theoretical models that explain STEM student persistence. SIPs have the potential to provide and/or facilitate meaningful and critical support, and students without those intentional supports may be left behind.

Abstract Background While the striking impact of the COVID-19 pandemic on mental health, heath care access and lifestyle behaviors, including perceived health, diet, physical activity, and sleep has been reported, few studies have examined these domains jointly among pregnant and postpartum people in the early stages of the COVID-19 pandemic. Methods This mixed methods study was conducted among a subset of participants (n = 22) in a cohort study in Austin, Texas, who were pregnant or had recently delivered when the outbreak occurred. Measures were from the early second trimester up to 6 months postpartum. Findings from questionnaires were complemented by qualitative interviews during Spring/Summer 2020 regarding experiences during the early pandemic. Results From our quantitative data (n = 22), most participants reported that the pandemic generally had a negative impact on their lives (81%), that they shifted to eating more at home (71%), and that they were less physically active (62%). Five major themes emerged in our qualitative interviews (n = 22): (1) adaptation to pandemic restrictions; (2) psychosocial experiences, such as feelings of anxiety, guilt, sadness, isolation, and frustration; (3) health behavior changes; (4) health care experiences; and (5) where they obtained general and perinatal related pandemic information. Of those who completed both pregnancy and postpartum interviews (n = 8), all reported anxiety during both periods; however, those who delivered in Spring 2020 experienced more anxiety surrounding delivery and less social support than those who delivered in Summer 2020, who reported less anxiety surrounding hospital birth and greater social support, particularly after delivery. Conclusions Overall, our findings confirm prior evidence that the COVID-19 pandemic had a marked impact on stress, anxiety, and worries, as well as lifestyle behaviors among pregnant and postpartum people. Our work provides lessons for health care practitioners about support need for pregnant and postpartum persons amid societal disruption.

Model representations of the stratospheric semi-annual oscillation (SAO) show a common easterly bias, with a weaker westerly phase and stronger easterly phase compared to observations. Previous studies have shown that both resolved and parameterized tropical waves in the upper stratosphere are too weak. These waves propagate vertically through the underlying region dominated by the stratospheric quasi-biennial oscillation (QBO) before reaching the SAO altitudes. The influence of biases in the modelled QBO on the representation of the SAO is therefore explored. Correcting the QBO biases helps to reduce the SAO easterly bias through improved filtering of resolved and parameterized waves that contribute to improving both the westerly and the easterly phases of the SAO. The time-averaged zonal-mean zonal winds at SAO altitudes change by up to 25 % in response to the QBO bias corrections. The annual cycle in the equatorial upper stratosphere is improved as well. Most of the improvements in the SAO occur during the QBO easterly phase, coinciding with the period when the model's QBO exhibits the largest bias. Nevertheless, despite correcting for the QBO bias, there remains a substantial easterly bias in the SAO, suggesting that westerly wave forcing in the upper stratosphere and lower mesosphere is still severely under-represented.

Abstract Background Opisthorchis viverrini (OV) and soil-transmitted helminths (STH) are two of the most common helminths contributing to the Neglected Tropical Disease (NTDs) burden in the Lower Mekong Basin. Although mass drug administration is the cornerstone of control programs to reduce morbidity caused by these infections, this approach has limitations in preventing re-infections. Elimination requires additional measures such as reservoir host treatment, improved hygiene and health education to reinforce MDA's impact. This study aims to examine the impact of a scalable multi-component One Health Helminth Elimination program in the Lower Mekong Basin (HELM) that combines human praziquantel (PZQ) and albendazole (ALB) treatment with a program that includes the “Magic Glasses” and the “Lawa Model” interventions with health promotion at their core. Methods This study will employ a cluster randomized controlled trial (cRCT) in 18 rural communities (with sub-district or villages as cluster units) across Cambodia, Laos and Thailand. The control arm will receive one round of PZQ/ALB treatment, while in the intervention arm, multi-component HELM program will be implemented, which includes PZQ/ALB treatment together with the Magic Glasses and Lawa Model interventions. OV and STH infections levels will be evaluated in individuals aged 5–75 years at baseline and will be repeated at follow-up (12 months after the HELM intervention), using modified formalin ethyl-acetate concentration technique and quantitative PCR. The primary outcome of the study will be cumulative incidence of human OV and STH infections. Outcomes between the study arms will be compared using generalized linear mixed models, accounting for clustering. Discussion Evidence from this trial will quantify the impact of a multi-component One Health control strategy in interrupting Ov and STH infections in the Lower Mekong Basin. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000353796. Prospectively registered 28 February 2022.

Abstract Thermal Infrared (TIR) drones are emerging as effective tools for wildlife ecology monitoring and are increasingly employed in primate surveys. However, systematic methods for assessing primate detectability are lacking. We present a comprehensive approach utilizing a novel Thermal Detection Index (TDI) to evaluate the potential of TIR drones for primate monitoring. We developed TDIs for 389 primate species, considering activity patterns, locomotion types, body mass, densities, habitat utilization, and sleeping behaviors during diurnal and nocturnal surveys. Through the integration of TDIs with primates’ distribution and climatic variables (average annual temperature, precipitation, and wind speed), we established a Global TDI Suitability Score aimed at pinpointing species and regions most compatible with TIR drone-based monitoring. Atelidae, Cercopithecidae, and Indridae showed the highest TDI values, suggesting their suitability for TIR-drone surveys. We identified optimal regions in Africa, Asia and Latin America for primate monitoring with TIR drones, driven by favorable ecological conditions, habitat types, and high TDI species diversity. However, local ecological factors and regulatory frameworks also influence drone survey feasibility, necessitating careful consideration prior to implementation. Overall, our study provides a valuable framework for prioritizing primate species and regions for TIR drone-based monitoring, facilitating targeted conservation efforts and advancing primate monitoring research.

Over the past two decades, therapeutic antibodies have emerged as a rapidly expanding domain within the field of biologics. In silico tools that can streamline the process of antibody discovery and optimization are critical to support a pipeline that is growing more numerous and complex every year. High-quality structural information remains critical for the antibody optimization process, but antibody-antigen complex structures are often unavailable and in silico antibody docking methods are still unreliable. In this study, DeepAb, a deep learning model for predicting antibody Fv structure directly from sequence, was used in conjunction with single-point experimental deep mutational scanning (DMS) enrichment data to design 200 potentially optimized variants of an anti-hen egg lysozyme (HEL) antibody. We sought to determine whether DeepAb-designed variants containing combinations of beneficial mutations from the DMS exhibit enhanced thermostability and whether this optimization affected their developability profile. The 200 variants were produced through a robust high-throughput method and tested for thermal and colloidal stability (Tonset, Tm, Tagg), affinity (KD) relative to the parental antibody, and for developability parameters (nonspecific binding, aggregation propensity, self-association). Of the designed clones, 91% and 94% exhibited increased thermal and colloidal stability and affinity, respectively. Of these, 10% showed a significantly increased affinity for HEL (5- to 21-fold increase) and thermostability (>2.5C increase in Tm1), with most clones retaining the favorable developability profile of the parental antibody. Additional in silico tests suggest that these methods would enrich for binding affinity even without first collecting experimental DMS measurements. These data open the possibility of in silico antibody optimization without the need to predict the antibody–antigen interface, which is notoriously difficult in the absence of crystal structures.

Summary: Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and upon SARS-CoV-2 infection, we collected peripheral blood mononuclear cells and plasma from 226 women, including 152 pregnant individuals and 74 non-pregnant women. We find that SARS-CoV-2 infection is associated with altered T cell responses in pregnant women, including a clonal expansion of CD4-expressing CD8+ T cells, diminished interferon responses, and profound suppression of monocyte function. We also identify shifts in cytokine and chemokine levels in the sera of pregnant individuals, including a robust increase of interleukin-27, known to drive T cell exhaustion. Our findings reveal nuanced pregnancy-associated immune responses, which may contribute to the increased susceptibility of pregnant individuals to viral respiratory infection.

Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, and drug development. Here, we interrogated the cell signaling environment within the developing human intestine to identify niche cues that may be important for epithelial development and homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed in the developing human crypt. Enteroids generated from the developing human intestine grown in standard culture conditions, which contain EGF, are dominated by stem and progenitor cells and feature little differentiation and no spatial organization. Our results demonstrate that EREG can replace EGF in vitro, and EREG leads to spatially resolved enteroids that feature budded and proliferative crypt domains and a differentiated villus-like central lumen. Multiomic (transcriptome plus epigenome) profiling of native crypts, EGF-grown enteroids, and EREG-grown enteroids showed that EGF enteroids have an altered chromatin landscape that is dependent on EGF concentration, downregulate the master intestinal transcription factor CDX2, and ectopically express stomach genes, a phenomenon that is reversible. This is in contrast to EREG-grown enteroids, which remain intestine like in culture. Thus, EREG creates a homeostatic intestinal niche in vitro, enabling interrogation of stem cell function, cellular differentiation, and disease modeling.

Our ancestors acquired morphological, cognitive and metabolic modifications that enabled humans to colonize diverse habitats, develop extraordinary technologies and reshape the biosphere. Understanding the genetic, developmental and molecular bases for these changes will provide insights into how we became human. Connecting human-specific genetic changes to species differences has been challenging owing to an abundance of low-effect size genetic changes, limited descriptions of phenotypic differences across development at the level of cell types and lack of experimental models. Emerging approaches for single-cell sequencing, genetic manipulation and stem cell culture now support descriptive and functional studies in defined cell types with a human or ape genetic background. In this Review, we describe how the sequencing of genomes from modern and archaic hominins, great apes and other primates is revealing human-specific genetic changes and how new molecular and cellular approaches - including cell atlases and organoids - are enabling exploration of the candidate causal factors that underlie human-specific traits.

BackgroundHelminths are a major global health issue, impacting health, educational, and socioeconomic outcomes. Infections, often starting in childhood, are linked to anemia, malnutrition, cognitive deficit, and in chronic cases of Opisthorchis viverrini (OV), cholangiocarcinoma. The main control strategy for helminth infection is mass drug administration; however, this does not prevent reinfection. As such, prevention strategies are needed. The “Magic Glasses” is a school-based cartoon health education package that has demonstrated success in improving knowledge, attitudes, and practices (KAP) surrounding soil-transmitted helminths (STH) in China and the Philippines. This study is designed to assess the acceptability and impact of the 2 new versions of the Magic Glasses targeting STH and OV designed for the Lower Mekong audience in Cambodia, Lao People’s Democratic Republic (PDR), and Thailand. ObjectiveThe objective of this study is to evaluate the acceptability of the “Magic Glasses Lower Mekong” and “Magic Glasses Opisthorchiasis” education packages among schoolchildren in the Lower Mekong Basin, and the impact of these education packages on students’ KAP surrounding STH and OV, respectively. MethodsSchoolchildren will be recruited into a cluster randomized controlled trial with intervention and control arms in rural schools in Cambodia, Lao PDR, and Thailand. Schoolchildren’s initial acceptability of the intervention will be evaluated using an adapted questionnaire. Sustained acceptability will be assessed at 9-month follow-up through focus group discussions with students and interviews with teachers. Impact will be evaluated by KAP questionnaires on STH and OV. KAP questionnaires will be administered to children at baseline and at follow-up. Indirect impact on parents' KAP of OV and STH will be assessed through focus group discussions at follow-up. ResultsThe trial is in progress in Lao PDR and Thailand and is expected to commence in Cambodia in January 2024. The results of the study are expected to be available 18 months from the start of recruitment. We hypothesize that participants enrolled in the intervention arm of the study will have higher KAP scores for STH and OV, compared with the participants in the control arm at follow-up. We expect that students will have initial and sustained acceptability of these intervention packages. ConclusionsThis trial will examine the acceptability of the “Magic Glasses Opisthorchiasis” and “Magic Glasses Lower Mekong” interventions and provide evidence on the effectiveness of the “Magic Glasses” on KAP related to OV and STH among schoolchildren in the Lower Mekong Basin. Study results will provide insight on acceptability and impact indicators and inform a scaling up protocol for the “Magic Glasses” education packages in Cambodia, Lao PDR, and Thailand. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12623000271606; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385315&isReview=true International Registered Report Identifier (IRRID)DERR1-10.2196/55290

Background Guidelines recommend the use of risk scores to select patients for further investigation after myocardial infarction has been ruled out but their utility to identify those with coronary artery disease is uncertain.Methods In a prospective cohort study, patients with intermediate high-sensitivity cardiac troponin I concentrations (5 ng/L to sex-specific 99th percentile) in whom myocardial infarction was ruled out were enrolled and underwent coronary CT angiography (CCTA) after hospital discharge. History, ECG, Age, Risk factors, Troponin (HEART), Emergency Department Assessment of Chest Pain Score (EDACS), Global Registry of Acute Coronary Event (GRACE), Thrombolysis In Myocardial Infarction (TIMI), Systematic COronary Risk Evaluation 2 and Pooled Cohort Equation risk scores were calculated and the odds ratio (OR) and diagnostic performance for obstructive coronary artery disease were determined using established thresholds.Results Of 167 patients enrolled (64±12 years, 28% female), 29.9% (50/167) had obstructive coronary artery disease. The odds of having obstructive disease were increased for all scores with the lowest and highest increase observed for an EDACS score ≥16 (OR 2.2 (1.1–4.6)) and a TIMI risk score ≥1 (OR 12.9 (3.0–56.0)), respectively. The positive predictive value (PPV) was low for all scores but was highest for a GRACE score >88 identifying 39% as high risk with a PPV of 41.9% (30.4–54.2%). The negative predictive value (NPV) varied from 77.3% to 95.2% but was highest for a TIMI score of 0 identifying 26% as low risk with an NPV of 95.2% (87.2–100%).Conclusions In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been excluded, clinical risk scores can help identify patients with and without coronary artery disease, although the performance of established risk thresholds is suboptimal for utilisation in clinical practice.Trial registration number NCT04549805.

Abstract Regional and global trade of live animals can contribute to the spread and emergence of novel pathogens, including several important pathogens of amphibians. However, understanding the spread or even frequency of infections in large, complex amphibian trade networks has been difficult, in part because businesses tend to be reluctant to participate in surveillance programs. Thus, we developed a novel approach to surveillance in which anonymous participating businesses were sent surveillance kits through a trusted trade advocacy partner, samples were returned to researchers via anonymous prepaid envelopes, and results were provided via a secure website with access regulated by a unique personal identification number (PIN) created by the business. We tested samples for the amphibian pathogens, Batrachochytrium salamandrivorans (Bsal), Batrachochytrium dendrobatidis (Bd), and Ranavirus spp. (Rv), as well as the beneficial microbe, Janthinobacterium lividum (Jliv), using quantitative real‐time polymerase chain reaction (qPCR). Out of 120 businesses invited to complete an anonymous socioeconomic survey, 24 volunteered to participate in pathogen surveillance, of which 14 were sent surveillance kits. Eight of these businesses returned samples consisting of swabs collected from amphibians in 78 terrestrial habitats and water filters from 49 aquatic habitats. Copies of a highly conserved vertebrate gene (EBF3N), quantified using qPCR, were consistently low (

Abstract Background Self-management education programmes are cost-effective in helping people with type 2 diabetes manage their diabetes, but referral and attendance rates are low. This study reports on the effectiveness of the Embedding Package, a programme designed to increase type 2 diabetes self-management programme attendance in primary care. Methods Using a cluster randomised design, 66 practices were randomised to: (1) a wait-list group that provided usual care for nine months before receiving the Embedding Package for nine months, or (2) an immediate group that received the Embedding Package for 18 months. ‘Embedders’ supported practices and self-management programme providers to embed programme referral into routine practice, and an online ‘toolkit’ contained embedding support resources. Patient-level HbA1c (primary outcome), programme referral and attendance data, and clinical data from 92,977 patients with type 2 diabetes were collected at baseline (months − 3–0), step one (months 1–9), step 2 (months 10–18), and 12 months post-intervention. An integrated ethnographic study including observations, interviews, and document analysis was conducted using interpretive thematic analysis and Normalisation Process Theory. Results No significant difference was found in HbA1c between intervention and control conditions (adjusted mean difference [95% confidence interval]: -0.10 [-0.38, 0.18] mmol/mol; -0.01 [-0.03, 0.02] %). Statistically but not clinically significantly lower levels of HbA1c were found in people of ethnic minority groups compared with non-ethnic minority groups during the intervention condition (-0.64 [-1.08, -0.20] mmol/mol; -0.06% [-0.10, -0.02], p = 0.004), but not greater self-management programme attendance. Twelve months post-intervention data showed statistically but not clinically significantly lower HbA1c (-0.56 [95% confidence interval: -0.71, -0.42] mmol/mol; -0.05 [-0.06, -0.04] %; p

The 2020 moment magnitude (Mw) 6.5 Stanley, Idaho, earthquake raised questions about the history and extent of complex faulting in the northwestern Centennial Tectonic Belt (CTB) and its relation to the Sawtooth normal fault and Eocene Trans-Challis fault system (TCFS). To explore faulting in this area, we excavated a paleoseismic trench across the Sawtooth fault along the western margin of the CTB, and compared an early Holocene (9.1 ± 2.1 ka, 1σ) rupture at the site with lacustrine paleoseismic data and fault mapping in the 2020 epicentral region. We find: (1) a history of partial to full rupture of the Sawtooth fault (Mw 6.8–7.4), (2) that shorter ruptures (Mw≤6.9) are likely along distributed and discontinuous faults in the epicentral region, (3) that this complex system that hosted the 2020 earthquake is not directly linked to the Sawtooth fault, (4) that the northeast-trending TCFS likely plays a role in controlling fault length and rupture continuity for adjacent faults, and (5) that parts of the TCFS may facilitate displacement transfer between normal faults that accommodate crustal extension and rotation. Our results help unravel complex faulting in the CTB and imply that relict structures can help inform regional seismic hazard assessments.

Background/Objectives: Although wild poliovirus type 2 has been eradicated, the prolonged transmission of the live- attenuated virus contained in the type-2 oral polio vaccine (OPV2) in under-immunized populations has led to the emergence of circulating vaccine-derived poliovirus type 2 (cVDPV2). The novel OPV2 (nOPV2) was designed to be more genetically stable and reduce the chance of cVDPV2 emergence while retaining comparable immunogenicity to the Sabin monovalent OPV2 (mOPV2). This study aimed to estimate the relative reduction in the emergence risk due to the use of nOPV2 instead of mOPV2. Methods: Data on OPV2 vaccination campaigns from May 2016 to 1 August 2024 were analyzed to estimate type-2 OPV-induced immunity in children under 5 years of age. Poliovirus surveillance data were used to estimate seeding dates and classify cVDPV2 emergences as mOPV2- or nOPV2-derived. The expected number of emergences if mOPV2 was used instead of nOPV2 was estimated, accounting for the timing and volume of nOPV2 doses, the known risk factors for emergence from mOPV2, and censoring due to the incomplete observation period for more recent nOPV2 doses. Results: As of 1 August 2024, over 98% of the approximately 1.19 billion nOPV2 doses administered globally were in Africa. We estimate that approximately 76 (95% confidence interval 69–85) index isolates of cVDPV2 emergences would be expected to be detected by 1 August 2024 if mOPV2 had been used instead of nOPV2 in Africa. The 18 observed nOPV2-derived emergences represent a 76% (74–79%) lower risk of emergence by nOPV2 than mOPV2 in Africa. The crude global analysis produced similar results. Key limitations include the incomplete understanding of the drivers of heterogeneity in emergence risk across geographies and variance in the per-dose risk of emergence may be incompletely captured using known risk factors. Conclusions: These results are consistent with the accumulating clinical and field evidence showing the enhanced genetic stability of nOPV2 relative to mOPV2, and this approach has been implemented in near-real time to contextualize new findings during the roll-out of this new vaccine. While nOPV2 has resulted in new emergences of cVDPV2, the number of cVDPV2 emergences is estimated to be approximately four-fold lower than if mOPV2 had been used instead.

In this work, we present a solvothermal, in situ doping methodology for synthesizing crystalline doped 2D bismuth telluride (Bi2Te3) nanoplates. Isoelectronic antimony (Sb) substitution at the bismuth (Bi) site is chosen to minimize the lattice strain in the nanostructure. Using a combination of x-ray techniques and electron microscopy, we demonstrate that the rhombohedral crystal structure (space group R3̄m), characteristic of Bi2Te3 is preserved in few-quintuple-layer, hexagonal nanoplates. Our findings reveal a uniform dispersion of Sb within the nanoplates up to an atomic concentration of 1%. Beyond this threshold, a disordered SbTe alloy begins to form along the crystal edges in addition to Sb substitution at the Bi sites in the bulk, restricting further growth of the nanoplates. In addition, we examine the different stresses that develop within the nanoplates as lattice strain increases due to Sb substitution. This study provides fundamental insights into the dopant’s effect on the self-assembled growth of electronically relevant 2D crystals.

Carbohydrates and glycoproteins modulate key biological functions. However, experimental structure determination of sugar polymers is notoriously difficult. Computational approaches can aid in carbohydrate structure prediction, structure determination, and design. In this work, we developed a glycan-modeling algorithm, GlycanTreeModeler, that computationally builds glycans layer-by-layer, using adaptive kernel density estimates (KDE) of common glycan conformations derived from data in the Protein Data Bank (PDB) and from quantum mechanics (QM) calculations. GlycanTreeModeler was benchmarked on a test set of glycan structures of varying lengths, or "trees". Structures predicted by GlycanTreeModeler agreed with native structures at high accuracy for both de novo modeling and experimental density-guided building. We employed these tools to design de novo glycan trees into a protein nanoparticle vaccine to shield regions of the scaffold from antibody recognition, and experimentally verified shielding. This work will inform glycoprotein model prediction, glycan masking, and further aid computational methods in experimental structure determination and refinement.

Our knowledge of the organisation of the human brain at the population-level is yet to translate into power to predict functional differences at the individual-level, limiting clinical applications and casting doubt on the generalisability of inferred mechanisms. It remains unknown whether the difficulty arises from the absence of individuating biological patterns within the brain, or from limited power to access them with the models and compute at our disposal.Here we comprehensively investigate the resolvability of such patterns with data and compute at unprecedented scale. Across 23 810 unique participants from UK Biobank, we systematically evaluate the predictability of 25 individual biological characteristics, from all available combinations of structural and functional neuroimaging data. Over 4526 GPU*hours of computation, we train, optimize, and evaluate out-of-sample 700 individual predictive models, including fully-connected feed-forward neural networks of demographic, psychological, serological, chronic disease, and functional connectivity characteristics, and both uni- and multi-modal 3D convolutional neural network models of macro- and micro-structural brain imaging.We find a marked discrepancy between the high predictability of sex (balanced accuracy 99.7%), age (mean absolute error 2.048 years, R2 0.859), and weight (mean absolute error 2.609Kg, R2 0.625), for which we set new state-of-the-art performance, and the surprisingly low predictability of other characteristics. Neither structural nor functional imaging predicted an individual's psychology better than the coincidence of common chronic disease (p < 0.05). Serology predicted chronic disease (p < 0.05) and was best predicted by it (p < 0.001), followed by structural neuroimaging (p < 0.05).Our findings suggest either more informative imaging or more powerful models will be needed to decipher individual level characteristics from the human brain. We make our models and code openly available.

Abstract Introduction Non-compliance is a common challenge for researchers and may reduce the power of an intention-to-treat analysis. Whilst a per protocol approach attempts to deal with this issue, it can result in biased estimates. Several methods to resolve this issue have been identified in previous reviews, but there is limited evidence supporting their use. This review aimed to identify simulation studies which compare such methods, assess the extent to which certain methods have been investigated and determine their performance under various scenarios. Methods A systematic search of several electronic databases including MEDLINE and Scopus was carried out from conception to 30th November 2022. Included papers were published in a peer-reviewed journal, readily available in the English language and focused on comparing relevant methods in a superiority randomised controlled trial under a simulation study. Articles were screened using these criteria and a predetermined extraction form used to identify relevant information. A quality assessment appraised the risk of bias in individual studies. Extracted data was synthesised using tables, figures and a narrative summary. Both screening and data extraction were performed by two independent reviewers with disagreements resolved by consensus. Results Of 2325 papers identified, 267 full texts were screened and 17 studies finally included. Twelve methods were identified across papers. Instrumental variable methods were commonly considered, but many authors found them to be biased in some settings. Non-compliance was generally assumed to be all-or-nothing and only occurring in the intervention group, although some methods considered it as time-varying. Simulation studies commonly varied the level and type of non-compliance and factors such as effect size and strength of confounding. The quality of papers was generally good, although some lacked detail and justification. Therefore, their conclusions were deemed to be less reliable. Conclusions It is common for papers to consider instrumental variable methods but more studies are needed that consider G-methods and compare a wide range of methods in realistic scenarios. It is difficult to make conclusions about the best method to deal with non-compliance due to a limited body of evidence and the difficulty in combining results from independent simulation studies. PROSPERO registration number CRD42022370910.

Abstract Background To enhance the impact of interventions, it is important to understand how intervention engagement relates to study outcomes. We report on the level of implementation and engagement with the SMART Work & Life (SWAL) programme (delivered with (SWAL plus desk) and without a height-adjustable desk (SWAL)) and explore the effects of different levels of this on change in daily sitting time in comparison to the control group. Methods The extent of intervention delivery by workplace champions and the extent of engagement by champions and participants (staff) with each intervention activity was assessed by training attendance logs, workplace champion withdrawal dates, intervention activities logs and questionnaires. These data were used to assess whether a cluster met defined criteria for low, medium, or high implementation and engagement or none of these. Mixed effects linear regression analyses tested whether change in sitting time varied by: (i) the number of intervention activities implemented and engaged with, and (ii) the percentage of implementation and engagement with all intervention strategies. Results Workplace champions were recruited for all clusters, with 51/52 (98%) attending training. Overall, 12/27 (44.4%) SWAL and 9/25 (36.0%) SWAL plus desk clusters implemented all main intervention strategies. Across remaining clusters, the level of intervention implementation varied. Those in the SWAL (n = 8 (29.6%) clusters, 80 (32.1%) participants) and SWAL plus desk (n = 5 (20.0%) clusters, 41 (17.1%) participants) intervention groups who implemented and engaged with the most intervention strategies and had the highest percentage of cluster implementation and engagement with all intervention strategies sat for 30.9 (95% CI -53.9 to -7.9, p = 0.01) and 75.6 (95% CI -103.6 to -47.7, p

Abstract Background Patient and Public Involvement and Engagement (PPIE) is important to all aspects of health research. However, there are few examples of successful PPIE in statistical methodology research. One of the reasons for this relates to challenges in the identification of individuals interested in statistical methodology research projects, and ambiguities over the importance of PPIE to these projects. Methods This project was conducted between August 2022 and August 2023. The aim is to report the process of the development of an accessible animation to describe what statistical methodology is and the importance of PPIE in statistical methodology research projects. For this, we combined storyboarding and scriptwriting with feedback from PPIE members and researchers. Results After three stages that incorporated feedback from the relevant stakeholders, we produced a final animation about PPIE in statistical methodology. The resulting animation used minimal text, simple animation techniques and was of short duration (

Abstract Background Healthcare workers’ (HCW) well-being has a direct effect on patient care. However, little is known about the prevalence and patterns of long-term medical conditions in HCWs, especially those from ethnic minorities. This study evaluated the burden of multiple long-term conditions (MLTCs), i.e. the presence of two or more single long-term conditions (LTCs), among HCWs in the United Kingdom (UK) and variation by ethnicity and migration status. Methods We used baseline data from the UK-REACH cohort study collected December 2020–March 2021. We used multivariable logistic regression, adjusting for demographic, occupational and lifestyle factors to examine the relationship between self-reported LTCs/MLTCs and ethnicity, migration status and time since migration to the UK. Results Of 12,100 included HCWs, with a median age of 45 years (IQR: 34–54), 27% were overseas-born, and 30% were from non-White ethnic groups (19% Asian, 4% Black, 4% Mixed, 2% Other). The most common self-reported LTCs were anxiety (14.9%), asthma (12.2%), depression (10.7%), hypertension (8.7%) and diabetes (4.0%). Mental health conditions were more prevalent among UK-born than overseas-born HCWs for all ethnic groups (adjusted odds ratio (aOR) using White UK-born as the reference group each time: White overseas-born 0.77, 95%CI 0.66–0.95 for anxiety). Diabetes and hypertension were more common among Asian (e.g. Asian overseas, diabetes aOR 2.97, 95%CI 2.30–3.83) and Black (e.g. Black UK-born, hypertension aOR 1.77, 95%CI 1.05–2.99) groups than White UK-born. After adjustment for age, sex and deprivation, the odds of reporting MLTCs were lower in most ethnic minority groups and lowest for those born overseas, compared to White UK-born (e.g. White overseas-born, aOR 0.68, 95%CI 0.55–0.83; Asian overseas-born aOR 0.75, 95%CI 0.62–0.90; Black overseas-born aOR 0.52, 95%CI 0.36–0.74). The odds of MLTCs in overseas-born HCWs were equivalent to the UK-born population in those who had settled in the UK for ≥ 20 years (aOR 1.14, 95%CI 0.94–1.37). Conclusions Among UK HCWs, the prevalence of common LTCs and odds of reporting MLTCs varied by ethnicity and migrant status. The lower odds of MLTCs in migrant HCWs reverted to the odds of MLTCs in UK-born HCWs over time. Further research on this population should include longitudinal studies with linkage to healthcare records. Interventions should be co-developed with HCWs from different ethnic and migrant groups focussed upon patterns of conditions prevalent in specific HCW subgroups to reduce the overall burden of LTCs/MLTCs.

Abstract Background A cluster randomised controlled trial demonstrated the effectiveness of the SMART Work & Life (SWAL) behaviour change intervention, with and without a height-adjustable desk, for reducing sitting time in desk-based workers. Staff within organisations volunteered to be trained to facilitate delivery of the SWAL intervention and act as workplace champions. This paper presents the experiences of these champions on the training and intervention delivery, and from participants on their intervention participation. Methods Quantitative and qualitative feedback from workplace champions on their training session was collected. Participants provided quantitative feedback via questionnaires at 3 and 12 month follow-up on the intervention strategies (education, group catch ups, sitting less challenges, self-monitoring and prompts, and the height-adjustable desk [SWAL plus desk group only]). Interviews and focus groups were also conducted at 12 month follow-up with workplace champions and participants respectively to gather more detailed feedback. Transcripts were uploaded to NVivo and the constant comparative approach informed the analysis of the interviews and focus groups. Results Workplace champions rated the training highly with mean scores ranging from 5.3/6 to 5.7/6 for the eight parts. Most participants felt the education increased their awareness of the health consequences of high levels of sitting (SWAL: 90.7%; SWAL plus desk: 88.2%) and motivated them to change their sitting time (SWAL: 77.5%; SWAL plus desk: 85.77%). A high percentage of participants (70%) reported finding the group catch up session helpful and worthwhile. However, focus groups highlighted mixed responses to the group catch-up sessions, sitting less challenges and self-monitoring intervention components. Participants in the SWAL plus desk group felt that having a height-adjustable desk was key in changing their behaviour, with intrinsic as well as time based factors reported as key influences on the height-adjustable desk usage. In both intervention groups, participants reported a range of benefits from the intervention including more energy, less fatigue, an increase in focus, alertness, productivity and concentration as well as less musculoskeletal problems (SWAL plus desk group only). Work-related, interpersonal, personal attributes, physical office environment and physical barriers were identified as barriers when trying to sit less and move more. Conclusions Workplace champion and participant feedback on the intervention was largely positive but it is clear that different behaviour change strategies worked for different people indicating that a ‘one size fits all’ approach may not be appropriate for this type of intervention. The SWAL intervention could be tested in a broader range of organisations following a few minor adaptations based on the champion and participant feedback. Trial registration ISCRCTN registry (ISRCTN11618007).

Abstract Many areas of medicine would benefit from deeper, more accurate phenotyping, but there are limited approaches for phenotyping using clinical notes without substantial annotated data. Large language models (LLMs) have demonstrated immense potential to adapt to novel tasks with no additional training by specifying task-specific instructions. Here we report the performance of a publicly available LLM, Flan-T5, in phenotyping patients with postpartum hemorrhage (PPH) using discharge notes from electronic health records (n = 271,081). The language model achieves strong performance in extracting 24 granular concepts associated with PPH. Identifying these granular concepts accurately allows the development of interpretable, complex phenotypes and subtypes. The Flan-T5 model achieves high fidelity in phenotyping PPH (positive predictive value of 0.95), identifying 47% more patients with this complication compared to the current standard of using claims codes. This LLM pipeline can be used reliably for subtyping PPH and outperforms a claims-based approach on the three most common PPH subtypes associated with uterine atony, abnormal placentation, and obstetric trauma. The advantage of this approach to subtyping is its interpretability, as each concept contributing to the subtype determination can be evaluated. Moreover, as definitions may change over time due to new guidelines, using granular concepts to create complex phenotypes enables prompt and efficient updating of the algorithm. Using this language modelling approach enables rapid phenotyping without the need for any manually annotated training data across multiple clinical use cases.

The world’s reptiles and amphibians are experiencing dramatic and ongoing losses in biodiversity, changes that can have substantial effects on ecosystems and human health. In 2022, the first Global Amphibian and Reptile Disease Conference was held, using One Health as a guiding principle. The conference showcased knowledge on numerous reptile and amphibian pathogens from several standpoints, including epidemiology, host immune defenses, wild population effects, and mitigation. The conference also provided field experts the opportunity to discuss and identify the most urgent herpetofaunal disease research directions necessary to address current and future threats to reptile and amphibian biodiversity.

Abstract Background Patient and public involvement (PPI) ensures that research is designed and conducted in a manner that is most beneficial to the individuals whom it will impact. It has an undisputed place in applied research and is required by many funding bodies. However, PPI in statistical methodology research is more challenging and work is needed to identify where and how patients and the public can meaningfully input in this area. Methods A descriptive cross-sectional research study was conducted using an online questionnaire, which asked statistical methodologists about themselves and their experience conducting PPI, either to inform a grant application or during a funded statistical methodology project. The survey included both closed-text responses, which were reported using summary statistics, and open-ended questions for which common themes were identified. Results 119 complete responses were recorded. Individuals who completed the survey displayed an even range of ages, career lengths and positions, with the majority working in academia. 40.3% of participants reported undertaking PPI to inform a grant application and the majority reported that the inclusion of PPI was received positively by the funder. Only 21.0% of participants reported undertaking PPI during a methodological project. 31.0% of individuals thought that PPI was “very” or “extremely” relevant to statistical methodology research, with 45.5% responding “somewhat” and 24.4% answering “not at all” or “not very”. Arguments for including PPI were that it can provide the motivation for research and shape the research question. Negative opinions included that it is too technical for the public to understand, so they cannot have a meaningful impact. Conclusions This survey found that the views of statistical methodologists on the inclusion of PPI in their research are varied, with some individuals having particularly strong opinions, both positive and negative. Whilst this is clearly a divisive topic, one commonly identified theme was that many researchers are willing to try and incorporate meaningful PPI into their research but would feel more confident if they had access to resources such as specialised training, guidelines, and case studies.

Abstract Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain’s affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.05 mg/kg ketamine, and 0.5 mg/kg ketamine in nonclinical adult participants (NCT03475277). Licensed clinicians monitored infusions for safety. Linear mixed effects models, analysis of variance, t-tests, and mediation models were used for statistical analyses. Our design enabled us to test our pre-specified primary and secondary endpoints, which were met: effects of ketamine across dose conditions on (1) emotional task-evoked brain activity, and (2) sub-components of dissociation and other ASCs. With this design, we also could disentangle which ketamine-induced affective brain states are dependent upon specific aspects of ASCs. Differently valenced ketamine-induced ASCs mediated opposing effects on right anterior insula activity. Participants experiencing relatively higher depersonalization induced by 0.5 mg/kg of ketamine showed relief from negative brain states (reduced task-evoked right anterior insula activity, 0.39 SD). In contrast, participants experiencing dissociative amnesia showed an exacerbation of insula activity (0.32 SD). These results in nonclinical participants may shed light on the mechanisms by which specific dissociative states predict response to ketamine in depressed individuals.

Abstract Background The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors — age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death. Methods Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care. Results The external validation showed the risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Furthermore, accounting for the competing risk of death improved prediction. Using criteria of 5 years ≥ 5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. Hybrid criteria of predicted risk using the competing risks model and ACR ≥ 70 mg/mmol should be used in referrals to secondary care. Conclusions The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce unnecessary referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities.

This study provides an update on the movement ecology of the Sunda pangolin (Manis javanica) in three distinct ecoregions of Vietnam. Using radio telemetry, we tracked 12 pangolins rescued from the illegal wildlife trade and translocated to protected areas. We found that the average home range of translocated Sunda pangolins was 1.58 km2 and did not vary significantly between sexes, mass, or habitat. However, there was a marked decrease in range size with decreasing sizes of suitable forest space and terrain, or a localized abundance of resources in some locations. Pangolins were most active from 03:00 to 04:00. The study highlights the need for further research to fully understand the ecology of this unique and enigmatic species.

Abstract Atmospheric muon neutrinos are produced by meson decays in cosmic-ray-induced air showers. The flux depends on meteorological quantities such as the air temperature, which affects the density of air. Competition between decay and re-interaction of those mesons in the first particle production generations gives rise to a higher neutrino flux when the air density in the stratosphere is lower, corresponding to a higher temperature. A measurement of a temperature dependence of the atmospheric $$\nu _{\mu }$$ ν μ flux provides a novel method for constraining hadronic interaction models of air showers. It is particularly sensitive to the production of kaons. Studying this temperature dependence for the first time requires a large sample of high-energy neutrinos as well as a detailed understanding of atmospheric properties. We report the significant ( $$> 10 \; \sigma $$ > 10 σ ) observation of a correlation between the rate of more than 260,000 neutrinos, detected by IceCube between 2012 and 2018, and atmospheric temperatures of the stratosphere, measured by the Atmospheric Infrared Sounder (AIRS) instrument aboard NASA’s AQUA satellite. For the observed 10 $$\%$$ % seasonal change of effective atmospheric temperature we measure a 3.5(3) $$\%$$ % change in the muon neutrino flux. This observed correlation deviates by about 2-3 standard deviations from the expected correlation of 4.3 $$\%$$ % as obtained from theoretical predictions under the assumption of various hadronic interaction models.

Abstract Complex systems often comprise many kinds of components which vary over many orders of magnitude in size: Populations of cities in countries, individual and corporate wealth in economies, species abundance in ecologies, word frequency in natural language, and node degree in complex networks. Here, we introduce ‘allotaxonometry’ along with ‘rank-turbulence divergence’ (RTD), a tunable instrument for comparing any two ranked lists of components. We analytically develop our rank-based divergence in a series of steps, and then establish a rank-based allotaxonograph which pairs a map-like histogram for rank-rank pairs with an ordered list of components according to divergence contribution. We explore the performance of rank-turbulence divergence, which we view as an instrument of ‘type calculus’, for a series of distinct settings including: Language use on Twitter and in books, species abundance, baby name popularity, market capitalization, performance in sports, mortality causes, and job titles. We provide a series of supplementary flipbooks which demonstrate the tunability and storytelling power of rank-based allotaxonometry.

Abstract We developed and validated a next generation sequencing-(NGS) based NIPT assay using quantitative counting template (QCT) technology to detect RhD, C, c, E, K (Kell), and Fya (Duffy) fetal antigen genotypes from maternal blood samples in the ethnically diverse U.S. population. Quantitative counting template (QCT) technology is utilized to enable quantification and detection of paternally derived fetal antigen alleles in cell-free DNA with high sensitivity and specificity. In an analytical validation, fetal antigen status was determined for 1061 preclinical samples with a sensitivity of 100% (95% CI 99–100%) and specificity of 100% (95% CI 99–100%). Independent analysis of two duplicate plasma samples was conducted for 1683 clinical samples, demonstrating precision of 99.9%. Importantly, in clinical practice the no-results rate was 0% for 711 RhD-negative non-alloimmunized pregnant people and 0.1% for 769 alloimmunized pregnancies. In a clinical validation, NIPT results were 100% concordant with corresponding neonatal antigen genotype/serology for 23 RhD-negative pregnant individuals and 93 antigen evaluations in 30 alloimmunized pregnancies. Overall, this NGS-based fetal antigen NIPT assay had high performance that was comparable to invasive diagnostic assays in a validation study of a diverse U.S. population as early as 10 weeks of gestation, without the need for a sample from the biological partner. These results suggest that NGS-based fetal antigen NIPT may identify more fetuses at risk for hemolytic disease than current clinical practice, which relies on paternal genotyping and invasive diagnostics and therefore is limited by adherence rates and incorrect results due to non-paternity. Clinical adoption of NIPT for the detection of fetal antigens for both alloimmunized and RhD-negative non-alloimmunized pregnant individuals may streamline care and reduce unnecessary treatment, monitoring, and patient anxiety.

Abstract Background In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. Methods The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5–5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. Discussion There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. Trial registration Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

Introduction Physical activity (PA) is protective against type 2 diabetes (T2D). However, data on pragmatic long-term interventions to reduce the risk of developing T2D via increased PA are lacking. This study investigated the cost-effectiveness of a pragmatic PA intervention in a multiethnic population at high risk of T2D.Materials and methods We adapted the School for Public Health Research diabetes prevention model, using the PROPELS trial data and analyses of the NAVIGATOR trial. Lifetime costs, lifetime quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each intervention (Walking Away (WA) and Walking Away Plus (WA+)) versus usual care and compared with National Institute for Health and Care Excellence’s willingness-to-pay of £20 000–£30 000 per QALY gained. We conducted scenario analyses on the outcomes of the PROPELS trial data and a threshold analysis to determine the change in step count that would be needed for the interventions to be cost-effective.Results Estimated lifetime costs for usual care, WA, and WA+ were £22 598, £23 018, and £22 945, respectively. Estimated QALYs were 9.323, 9.312, and 9.330, respectively. WA+ was estimated to be more effective and cheaper than WA. WA+ had an ICER of £49 273 per QALY gained versus usual care. In none of our scenario analyses did either WA or WA+ have an ICER below £20 000 per QALY gained. Our threshold analysis suggested that a PA intervention costing the same as WA+ would have an ICER below £20 000/QALY if it were to achieve an increase in step count of 500 steps per day which was 100% maintained at 4 years.Conclusions We found that neither WA nor WA+ was cost-effective at a limit of £20 000 per QALY gained. Our threshold analysis showed that interventions to increase step count can be cost-effective at this limit if they achieve greater long-term maintenance of effect.Trial Registration number ISRCTN registration: ISRCTN83465245: The PRomotion Of Physical activity through structuredEducation with differing Levels of ongoing Support for those with pre-diabetes (PROPELS)https://doi.org/10.1186/ISRCTN83465245.

The pathological accumulation of GM2 ganglioside associated with Tay-Sachs disease (TSD) and Sandhoff disease (SD) occurs in individuals who possess mutant forms of the heterodimer β-hexosaminidase A (Hex A) because of mutation of the HEXA and HEXB genes, respectively. With a lack of approved therapies, patients experience rapid neurological decline resulting in early death. A novel bicistronic vector carrying both HEXA and HEXB previously demonstrated promising results in mouse models of SD following neonatal intravenous administration, including significant reduction in GM2 accumulation, increased levels of Hex A, and a 2-fold extension of survival. The aim of the present study was to identify an optimal dose of the bicistronic vector in 6-week-old SD mice by an intrathecal route of administration along with transient immunosuppression, to inform possible clinical translation. Three doses of the bicistronic vector were tested: 2.5e11, 1.25e11, and 0.625e11 vector genomes per mouse. The highest dose provided the greatest increase in biochemical and behavioral parameters, such that treated mice lived to a median age of 56 weeks (>3 times the lifespan of the SD controls). These results have direct implications in deciding a human equivalent dose for TSD/SD and have informed the approval of a clinical trial application (NCT04798235).

Western palearctic salamander susceptibility to the skin disease caused by the amphibian chytrid fungus Batrachochytrium salamandrivorans (Bsal) was recognized in 2014, eliciting concerns for a potential novel wave of amphibian declines following the B. dendrobatidis (Bd) chytridiomycosis global pandemic. Although Bsal had not been detected in North America, initial experimental trials supported the heightened susceptibility of caudate amphibians to Bsal chytridiomycosis, recognizing the critical threat this pathogen poses to the North American salamander biodiversity hotspot. Here, we take stock of 10 years of research, collaboration, engagement, and outreach by the North American Bsal Task Force. We summarize main knowledge and conservation actions to both forestall and respond to Bsal invasion into North America. We address the questions: what have we learned; what are current challenges; and are we ready for a more effective reaction to Bsal’s eventual detection? We expect that the many contributions to preemptive planning accrued over the past decade will pay dividends in amphibian conservation effectiveness and can inform future responses to other novel wildlife diseases and extreme threats.

Summary: Background: The Philippines reports a high prevalence of soil-transmitted helminth (STH) infections despite the implementation of nationwide mass drug administration since 2006. The spatial variation of STH infections in the Philippines was last described using the 2005–2007 national STH and schistosomiasis survey. This study aimed to identify sociodemographic and environmental factors that drive STH transmission and predict high-risk areas in the Philippines. Methods: Epidemiological data on STH for students aged 5–16 years were obtained from the 2015 Philippines National Prevalence survey, while environmental data were extracted from satellite images and publicly available sources. Model-based geostatistics, implemented in a Bayesian framework, was used to identify sociodemographic and environmental correlates and predict high-risk areas for STH across the Philippines. The best-fitting model with the lowest deviance information criterion (DIC) was used to interpret the findings of the model and predict STH infection risk for the entire country. Risk maps were developed for each STH infection using the posterior means derived from the model. Findings: The prevalence of Ascaris lumbricoides (20.0%) and Trichuris trichiura (29.3%) was higher in the Visayas Island than in the Luzon and Mindanao Islands. Hookworm prevalence was highest in Mindanao Island (1.3%). Risk of A. lumbricoides was positively associated with males (odds ratio [OR]: 1.197; 97.5% Credible Interval [CrI]: 1.114, 1.286) and temperature (OR: 1.148; 97.5% CrI: 1.033, 1.291), while normalized difference vegetation index (OR: 0.354; 97.5% CrI: 0.138, 0.930) and soil pH (OR: 0.606; 97.5% CrI: 0.338, 0.949) were negatively associated with the transmission. T. trichiura risk was positively associated with males (OR: 1.261; 97.5% CrI: 1.173, 1.341), temperature (OR: 1.153; 97.5% CrI: 1.001, 1.301), and rainfall (OR: 1.004; 97.5% CrI: 1.011, 1.069). Hookworm risk was positively associated with males (OR: 2.142; 97.5% CrI: 1.537, 2.998), while children aged ≤12 years (OR: 0.435; 97.5% CrI: 0.252, 0.753) had a negative association with risk compared to those over 12 years. Focal areas of high risk were identified for A. lumbricoides and T. trichiura in the Visayas Island, and hookworm in the Mindanao Island. Interpretation: The spatial distribution of all three STH infections has considerably decreased since a previous national risk-mapping exercise. The high-risk areas identified in the study can be used to strategically target deworming and health education activities to further reduce the burden of STH and support progress toward elimination. Funding: The Australian Centre for the Control and Elimination of Neglected Tropical Diseases and the Australian National Health and Medical Research Council.

IntroductionThe article describes and analyzes the emergence of the field of global marine biodiversity conservation over the past fifteen years. We draw on collaborative research at international meetings, which we position as ‘field’ sites, places where diverse actors come together to negotiate the meaning and terms of global environmental governance and where that work is accessible and visible to researchers.MethodsBased on Collaborative Event Ethnography (CEE), a method developed to facilitate study of large meetings, we mobilize research from seven meetings since 2008 to describe the field of global marine biodiversity conservation, but more importantly to specifying how that field has been configured.ResultsWe identify practices of orchestration, narrative, performance, alliance, social objects, devices, and technologies, formal outcomes, and formal procedures, and their use at three phases of field configuration: building, framing, and bounding.DiscussionThe results: 1) enhance our understanding of the role of international conferences in global environmental governance generally, and for marine biodiversity conservation specifically; 2) demonstrate the relevance of field and field configuration theory; 3) contribute to theory on institutional fields by specifying practices of field configuration.

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.