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This paper describes a Capability Approach analysis of the capabilities, functionings, and conversion factors reported by learners on workplace-based mobile language learning courses. The study used secondary data from student satisfaction surveys from 556 learners who were all recent migrants to the US and who were using the courses to study English. Use of the Capability Approach highlights that the promises of mobile learning were not available to all learners as conversion factors (individual, social, environmental, and technological) inhibited their participation in the courses. The study shows how some learners experienced a tension between well-being and agency as they were unable to study the content they wanted in the way they wanted. It also demonstrates that factors around the business model of the company that created the courses impacted the level to which learners were able to participate in the program. Finally, the study illustrates that learners were able to extend the language they learned through the course into other areas of their lives and to help others.

Advancing the capabilities of earthquake nowcasting, the real-time forecasting of seismic activities, remains crucial for reducing casualties. This multifaceted challenge has recently gained attention within the deep learning domain, facilitated by the availability of extensive earthquake datasets. Despite significant advancements, the existing literature on earthquake nowcasting lacks comprehensive evaluations of pre-trained foundation models and modern deep learning architectures; each focuses on a different aspect of data, such as spatial relationships, temporal patterns, and multi-scale dependencies. This paper addresses the mentioned gap by analyzing different architectures and introducing two innovative approaches called Multi Foundation Quake and GNNCoder. We formulate earthquake nowcasting as a time series forecasting problem for the next 14 days within 0.1-degree spatial bins in Southern California. Earthquake time series are generated using the logarithm energy released by quakes, spanning 1986 to 2024. Our comprehensive evaluations demonstrate that our introduced models outperform other custom architectures by effectively capturing temporal-spatial relationships inherent in seismic data. The performance of existing foundation models varies significantly based on the pre-training datasets, emphasizing the need for careful dataset selection. However, we introduce a novel method, Multi Foundation Quake, that achieves the best overall performance by combining a bespoke pattern with Foundation model results handled as auxiliary streams.

Adults often learn new semantic information in face-to-face communication with other adults (e.g., teachers, colleagues). More knowledgeable individuals provide an ensemble of multimodal behaviours that can shape the information that their interlocutors learn. Using the naturalistic ECOLANG corpus of dyadic conversations, we ask whether multimodal behaviours (pitch, speaking rate, representational gestures, points, object manipulations, and gaze) support adults' semantic learning of unknown objects above and beyond verbal properties of utterances (number of utterances, lexical diversity, mean length of utterances, concreteness) and learners' individual differences (vocabulary, working memory). We found that individual differences, pointing and object manipulations affected learning, with verbal and multimodal factors also interacting to predict adult semantic learning. Our results highlight the relevance of accounts of multimodal learning in adulthood and the importance of considering naturalistic interaction in its complexity to understand the factors that influence adult learning.

Alongside the linguistic input, young children leverage multimodal cues (e.g., prosody, gestures) to learn novel words in face-to-face interactions. It is unclear whether multimodal cues play a similar role in adults. Here, we used ECOLANG, a corpus of semi-naturalistic dyadic conversations where English-speaking adults incidentally learned about unknown objects and their names by interacting with a partner who knew those objects. We examined whether multimodal cues (prosodic, indexical, and iconic) predicted learners' ability to learn the objects' names, above and beyond individual differences and linguistic predictors. We found that the number of repetitions of the label predicted word learning. Additionally, learners with lower working memory abilities benefited from speakers producing representational gestures while labelling the unknown objects. We discuss implications for theories of word learning and approaches of situated cognition.

Abstract Introduction and Objectives Voiding dysfunction remains a common side effect postprostate biopsy leading to significant morbidity. Alpha blockers have emerged as a potential therapeutic option to mitigate this risk, with various centres already incorporating its use in practice. Despite this, the literature regarding its efficacy remains inconclusive. Hence, a systematic review was performed to quantify the effect of perioperative alpha blockers on prostate biopsy‐related voiding function. Methods A systematic search in MEDLINE, Embase and PubMed between January 1989 and July 2023 was performed to identify relevant articles. Two independent reviewers independently screened abstracts, full texts and performed data extraction. Data including International Prostate Symptom Scores (IPSS), voiding flow rates (Qmax), postvoid residuals (PVR), rates of acute urinary retention (AUR) and quality of life (QoL) scores were extracted. Results were combined in an inverse variance random effects meta‐analysis. Results A total 808 patients from six randomised controlled trials (RCTs) comparing alpha blockers to controls were included. All articles excluded patients with pre‐existing voiding dysfunction. Pooled outcomes demonstrated statistically significant differences favouring alpha blocker usage in all objective and subjective measures including IPSS (mean difference 4.21, 95% confidence interval [CI] 2.58–5.84, p

Situated in a Japanese university ELT context, this qualitative exploratory interview-based study offers insights into how ten teachers responded to the challenges of transitioning to emergency remote teaching (ERT). The research was conducted to understand the implications of pandemic-instigated educational changes on teaching practices and perspectives towards effective teaching. An activity theory perspective accounts for the complex interlinking internal and external factors influencing teachers' experiences during and since the ERT. Data were obtained through semi-structured interviews with the ten teachers following the initial period of ERT and through reflective writing by the same teachers 12 months later. Key findings from a content analysis were that perspectives towards effective teaching were generally reinforced and that following reflection on pedagogical practices and professional learning directions many teachers were able to respond effectively to ongoing educational changes. We argue that the implications of the study may reveal important areas of comparison with other systems of activity in heightened states of transition and reveal pathways to the development of new practices.

We hypothesise that antimicrobial resistance (AMR) cannot be overcome by simply ‘drugging’ single biological targets, therefore, our focus is developing broad-spectrum therapeutics. Herein we present the synthesis of two novel spacer-linked, anthraquinone-triphenylphosphonium (AQ-TPP) conjugates (4) and (5) as early lead compounds in a new class of agent designed to penetrate the lipophilic barriers of the membranes of a diverse family of species; and establish bacterial growth inhibitory properties against methicillin-resistant Staphylococcus aureus (NCTC 13616) and Mycobacterium smegmatis [mc2155] (as a surrogate for Mycobacterium tuberculosis). The MIC and MBC values of (4) and (5) were determined against MRSA and found to be equipotent [MIC for each: 1 µg/mL (1.2 µM)]. Whereas the amide-linked conjugate (5) was determined to have 2-fold greater bactericidal potency [MBC 1 µg/mL (1.2 µM] than ester-linked (4). The anthraquinone-TPP conjugates (4) and (5) were active in vitro against Mycobacterium smegmatis (graphical abstract) and were equipotent as determined by their MIC values; in contrast to MRSA, the less hydrophobic (4) had 2-fold greater bactericidal potency than (5) as measured by their MBC values. Notably, both conjugates showed potent intracellular growth inhibitory activity in infected THP-1 macrophages. The conjugates are promising leads for the development of new antibacterial drugs. Key policy highlights Development of a novel class of antimicrobial compounds Drug screen against a WHO ‘high’ priority drug-resistant pathogen that poses the greatest threat to human health (methicillin-resistant Staphylococcus aureus) Drug screen against a surrogate for Mycobacterium tuberculosis, one of the leading causes of mortality worldwide.

ABSTRACT Aims Increasing attention has been given to the concept resilience in the context of healthcare especially during and post the COVID pandemic. Much of the inquiry and evidence reported has focused on promoting or enhancing resilience in healthcare for improving the quality of care and reducing medical negligence. This discursive paper aims to highlight how resilience is conceptualised and identify any potential limitations or gaps in the context of healthcare students, acknowledging considerations for further development and research into this topic. Design and Methods This discursive discussion draws on relevant theoretical underpinnings from the fields of adjustment and coping psychology, and research and evidence from health sciences, for facilitating an understanding of resilience in supporting healthcare students to adapt into professional practice. Results Investigation of resilience in healthcare students is mainly identified at an individual level as personal traits or skills for working within complex healthcare systems and clinical environments. Less attention has been given to examining resilience at the organisation or systemic level. This is primarily because of limited frameworks for investigating resilience from a multidimensional perspective recognising a wider systemic level influenced by external factors including socioecological determinants, for example, available support services for healthcare students. Conclusions The link between resilience and its function to mitigate against associated neuropsychological distress and subsequent pathopsychological disorders in healthcare student cohorts is recognised; however, greater understanding of resilience as a multidimensional construct is warranted. Relevance to Clinical Practice A multidimensional investigation of resilience is critical for the preparation and readiness of healthcare structures and organisations in facilitating the needs of healthcare students entering challenging and diverse healthcare working environments. Patient or Public Contribution No patient or public contribution.

Background: The incidence of colorectal cancer (CRC) is decreasing in individuals >50 years due to organised screening but has increased for younger individuals. We characterized symptoms and their timing before diagnosis in young individuals. Methods: We identified all patients diagnosed with CRC between 1990–2017 in British Columbia, Canada. Individuals n = 2544, EoCRC) and a matched cohort >50 (n = 2570, LoCRC) underwent chart review to identify CRC related symptoms at diagnosis and determine time from symptom onset to diagnosis. Results: Across all stages of CRC, EoCRC presented with significantly more symptoms than LoCRC (Stage 1 mean ± SD: 1.3 ± 0.9 vs. 0.7 ± 0.9, p = 0.0008; Stage 4: 3.3 ± 1.5 vs. 2.3 ± 1.7, p < 0.0001). Greater symptom burden at diagnosis was associated with worse survival in both EoCRC (p < 0.0001) and LoCRC (p < 0.0001). When controlling for cancer stage, both age (HR 0.87, 95% CI 0.8–1.0, p = 0.008) and increasing symptom number were independently associated with worse survival in multivariate models. Conclusions: Patients with EoCRC present with a greater number of symptoms of longer duration than LoCRC; however, time from patient reported symptom onset was not associated with worse outcomes.

Representational gestures are co-speech gestures that carry semantic content related to the content of speech. Previous studies focusing on adult-adult conversation have investigated the temporal alignment of gestures and speech finding that the overwhelming majority of representational gestures are produced right before the lexical content they refer to (their lexical affiliate, LA). However, nothing is yet known about whether caregivers would also time their gestures in the same way in naturalistic interactions. We annotated representational gestures from a large corpus (ECOLANG) of semi-naturalistic conversations between caregivers and their 3-4 year old children (n = 899 gestures from n=36 caregivers). We found that, just as in adult-directed language (ADL), representational gestures in child-directed language (CDL) were more tightly linked to the onset of LAs than the onset of the utterance in which LAs were produced (hence planned when full events are encoded); with the overall majority of the representational gestures starting before their LAs. We further found that age of acquisition (AoA) rating of the LA had a significant effect on the speech-gesture latency. We found that for words acquired earlier, the gesture’s stroke (the meaningful part of a gesture) tended to be produced before the LA’s onset; for the later acquired word, the stroke tended to be produced at the same time or after the onset of the LA in speech. Our findings suggest that: (1) Regardless of their addressee, speakers always time the production of representational gestures to specific conceptual/linguistic units, rather than the full event/utterance. (2) In contrast to ADL, caregivers’ gestures may support addresses’ linguistic processing not only by supporting word prediction (of likely better-known words), but also by supporting the learning of conceptual features (of likely less well-known words).

Studies have shown the importance of caregivers’ multimodal behaviours (e.g., prosody, gestures, gaze) on children’s word learning. However, most studies focus on only one specific behaviour (e.g., only prosody). Here, we investigate which multimodal behaviours used by caregivers best predict children’s word learning and vocabulary growth. Using data from the ECOLANG corpus, we analysed caregiver behaviour in semi-naturalistic interactions with their child (3 to 4 years old) in which they talked about known and unknown toys. We analysed caregivers’ (n=36) use of multimodal cues while labelling the objects, specifically their use of yes/no questions, pitch, representational gestures, pointing, object manipulations and gaze. Caregivers’ pitch, use of yes/no questions and pointing predicted children’s word learning. In particular, higher pitch when labelling unknown toys predicted immediate word learning. The degree to which caregivers used higher pitch when producing the label for known compared to unknown toys predicted both immediate learning and vocabulary growth. Furthermore, the degree to which caregivers used yes/no questions more for unknown toys predicted immediate learning, while the frequency of yes/no questions when naming unknown toys predicted vocabulary growth. Lastly, caregiver pointing also predicted immediate label learning and vocabulary growth, but in the opposite direction from prosody: the more they pointed towards known toys, the better children’s learning of novel toy labels. Other behaviours did not predict word learning. Overall, these results provide evidence for the important role of multimodal caregiver behaviours, particularly prosody, on children’s lexical development.

COVID-19 was a novel stressor that gave rise to pandemic related anxiety and increased the risk of mental health issues, particularly in youth. It is important to understand how such events contribute to psychological distress in young people to adequately intervene in the aftermath and to plan for future similar events. Using cross-sectional data from the CoSPACE Ireland study dataset this paper reports on the predictive relationship between COVID-19 anxiety and psychological distress for Irish adolescents (N = 314, M = 14.05, SD = 2.7, 11–18 years), while controlling for other influencing factors across multiple levels of a bioecological systems approach. Covariates were age, gender, ethnicity, social economic status, Peer Support, School Support and Parent–Child Closeness. Findings indicate that COVID-19 anxiety was a significant predictor of adolescents’ psychological distress. Specifically, Consequence Anxiety (worries about the indirect consequences of COVID-19) was found to be a predictor of adolescents’ psychological distress rather than Disease Anxiety (worries about the COVID-19 virus itself). Individual factors (e.g., age, ethnicity, special educational needs) and microsystem factors (e.g., parent child closeness, peer support) were also found to impact on adolescents’ levels of psychological distress. A significant moderation analysis revealed that greater parent–child closeness reduced the strength of the positive association between Consequence Anxiety and psychological distress. These findings suggest that strategies to alleviate adolescents’ psychological distress during pandemics should focus on reducing pandemic-related anxiety, specifically Consequence Anxiety. A multisystemic approach is also recommended to reduce the negative mental health impacts of the pandemic on adolescents.

Nowcasting is a term originating from economics, finance, and meteorology. It refers to the process of determining the uncertain state of the economy, markets or the weather at the current time by indirect means. In this paper, we describe a simple two-parameter data analysis that reveals hidden order in otherwise seemingly chaotic earthquake seismicity. One of these parameters relates to a mechanism of seismic quiescence arising from the physics of strain-hardening of the crust prior to major events. We observe an earthquake cycle associated with major earthquakes in California, similar to what has long been postulated. An estimate of the earthquake hazard revealed by this state variable time series can be optimized by the use of machine learning in the form of the Receiver Operating Characteristic skill score. The ROC skill is used here as a loss function in a supervised learning mode. Our analysis is conducted in the region of 5° × 5° in latitude-longitude centered on Los Angeles, a region which we used in previous papers to build similar time series using more involved methods (Rundle & Donnellan, 2020, https://doi.org/10.1029/2020EA001097; Rundle, Donnellan et al., 2021, https://doi.org/10.1029/2021EA001757; Rundle, Stein et al., 2021, https://doi.org/10.1088/1361-6633/abf893). Here we show that not only does the state variable time series have forecast skill, the associated spatial probability densities have skill as well. In addition, use of the standard ROC and Precision (PPV) metrics allow probabilities of current earthquake hazard to be defined in a simple, straightforward, and rigorous way.

Abstract No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org ). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

Abstract Background The evolutionary origins of animal nervous systems remain contentious because we still have a limited understanding of neural development in most major animal clades. Annelids — a species-rich group with centralised nervous systems — have played central roles in hypotheses about the origins of animal nervous systems. However, most studies have focused on adults of deeply nested species in the annelid tree. Recently, Owenia fusiformis has emerged as an informative species to reconstruct ancestral traits in Annelida, given its phylogenetic position within the sister clade to all remaining annelids. Methods Combining immunohistochemistry of the conserved neuropeptides FVamide-lir, RYamide-lir, RGWamide-lir and MIP-lir with gene expression, we comprehensively characterise neural development from larva to adulthood in Owenia fusiformis. Results The early larval nervous system comprises a neuropeptide-rich apical organ connected through peripheral nerves to a prototroch ring and the chaetal sac. There are seven sensory neurons in the prototroch. A bilobed brain forms below the apical organ and connects to the ventral nerve cord of the developing juvenile. During metamorphosis, the brain compresses, becoming ring-shaped, and the trunk nervous system develops several longitudinal cords and segmented lateral nerves. Conclusions Our findings reveal the formation and reorganisation of the nervous system during the life cycle of O. fusiformis, an early-branching annelid. Despite its apparent neuroanatomical simplicity, this species has a diverse peptidergic nervous system, exhibiting morphological similarities with other annelids, particularly at the larval stages. Our work supports the importance of neuropeptides in animal nervous systems and highlights how neuropeptides are differentially used throughout development.

Abstract Skinks are the most diverse component of the reptile fauna in the mountains of New Guinea and many seemingly specialised high-elevation species remain undescribed. Here we describe two spectacular new gold-patterned skinks in the montane-specialist genus Papuascincus. Both species can be diagnosed from all congeners by their distinctive colouration, in addition to aspects of scalation and body size. One new species is mainly recorded from lower montane forest in karst habitats spanning more than five hundred kilometres along the southern edge of New Guinea’s Central Cordillera and is likely to warrant an IUCN conservation status of Least Concern. The second new species has thus far only been recorded from cloud forest on the summit of Mt. Menawa in the North Coastal Ranges and we suggest it should be considered Data Deficient. However, if further survey work confirms a restricted distribution with little scope for upslope elevational retreat under future warming climates it will likely qualify for Endangered or Critically Endangered status.

Abstract: The earthquake cycle of stress accumulation and release is associated with the elastic rebound hypothesis proposed by H.F. Reid following the M7.9 San Francisco earthquake of 1906. However, observing details of the actual values of time- and space-dependent tectonic stress is not possible at the present time. In two previous papers, we have proposed methods to image the earthquake cycle in California by means of proxy variables. These variables are based on correlations in patterns of small earthquakes that occur nearly continuously in time. The purpose of the present paper is to compare these two methods by evaluating their information content using decision thresholds and Receiver Operating Characteristic methods together with Shannon information entropy. Using seismic data from 1940 to present in California, we find that both methods provide nearly equivalent information on the rise and fall of earthquake correlations associated with major earthquakes in the region. We conclude that the resulting timeseries can be viewed as proxies for the cycle of stress accumulation and release associated with major tectonic activity. Article Highlights: The current state of the earthquake cycle of tectonic stress accumulation and release is unobservableWe review two methods for visualizing the current state of the earthquake cycle from correlation in small earthquake patternsMachine learning techniques indicate that signals in a correlation time series corresponding to future large earthquakes can be detected

GeoGateway (http://geo-gateway.org) is a web-based interface for analysis and modeling of geodetic imaging data and to support response to related disasters. Geodetic imaging data product currently supported by GeoGateway include Global Navigation Satellite System (GNSS) daily position time series and derived velocities and displacements and airborne Interferometric Synthetic Aperture Radar (InSAR) from NASA's UAVSAR platform. GeoGateway allows users to layer data products in a web map interface and extract information from various tools. Extracted products can be downloaded for further analysis. GeoGateway includes overlays of California fault traces, seismicity from user selected search parameters, and user supplied map files. GeoGateway also provides earthquake nowcasts and hazard maps as well as products created for related response to natural disasters. A user guide is present in the GeoGateway interface. The GeoGateway development team is also growing the user base through workshops, webinars, and video tutorials. GeoGateway is used in the classroom and for research by experts and non-experts including by students.

Research about explanation processes is gaining relevance because of the increased popularity of artificial systems required to explain their function or outcome. Following an interactive approach, not only explainers but also explainees contribute to successful interactions. However, little is known about how explainees actively guide explanation processes and how their involvement relates to learning. We explored the occurrence and type of explainees’ questions in 20 adult–adult explanation dialogues about unknown present and absent objects. Crucially, we related the question types to the explainees’ subsequent recall of the unknown object labels. We found that explainees asked different types of questions, especially about the object’s label and facts. Questions about the object’s function were asked more when objects were present. In addition, requests for labeling were linked to better recall. The results contribute to designing explainable AI that aim to provide relevant explanations and to further experimental approaches to study explanations.

Theories suggest that representational gestures depicting properties of referents in accompanying speech could facilitate language production and comprehension. In order to shed light on how gesture and speech are coordinated during production, we investigate whether representational gestures are time-locked to the onset of utterances (hence planned when full events are encoded) or Lexical Affiliates (LAs; words most closely aligned with the gesture meaning; hence planned when individual concepts are encoded) in a large corpus of naturalistic conversation (n = 1803 gestures from n = 24 speakers). Our data shows that representational gestures are more tightly tied to LA onsets than utterance onsets, which is consistent with theories of multimodal communication in which gestures aid conceptual packaging or retrieval of individual concepts rather than events. We also demonstrate that in naturalistic speech, representational gestures tend to precede their LAs by around 370ms, which means that they could plausibly allow for an addressee to predict upcoming words (ter Bekke, Drijvers & Holler, 2021; Ferré, 2010; Habets et al., 2011).

A promising tsunami warning system outlined here links Total Electron Content (TEC) disturbances in the ionosphere detected by GNSS satellites to maps of inundated areas along the affected coastlines. This will be accomplished through a pipeline of earthquake, ionosphere, and tsunami simulations. The focus of this paper is to demonstrate the feasibility and validity of our tsunami simulator for use in this simulation pipeline. The simulator we have developed is called Tsunami Squares, a computationally inexpensive program that employs a unique method of propagating water according to shallow water theory. Unlike other wave simulators, Tsunami Squares can easily propagate waves from sea to land, allowing flooded areas along the coast to be mapped. To validate its accuracy, a comparison is made to the Regional Ocean Modeling System tsunami simulator, which solves the Navier Stokes equations directly using a finite-difference method. The two simulation techniques show good agreement when compared over the 2011 Japan event and the 2010 Chile event. In addition, examples of inundation plots are displayed here to demonstrate its capability for such a warning system.

We propose a new machine learning-based method for nowcasting earthquakes to image the time-dependent earthquake cycle. The result is a timeseries that may correspond to the process of stress accumulation and release. The timeseries are constructed by using principal component analysis of regional seismicity. The patterns are found as eigenvectors of the cross-correlation matrix of a collection of seismicity timeseries in a coarse grained regional spatial grid (pattern recognition via unsupervised machine learning). The eigenvalues of this matrix represent the relative importance of the various eigenpatterns. Using the eigenvectors and eigenvalues, we compute the weighted correlation timeseries of the regional seismicity. This timeseries has the property that the weighted correlation generally decreases prior to major earthquakes in the region, and increases suddenly just after a major earthquake occurs. As in a previous paper (Rundle & Donnellan, 2020, https://doi.org/10.1029/2020ea001097), we find that this method produces a nowcasting timeseries that resembles the hypothesized regional stress accumulation and release process characterizing the earthquake cycle. We then address the problem of whether the timeseries contain information regarding future large earthquakes. For this, we compute a receiver operating characteristic and determine the decision thresholds for several future time periods of interest (optimization via supervised machine learning). We find that signals can be detected that can be used to characterize the information content of the timeseries. These signals may be useful in assessing present and near-future seismic hazards.

We present a data-driven approach to clustering or grouping Global Navigation Satellite System (GNSS) stations according to observed velocities, displacements or other selected characteristics. Clustering GNSS stations provides useful scientific information, and is a necessary initial step in other analysis, such as detecting aseismic transient signals (Granat et al., 2013, https://doi.org/10.1785/0220130039). Desired features of the data can be selected for clustering, including some subset of displacement or velocity components, uncertainty estimates, station location, and other relevant information. Based on those selections, the clustering procedure autonomously groups the GNSS stations according to a selected clustering method. We have implemented this approach as a Python application, allowing us to draw upon the full range of open source clustering methods available in Pythons scikit-learn package (Pedregosa et al., 2011, https://doi.org/10.5555/1953048.2078195). The application returns the stations labeled by group as a table and color coded KML file and is designed to work with the GNSS information available from GeoGateway (Donnellan et al., 2021, https://doi.org/10.1007/s12145-020-00561-7; Heflin et al., 2020, https://doi.org/10.1029/2019ea000644) but is easily extensible. We demonstrate the methodology on California and western Nevada. The results show partitions that follow faults or geologic boundaries, including for recent large earthquakes and post-seismic motion. The San Andreas fault system is most prominent, reflecting Pacific-North American plate boundary motion. Deformation reflected as class boundaries is distributed north and south of the central California creeping section. For most models a cluster boundary connects the southernmost San Andreas fault with the Eastern California Shear Zone (ECSZ) rather than continuing through the San Gorgonio Pass.

Abstract Background This retrospective cohort study used an electronic health record‐derived, de‐identified, US patient‐level database to better understand the real‐world treatment experience, in a predominantly community setting (80.3% of patients), of venetoclax+hypomethylating agents (HMAs) in routine clinical care, pre‐ and post‐VIALE‐A, to determine whether the post‐remission cytopenia management insight from VIALE‐A was reflected in real‐world clinical practice. Methods Patients with newly diagnosed acute myeloid leukemia (AML; N = 498), who initiated venetoclax+HMA ≤30 days from AML diagnosis from June 1, 2018, to March 31, 2021, were stratified into pre‐(n = 330) and post‐(n = 168) VIALE‐A cohorts. Results More patients in the post‐(61%) versus pre‐(45%) VIALE‐A cohort had their first biopsy by 28 ± 14 days post‐treatment initiation. Patients underwent bone marrow (BM) assessment earlier in the post‐ versus pre‐VIALE‐A cohort, and first identification of response was also earlier (2.5 vs 5.1 months, respectively). More venetoclax schedule modifications post‐remission occurred among post‐(82.1%) versus pre‐(73.8%) VIALE‐A responders; the most common reason for modification was treatment toxicities, specifically cytopenia. Treatment survival outcomes were comparable with or without venetoclax schedule modifications. Conclusions Findings suggest that venetoclax schedule modifications can be used to manage cytopenia events without adversely affecting outcomes. Opportunities remain to improve earlier BM assessment to determine venetoclax schedule modifications, providing the best chance for optimal treatment outcomes.

Apalutamide is a novel nonsteroidal androgen receptor inhibitor that has been shown to improve outcomes for patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer when combined with androgen deprivation therapy. Apalutamide-induced skin rash occurred commonly in clinical trials, with 23.8–27.1% of patients experiencing a rash of any grade, and 5.2–6.3% experiencing a rash of grade three or higher. There were no cases of severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) reported in clinical trials; however, there are rare cases reported in the literature with the majority occurring in Asian patients. An 83-year-old Caucasian male was commenced on apalutamide, combined with degarelix, for the management of metastatic castration-sensitive prostate cancer. During week five of apalutamide treatment, the patient developed a widespread erythematous maculopapular rash. On presentation, the rash affected 80% of his body surface area (BSA) and a diagnosis of a severe cutaneous drug eruption was made. He was commenced on methylprednisolone (MP) therapy. Despite 5 days of MP, the rash continued to deteriorate involving 95% of his BSA. Nikolsky’s sign was positive. A diagnosis of overlap SJS/TEN was made, supported by skin biopsy. His SCORTEN score was three. He was then commenced on intravenous immunoglobulin and transferred to the intensive care unit. Over the coming days, the rash began to stabilise, and his steroid dose was weaned. He was discharged from hospital 38 days after rash onset. We report the first suggested case of apalutamide-induced SJS/TEN in a Caucasian patient. We discuss other cases of apalutamide-induced SCARs reported in the literature. Risk factors seem to include low body weight and Japanese race, as well as short time to onset of rash.

Abstract Understanding fish movement is critical in determining the spatial scales in which to appropriately manage wild populations. Genetic markers provide a natural tagging approach to assess the degree of gene flow and population connectivity across a species distribution. We investigated the genetic structure of black bream Acanthopagrus butcheri across its entire distribution range in Australia, as well as regional scale gene flow across south‐eastern Australia by undertaking a comprehensive analysis of the populations in estuaries across the region. We applied genome‐wide sampling of single‐nucleotide polymorphism (SNP) markers generated from restriction site‐associated DNA sequencing. Genetic structure and potential gene flow was assessed using principal component analyses and admixture analyses (STRUCTURE). Using 33,493 SNPs, we detected broad scale genetic structuring, with limited gene flow among regional clusters (i.e. Western Australia, South Australia and western Victoria; and eastern Victoria, Tasmania and New South Wales). This is likely the result of unsuitable habitats, strong ocean currents (e.g. the Leeuwin Current and the East Australian Current), large water bodies (e.g. Bass Strait) and known biogeographical provinces across the continent. Local‐scale genetic structuring was also identified across the south‐eastern Australian estuaries sampled, reflecting that the coexistence of both migratory and resident individuals within populations (i.e. partial migration), and the movement of fish into coastal waters, still results in strong philopatry across the region. Instances of movement among estuaries at this spatial scale were primarily found between adjacent estuaries and were likely attributed to lone migrants utilising inshore coastal currents for movement beyond nearby habitats. Targeting SNP markers in A. butcheri at this continental scale highlighted how neither spatial proximity of estuaries nor black bream's ability to move into coastal waters reflects increased gene flow. Overall, our findings highlight the importance of location‐specific management.

Abstract Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ‐67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first‐in‐human, open‐label, phase I, dose‐escalation/dose‐expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ‐67571244 was administered intravenously or subcutaneously using step‐up dosing until ≥1 discontinuation condition was met. Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose‐escalation cohorts (n = 68) and before starting dose‐expansion. Overall, 11 (16.2%) patients experienced ≥1 dose‐limiting toxicity; all experienced ≥1 treatment‐emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ‐67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion‐related reactions, and elevated liver function tests. A prolonged step‐up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T‐cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ‐67571244 efficacy was not achieved, thus MTD and RP2D were not determined.

Listeria monocytogenes, a bacterium responsible for listeriosis, is an environmental and food-borne pathogen that poses a particular risk to pregnant women and the elderly. While traditionally associated with animal products, ready-to-eat salads are increasingly recognised as a source of Listeria outbreaks. However, little is known about the potential virulence of Listeria isolates from the fresh produce environment. This study assessed the virulence potential of nine L. monocytogenes strains from the fresh produce chain using the Galleria mellonella invertebrate infection model. Larvae were infected with 106 CFU of each strain via their circulatory system and compared to a reference strain L. monocytogenes (EGD-e) and Listeria ivanovii. Virulence was evaluated by measuring mortality rates, health index score of larvae, viable bacterial counts in the larvae, and the larvae's immune. Significant differences in larval mortality were observed among strains. Strains NLmo4 and NLmo5 caused the highest mortality rates (98.8% and 96.7%, respectively at 7 days post-infection), while strain NLmo20 had a significantly lower mortality rate of 65% at the same time point (p

Abstract Objective: To understand the relationship between adolescents’ unhealthy snacking behaviour during their school journey and their perceived and objective measures of food outlet availability in the school neighbourhood. Design: A cross-sectional survey enquired about socio-demographic information, school transport modes, perceived presence of food outlets in the school neighbourhood and unhealthy food purchase and consumption on the school journey. A geographical information system analysis of the food outlets within 500 m and 1000 m school buffers was undertaken. Data were analysed using generalised linear mixed modelling. Setting: All twelve secondary schools in Dunedin, Aotearoa New Zealand, March 2020–June 2022. Participants: Adolescents aged 13–18 years (n 725) who reported being familiar with their school neighbourhood. Results: Perceived availability of food outlets in the school neighbourhood was inversely correlated with distance to the closest food outlet from school and positively correlated with food outlet density within 500 m and 1000 m school buffers. Adolescents’ purchase and consumption of unhealthy snacks and drinks during the school journey were associated with perceived availability of food outlets and with shorter distance to the closest food outlet from school. Mixed transport users, girls and those living in high-deprivation neighbourhoods had higher odds of purchasing and consuming unhealthy snacks and drinks during the school journey than active transport users, boys and those living in low-deprivation neighbourhoods, respectively. Conclusions: Adolescents perceptions of the food environment and close access to food outlets in the school neighbourhood may influence adolescents’ food purchase and consumption behaviours during the school journey.

Power Up Schools (Power Up) was a temporary intervention involving a range of activities aimed at increasing children's active school travel (AST) with a focus on physical and social aspects of schools and their surrounding environs. We evaluated the impact of Power Up on children's AST and how multiple stakeholders (children, school representatives, parents, residents) perceived the overall intervention and its components. This was a multiple methods evaluation study with four primary (elementary) schools in Auckland and their wider communities. The study involved longitudinal data collection (daily travel modes reported by children), repeat cross-sectional surveys with parents, single time-point cross-sectional surveys with residents, post intervention focus groups with children and parents, and post intervention interviews with school representatives. Findings showed evidence for increased AST; general support for Power Up by children, parents, and school representatives; mixed support by residents for some components; the importance of considering diverse needs and preferences in future interventions; the need for more comprehensive communication across stakeholders; and the value of streamlining processes for schools and parents. Comprehensive approaches that are embedded within, and accepted by, the wider school community are recommended for sustainable and effective AST interventions.

Introduction The Package of Essential Noncommunicable Disease Interventions—Plus (PEN-Plus) is a strategy decentralising care for severe non-communicable diseases (NCDs) including type 1 diabetes, rheumatic heart disease and sickle cell disease, to increase access to care. In the PEN-Plus model, mid-level clinicians in intermediary facilities in low and lower middle income countries are trained to provide integrated care for conditions where services traditionally were only available at tertiary referral facilities. For the upcoming phase of activities, 18 first-level hospitals in 9 countries and 1 state in India were selected for PEN-Plus expansion and will treat a variety of severe NCDs. Over 3 years, the countries and state are expected to: (1) establish PEN-Plus clinics in one or two district hospitals, (2) support these clinics to mature into training sites in preparation for national or state-level scale-up, and (3) work with the national or state-level stakeholders to describe, measure and advocate for PEN-Plus to support development of a national operational plan for scale-up.Methods and analysis Guided by Proctor outcomes for implementation research, we are conducting a mixed-method evaluation consisting of 10 components to understand outcomes in clinical implementation, training and policy development. Data will be collected through a mix of quantitative surveys, routine reporting, routine clinical data and qualitative interviews.Ethics and dissemination This protocol has been considered exempt or covered by central and local institutional review boards. Findings will be disseminated throughout the project’s course, including through quarterly M&E discussions, semiannual formative assessments, dashboard mapping of progress, quarterly newsletters, regular feedback loops with national stakeholders and publication in peer-reviewed journals.