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Cross-series dependencies are crucial in obtaining accurate forecasts when forecasting a multivariate time series. Simultaneous Graphical Dynamic Linear Models (SGDLMs) are Bayesian models that elegantly capture cross-series dependencies. This study forecasts returns of a $40$ 40 -dimensional time series of stock data from the Johannesburg Stock Exchange (JSE) using SGDLMs. The SGDLM approach involves constructing a customised dynamic linear model (DLM) for each univariate time series. At each time point, the DLMs are recoupled using importance sampling and decoupled using mean-field variational Bayes. Our findings indicate that the SGDLM forecasts stock data similarly to decoupled DLMs, as evident from values of root mean square errors and mean absolute deviations. The SGDLM forecasts the returns quite accurately as seen from the slightly overestimated prediction interval coverages. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome (CRS) refers to concomitant dysfunction of both the heart and kidneys. The pathology in CRS is bidirectional. Many individuals with kidney disease will develop cardiovascular complications. Conversely, rates of acute kidney injury and chronic kidney disease are high in cardiac patients. While our understanding of CRS has greatly increased over the past 15 years, most research has occurred in adult populations. Improving cardiorenal outcomes in children and adolescents requires increased collaboration and research that spans organ systems. The purpose of this review is to discuss key features of CRS and help bring to light future opportunities for pediatric-specific research. [ABSTRACT FROM AUTHOR]

Key Points: Question: How did measures of patient care experience change after private equity acquisition of US hospitals? Findings: In this difference-in-differences analysis of 73 private equity–acquired hospitals and 293 matched control hospitals, global measures of patient care experience worsened after private equity acquisition of hospitals, as did patient-reported staff responsiveness. The difference in these measures of patient care experience at private equity–acquired hospitals compared with matched control hospitals increased with each subsequent year after acquisition. Meaning: Patient-reported care experience, an important dimension of care quality, worsened after private equity acquisition of US hospitals. Importance: Private equity acquisitions of health care facilities have rapidly increased over the past decade. However, little is known about the effects of private equity acquisitions of US hospitals on patient care experience. Objective: To evaluate whether the acquisition of hospitals by private equity firms was associated with changes in measures of patient-reported experience compared with matched control hospitals from 2008 through 2019. Design, Settings, and Participants: This cohort study identified 73 US hospitals newly acquired by private equity firms and 293 matched control (nonacquired) US hospitals from 2008 through 2019. An event study, difference-in-differences design was used to evaluate changes in patient experiences measures from 3 years before to 3 years after private equity acquisition. Main Outcomes and Measures: The primary outcomes were 2 global measures of patient-reported care experience from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, which included patients' overall hospital rating and willingness to recommend the hospital. Secondary outcomes included the 7 other HCAHPS measures encompassing clinical process, communication, and environmental measures. Results: There were 73 private equity–acquired hospitals and 293 matched control hospitals. The percentage of patients rating hospitals as a 9 or 10, on a scale of 0 to 10, decreased at private equity–acquired hospitals (65.0% before acquisition and 65.2% after acquisition) when compared with control hospitals (66.2% to 69.2%) during the postacquisition period relative to the preacquisition period with a difference-in-differences estimate of −2.4 percentage points (95% CI, −3.9 to −0.9). In addition, the percentage of patients who would definitely recommend the hospital also decreased at private equity–acquired hospitals (66.9% before acquisition and 65.5% after acquisition) compared with control hospitals (68.2% to 69.3%) with a difference-in-difference estimate of −2.1 percentage points (95% CI, −3.6 to −0.7). For both of these global measures of patient experience, the difference between private equity–acquired and control hospitals increased over time and was largest in year 3 after acquisition (−5.2 percentage points [95% CI, −8.8 to −1.5] and −4.4 percentage points [95% CI, −8.0 to −0.70] for each measure, respectively). For secondary measures of patient care experience, there was a decrease in patient-reported responsiveness of hospital staff at private equity–acquired hospitals compared with control hospitals (−1.3 percentage points [95% CI, −2.4 to −0.2]), but no differential change across other measures of clinical process, communication, and environment. Conclusions and Relevance: Patient care experience worsened after private equity acquisition of hospitals. These findings raise concern about the implications of private equity acquisitions on patient care experience at US hospitals. This cross-sectional study compares global patient measures to determine whether patients experienced a change in care and whether hospital communication, clinical process, and environment changed from before a hospital had been acquired to after it had been acquired by private equity firms. [ABSTRACT FROM AUTHOR]

Automation transformed various aspects of our human civilization, revolutionizing industries and streamlining processes. In the domain of scientific inquiry, automated approaches emerged as powerful tools, holding promise for accelerating discovery, enhancing reproducibility, and overcoming the traditional impediments to scientific progress. This article evaluates the scope of automation within scientific practice and assesses recent approaches. Furthermore, it discusses different perspectives to the following questions: where do the greatest opportunities lie for automation in scientific practice?; What are the current bottlenecks of automating scientific practice?; and What are significant ethical and practical consequences of automating scientific practice? By discussing the motivations behind automated science, analyzing the hurdles encountered, and examining its implications, this article invites researchers, policymakers, and stakeholders to navigate the rapidly evolving frontier of automated scientific practice. [ABSTRACT FROM AUTHOR]

There is a need for standards for generation and reporting of Biological Variation (BV) reference data. The absence of standards affects the quality and transportability of BV data, compromising important clinical applications. To address this issue, international expert groups under the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) have developed an online resource (https://tinyurl.com/bvmindmap) in the form of an interactive mind map that serves as a guideline for researchers planning, performing and reporting BV studies. The mind map addresses study design, data analysis, and reporting criteria, providing embedded links to relevant references and resources. It also incorporates a checklist approach, identifying a minimum data set (MDS) to enable the transportability of BV data and incorporates the Biological Variation Data Critical Appraisal Checklist (BIVAC) to assess study quality. The mind map is open to access and is disseminated through the EFLM BV Database website, promoting accessibility and compliance to a reporting standard, thereby providing a tool to be used to ensure data quality, consistency, and comparability of BV data. Thus, comparable to the STARD initiative for diagnostic accuracy studies, the mind map introduces a Standard for Reporting Biological Variation Data Studies (STARBIV), which can enhance the reporting quality of BV studies, foster user confidence, provide better decision support, and be used as a tool for critical appraisal. Ongoing refinement is expected to adapt to emerging methodologies, ensuring a positive trajectory toward improving the validity and applicability of BV data in clinical practice. [ABSTRACT FROM AUTHOR]

We show that loci of crystalline representations of G_K for K/\mathbb {Q}_p an unramified extension are irreducible when the Hodge–Tate weights are fixed and sufficiently small. This was previously known for weights in the interval [-p,0] and in this paper we show how that this bound can be relaxed provided the Hodge–Tate weights are sufficiently irregular at certain embeddings. This is motivated by the desire to extend the conjectures of Breuil–Mézard [Duke Math. J. 115 (2002), pp. 205–310] on loci of potentially crystalline representations to irregular weights. [ABSTRACT FROM AUTHOR]

Nonproportional hazards (NPH) have been observed in confirmatory clinical trials with time to event outcomes. Under NPH, the hazard ratio does not stay constant over time and the log rank test is no longer the most powerful test. The weighted log rank test (WLRT) has been introduced to deal with the presence of nonproportionality. We focus our attention on the WLRT and the complementary Cox model based on time varying treatment effect proposed by Lin and León. We investigate whether the proposed weighted hazard ratio (WHR) approach is unbiased in scenarios where the WLRT statistic is the most powerful test. In the diminishing treatment effect scenario where the WLRT statistic would be most optimal, the time varying treatment effect estimated by the Cox model estimates the treatment effect very close to the true one. However, when the true hazard ratio is large the proposed model overestimates the treatment effect and the treatment profile over time. In the delayed treatment scenario, the estimated treatment effect profile over time is typically close to the true profile. For both scenarios, we have demonstrated analytically that the hazard ratio functions are approximately equal under small treatment effects. When the assumed rate of how quickly the treatment effect profile is diminishing or delaying differs in the analysis from that in the true data generating mechanism, the estimated hazard ratio profile from the WHR approach is biased. Since in practice the true HR time profile may differ from that assumed in the WHR analysis, it may be preferable to use alternative approaches for effect estimation. [ABSTRACT FROM AUTHOR]

Electronic transitions are observed for the O 2 + –Ar and O 2 + –N2 complexes over the 225–350 nm range. The transitions are not associated with recognized electronic band systems of the respective atomic and diatomic constituents (Ar+, Ar, O 2 + , O2, N 2 + , and N2) but rather are due to charge transfer transitions. Onsets of the O 2 + –Ar and O 2 + –N2 band systems occur at 3.68 and 3.62 eV, respectively, corresponding to the difference in the ionization potentials of Ar and O2 (3.69 eV), and N2 and of O2 (3.51 eV), suggesting the band systems arise from intramolecular charge transfer transitions to states correlating with O2 (X 3 Σ g − ) + Ar+ (2Pu) and O2 (X 3 Σ g − ) + N 2 + (X 2 Σ g + ) limits, respectively. The dominant vibronic progressions have ωe values of 1565 cm−1 for O 2 + –Ar and 1532 cm−1 for O 2 + –N2, reasonably close to the value for the neutral O2 molecule in its X 3 Σ g − state (1580 cm−1). Higher energy band systems for O 2 + –Ar and O 2 + –N2 are assigned to transitions to states correlating with the O2 (a1Δg) + Ar+ (2Pu) and O2 (a1Δg) + N 2 + (X 2 Σ g + ) limits, respectively. [ABSTRACT FROM AUTHOR]

The i-propyl + O2 reaction mechanism has been investigated by definitive quantum chemical methods to establish this system as a benchmark for the combustion of secondary alkyl radicals. Focal point analyses extrapolating to the ab initio limit were performed based on explicit computations with electron correlation treatments through coupled cluster single, double, triple, and quadruple excitations and basis sets up to cc-pV5Z. The rigorous coupled cluster single, double, and triple excitations/cc-pVTZ level of theory was used to fully optimize all reaction species and transition states, thus, removing some substantial flaws in reference geometries existing in the literature. The vital i-propylperoxy radical (MIN1) and its concerted elimination transition state (TS1) were found 34.8 and 4.4 kcal mol−1 below the reactants, respectively. Two β-hydrogen transfer transition states (TS2, TS2′) lie above the reactants by (1.4, 2.5) kcal mol−1 and display large Born–Oppenheimer diagonal corrections indicative of nearby surface crossings. An α-hydrogen transfer transition state (TS5) is discovered 5.7 kcal mol−1 above the reactants that bifurcates into equivalent α-peroxy radical hanging wells (MIN3) prior to a highly exothermic dissociation into acetone + OH. The reverse TS5 → MIN1 intrinsic reaction path also displays fascinating features, including another bifurcation and a conical intersection of potential energy surfaces. An exhaustive conformational search of two hydroperoxypropyl (QOOH) intermediates (MIN2 and MIN3) of the i-propyl + O2 system located nine rotamers within 0.9 kcal mol−1 of the corresponding lowest-energy minima. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodResultConclusionTo explore caregivers’ experiences and engagement during the 16-week Target Word™ Hanen® program for parents designed to support late talkers.Qualitative interpretative description methodology was used to understand the experience of five caregivers who had completed Target Word™ to support their children (aged 18-36 months). Caregivers attended a focus group to share their perspectives. Transcripts of these focus groups were analysed using reflexive thematic analysis.Two themes were identified regarding caregiver engagement during Target Word™ intervention. Firstly, caregivers described explicit support roles for speech-language pathologists: (a) Beginning phase (clarify expectations), (b) middle phase (enable caregiver to link changes in their behaviour to positive child outcomes), and (c) final phase (empowered caregivers). Secondly, caregiver engagement is influenced by: (a) Individual needs and expectations, (b) active engagement during key learning moments, and (c) influence of the broader environment.Each caregiver participating in Target Word™ experienced unique engagement journeys over the course of the program. Speech-language pathologists can explicitly facilitate engagement at each phase of Target Word™ to promote active engagement for learning and ultimately caregiver empowerment to support their children’s language growth. [ABSTRACT FROM AUTHOR]

During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme - the senescence-associated secretory phenotype (SASP) - driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear. Here, we show that TPR, a protein of the nuclear pore complex basket required for heterochromatin re-organisation during senescence, is also required for the very early activation of NF-κB signalling during the stress-response phase of oncogene-induced senescence. This is prior to activation of the SASP and occurs without affecting NF-κB nuclear import. We show that TPR is required for the activation of innate immune signalling at these early stages of senescence and we link this to the formation of heterochromatin-enriched cytoplasmic chromatin fragments thought to bleb off from the nuclear periphery. We show that HMGA1 is also required for cytoplasmic chromatin fragment formation. Together these data suggest that re-organisation of heterochromatin is involved in altered structural integrity of the nuclear periphery during senescence, and that this can lead to activation of cytoplasmic nucleic acid sensing, NF-κB signalling, and activation of the SASP. [ABSTRACT FROM AUTHOR]

Summary Background Purpose Methods Results Conclusions Metabolic dysfunction‐associated steatotic liver disease (MASLD) is increasingly common in the pediatric population and may increase risk for developing cardiovascular disease (CVD) in people with MASLD. Oxidized high‐density lipoprotein (oxHDL) and oxidized low‐density lipoprotein (oxLDL) are modified, pro‐atherosclerotic lipoproteins that are increased in adults with MASLD and CVD but have not been reported in adolescents with MASLD.To determine if oxLDL and oxHDL are increased in adolescents with MASLD.Fasting oxHDL and oxLDL were measured in adolescents (11–20 years) with obesity and biopsy‐confirmed MASLD (n = 47), and peers without MASLD but with obesity (Ob; n = 28), or normal weight (NW; n = 29).oxHDL was 27% higher (p < 0.05) in the MASLD group (mean ± SD: 11.9 ± 4.7 ng/mL) compared to the Ob group (9.3 ± 3.7 ng/mL, p < 0.05) but only 7% higher than the NW group (11.1 ± 3.8 ng/mL, p > 0.05). However, HDL‐C was 19% and 32% lower in the MASLD group than in the Ob and NW groups, respectively. Thus, oxHDL/HDL‐C ratio was 55% and 66% higher in MASLD compared to the Ob group (p < 0.004) and the NW group (p < 0.001), respectively. oxLDL (52.4 ± 16.0, 46.7 ± 10.1 and 47.1 ± 15.2 U/L for MASLD, Ob and NW, respectively), LDL‐C and the oxLDL/LDL‐C ratio did not differ among groups.The elevated oxHDL and oxHDL/HDL‐C in adolescents with MASLD compared to peers with Ob or NW suggests that there is some oxidative stress in MASLD independent of obesity and potential for increased CVD risk in the future. [ABSTRACT FROM AUTHOR]

During the late nineteenth century, techniques that would one day be called astrophysical moved from physics and chemical laboratories into astronomical observatories and challenged the traditional astronomical measurements of positions and brightness. During the same period, the chemical processes of photography revolutionized the recording of astronomical observations, whether traditional or physical. Their entry into mainstream American astronomy was motivated by a quasi-stochastic penomenon: a total eclipse of the Sun visible between the contiguous borders of the United States of America (US). To prepare for the total solar eclipse of 7 August 1869, the US Nautical Almanac Office (NAO), a government agency, invested time, staff, and substantial appropriations into physical astronomy measurements and the recording of the event photographically. Although no NAO employee had previous expertise, these efforts led the way for the adoption of astronomical photography at the US Naval Observatory, which would eventually absorb the NAO. In addition, an NAO associate would go on to lead the Harvard College Observatory, which would develop the most extensive US collection of photographic astronomical observations. The resulting photographic plate archives continue to be a resource for twenty-first century astronomers. [ABSTRACT FROM AUTHOR]

Attempts in the UK to regulate the sharing and use of health data for secondary purposes such as research have been dogged by controversy and failure. This article considers health data stewardship as a response to these challenges. It develops a normative understanding of the concept through an examination of stewardship in a variety of contexts. This leads to a definition of health data stewardship which encapsulates the necessary constituent elements that focus group participants viewed as crucial to an accountable health data sharing scheme in which they could place their trust. It examines two potential mechanisms for facilitating health data stewardship, the data trust and the data cooperative, arguing that whichever regulatory mechanism is adopted must incorporate mechanisms responsive to citizens' requirements for accountable stewardship of their data. Without this, their wishes, and societal aims of improving health through research using comprehensive data sets may be unachievable. [ABSTRACT FROM AUTHOR]

Advanced artificial intelligence (AI) techniques such as 'deep learning' holds promise in healthcare but introduces novel legal problems. Complex machine learning algorithms are intrinsically opaque, and the autonomous nature of systems can produce unexpected harms, which leaves open questions around responsibility for error at the clinician/AI interface. This raises concerns for compensation systems based in negligence because claimants must establish that a duty exists and demonstrate the specific fault that caused harm.This paper argues that clinicians should not ordinarily be negligent for following AI recommendations, and developers are unlikely to hold a duty of care to patients. The healthcare provider is likely to be the duty holder for AI systems. There are practical and conceptual problems with comparing AI errors to human performance or other AI systems to determine negligence. This could leave claimants with unsurmountable technical and legal challenges to obtaining compensation. Res ipsa loquitur could solve these problems by allowing the courts to draw an inference of negligence when unexpected harm occurs that would not ordinarily happen without negligence. This legal framework is potentially well-suited to addressing the challenges of AI systems. However, I argue res ipsa loquitur is primarily an instrument of discretion, which may perpetuate legal uncertainty and still leave some claimants without a remedy. [ABSTRACT FROM AUTHOR]

ObjectiveMethodResultsConclusions\nKey PointsThe Specific Phobia Dimensional Scale (SP-D) is a 10-item scale developed by the Diagnostic and Statistical Manual (Fifth Edition) Anxiety, Obsessive-Compulsive Spectrum, Posttraumatic and Dissociative Disorder work group to supplement current categorical approaches to Specific Phobia (SP) assessment. The aim of the current study was to examine the psychometric properties of the SP-D in an Australian community sample.A total of 285 participants (74% female) aged 18–76 years (M = 28.15; SD = 12.01) completed the study. A smaller subsample (n = 18) completed the measures of interest a second time to examine test–retest reliability.Confirmatory factor analysis indicated a unidimensional factor structure of the SP-D (root mean square error of approximation [RMSE] = 0.13; comparative fit index [CFI] = 0.94). Internal consistency and test–retest reliability was high (a = 0.95 and Intraclass Correlation Coefficient [ICC] = 0.95, respectively). The measure demonstrated adequate convergent validity with the Specific Phobia Questionnaire (SPQ; rs = 0.54), and unsatisfactory divergent validity with the Fear Questionnaire – Agoraphobia subscale (FQ-Ag; rs = 0.45).Overall, the findings suggest that the SP-D can reliably and briefly measure SP symptoms within an Australian community sample. Further research is required to investigate divergent validity. Replication of the test–retest results are required due to small sample size. Overall, this study is limited in its female-biased convenience sample and recruitment methodologies.What is already known about this topic: Specific phobia (SP) is an anxiety disorder associated with significant functional impairment.The Specific Phobia Dimensional Scale (SP-D) captures information unattainable by the traditional categorical classification system, including changes in presentation, severity and symptomology over time.It is important to validate the SP-D in more diverse samplesSpecific phobia (SP) is an anxiety disorder associated with significant functional impairment.The Specific Phobia Dimensional Scale (SP-D) captures information unattainable by the traditional categorical classification system, including changes in presentation, severity and symptomology over time.It is important to validate the SP-D in more diverse samplesWhat this topic adds: This paper is the first to investigate the psychometric properties of the SP-D in an Australian sample.The SP-D is a reliable and valid tool to dimensionally assess SP symptomatology in Australian adults.The divergent validity of the SP-D requires further investigationThis paper is the first to investigate the psychometric properties of the SP-D in an Australian sample.The SP-D is a reliable and valid tool to dimensionally assess SP symptomatology in Australian adults.The divergent validity of the SP-D requires further investigation [ABSTRACT FROM AUTHOR]

Liquid metal (LM) elastomer composites offer promising potential in soft robotics, wearable electronics, and human‐machine interfaces. Direct ink write (DIW) 3D printing offers a versatile manufacturing technique capable of precise control over LM microstructures, yet challenges such as interfilament void formation in multilayer structures impact material performance. Here, a DIW strategy is introduced to control both LM microstructure and material architecture. Investigating three key process parameters–nozzle height, extrusion rate, and nondimensionalized nozzle velocity–it is found that nozzle height and velocity predominantly influence filament geometry. The nozzle height primarily dictates the aspect ratio of the filament and the formation of voids. A threshold print height based on filament geometry is identified; below the height, significant surface roughness occurs, and above the ink fractures, which facilitates the creation of porous structures with tunable stiffness and programmable LM microstructure. These porous architectures exhibit reduced density and enhanced thermal conductivity compared to cast samples. When used as a dielectric in a soft capacitive sensor, they display high sensitivity (gauge factor = 9.0), as permittivity increases with compressive strain. These results demonstrate the capability to simultaneously manipulate LM microstructure and geometric architecture in LM elastomer composites through precise control of print parameters, while maintaining geometric fidelity in the printed design. [ABSTRACT FROM AUTHOR]

Current anticancer therapies suffer from issues such as off‐target side effects and the emergence of drug resistance; therefore, the discovery of alternative therapeutic approaches is vital. These can include the development of drugs with different modes of action, and the exploration of new biomolecular targets. For the former, there has been increasing interest in drugs that are activated by an external stimulus (e. g. light irradiation) to generate cytotoxic chemicals such as reactive oxygen species (ROS). For the latter, significant efforts are being directed to explore non‐canonical DNA and RNA structures (e. g. guanine‐quadruplexes), as alternative biomolecular targets. Herein we report the synthesis of a library of 21 new platinum(II)‐Salphen complexes (square planar platinum(II) complexes coordinated to tetradentate O,N,N,O‐Schiff base ligands), and the investigation, for all complexes, of their photophysical and photochemical properties, their interactions with duplex and quadruplex DNA, and their cytotoxicity against HeLa cancer cells both in the dark and upon light irradiation. Thanks to the intrinsic phosphorescence of the platinum(II) complexes, confocal microscopy was used for six of the complexes to determine their cellular permeability and localisation in two cancer cell lines (HeLa and U2OS). Altogether, these studies have allowed us to identify two lead platinum(II) complexes with high guanine‐quadruplex DNA affinity and selectivity, good cell permeability and nuclear localisation, and high cytotoxicity against HeLa cancer cells upon irradiation with no detected cytotoxicity in the dark. [ABSTRACT FROM AUTHOR]

Discrete-time survival analysis (DTSA) models are a popular way of modeling events in the social sciences. However, the analysis of discrete-time survival data is challenged by missing data in one or more covariates. Negative consequences of missing covariate data include efficiency losses and possible bias. A popular approach to circumventing these consequences is multiple imputation (MI). In MI, it is crucial to include outcome information in the imputation models. As there is little guidance on how to incorporate the observed outcome information into the imputation model of missing covariates in DTSA, we explore different existing approaches using fully conditional specification (FCS) MI and substantive-model compatible (SMC)-FCS MI. We extend SMC-FCS for DTSA and provide an implementation in the smcfcs R package. We compare the approaches using Monte Carlo simulations and demonstrate a good performance of the new approach compared to existing approaches. [ABSTRACT FROM AUTHOR]

Introduction: Dynamic interaction of cam and pincer deformities can result in pathological contact forces in femoroacetabular impingement (FAI) syndrome. Similar deformities were noted during acetabular fracture reconstruction. We hypothesise that the prevalence of FAI deformity is higher in patients sustaining acetabular fractures than in a control group. Methods: This retrospective radiographic study compared the parameters that define FAI deformity in 100 patients consecutively admitted to a trauma unit with an acetabular fracture and a control group of 100 patients with lateral compression pelvic fracture without acetabular injury. Both underwent identical clinical imaging. Centre-edge angles (CEA) and alpha angles were used to define patients with pincer, cam, or mixed FAI deformity. Results: There were significantly more patients with FAI deformity in the acetabular fracture group than in the control group (71% vs. 18%, p < 0.0001). There were considerably more fractures involving both anterior and posterior acetabular columns in patients with 'pincer' sockets (p = 0.02, OR = 2.95, 95% CI, 1.12–7.78). Conclusions: There is a high prevalence of cam and pincer deformities in patients with acetabular fractures, particularly bi-column fractures. [ABSTRACT FROM AUTHOR]

Background: Variation in snake venoms is well documented, both between and within species, with intraspecific venom variation often correlated with geographically distinct populations. The puff adder, Bitis arietans, is widely distributed across sub-Saharan Africa and into the Arabian Peninsula where it is considered a leading cause of the ~310,000 annual snakebites across the region, with its venom capable of causing substantial morbidity and mortality. Despite its medical importance and wide geographic distribution, there is little known about venom variation between different B. arietans populations and the potential implications of this variation on antivenom efficacy. Methodology: We applied a range of analyses, including venom gland transcriptomics, in vitro enzymatic assays and reverse phase chromatography to comparatively analyse B. arietans venoms originating from Nigeria, Tanzania, and South Africa. Immunological assays and in vitro enzymatic neutralisation assays were then applied to investigate the impact of venom variation on the potential efficacy of three antivenom products; SAIMR Polyvalent, EchiTAb-Plus and Fav-Afrique. Findings: Through the first comparison of venom gland transcriptomes of B. arietans from three geographically distinct regions (Nigeria, Tanzania, and South Africa), we identified substantial variation in toxin expression. Findings of venom variation were further supported by chromatographic venom profiling, and the application of enzymatic assays to quantify the activity of three pathologically relevant toxin families. However, the use of western blotting, ELISA, and in vitro enzymatic inhibition assays revealed that variation within B. arietans venom does not appear to substantially impact upon the efficacy of three African polyvalent antivenoms. Conclusions: The large distribution and medical importance of B. arietans makes this species ideal for understanding venom variation and the impact this has on therapeutic efficacy. The findings in this study highlight the likelihood for considerable venom toxin variation across the range of B. arietans, but that this may not dramatically impact upon the utility of treatment available in the region. Author summary: The puff adder (Bitis arietans) is found across sub-Saharan Africa and the Arabian Peninsula and is capable of causing life threatening pathology due to its potent venom. The extensive range of B. arietans exposes populations to different ecological pressures which may impact upon the composition of venom toxins. In this study, we examined the venom composition of B. arietans from three countries separated by large geographic distance: Nigeria, Tanzania and South Africa. By integrating venom gland transcriptomes, venom chromatography, and in vitro functional assays to profile B. arietans venom composition, we uncovered extensive variation between the three locales. Given that venom variation can have a significant impact on the efficacy of antivenom treatment, we also investigated the ability of three African antivenoms to recognise and inhibit in vitro venom activity. Through these analyses, we were able to determine that venom variation did not have a substantial impact on the neutralising effect of selected antivenoms. This study has highlighted the potentially extensive venom variation found across the range of B. arietans and initiated valuable investigations into the efficacy of African antivenoms to protect human populations vulnerable to snakebite envenoming. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Design Data Sources Method Results Conclusion Implications Patient or Public Contribution Transitions are broadly defined as movements from one place, stage, or subject to another. However, transitions which are broken and incomplete are referred to fragmented transitions. The aims of this concept analysis were to analyze the navigation of fragmented occupational transitions among long‐term care nurses and to develop a working conceptual definition of fragmented occupational transitions to inform diverse stakeholders.Concept analysis.Google Scholar, PubMed, and the Cumulative Index of Nursing and Allied Health Literature databases were accessed. Identified sources were interprofessional scholarly literature published between January 1, 2018, and January 1, 2024, and seminal references.Walker and Avant's eight‐stage concept analysis method.Occupational transitions in long‐term care are fragmented leading to grievous challenges across multiple aspects of nurses' lives. An analysis of the literature using a Transitions Theory lens reveals that their thoughts, feelings and ethical decisions are influenced over time by these transitions. Cardinal attributes include: (1) Fragmentation, (2) Ill‐timing, (3) Disruption, (4) Liminality, (5) Ambiguity, (6) Ambivalence and (7) Facilitators/Inhibitors. Antecedents stem from external sources and facility‐led initiatives. Consequences encompass product and process outcomes. Product outcomes include physical and psychological conditions, and process outcomes encompass resilience, flexibility, connection, coping, creativity, and communication.This concept analysis advances the science for understanding nurses' occupational transitional experiences in long‐term care. It will assist in risk assessment and instrument development ultimately improving the quality of long‐term care.Fragmented occupational transitions in long‐term care are multifaceted and complex phenomena that require distinct responses from government, healthcare leaders, and scholars to improve the plight of long‐term care nurses and stakeholders.Dr. A. I. Meleis contributed to this article by sharing her vast insight into transitions. [ABSTRACT FROM AUTHOR]

Legislation produced under the EU Commission's Better Regulation Agenda sometimes fails to achieve the Treaty obligation to ensure a high level of health protection in all EU policies and activities. Public health advocates have raised the question of whether EU law can be employed to challenge this apparent breach of Treaty obligations at the proposal preparation stage, compelling the Commission to amend prospective EU legislation so that it better protects health. This article will demonstrate that unfortunately this is not possible due to the justiciability of both Article 168 TFEU and the Better Regulation Agenda. However, this awareness can help public health advocates to re-focus their efforts on strategies that will likely have a greater impact in swaying the direction of EU health policy. [ABSTRACT FROM AUTHOR]

Working memory (WM) is a critical cognitive function allowing recent information to be temporarily held in mind to inform future action. This process depends on coordination between prefrontal cortex (PFC) subregions and other connected brain areas. However, few studies have examined the degree of functional specialization between these subregions throughout WM using electrophysiological recordings in freely-moving mice. Here we record single-units in three neighboring mouse medial PFC (mPFC) subregions—supplementary motor area (MOs), dorsomedial PFC (dmPFC), and ventromedial (vmPFC)—during a freely-behaving non-match-to-position WM task. The MOs is most active around task phase transitions, when it transiently represents the starting sample location. Dorsomedial PFC contains a stable population code, including persistent sample-location-specific firing during the delay period. Ventromedial PFC responds most strongly to reward-related information during choices. Our results reveal subregionally segregated WM computation in mPFC and motivate more precise consideration of the dynamic neural activity required for WM. Neural recordings from three mouse prefrontal cortex subregions reveal divergent and dynamic task-related representations during working memory. [ABSTRACT FROM AUTHOR]

During Covid-19, most in-person intergenerational service-learning programs were halted or transitioned to virtual formats due to social-distancing guidelines. This study qualitatively examined in-person and virtual versions of the Lives Well Lived program, which matches older adults (OAs) with undergraduate students to participate in a mutual interviewing, life review project. Post-test data from open-ended questions were analyzed to compare themes regarding program outcomes. Recognition of OA interindividual differences, intergenerational relationship's value, and decreased fear of aging themes developed in both program versions but there were also differences. Participants in the virtual version regretted not engaging in person, did not mention altruism/empathy, expressed appreciation of peer relationships in addition to OA relationships, and disliked writing reflection papers. Recommendations are given for ensuring similar learning outcomes when engaging in virtual programming, whether due to COVID-19 or in additional situations to pandemics, such as rural settings, lack of transportation/mobility, or time limitations. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Determination of energy requirements for growth depends on measuring the composition of BW gain. Previous studies have shown that the composition of gain can be altered in young dairy calves by the composition of the milk replacer diet. Here, our objective was to determine body composition and the composition of empty body gain in young calves fed increasing amounts of a milk replacer containing adequate CP. Male Holstein calves underwent an adjustment period of 14 d after birth in which they were fed whole-waste milk at 10% of BW. Calves were then stratified by BW and randomly assigned to either an initial slaughter group (n = 11) or to groups fed 1 of 3 milk replacer amounts and slaughtered after 35 d of growth. Calves in all treatments consumed the same milk replacer containing 24.8% CP (DM basis; from all milk proteins) and 18.9% fat, reconstituted to 12.5% solids. Treatments were milk replacer fed at 1.25% of BW (DM basis; n = 6), 1.75% of BW (n = 6), or 2.25% of BW (n = 8), adjusted weekly as calves grew. Calves fed at 1.25% or 1.75% of BW were fed twice daily and those fed 2.25% of BW were fed 3 times daily. No starter was offered. Postslaughter, the bodies of calves were separated into 4 fractions: carcass; total viscera minus digesta; head, hide, feet, and tail;, and blood. The sum of those 4 fractions was empty BW (EBW), which increased linearly as the amount of milk replacer increased. Final heart girth and body length, but not withers height, increased linearly as intake increased. Gain:feed increased linearly with increasing milk replacer. Feeding more milk replacer increased the amounts of lean tissue and fat in the body. The percentages of water and protein in the final body decreased linearly, whereas fat percentage and energy content increased linearly as intake increased. As gain increased, the percentage of protein in gain decreased and the percentage of fat increased, resulting in an increase of energy content of EBW gain. Efficiency of energy use (retained energy:gross energy intake) increased linearly but retained energy:ME available for growth was not different among treatments. Efficiency of protein use increased quadratically as feeding rate increased; there was no further increase at 2.25% of BW. Plasma insulin-like growth factor 1, insulin, and glucose increased linearly, whereas urea-N decreased linearly, as milk replacer intake increased. Our data document changes in body composition that affect estimates of retained energy in the bodies of calves slaughtered at a common age. These data are important for calculations of energy requirements for young calves. [ABSTRACT FROM AUTHOR]

Iterative diagonalization of large matrices to search for a subset of eigenvalues that may be of interest has become routine throughout the field of quantum chemistry. Lanczos and Davidson algorithms hold a monopoly, in particular, owing to their excellent performance on diagonally dominant matrices. However, if the eigenvalues happen to be clustered inside overlapping Gershgorin disks, the convergence rate of both strategies can be noticeably degraded. In this work, we show how Davidson, Jacobi–Davidson, Lanczos, and preconditioned Lanczos correction vectors can be formulated using the reduced partitioning procedure, which takes advantage of the inherent flexibility promoted by Brillouin–Wigner perturbation (BW-PT) theory's resolvent operator. In doing so, we establish a connection between various preconditioning definitions and the BW-PT resolvent operator. Using Natural Localized Molecular Orbitals (NLMOs) to construct Configuration Interaction Singles (CIS) matrices, we study the impact the preconditioner choice has on the convergence rate for these comparatively dense matrices. We find that an attractive by-product of preconditioning the Lanczos algorithm is that the preconditioned variant only needs 21%–35% and 54%–61% of matrix-vector operations to extract the lowest energy solution of several Hartree–Fock- and NLMO-based CIS matrices, respectively. On the other hand, the standard Davidson preconditioning definition seems to be generally optimal in terms of requisite matrix-vector operations. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions So What? Systems change approaches are increasingly adopted in public health to address complex problems. It is important that measures of systems change be developed so that the effects of systems change on health outcomes can be evaluated. Organisational practices are potential levers for systems change. However, robust measures of organisational capacity to engage in these practices are lacking. Informed by the Theory of Systems Change, we developed and tested the Capacity of Organisations for System Practices (COSP) scale. The COSP scale comprises four inter‐related system practices within organisations—adaptation, alignment, collaboration and evidence‐driven action and learning.We applied a three‐stage process: (1) Item generation; (2) Scale pre‐testing; and (3) Structural analyses. Item response theory tests and semantic review, together with factor analytic techniques, were applied to refine the item set and determine the scale structure.An initial pool of 97 items was generated and pre‐tested with six content experts and four target audience representatives. Modifications resulted in 60 items. In total, 126 participants provided data for the structural analysis. A second‐order hierarchical four‐factor model fit the data better than the more basic correlated factor model (Δχ2 = 1.758, p = .415). The fit indices for the final 31‐item model were acceptable (RMSEA = .084, TLI = .819).The COSP scale is ready for further testing to ensure construct validity, stability and utility.Once validated, the Capacity of Organisations for System Practices (COSP) scale has the potential to advance the theory and practice of systems change approaches. [ABSTRACT FROM AUTHOR]

This article examines the theme of intentional action in "The Graduate" novel and film adaptation. It explores how the protagonist, Benjamin Braddock, grapples with the question of what to do after college. The article connects this theme to two philosophical symposia from the 1960s and discusses the shift in the philosophy of action. It also analyzes specific scenes and objects in the story that symbolize different relationships and meanings. The overall focus is on the differences in portraying intentional action between the novel and film. [Extracted from the article]

Changes in leaf temperature are known to drive stomatal responses, because the leaf‐to‐air water vapour gradient (Δw) increases with temperature if ambient vapour pressure is held constant, and stomata respond to changes in Δw. However, the direct response of stomata to temperature (DRST; the response when Δw is held constant by adjusting ambient humidity) has been examined far less extensively. Though the meagre available data suggest the response is usually positive, results differ widely and defy broad generalisation. As a result, little is known about the DRST. This review discusses the current state of knowledge about the DRST, including numerous hypothesised biophysical mechanisms, potential implications of the response for plant adaptation, and possible impacts of the DRST on plant‐atmosphere carbon and water exchange in a changing climate. Summary statement: The direct response of stomata to temperature (the response when evaporative demand is held constant by adjusting ambient humidity) is very poorly known. This review summarises the current state of knowledge about the response, a range of potential biophysical mechanisms, and its possible implications for plant‐atmosphere gas exchange and evolution. [ABSTRACT FROM AUTHOR]

OBJECTIVES The primary aim of this study was to determine continuation rates of stress ulcer prophylaxis (SUP) upon transfer from a pediatric intensive care unit (PICU) to a general medicine unit and upon hospital discharge. The secondary aim was to identify patient characteristics or concomitant medications that were associated with continuation of SUP at transfer from the PICU. METHODS This retrospective chart review included patients who were initiated on acid suppression for SUP in the PICU between June 2021 and May 2022 and subsequently transferred to a general medicine unit prior to discharge. Patients were excluded if they were receiving acid suppressant therapy prior to admission or were started on acid suppressants for an indication other than SUP. RESULTS Two hundred three patients (median age, 3.3 years) were included. The rates of SUP continuation at the time of transfer from the PICU to a general medicine unit and at hospital discharge were 61.6% and 9.9%, respectively. Patients continued on SUP at the time of transfer from the PICU were more likely to be prescribed concomitant corticosteroids (p < 0.01), anticoagulants or antiplatelet medications (p < 0.01). CONCLUSIONS The continuation of SUP from the PICU to the general medicine unit is common at our institution and calls into question the appropriateness of this practice. Future research is warranted to investigate the appropriateness of the continuation of SUP at transitions of care. Additionally, implementation of institutional protocols standardizing review of SUP may help reduce unnecessary prescribing of acid suppressants in general medicine units and at discharge. [ABSTRACT FROM AUTHOR]

Design ideation activities that involve the manipulation of geometry rely heavily on manual input. For feasibility reasons, the generation of design alternatives must often be limited, particularly when these alternatives need to be prototyped and tested. This paper describes a conceptual design strategy that leverages variational three-dimensional geometry to automatically generate a large number of design alternatives from a template model and their corresponding physical prototypes for evaluation and testing. In our approach, 3D geometric variations are produced automatically from a single design concept modeled parametrically, which are then used to generate 3D-printable files. Our method is suitable for design scenarios where real-world testing is preferred over virtual simulation and requires designers to consider a concept idea as a family of solutions, instead of a single design option. Our strategy enables an effective exploration of conceptual design spaces in highly constrained situations and facilitates parallel prototyping, which is known to produce better results than serial prototyping. We demonstrate the feasibility and effectiveness of the proposed method through a case study that involves the design of an instrument for ophthalmic surgery for extracting an intraocular lens (IOL) from the eye. Using our approach, nine unique concept families comprising a total of 150 designs were rapidly and successfully prototyped and tested. [ABSTRACT FROM AUTHOR]

The article discusses the properties and applications of liquid metals, which are metals with low melting points. Liquid metals, such as gallium, have unique characteristics that make them useful in various fields, including electronics, biomedical devices, energy storage, and catalysis. The special issue on Liquid Metals for Functional Materials features 49 manuscripts that cover different aspects of liquid metal research, including energy and electrochemistry, biomedical and healthcare applications, catalysts and reactions, composites and multiphase materials, electronics and conductors, fabrication and patterning, and interfacial properties. The articles highlight the multidisciplinary nature of liquid metal research and provide insights into future directions in this field. [Extracted from the article]

A pediatric dosage form for crizotinib (Xalkori) was commercialized using quality-by-design principles in a material-sparing fashion. The dosage form consists of spherical multiparticulates (microspheres or pellets) that are coated and encapsulated in capsules for opening. The crizotinib (Xalkori)-coated pellet product is approved in the US for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) and unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive. The product is also approved in the US for adult patients with non-small cell lung cancer (NSCLC) who are unable to swallow intact capsules. The lipid multiparticulate is composed of a lipid matrix, a dissolution enhancer, and an active pharmaceutical ingredient (API). The API, which remains crystalline, is embedded within the microsphere at a 60% drug loading in the uncoated lipid multiparticulate to enable dose flexibility. The melt spray congealing technique using a rotary atomizer is used to manufacture the lipid multiparticulate. Following melt spray congealing, a barrier coating is applied via fluid bed coating. Due to their particle size and content uniformity, this dosage form provides the dosing flexibility and swallowability needed for the pediatric population. The required pediatric dose is achieved by opening the capsules and combining doses of different encapsulated dose strengths, followed by administration of the multiparticulates directly to the mouth. The encapsulation process was optimized through equipment modifications and by using a design of experiments approach to understand the operating space. A limited number of development batches produced using commercial-scale equipment were leveraged to design, understand, and verify the manufacturing process space. The quality by design and material-sparing approach taken to design the melt spray congeal and encapsulation manufacturing processes resulted in a pediatric product with exceptional content uniformity (a 95% confidence and 99% probability of passing USP <905> content uniformity testing for future batches). [ABSTRACT FROM AUTHOR]

From the 1950s to the 2000s, Walt Disney Animation Studios have used jazz to import specific sociocultural meanings into their films. Through an examination of the feature-length animated Disney films that incorporate "jazz" idioms—namely Lady and the Tramp (1955), One Hundred and One Dalmatians (1961), The Jungle Book (1967), The Aristocats (1970), and The Princess and the Frog (2009)—this article will explore how Disney has consistently used jazz to depict wildness and "Otherness" and will consider how the films effectively typecast those characters associated with jazz, which meaningfully impacts Disney's portrayals of social morality, race, and gender in these films. [ABSTRACT FROM AUTHOR]

High alloyed by Si cast iron with spherical graphite (SGI) has a unique combination of mechanical properties at room temperature and high oxidation resistance at elevated temperature. The performance of this cast material can be improved by precise alloying and for the development of desired microstructural dispersity, using an effective melt inoculation in combination with an optimal cooling rate during solidification. There is consensus in the metalcasting community that high microstructural dispersity is desirable for good mechanical performance of high Si SGI at room temperature. However, it could not be the case for high-temperature applications. In this study, static high-temperature oxidation of heavy (100 mm), medium (18 mm), and thin (5 mm) wall castings from two SGI (base, referred to as SiMo and alloyed by 3% Al (SiMoAl) were investigated. Microstructural dispersity was characterized in 2D sections and in 3D space by µCT. Surface degradation was quantified by SEM and TEM analysis in cross sections after 100 h static oxidation in air at 800 °C. Carbon analysis was used to decouple the scale formation and decarburization (deC) processes which occurred simultaneously. Scale topology was determined by microcomputed tomography (µCT) analysis. Additional thermo-cycling tests of constrained specimens were performed to determine resistance to SGI failure during transient thermomechanical loading. These methods provided the quantification of the effects of microstructural dispersity parameters on high-temperature performance in SGI. The different trends were observed in the base SiMo and alloyed SiMoAl SGI. Methods for improving high-temperature performance by optimizing microstructural dispersity are suggested based on trends in surface degradation. [ABSTRACT FROM AUTHOR]

The article focuses on the cultural and literary significance of walking in the context of nineteenth-century imperial geographies. Topics include the role of walking in nation-building, contradictions between pedestrian travel and its historical documentation, and how walking intersects with modernity in various imperial spaces.

The way horses are trained has implications for equine welfare and training success, yet little is known about the factors that influence horse-owners’ choice of training approach (TA). Limited understanding in area will likely hinder the development and dissemination of evidence-based training advice to owners. Consequently, this study aims to identify demographic and attitudinal factors that influence horse-owner TA selection. A 22-question online survey collected information from 1,593 horse-owners about their demographics, equestrian activities, goals and beliefs. Participants rated how likely they were to use six different horse TAs on a five-point scale. Multinomial regression analysis and Spearman’s correlation coefficients were used to identify factors associated with their likelihood of using each TA. Several factors were associated with reported TA use, including age, gender identity, goals, activities, industry role and whether they had training in animal behavior. Beliefs about equine sentience, cognitive ability and whether science should inform horse training correlated with likelihood of applying aversives. This study provides insight for further research and development of educational strategies to reduce the use of training approaches that may compromise equine welfare. [ABSTRACT FROM AUTHOR]

Spotted-wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), is one of the most detrimental pests of small fruit crops worldwide and its control relies heavily on pesticides, so there is a need to develop alternative management practices. Cultural practices that make the microclimate hotter, drier, and brighter than optimal conditions for the pest may be highly effective. In this two-year study, we evaluated how black, white, and metallic plastic mulches influence the raspberry plants' microclimate to reduce D. suzukii larval infestation of fruit in the canopy and increase mortality of fallen larvae and pupae on the ground. All three plastic mulches reduced D. suzukii larval infestation of fruit by 40–72% and killed 80–100% of larvae and pupae placed on the mulch surface. The mechanisms at play are likely the compounded effects of increased ultraviolet (UV) light, hotter and drier conditions in the low canopy, and hot mulch surface temperature. UV light may be especially important since it reduced D. suzukii oviposition in the lab. Overall, plastic mulches can effectively modify the microclimate to make it less favorable for D. suzukii, reducing infestation in fruit and on the ground. [ABSTRACT FROM AUTHOR]

Objective: To systematically review evaluated local, community or peer‐delivered well‐being and employment interventions delivered within regional, rural and remote Australia. Design: Searches within nine databases retrieved peer‐reviewed and grey literature from an initial pool of 3186 papers published between 2012 and 2022. PRISMA guidelines were adhered to, and the Mixed Methods Appraisal Tool (MMAT) was used to assess the quality of the well‐being or employment (or both) articles. Findings: A total of 19 items met the inclusion criteria, which included two quantitative, 12 qualitative and five mixed‐methods evaluations. Intervention cohorts included Indigenous Australians, youth, older people, workers and the general community. The average methodological rating was 83%. The overall level of evidence for the interventions was low due to mostly descriptive studies. Discussion: Interventions that appeared effective in improving well‐being tended to focus on addressing social connectedness and self‐determination. Unexpected employment outcomes were evident across many of the studies, which highlighted the reciprocity between well‐being and employment. Conclusion: This review highlights promising interventions for improving well‐being by focusing on social connectedness and self‐determination. Further empirical evidence is encouraged to explore the reciprocal relationship between well‐being and employment, emphasising the significance of social connectedness and self‐determination in this context. [ABSTRACT FROM AUTHOR]

Background Chronic pulmonary conditions such as asthma and chronic obstructive pulmonary disease increase the risk of morbidity and mortality during infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). We hypothesized that individuals with such comorbidities are more susceptible to MERS-CoV infection due to increased expression of its receptor, dipeptidyl peptidase 4 (DPP4). Methods We modeled chronic airway disease by treating primary human airway epithelia with the Th2 cytokine interleukin 13 (IL-13), examining how this affected DPP4 protein levels with MERS-CoV entry and replication. Results IL-13 exposure for 3 days led to greater DPP4 protein abundance, while a 21-day treatment raised DPP4 levels and caused goblet cell metaplasia. Surprisingly, despite this increase in receptor availability, MERS-CoV entry and replication were not significantly affected by IL-13 treatment. Conclusions Our results suggest that greater DPP4 abundance is likely not the primary mechanism leading to increased MERS severity in the setting of Th2 inflammation. Transcriptional profiling analysis highlighted the complexity of IL-13–induced changes in airway epithelia, including altered expression of genes involved in innate immunity, antiviral responses, and maintenance of the extracellular mucus barrier. These data suggest that additional factors likely interact with DPP4 abundance to determine MERS-CoV infection outcomes. [ABSTRACT FROM AUTHOR]

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often causes permanent injury via tissue-destructive dermonecrosis at the bite site, which is ineffectively treated by current antivenoms. To address this therapeutic gap, we identified the etiological venom toxins in Naja nigricollis venom responsible for causing local dermonecrosis. While cytotoxic three-finger toxins were primarily responsible for causing spitting cobra cytotoxicity in cultured keratinocytes, their potentiation by phospholipases A2 toxins was essential to cause dermonecrosis in vivo. This evidence of probable toxin synergism suggests that a single toxin-family inhibiting drug could prevent local envenoming. We show that local injection with the repurposed phospholipase A2-inhibiting drug varespladib significantly prevents local tissue damage caused by several spitting cobra venoms in murine models of envenoming. Our findings therefore provide a therapeutic strategy that may effectively prevent life-changing morbidity caused by snakebite in rural Africa. [ABSTRACT FROM AUTHOR]

This paper outlines a proposal, based on Blackfoot worldview, for a collective method to stand alongside Western qualitative and quantitative methods and highlights the value of collective methods in collaborative social-ecological research. Neither qualitative nor quantitative methods are adequate to disclose a world where all things are alive, where "objects" are subjects—agentive beings in their own right. Most Indigenous cultures understand and experience the world as a network of living beings, a collective, with whom they are interrelated/connected and therefore, any efforts to collaborate with Indigenous peoples must acknowledge comprehensive relational animacy. Applying coproduction principles in concert with Blackfoot ways of knowing and being, the authors collaborate to articulate and advance a collective method wherein the many and diverse collective methods of Blackfoot and other Indigenous peoples might find quarter. [ABSTRACT FROM AUTHOR]