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The dielectric constant is a critical parameter in many energy-related applications. Typically, increasing the dielectric constant of soft materials involves adding high dielectric constant polar liquids or inorganic fillers, but there are limitations to this approach due to safety concerns with volatile and flammable solvents and the agglomeration of inorganic fillers. An alternative approach is to add zwitterionic liquids that exhibit exceptionally high dielectric constants with negligible volatility. Here, we report the synthesis of a series of zwitterionic liquids containing an imidazolium cation, exhibiting the highest dielectric constant among all organic molecules (∼350 at 293 K). The cation–anion linkage was tailored in a wide range between three and nine carbons, rendering the zwitterion dipole from 25 to 52 D. Comparing the dielectric constant for zwitterions with different anions (i.e., sulfonylimide, sulfonate, and carboxylate) reveals the beneficial impacts of the delocalized sulfonylimide anion vs the carboxylate anion due to the enlarged molecular dipole and more homogenous liquid morphology. Molecular dipole and liquid morphology are identified as the keys to developing high dielectric constant zwitterionic liquids. The extremely high dielectric constant accessible with the proposed molecular design paves new avenues for developing high dielectric constant zwitterions that act as dielectricizers. [ABSTRACT FROM AUTHOR]

For two-dimensional (2D) materials, the exact thickness of the material often dictates its physical and chemical properties. The 2D quantum material WTe2 possesses properties that vary significantly from a single layer to multiple layers, yet it has a complicated crystal structure that makes it difficult to differentiate thicknesses in atomic-resolution images. Furthermore, its air sensitivity and susceptibility to electron beam-induced damage heighten the need for direct ways to determine the thickness and atomic structure without acquiring multiple measurements or transferring samples in ambient atmosphere. Here, we demonstrate a new method to identify the thickness up to ten van der Waals layers in Td-WTe2 using atomic-resolution high-angle annular dark-field scanning transmission electron microscopy image simulation. Our approach is based on analyzing the intensity line profiles of overlapping atomic columns and building a standard neural network model from the line profile features. We observe that it is possible to clearly distinguish between even and odd thicknesses (up to seven layers), without using machine learning, by comparing the deconvoluted peak intensity ratios or the area ratios. The standard neural network model trained on the line profile features allows thicknesses to be distinguished up to ten layers and exhibits an accuracy of up to 94% in the presence of Gaussian and Poisson noise. This method efficiently quantifies thicknesses in Td-WTe2, can be extended to related 2D materials, and provides a pathway to characterize precise atomic structures, including local thickness variations and atomic defects, for few-layer 2D materials with overlapping atomic column positions. [ABSTRACT FROM AUTHOR]

Background: Essential amino acid (EAA) and omega-3 fatty acid ingestion independently attenuate leg skeletal muscle disuse atrophy in uninjured persons. However, no data exist regarding the effectiveness of combined EAA and omega-3 fatty acid ingestion to mitigate skeletal muscle disuse atrophy in response to anterior cruciate ligament reconstruction (ACLR) surgery. This pilot trial will explore the feasibility of recruitment and retention of ACLR outpatients from a single center across 18 months to consume either a combination of omega-3 fatty acids and EAAs, or a placebo control, for 4 weeks before and 2 weeks after surgery. Methods: Thirty adult (≥ 18 years old) ACLR outpatients will be recruited for this single center, double-blind, two-arm randomized controlled feasibility pilot trial. Participants will consume either 5 g⋅day−1 of omega-3 fatty acids (fish oil) and 40 g⋅day−1 of EAAs or 5 g⋅day−1 of a control fatty acid mixture (safflower oil) and 40 g⋅day−1 of non-essential amino acids (NEAAs). Fatty acid supplements will be consumed 4 weeks before and for 2 weeks after ACLR surgery, whereas the EAAs and NEAAs will be consumed 1 week before and for 2 weeks after ACLR surgery. The primary outcomes are feasibility of recruitment and retention, with the goal to recruit 30 outpatients across 18 months and retain 22 participants upon completion of the study protocol following 12 weeks of data collection. These results will be reported using descriptive statistics, along with reasons and timepoints for study dropout. Secondary exploratory outcomes will be reported using inferential statistics for purposes of hypothesis generation and elucidation of mechanistic targets for future work; no inferences to clinical efficacy will be made. These outcomes include integrated rates of skeletal muscle protein synthesis, skeletal muscle protein content and expression of translation factors, skeletal muscle and erythrocyte phospholipid composition, and measures of skeletal muscle mass, strength, and power. Impact: This work will set the foundation for a future randomized controlled trial powered to detect an effect of EAA + omega-3 fatty acid intake on skeletal muscle size or function in response to ACLR surgery. Trial registration: ClinicalTrials.gov, NCT06233825. Registered 31 January 2024. https://clinicaltrials.gov/study/NCT06233825?term=NCT06233825&rank=1 [ABSTRACT FROM AUTHOR]

Simple Summary: Parkinson's disease (PD) is one of the most common chronic, degenerative brain diseases worldwide. Patients are diagnosed on the basis of slowness of movement and/or tremor and/or stiffness. However, many symptoms that are not movement related are now well recognized. Patients show changes in skin sensation, and the vast majority of patients show loss of sensory neurites, which enable sensation in skin. These changes in skin sensation occur prior to diagnosis; however, sensory issues may also be exacerbated by levodopa, an important drug used in the treatment of PD. Undoubtedly, levodopa is critical for the treatment of PD, but at high doses, it has repeatedly been shown to impair sensation in PD patients. Here, we show for the first time that high-dose levodopa impairs function of sensory neurons. Importantly, we also show for the first time that lysosomes, a critical organelle involved in recycling, are impaired by levodopa concentrations observed in patients. These data are important given the well-known lysosomal dysfunction observed in PD. Our data shed light on how levodopa, the most important drug in the treatment of PD, may contribute to sensory deficits in PD. Parkinson's disease (PD) is the second-most common neurodegenerative disease worldwide. Patients are diagnosed based upon movement disorders, including bradykinesia, tremor and stiffness of movement. However, non-motor signs, including constipation, rapid eye movement sleep behavior disorder, smell deficits and pain are well recognized. Peripheral neuropathy is also increasingly recognized, as the vast majority of patients show reduced intraepidermal nerve fibers, and sensory nerve conduction and sensory function is also impaired. Many case studies in the literature show that high-dose levodopa may induce or exacerbate neuropathy in PD, which is thought to involve levodopa's metabolism to homocysteine. Here, we treated primary cultures of dorsal root ganglia and a sensory neuronal cell line with levodopa to examine effects on cell morphology, mitochondrial content and physiology, and lysosomal function. High-dose levodopa reduced mitochondrial membrane potential. At concentrations observed in the patient, levodopa enhanced immunoreactivity to beta III tubulin. Critically, levodopa reduced lysosomal content and also reduced the proportion of lysosomes that were acidic, thereby impairing their function, whereas homocysteine tended to increase lysosome content. Levodopa is a critically important drug for the treatment of PD. However, our data suggest that at concentrations observed in the patient, it has deleterious effects on sensory neurons that are not related to homocysteine. [ABSTRACT FROM AUTHOR]

Volcano deformation models contribute to hazard assessment by simulating magma system dynamics. Traditional magma reservoir pressure source shape assumptions often fail to replicate irregular, geophysically identified geometries. Uncertainties regarding the influence of reservoir geometry can limit the effectiveness of using deformation models to decipher unrest signals. Here, we aim to determine the feasibility of using a magma reservoir geometry directly derived from a seismic tomography survey in a volcano deformation model for Soufrière Hills Volcano, Montserrat. Three‐dimensional deformation models are created to simulate displacement using a pressure source geometry constrained from a low seismic velocity anomaly, inferred to be a region of partial melt, and contrasted against a traditional ellipsoid reservoir geometry. We also test a "hybrid" model combining a seismically inferred reservoir upper geometry and ellipsoidal base. Results of each model are evaluated against ground displacement observed on Montserrat from 2010 to 2022. Our results show that different reservoir geometries change the horizontal and vertical displacement fields across the island: the ellipsoid reservoir best reproduces vertical displacement magnitude, while the hybrid reservoirs best simulate horizontal displacement vectors and the region of maximum uplift. Overall, the ellipsoid‐shaped reservoir provides our best‐fit to the observed data, but we note this result could be biased due to prior years of optimization helping constrain the ellipsoid shape, size, and location. Our results show the potential for further use of geophysically constrained reservoir geometries in deformation modeling, and our methods could be applied to other deforming volcanoes worldwide. Plain Language Summary: Volcano deformation models are used to simulate volcanic processes at depth to inform hazard assessment in volcanically active areas by comparing modeled results to observed ground surface deformation. Traditional models use spherical or ellipsoidal magma reservoir geometries, not realistic compared to the irregular and complex structures identified in geophysical surveys. The study presented here uses a geophysically defined magma reservoir geometry in a deformation model for the case study area of Soufrière Hills Volcano, Montserrat. A traditional ellipsoid reservoir and two "hybrid" reservoirs that combine the upper surface of the geophysical reservoir with a simplified base are also modeled. The results of each model are compared to GPS data from 2010–2022 to identify the best fitting reservoir geometry to observed ground deformation. Our results indicate that changing the reservoir geometry changes the direction and magnitude of deformation, with the hybrid reservoir best reproducing the direction of horizontal displacement and the region of maximum uplift. Despite this, the ellipsoid reservoir best replicates overall deformation, but we note that years optimizing the shape, size and location of the reservoir may bias the result. Our results show it is feasible to use a geophysically derived magma reservoir in volcano deformation models. Key Points: We test seismically inferred magma reservoir geometries in a volcano deformation model, compared against typical simple geometries and hybrid combinationsSimple ellipsoid reservoir geometry best replicates total overall deformation at Soufrière Hills Volcano, but hybrid reservoir shows promiseDifferent reservoir geometries better replicate observed deformation at different parts of the island [ABSTRACT FROM AUTHOR]

Introduction: Perspectives on long‐acting injectable cabotegravir/rilpivirine (CAB/RPV‐LA) from HIV health disparity populations are under‐represented in current literature yet crucial to optimize delivery. Methods: Between August 2022 and May 2023, we conducted in‐depth interviews with people with HIV (PWH) at four HIV clinics in Atlanta, Chicago and San Francisco. Eligibility criteria were current CAB/RPV‐LA use with receipt of ≥3 injections or CAB/RPV‐LA discontinuation. We purposefully sampled for PWH who initiated with viraemia (plasma HIV RNA >50 copies/ml) due to adherence challenges, discontinuers, and cis and trans women. Interviews were coded and analysed using thematic methods grounded in descriptive phenomenology. Clinical data were abstracted from the medical record. Results: The sample (San Francisco n = 25, Atlanta n = 20, Chicago n = 14 for total n = 59, median number of injections = 6) consisted of 48 PWH using CAB/RPV‐LA and 11 who had discontinued. The median age was 50 (range 25–73) and 40 (68%) identified as racial/ethnic minorities, 19 (32%) cis or trans women, 16 (29%) were experiencing homelessness/unstable housing, 12 (20%) had recently used methamphetamine or opioids and 11 (19%) initiated with viraemia. All participants except one (who discontinued) had evidence of viral suppression at interview. Typical benefits of CAB/RPV‐LA included increased convenience, privacy and freedom from being reminded of HIV and reduced anxiety about forgetting pills. However, PWH who became virally suppressed through CAB/RPV‐LA use also experienced an amelioration of feelings of shame and negative self‐worth related to oral adherence challenges. Regardless of baseline viral suppression status, successful use of CAB/RPV‐LA amplified positive provider/clinic relationships, and CAB/RPV‐LA was often viewed as less "work" than oral antiretroviral therapy, which created space to attend to other aspects of health and wellness. For some participants, CAB/RPV‐LA remained "work," particularly with regard to injection site pain and visit frequency. At times, these burdens outweighed the aforementioned benefits, resulting in discontinuation. Conclusions: CAB/RPV‐LA offers a range of logistical, psychosocial and care engagement benefits, which are experienced maximally by PWH initiating with viraemia due to adherence challenges; however, benefits do not always outweigh treatment burdens and can result in discontinuation. Our findings on rationales for persistence versus discontinuation can inform both initial and follow‐up patient counselling. [ABSTRACT FROM AUTHOR]

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder (LSD) caused by reduced activity of the acid sphingomyelinase (ASM) enzyme, which leads to progressive storage of sphingomyelin and related lipids in the body. ASMD is caused by biallelic variants in the SMPD1 gene, which encodes for the ASM enzyme. Current estimates of disease incidence range from 0.4 to 0.6 in 100 000 livebirths, although this is likely an underestimation of the true frequency of the disorder. While there is no cure for ASMD, comprehensive care guidelines and enzyme replacement therapy are available, making an early diagnosis crucial. Newborn screening (NBS) for ASMD is possible through measurement of ASM activity in dried blood spots and offers the opportunity for early diagnosis. In 2015, Illinois (IL) became the first to initiate statewide implementation of NBS for ASMD. This study describes the outcomes of screen‐positive patients referred to Ann & Robert H. Lurie Children's Hospital (Lurie). Ten infants were referred for diagnostic evaluation at Lurie, and all 10 infants were classified as confirmed ASMD or at risk for ASMD through a combination of molecular and biochemical testing. Disease incidence was calculated using data from this statewide implementation program and was ~0.79 in 100 000 livebirths. This study demonstrates successful implementation of NBS for ASMD in IL, with high screen specificity and a notable absence of false positive screens. [ABSTRACT FROM AUTHOR]

Introduction: To the best of our knowledge, clinically significant endogenous ethylene glycol production has never been reported in humans, very seldom reported in other animals or microorganisms, and then only under rare and specific conditions. We describe the detailed investigations we undertook in two adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol. Methods: Two previously healthy monozygotic adult twin sisters presented with recurrent episodes of apparent ethylene glycol poisoning beginning at age 35, requiring chronic hemodialysis to remove ethylene glycol and its metabolites as well as to restore metabolic homeostasis. The sisters denied ingestion or exposure to ethylene glycol. At their request, they were admitted to hospital under strict supervision to exclude surreptitious ingestion of ethylene glycol and to evaluate the need for treatment. Hemodialysis was withheld during this prospective study. Twin A was admitted for 14 days and twin B for 11 days. Serial biochemical analyses were performed in blood and urine. Clinical exome sequencing and mitochondrial deoxyribonucleic acid sequencing were also completed. Results: In both twins, ethylene glycol was detected in urine, along with intermittent increases in concentrations of lactate, glycolate, and glycine in blood and/or urine. Blood ethylene glycol concentrations, however, remained <62 mg/L (<1 mmol/L) but became positive soon after discharge. The oxalate concentration remained normal in blood and urine. Plasma and urine amino acid profiles showed intermittent small increases in glycine, serine, taurine, proline, and/or alanine concentrations. Exome sequencing and mitochondrial deoxyribonucleic acid sequencing were non-diagnostic. Neither twin has been admitted with metabolic acidosis nor ethylene glycol poisoning since chronic hemodialysis was started. Twin A developed a calcium oxalate dihydrate lithiasis. Discussion: Mitochondrial disease, methylmalonic/propionic/isovaleric aciduria, primary hyperoxaluria, and analyte error were all excluded in these twins, as were obvious common environmental exposures. Conclusion: Detailed investigations were performed in adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol. Alternative explanations were excluded to the very best of our efforts and knowledge. Global metabolomics, gut microbiome analyses, and whole genome sequencing are pending. [ABSTRACT FROM AUTHOR]

Dependency between the conventional imbalance diagnostic feature and the shaft rotational speed makes imbalance diagnosis challenging for variable-speed machines. This paper focuses on an investigation of this dependency and on a proposal for a novel imbalance diagnostic feature and a novel simplified version for this feature, which are independent of shaft rotational speed. An equivalent mass–spring–damper system is investigated to find a closed-form expression describing this dependency. By normalizing the conventional imbalance diagnostic feature by the obtained dependency, a diagnostic feature is proposed. By conducting comprehensive experimental trials with a wind turbine with a permissible imbalance, it is justified that the proposed simplified version of imbalance diagnostic feature is speed-invariant. [ABSTRACT FROM AUTHOR]

This paper develops benchmark cases for low- and very-low-frequency passive acoustic source localization (ASL) using synthetic data. These cases can be potentially applied to the detection of turbulence-generated low-frequency acoustic emissions in the atmosphere. A deep learning approach is used as an alternative to conventional beamforming, which performs poorly under these conditions. The cases, which include two- and three-dimensional ASL, use a shallow and inexpensive convolutional neural network (CNN) with an appropriate input feature to optimize the source localization. CNNs are trained on a limited dataset to highlight the computational tractability and viability of the low-frequency ASL approach. Despite the modest training sets and computational expense, detection accuracies of at least 80% and far superior performance compared with beamforming are achieved—a result that can be improved with more data, training, and deeper networks. These benchmark cases offer well-defined and repeatable representative problems for comparison and further development of deep learning-based low-frequency ASL. [ABSTRACT FROM AUTHOR]

Navigating whether to prescribe hormone replacement therapy (HRT) requires that health practitioners approach a woman's individual life circumstances, and early menopause (EM) as a particularly intricate experience and condition. Drawing on qualitative interviews with 16 practitioners in Australia, this article examines the modalities of care that emerge in the nexus of EM and HRT. Early menopause emerges in participants' narratives as far from a 'unitary' medical condition, but rather one that reaches across other embodied changes for women which may be moderated by HRT. Thus, different modes of care and tensions surface, and we suggest that these constitute an oscillation between 'caring for' and 'caring with' in medical practice. This oscillation combines experimentation with and adjustment of HRT, while contending with responsibility, risk and choice, and shared, knowledgeable care. Our goal is not to neatly split 'caring for' from 'caring with'. Rather, we discuss how ambiguities of care circulate through a complex diagnosis and its treatment options. We argue that care, in this context, manifests as potentiality and as a set of flexible practices that at times cannot be fully disentangled from issues of choice and control, and HRT itself. [ABSTRACT FROM AUTHOR]

The clinical laboratory uses commercial products with limited shelf life or certain expiry dates requiring frequent lot changes. Prior to implementation for clinical use, laboratories should determine the performance of the new reagent lot to ensure that there is no significant shift in reagent performance or reporting of patient data. This guideline has been written on behalf of the International Council for Standardization in Haematology (ICSH) to provide the framework and provisional guidance for clinical laboratories for evaluating and verifying the performance of new lot reagents used for coagulation testing. These ICSH Working Party consensus recommendations are based on good laboratory practice, regulatory recommendations, evidence emerged from scientific publications, and expert opinion and are meant to supplement regional standards, regulations, or requirements. [ABSTRACT FROM AUTHOR]

This paper outlines a conceptual framework for enacting relational pedagogy. Commencing with a description of a relational ontology that can work to provide the foundation for engaged and participatory enactments of teaching and learning, the paper moves to consider the dynamics that support inclusive modes of education and the dimensions of relational pedagogical encounters. In particular, the pedagogical encounter is examined with a view to illuminating how the ontological and epistemological dynamics and dimensions of relational pedagogy open opportunities for inclusive and participatory modes of teaching and learning. In addition, the practical implications of pedagogical informality are considered, including the in-the-moment immediacy inherent to the relational encounter and concomitant enactments of the pedagogical exchange. In doing so, we argue for a relational pedagogy that widens the possibility for meaningful engagement with young people through pedagogical enactments that build upon the inter-relationality of teachers and students. [ABSTRACT FROM AUTHOR]

Background: This study focuses on the role of lysosomal trafficking in prostate cancer, given the essential role of lysosomes in cellular homoeostasis. Methods: Lysosomal motility was evaluated using confocal laser scanning microscopy of LAMP-1-transfected prostate cells and spot-tracking analysis. Expression of lysosomal trafficking machinery was evaluated in patient cohort databases and through immunohistochemistry on tumour samples. The roles of vesicular trafficking machinery were evaluated through over-expression and siRNA. The effects of R1881 treatment on lysosome vesicular trafficking was evaluated by RNA sequencing, protein quantification and fixed- and live-cell microscopy. Results: Altered regulation of lysosomal trafficking genes/proteins was observed in prostate cancer tissue, with significant correlations for co-expression of vesicular trafficking machinery in Gleason patterns. The expression of trafficking machinery was associated with poorer patient outcomes. R1881 treatment induced changes in lysosomal distribution, number, and expression of lysosomal vesicular trafficking machinery in hormone-sensitive prostate cancer cells. Manipulation of genes involved in lysosomal trafficking events induced changes in lysosome positioning and cell phenotype, as well as differential effects on cell migration, in non-malignant and prostate cancer cells. Conclusions: These findings provide novel insights into the altered regulation and functional impact of lysosomal vesicular trafficking in prostate cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Impactful, evidence-based solutions in surveillance, prevention, acute care, and rehabilitation for stroke survivors are required to address the high global burden of stroke. Patient and public involvement (PPI), where patients, their families, and the public are actively involved as research partners, enhances the relevance, credibility, and impact of stroke-related research. Aims: This scoping review, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Scoping Review guidelines, aims to identify and summarize how PPI is currently implemented and reported in empirical stroke research using a participatory approach. Summary of review: A comprehensive search strategy was developed and implemented across Medline, CINAHL, EMBASE, PsynchINFO, and Cochrane electronic databases, supplemented by gray literature searches. Empirical stroke research articles in the English language, published from 2014 up to 2023, and documenting PPI activity were included. Of the 18,143 original articles identified, 2824 full-text manuscripts matching from this time window were screened. Only 2% (n = 72) of these directly reported embedded PPI activity in empirical research. The majority were qualitative in design (60%) and conducted in high-income countries (96%). Only one included study originated from a developing country, where the burden of stroke is highest. Most studies (94%) provided some information about the activities carried out with their PPI partners, mainly centered on the study design (57%) and management (64%), with only 4% of studies integrating PPI across all research cycle phases from funding application to dissemination. When studies were examined for compliance with the Guidance for Reporting Involvement of Patients and the Public (GRIPP) short-form checklist, only 11% of included studies were 100% compliant. Twenty-one studies (29%) reported barriers and facilitators to including PPI in stroke research. Organization, authentic partnership, and experienced PPI representatives were common facilitators and identified barriers reflected concerns around adequate funding, time required, and diversity in perspectives. A positive reporting bias for PPI impact was observed, summarized as keeping the patient perspective central to the research process, improved care of study participants, validation of study findings, and improved communication/lay-summaries of complex research concepts. Conclusions: PPI is underutilized and inconsistently reported in current empirical stroke research. PPI must become more widely adopted, notably in low- and middle-income countries. Consensus-driven standards for inclusion of PPI by funding organizations and publishers are required to support its widespread adoption. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that rhythmic temporal cues in the environment influence the encoding of information into long-term memory. Here, we test the hypothesis that these mnemonic effects of rhythm reflect the coupling of high-frequency (gamma) oscillations to entrained lower-frequency oscillations synchronized to the beat of the rhythm. In Study 1, we first test this hypothesis in the context of global effects of rhythm on memory, when memory is superior for visual stimuli presented in rhythmic compared with arrhythmic patterns at encoding [Jones, A., & Ward, E. V. Rhythmic temporal structure at encoding enhances recognition memory, Journal of Cognitive Neuroscience, 31, 1549–1562, 2019]. We found that rhythmic presentation of visual stimuli during encoding was associated with greater phase-amplitude coupling (PAC) between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. In Study 2, we next investigated cross-frequency PAC in the context of local effects of rhythm on memory encoding, when memory is superior for visual stimuli presented in-synchrony compared with out-of-synchrony with a background auditory beat [Hickey, P., Merseal, H., Patel, A. D., & Race, E. Memory in time: Neural tracking of low-frequency rhythm dynamically modulates memory formation. Neuroimage, 213, 116693, 2020]. We found that the mnemonic effect of rhythm in this context was again associated with increased cross-frequency PAC between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. Furthermore, the magnitude of gamma power modulations positively scaled with the subsequent memory benefit for in- versus out-of-synchrony stimuli. Together, these results suggest that the influence of rhythm on memory encoding may reflect the temporal coordination of higher-frequency gamma activity by entrained low-frequency oscillations. [ABSTRACT FROM AUTHOR]

TANGO2 deficiency disorder (TDD) is a rare, autosomal recessive condition caused by pathogenic variants in TANGO2, a gene residing within the region commonly deleted in 22q11.2 deletion syndrome (22q11.2DS). Although patients with 22q11.2DS are at substantially higher risk for comorbid TDD, it remains underdiagnosed within 22q11.2DS, likely due to overlapping symptomatology and a lack of knowledge about TDD. Initiation of B‐vitamin supplementation may provide therapeutic benefit in TDD, highlighting the need for effective screening methods to improve diagnosis rates in this at‐risk group. In this retrospective, multicenter study, we evaluated two cohorts of patients with 22q11.2DS (total N = 435) for possible comorbid TDD using two different symptom‐based screening methods (free text‐mining and manual chart review versus manual chart review alone). The methodology of the cohort 1 screening method successfully identified a known 22q11.2DS patient with TDD. Combined, these two cohorts identified 21 living patients meeting the consensus recommendation for TANGO2 testing for suspected comorbid TDD. Of the nine patients undergoing TANGO2 sequencing with del/dup analysis, none were ultimately diagnosed with TDD. Of the 12 deaths in the suspected comorbid TDD cohort, some of these patients exhibited symptoms (rhabdomyolysis, cardiac arrhythmia, or metabolic crisis) suspicious of comorbid TDD contributing to their death. Collectively, these findings highlight the need for robust prospective screening tools for diagnosing comorbid TDD in patients with 22q11.2DS. [ABSTRACT FROM AUTHOR]

Bacterial populations that originate from a single bacterium are not strictly clonal and often contain subgroups with distinct phenotypes1. Bacteria can generate heterogeneity through phase variation—a preprogrammed, reversible mechanism that alters gene expression levels across a population1. One well-studied type of phase variation involves enzyme-mediated inversion of specific regions of genomic DNA2. Frequently, these DNA inversions flip the orientation of promoters, turning transcription of adjacent coding regions on or off2. Through this mechanism, inversion can affect fitness, survival or group dynamics3,4. Here, we describe the development of PhaVa, a computational tool that identifies DNA inversions using long-read datasets. We also identify 372 ‘intragenic invertons’, a novel class of DNA inversions found entirely within genes, in genomes of bacterial and archaeal isolates. Intragenic invertons allow a gene to encode two or more versions of a protein by flipping a DNA sequence within the coding region, thereby increasing coding capacity without increasing genome size. We validate ten intragenic invertons in the gut commensal Bacteroides thetaiotaomicron, and experimentally characterize an intragenic inverton in the thiamine biosynthesis gene thiC.Reversible DNA inversions found entirely within genes enable increased coding capacity by encoding multiple versions of a protein in bacteria and archaea. [ABSTRACT FROM AUTHOR]

Background: The number of patients who have experienced violence is increasing worldwide. These patients have specific psychosocial and forensic needs and can present unique challenges to the health care workers caring for them. Objective: To identify best practices for the care of patients with injuries from violence in the emergency department or inpatient setting. Methods: The framework for integrative reviews by Whittemore and Knafl was used to conduct a literature search in MEDLINE, CINAHL, and ProQuest Nursing and Allied Health databases. Fourteen qualitative, quantitative, and mixed-methods studies from peer-reviewed journals were included in the review. Results: Themes included identifying patients as survivors of intimate partner violence or child abuse, the need to collect forensic evidence, the need for emotional support of patients and their loved ones, support for health care workers caring for patients with injuries from violence, prevention of further violence, and the challenges of caring for patients with injuries from violence with concurrent substance use disorders. Best practices for these aspects of care are summarized on the basis of literature analysis. Conclusion: Screening procedures are needed to identify survivors of intimate partner violence and child abuse. Forensic evidence preservation policies should be in place. For survivors of sexual assault, a sexual assault nurse examiner should be available. Hospital systems should provide psychosocial resources for patients' and health care workers' mental health, implement violence reduction programs, and provide bias training. More research is needed to determine efficacy of care models and best practice. [ABSTRACT FROM AUTHOR]

High-grade prostatic intraepithelial neoplasia (HGPIN) is a well-characterised precursor lesion in prostate cancer. The term atypical intraductal proliferations (AIP) describes lesions with features that are far too atypical to be considered HGPIN, yet insufficient to be diagnosed as intraductal carcinoma of the prostate (IDCP). Here, a panel of biomarkers was assessed to provide insights into the biological relationship between IDCP, HGPIN, and AIP and their relevance to current clinicopathological recommendations. Tissue samples from 86 patients with prostate cancer were assessed by routine haematoxylin and eosin staining and immunohistochemistry (IHC) with a biomarker panel (Appl1/Sortilin/Syndecan-1) and a PIN4 cocktail (34βE12+P63/P504S). Appl1 strongly labelled atypical secretory cells, effectively visualising intraductal lesions. Sortilin labelling was moderate-to-strong in > 70% of cases, while Syndecan-1 was moderate-to-strong in micropapillary HGPIN/AIP lesions (83% cases) versus flat/tufting HGPIN (≤ 20% cases). Distinct biomarker labelling patterns for atypical intraductal lesions of the prostate were observed, including early atypical changes (flat/tufting HGPIN) and more advanced atypical changes (micropapillary HGPIN/AIP). Furthermore, the biomarker panel may be used as a tool to overcome the diagnostic uncertainty surrounding AIP by supporting a definitive diagnosis of IDCP for such lesions displaying the same biomarker pattern as cribriform IDCP. [ABSTRACT FROM AUTHOR]

* OBJECTIVE: To determine the Fragility Index of hamstring injury risk factors, defined as the minimum number of participants who would need to change classification to make a hamstring injury risk factor statistically nonsignificant. * DESIGN: Retrospective secondary data analysis. * METHODS: Studies that investigated 1 or more risk factors for hamstring injury, and presented sufficient data to develop a 2 x 2 contingency table were included. A systematic literature search and reference screening of a recent hamstring injury systematic review were conducted to identify 78 articles. Relative risk and 95% confidence intervals were determined and then systematically recalculated by removing 1 observation from the high-risk injury count and adding it to the high-risk noninjury count. The Fragility Index for a risk factor was the number of observations required to be moved between groups until the relative risk was no longer significant. * RESULTS: The median Fragility Index of all hamstring injury risk factors was 3 (Q1-Q3 = 2-6). The Fragility Index for nonmodifiable risk factors was 3 (Q1-Q3 = 2-6) and 3 (Q1-Q3 = 2-5) for modifiable risk factors. Over 35% of all included hamstring injury risk factors had a Fragility Index of ≤2. * CONCLUSION: Most statistically significant hamstring injury risk factors are fragile associations. The interpretation of significant hamstring injury risk factors should consider a range of statistical metrics, and while the Fragility Index should never be considered in isolation, it is an intuitive measure to help assess the robustness of findings. [ABSTRACT FROM AUTHOR]

Understanding regional sea level variations is crucial for assessing coastal vulnerability, with accurate sea level data playing a pivotal role. Utilizing historical sea level marigrams can enhance datasets, but current digitization techniques face challenges such as bends and skews in paper charts, impacting sea level values. This study explores often‐overlooked issues during marigram digitization, focusing on the case study of Dún Laoghaire in Ireland (1925–1931). The methodology involves digitizing the original marigram trace and underlying grid to assess offsets at the nearest ft (foot) interval on the paper chart, corresponding to changes in the water level trace for each hour interval. Subtracting the digitized value from the known value (the actual measurement) allows for the determination of differences, which are then subtracted from each hourly trace value. After adjusting for offsets ranging from −3.962 to 13.716 mm (millimetres), the study improves the final accuracy of sea level data to approximately the 10 mm level. Notably, data from 1926 and 1931 exhibit modest offsets (<7 mm), while other years show more substantial offsets (>9–14 mm), emphasizing the importance of adjustments for accuracy. Such 10 mm accuracy is compatible with requirements of the Global Sea Level Observing System. Comparing the adjusted digitized data with other survey data shows similar amplitudes and phases for Dún Laoghaire in both the historical and modern datasets, and there is an overall mean sea level rise of 1.5 mm/year when combined with the available data from the Dublin region. [ABSTRACT FROM AUTHOR]

Background: Benralizumab has been reported to lead to clinical remission of severe eosinophilic asthma (SEA) at 1 year in some patients. However, whether this is maintained over a longer term remains unclear. Additionally, the impact of pulmonary and extrapulmonary comorbidities on the ability to meet remission is poorly understood. Methods: Clinical outcomes including remission of SEA with benralizumab at 1 and 2 years were assessed retrospectively in a real‐world UK multi‐centre severe asthma cohort. The presence of clinically relevant pulmonary and extrapulmonary comorbidities associated with respiratory symptoms was recorded. Analyses to identify factors associated with the ability to meet remission were performed. Results: In total, 276 patients with SEA treated with benralizumab including 113 patients who had switched from a previous biologic to benralizumab were included. Overall, clinical remission was met in 17% (n = 31/186) and 32% (n = 43/133) of patients at 1 and 2 years, respectively. This increased to 28% at 1 year and 49% at 2 years once patients with pulmonary and/or extrapulmonary comorbidities were excluded. Body mass index (BMI) and maintenance OCS (mOCS) use demonstrated a negative association with clinical remission at 1 (BMI: OR: 0.89, 95% CI: 0.82–0.96, p < 0.01; mOCS: OR: 0.94, 95% CI: 0.89–0.99, p < 0.05) and 2 years (BMI: OR: 0.93, 95% CI: 0.87–0.99, p < 0.05; mOCS: OR: 0.95, 95% CI: 0.89–0.99, p < 0.05). Conclusions: In this long‐term, real‐world study, patients with SEA demonstrated the ability to meet and sustain clinical remission when treated with benralizumab. The presence of comorbidities including obesity, which are known to be independently associated with respiratory symptoms, reduced the likelihood of meeting clinical remission. [ABSTRACT FROM AUTHOR]

In this paper, we highlight the poor health of the Australian environment and propose a new framing for how we care for Maar Country. We identify the basis for our Law/Lore of the Land and describe six guiding principles for our proposed biocultural landscape restoration approach. We also explore the way that our ancestors used cultural stories to guide the management of Country and we reflect on how we are adopting these same approaches today by giving culturally significant entities primacy in our approach to caring for Country. Finally, we extend an invitation to non-Aboriginal scientists, conservationists, and government agencies to work with us to care for Country, in a respectful and holistic manner. Position statement. We, the authors of this paper, are all either Aboriginal Australians or employed by the Eastern Maar Aboriginal Corporation. We are all actively participating in the Pang-ngooteekeeya weeng malangeepa ngeeye project. [ABSTRACT FROM AUTHOR]

Background: Urinary incontinence (UI) is the most prevalent pelvic floor disorder following treatment for gynaecological cancer with a distressing impact on quality-of-life in survivors. Physiotherapist-supervised pelvic floor muscle (PFM) training is recommended as the first-line intervention for UI in community-dwelling women. However, it is not known if this intervention is effective in women following treatment for gynaecological cancer, nor whether PFM training can be delivered entirely remotely. The primary aim of this study is to investigate if a telehealth-delivered PFM training program incorporating a novel biofeedback device reduces UI compared with usual care, following gynaecological cancer. Methods: This is a pragmatic, two-arm parallel-group, stratified superiority randomised controlled trial recruiting 72 participants (ACTRN12622000580774). Recruitment sites include gynaecology-oncology outpatient clinics, supplemented by advertisements through community foundations/social media/care groups. Participants must have completed primary cancer treatment at least 6 months prior or adjuvant therapy at least 3 months prior, for Stage I, II or III uterine, cervical, fallopian tube, primary peritoneal or ovarian cancer or borderline ovarian tumour, and have UI occurring at least weekly. Participants randomised to the usual care group will receive bladder and bowel advice handouts and one audio telehealth physiotherapist consultation to answer any queries about the handouts. Participants randomised to the intervention group will receive the same handouts plus eight video telehealth physiotherapist consultations for PFM training with a biofeedback device (femfit®), alongside a home-based program over 16 weeks. The primary outcome measure is a patient-reported outcome of UI frequency, amount and interference with everyday life (measured using the International Consultation on Incontinence Questionnaire – Urinary Incontinence Short Form), immediately post-intervention compared with baseline. Secondary outcomes include quality-of-life measures, bother of pelvic floor symptoms, leakage episodes, use of continence pads and global impression of change. We will also investigate if the intervention improves intra-vaginal resting and squeeze pressure in women in the intervention arm, using data from the biofeedback device. Discussion: If clinical effectiveness of telehealth-delivered physiotherapist-supervised PFM training, supplemented with home biofeedback is shown, this will allow this therapy to enter pathways of care, and provide an evidence-based option for treatment of post-cancer UI not currently available. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ID 12622000580774. Registered 20 April 2022. [ABSTRACT FROM AUTHOR]

Neurobiological research relies heavily on imaging techniques, such as fluorescence microscopy, to understand neurological function and disease processes. However, the number and variety of fluorescent probes available for ex vivo tissue section imaging limits the advance of research in the field. In this review, we outline the current range of fluorescent probes that are available to researchers for ex vivo brain section imaging, including their physical and chemical characteristics, staining targets, and examples of discoveries for which they have been used. This review is organised into sections based on the biological target of the probe, including subcellular organelles, chemical species (e.g., labile metal ions), and pathological phenomenon (e.g., degenerating cells, aggregated proteins). We hope to inspire further development in this field, given the considerable benefits to be gained by the greater availability of suitably sensitive probes that have specificity for important brain tissue targets. [ABSTRACT FROM AUTHOR]

Single ion conducting gel polymer electrolytes (GPEs) are characterized as having a certain amount of ionic liquid or solvent incorporated into a single ion-conducting polymer matrix and may afford the advantages of high conductivity and low electrolyte polarization under battery operation. Single ion conducting polymers often suffer from low conductivity due to their reliance on polymer segmental motion to achieve sufficient ion mobility. However, by incorporating specific solvents into a single ion conducting matrix, mobility of the polymer can be enhanced while still maintaining the advantages of single ion conduction. Although many of the solvents used to swell GPEs are mixtures of flammable organic solvents (such as dimethyl carbonate), there are many potential non-reactive, low vapor pressure solvents that could effectively solvate alkali-ion based GPEs and plasticize the polymer matrix to enhance ion conductivity. Adipate-based solvents are a group of non-volatile plasticizers with low viscosities and low vapor pressures at room temperature derived from adipic acid. The ester groups in these solvents may effectively solvate alkali ions such as Na+, leading to higher conductivity, while circumventing issues of flammability found in current alkali-ion conducting electrolytes. This study investigates the properties of sodium-ion conducting GPEs that have been swollen with varying adipate-based solvents and the subsequent dielectric response from the solvent addition. Dielectric relaxation spectroscopy was used to characterize the Na+ conductivity, static dielectric constant, ion-conducting content, and mobility of the membranes before and after the non-volatile solvent uptake. Understanding this relationship will pave the path toward safer, more efff cient solid-state polymer electrolytes for battery applications. [ABSTRACT FROM AUTHOR]

The unconventional superconductor UTe2 exhibits numerous signatures of spin-triplet superconductivity--a rare state of matter which could enable quantum computation protected against decoherence. UTe2 possesses a complex phase landscape comprising two magnetic field-induced superconducting phases, a metamagnetic transition to a field-polarized state, along with pair- and charge-density wave orders. However, contradictory reports between studies performed on UTe2 specimens of varying quality have severely impeded theoretical efforts to understand the microscopic origins of the exotic superconductivity. Here, we report a comprehensive suite of high magnetic field measurements on a generation of pristine quality UTe2 crystals. Our experiments reveal a significantly revised high magnetic field superconducting phase diagram in the ultraclean limit, showing a pronounced sensitivity of field-induced superconductivity to the presence of crystalline disorder. We employ a Ginzburg-Landau model that excellently captures this acute dependence on sample quality. Our results suggest that in close proximity to a field-induced metamagnetic transition the enhanced role of magnetic fluctuations--that are strongly suppressed by disorder--is likely responsible for tuning UTe2 between two distinct spin-triplet superconducting phases. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) are crucial immune cells for tissue repair and regeneration. However, their potential as a cell-based regenerative therapy is not yet fully understood. Here, we show that local delivery of exogenous Tregs into injured mouse bone, muscle, and skin greatly enhances tissue healing. Mechanistically, exogenous Tregs rapidly adopt an injury-specific phenotype in response to the damaged tissue microenvironment, upregulating genes involved in immunomodulation and tissue healing. We demonstrate that exogenous Tregs exert their regenerative effect by directly and indirectly modulating monocytes/macrophages (Mo/MΦ) in injured tissues, promoting their switch to an anti-inflammatory and pro-healing state via factors such as interleukin (IL)-10. Validating the key role of IL-10 in exogenous Treg-mediated repair and regeneration, the pro-healing capacity of these cells is lost when Il10 is knocked out. Additionally, exogenous Tregs reduce neutrophil and cytotoxic T cell accumulation and IFN-γ production in damaged tissues, further dampening the pro-inflammatory Mo/MΦ phenotype. Highlighting the potential of this approach, we demonstrate that allogeneic and human Tregs also promote tissue healing. Together, this study establishes exogenous Tregs as a possible universal cell-based therapy for regenerative medicine and provides key mechanistic insights that could be harnessed to develop immune cell-based therapies to enhance tissue healing. Regulatory T cells (Tregs) are known for suppressing inflammatory processes, but their full capacity for tissue regeneration is yet to be harnessed. Here, the authors demonstrate the efficiency of Tregs in facilitating tissue healing in mouse models of bone, muscle, and skin injury, with monocytes/macrophages and interleukin-10 playing a key mechanistic role in the process. [ABSTRACT FROM AUTHOR]

This manuscript is designed to complement the previously published primer on salary structures for new pain physicians. The previous manuscript "Employment Contract Financial Models for the Pain Physician: A Primer" had a goal of increasing understanding of financial models by pain fellows when preparing for contract negotiations. This manuscript illustrates the many equally important considerations of "non‐monetary" values that are a significant part of contract negotiation outside of salary. It contributes to the overall education for trainees and pain physicians on benefits and job responsibilities. [ABSTRACT FROM AUTHOR]

We recently introduced calix[n]naphth[m]arenes as a novel class of deep-cavity hybrid macrocycles constituted by phenol (n) and naphthalene (m) units. In this study, we report the synthesis, conformational analysis, spectroscopic properties, and solid-state structures of calix[4]naphth[4]arene (C4N4) and its permethylated analog (C4N4-Me), thereby expanding the calix[n]naphth[m]arene family. C4N4 was synthesized through a 2 + 2 fragment coupling macrocyclization under acidic conditions, where the solvent played a crucial role in selectively forming the C4N4 derivative. The X-ray structure of C4N4 reveals a chair-like 1,2,3,4-alternate conformation characterized by two opposing 3/4-cone moieties stabilized by intramolecular hydrogen bonds. In contrast, the X-ray structure of C4N4-Me exhibits a 1,3,5,7-alternate conformation. [ABSTRACT FROM AUTHOR]

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme responsible for catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high-affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer's disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. The results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs), and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD. [ABSTRACT FROM AUTHOR]

Indigenous peoples in Canada are disproportionately exposed to environmental contaminants and may face elevated health risks related to their unique cultural, spiritual, and economic relationships with the land, including the use of traditional food systems. However, to date, institutionalized approaches to assess risks to human and ecological health from contaminants have not been well developed or implemented with Indigenous community contexts in mind. There is regulatory interest in developing new approach methods for risk assessment, and thus an opportunity to increase their relevance to Indigenous communities in which they will be ultimately applied. Therefore, we conducted an anonymous mixed‐methods survey of those involved with risk assessment in Indigenous communities in Canada to: (1) understand risk assessment practice in Indigenous communities, (2) explore challenges with conventional assessment methods and compare these across sectors, and (3) gather perspectives on the development of new approaches. In all, 38 completed survey responses were received (14% response rate). Respondents were from Indigenous community environment and health offices (21% of respondents), Indigenous governments (8%), federal and provincial governments (21%), and academia (45%). Risk communication was seen as the most challenging part of risk assessment (71% responded "difficult"), and nearly all respondents agreed that time (86%), cost (76%), and resource availability (86%) were "moderate" to "serious" problems. Few respondents (16%) had heard of "new approach methods" for risk assessment, and 76% of respondents (and 100% of community‐based respondents) agreed on the need to develop improved risk assessment approaches. To modernize risk assessment, respondents recommended advancing cumulative risk assessment methods, improving risk communication, and promoting Indigenous leadership and Traditional Knowledge in assessment activities. Integr Environ Assess Manag 2024;20:1677–1692. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Key Points: The online survey was completed by 38 respondents from across Canada who had experience with human health and ecological risk assessments, spanning a diversity of sectors including Indigenous communities, provincial and federal governments, and academia.Cumulative risk assessment, risk communication, and resource availability were identified as some of the most challenging aspects of risk assessment in the context of Indigenous communities in Canada and may be key considerations in the development of new, community‐relevant methods.Perspectives differed among groups (community‐based respondents, federal and provincial employees, and academics), signaling a need for further research in this area and implementation of strategies to improve multisectoral collaboration and communication.Most (76%) respondents agreed on the need for new approaches to risk assessment for Indigenous community contexts, and this agreement was unanimous (100%) among those who worked in communities themselves. [ABSTRACT FROM AUTHOR]

The aim of this scoping review was to establish the breadth of the academic literature regarding the barriers and facilitators to social work practice in schools as perceived by School Social Workers (SSWs). Following the PRISMA-ScR Scoping Review Framework, 42 articles were identified as meeting the inclusion criteria. Five interrelated themes related to the barriers and facilitators to SSW practice were identified: (1) Inadequacy of service delivery infrastructure; (2) SSWs' role ambiguities and expectations; (3) SSWs' competency, knowledge and support; (4) School climate and context; and (5) Cultivating relationships and engagement. This scoping review found that social workers perceive far greater barriers than facilitators when delivering services in school settings, with limited evidence related to the facilitators that enhance School Social Work (SSW) practice. Further research regarding the facilitators of SSW practice is needed, specifically in countries where research on this topic is emergent. [ABSTRACT FROM AUTHOR]

Social Stories™ are a story-based intervention commonly used to teach students with disabilities how to behave in new routines or changing environments, academic skills, and social interactions including tacting others' emotions. According to the National Standards Project, story-based interventions are considered an established trea™ent. However, the efficacy of Social Stories™ is confounded by limitations in chosen experimental designs, threats to internal validity, and additional interventions within trea™ent packages. The current study used Social Stories™ to teach classroom social skills to children diagnosed with an intellectual disability. We used a multiple baseline across participants design to evaluate changes in classroom social skills when using Social Stories™. We taught a total of four response classes, including: saying, "please," saying, "thank you," appropriate hand raising, and giving assistance. The results indicate that Social Stories™ may be an effective intervention to increase classroom social skills. This is one of the first studies to evaluate and demonstrate the effectiveness of Social Stories™ as a standalone intervention. The present study also extends the current social studies literature in several areas, such as developing ways to promote generalization and assessing the social validity of the goals, procedures, and outcomes of the study. [ABSTRACT FROM AUTHOR]

Simple Summary: Flight is a fundamental characteristic for the majority of bird species, but how well is this behaviour catered for when birds are housed in managed populations under human care? Zoo enclosure design and animal care practices often balance natural behaviour performance and what is feasible in a human-made environment. As zoos focus more on animal welfare, enclosures should be evaluated to ensure they provide adequate space, natural habitat features, and opportunities for natural behaviours. This paper highlights the need for a better understanding of behaviours, using flight in bird as the core example, and recommends posing and then answering directed questions to gather evidence for improved enclosure design to provide for what birds need to do. We call for changing "best practice" guidelines to "better practice guidelines" to emphasise continuous improvement in animal care based on evidence and regular reassessment, and to encourage all stakeholders in zoos to regularly consider the impacts of housing and husbandry on animal behaviour and welfare. Zoo enclosure design, and housing and husbandry protocols, will always be a compromise between what a species has evolved to do and what is possible to offer in a human-created environment. For some species, behaviours that are commonly performed in the wild may be constrained by husbandry practices that are used for ease or aesthetics or are accepted conventions. As zoos place more emphasis on positive animal welfare states, zoo enclosures should be scrutinised to check that what is provided, in terms of useful space, appropriate replication of habitat features, and maximal potential for natural behaviour performance, is relevant to the species and individuals being housed. For some species, zoos need to grapple with tough questions where the answer may not seem immediately obvious to ensure they are continuously improving standards of care, opportunities for the performance of species-typical behaviours, and advancing the attainment of positive welfare states. Determining the importance of flight, for example, and what this behaviour adds to the quality of life of a zoo-housed bird, is an important question that needs addressing to truly advance aviculture and how we determine bird welfare. This paper provides questions that should be answered and poses measures of what flight means to a bird, to provide evidence for the development and evolution of zoo bird housing. If we can devise some way of asking the animals in our care what they need, we can more firmly support decisions made that surround enclosure design, and housing decisions. Ultimately, this means gathering evidence on whether birds like to fly (e.g., from birds in training or demonstration activities) by applying mixed methods approaches of behavioural analysis, data on wild ecology, qualitative behavioural assessment, and cognitive bias testing to develop a robust suite of tools to address avian welfare considerations. Avian welfare scientists should attempt to define what meaningful flight is (i.e., flight that truly suggests a bird is flying) in order to support guidelines on aviary dimensions, space allowance, and welfare outputs from birds in both flighted and flight-restricted populations, and to determine what is most appropriate for an individual species. Changing the term "best practice" husbandry guidelines to "better practice" husbandry guidelines would instil the importance of regular review and reassessment of housing and management suitability for a species to ensure such care regimes remain appropriate. With an increasingly welfare-savvy public visiting zoos, it is essential that we seek more evidence to support and justify how birds are kept and ultimately use such evidence to enact changes to practices that are shown to infringe on avian welfare. [ABSTRACT FROM AUTHOR]

This paper investigates the influence of the volute geometry on the hydraulic performance of a low-specific-speed centrifugal pump using numerical simulations. The performance characteristics for the pump with the volute geometry designed using the constant velocity method show a significant discrepancy between the design point and the best efficiency point (BEP). This design methodology also results in a relatively flat head–capacity curve. These are both undesirable characteristics which can be mitigated by a reduction in the volute throat area. This design methodology also leads to a reduction in the power consumption and an increase in efficiency, especially at underload and design flow conditions. These impacts of the volute throat area on performance characteristics are investigated in terms of the change in internal flow characteristics due to the reduction in the volute throat area. Another aspect of the study is the impact of the width of the volute gap on performance characteristics. A reduction in the gap width results in a nearly vertical shift of the head–capacity curve, so that head delivered is higher across all the flow rates as the gap width is reduced. This is also accompanied by a slight improvement in efficiency under design flow and overload conditions. Numerical simulations are used to relate the change in performance characteristics with internal flow characteristics. [ABSTRACT FROM AUTHOR]

Local Area Coordination (LAC) roles have been implemented in disability services in many countries, supporting people living with disability to connect with formal and informal support in the community. Embedded in the National Disability Insurance Scheme in Australia, the aspiration is that this LAC role will connect people with disability to supports and enable the generation of greater community capacity and inclusion. Yet, with only a limited evidence base that demonstrates the impact of this approach, a clear measurement framework is needed to provide evidence of the realization of this aspiration. We propose that this impact could be demonstrated by applying a Community Capitals Framework (CCF) as the theoretical base for the LAC role and other community capacity initiatives, such as service navigation within disability reform of disability services. The CCF is premised on seven 'capitals'—social, natural, cultural, human, political, financial and built that intersect and interact with each other to create positive spirals of change in communities. In this critical literature review, we apply the CCF to map and synthesize existing research on the LAC's role in building community capital and examine the utility of the CCF as a map for LAC and service navigation practices to enhance community inclusion. For this review, we analyzed peer-reviewed journal papers and grey literature that focused on LAC community capacity building for people with disability in a disability service context published between 2000 and August 2023. Of the 17 publications that met the inclusion criteria, there was no published evidence that comprehensively examined or measured community capacity building consistent with the tenets of the CCF. However, our analysis showed that all capitals, with the exception of natural capital, had been considered, with some indication that investment in these capitals (particularly social capital) could be connected in the positive spiraling way suggested by the CCF. Given the paucity of existing evidence to inform the LAC aspiration for community capacity building, research informed by consumer priorities is needed to inform LAC and service navigation practices to address community needs. The CCF has the potential to develop our understanding of LAC and other community capacity-building initiatives through the measurement of LAC and service navigation services and consumer outcomes, as well as by informing investment to target growth capitals in communities. [ABSTRACT FROM AUTHOR]

Interprofessional collaboration (IPC) in stroke care is accepted as best practice and necessary given the multi-system challenges and array of professionals involved. Our two-part stroke team simulations offer an intentional interprofessional educational experience (IPE) embedded in pre-licensure occupational therapy, physical therapy, pharmacy, medicine, nursing and speech-language pathology curricula. This six-year mixed method program evaluation aimed to determine if simulation delivery differences necessitated by COVID-19 impacted students' IPC perception, ratings, and reported learning. Following both simulations, the Interprofessional Collaborative Competency Assessment Scale (ICCAS) and free-text self-reported learning was voluntarily and anonymously collected. A factorial ANOVA using the ICCAS interprofessional competency factors compared scores across delivery methods. Content and category analysis was done for free-text responses. Overall, delivery formats did not affect positive changes in pre-post ICCAS scores. However, pre and post ICCAS scores were significantly different for interprofessional competencies of roles/responsibilities and collaborative patient/family centered approach. Analysis of over 10,000 written response to four open-ended questions revealed the simulation designs evoked better understanding of others' and own scope of practice, how roles and shared leadership change based on context and client need, and the value of each team member's expertise. Virtual-experience-only students noted preference for an in-person stroke clinic simulation opportunity. [ABSTRACT FROM AUTHOR]

Background: Many older people are now living with co‐occurring physical and mental health disorders, but these often managed separately. The aim of this systematic review was to explore integrated physical‐mental health care services available internationally for older people living with mental health diagnoses, and whether these result in improved health outcomes. Methods: Medline, Embase, CINAHL, PsycINFO and Scopus were searched with a predefined search strategy (PROSPERO: CRD42022383824), generating 6210 articles. Studies were included where an integrated physical‐mental health care service model was utilised in a population of older people (aged >60 years) with a mental health diagnosis (including dementia or cognitive impairment) and at least one concomitant physical health condition requiring physical health care input. All studies were assessed for risk of bias (ROB 2.0, ROBINS‐I) and results were synthesised narratively. Results: Nine studies were included across inpatient (n = 6, 1262 patients) and community (n = 3, 466 patients) settings. Studies were rated as low‐moderate risk of bias. These covered joint physical‐mental health wards, liaison services, embedded physicians in mental health wards, and joint multidisciplinary teams. Services with greater integration (e.g., joint wards) had more benefits for patients and carers. There were few benefits to traditional outcomes (e.g., hospital admissions, mortality), but greater care quality, carer satisfaction, and improved mood and engagement were demonstrated. Conclusions: Multidisciplinary integrated care resulted in improvement of a range of health outcomes for older people with combined physical and mental health needs. Larger and more robust studies are needed to explore the development of these service models further, with cost‐effectiveness analyses. [ABSTRACT FROM AUTHOR]

The article outlines the British Society for Haematology's guidelines for investigating and managing antiphospholipid syndrome (APS), an autoimmune disease linked to thrombosis and pregnancy complications. Diagnosis requires clinical events and detection of antiphospholipid antibodies on multiple occasions. It covers the pathophysiology, clinical signs, and lab tests for APS, with specific recommendations for managing patients in different scenarios, like surgery or pregnancy. The guidance stresses accurate testing, tailored treatment plans, and a holistic approach considering individual risks and needs. [Extracted from the article]

Impact statementThe original paper provides a suggested pathway of investigative criteria to determine viability and pathogenicity of agents detected by molecular methods in fish for the purpose of interpreting biological significance for fish health management. This response defends this position regarding the requirement of certain scientific facts to determine the importance of a particular molecular discovery. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review summarizes key implementation strategies to advance oral and long-acting PrEP delivery for unstably housed people in the United States. Recent Findings: People experiencing homelessness and housing instability face barriers to PrEP uptake and adherence including lack of safe medication storage, competing basic needs, insurances issues, and/or mental health or substance use disorders. Recent advancements in HIV treatment and prevention provide evidence on high-touch, low-barrier implementation approaches to address these challenges. We compiled these approaches into a multi-component implementation strategy, “SHELTER”, which includes: low-barrier primary care, case management, incentives, outreach, care coordination, multidisciplinary provider collaboration, data tracking, and robust provider-patient relationships. Summary: The US has fallen short of our Ending the Epidemic targets, in part due to challenges in PrEP delivery for people experiencing housing instability. SHELTER provides a comprehensive approach for considering critical components of HIV prevention for this population that can be used in future oral and long-acting PrEP programs. [ABSTRACT FROM AUTHOR]

Improved sustainability of aquaculture can be achieved by reducing product wastage post-harvest. Aquaculture of the green-lipped mussel, Perna canaliculus, is an important industry for New Zealand, which increasingly exports to live markets. Live transport can keep mussels fresh, but mussels could also be susceptible to handling stresses. To remedy this, pre-treatments that make mussels metabolically depressed, and thus potentially less sensitive to external stressors, were explored. As indicators of depressed metabolism, heart rate (HR), inferred cardiac output (PCO), and relative gaping magnitude (RGM) were simultaneously monitored in mussels experiencing different temperatures, dissolved oxygen levels and anaesthetic (MgCl2) concentrations to compare their efficacy in inducing suppressed metabolism of adult P. canaliculus. We found complex interactions between HR, PCO, and RGM in response to these conditions; however, overall, these response variables were significantly correlated. Mussels showed depressed HR and PCO by up to 100% at 4 °C within 2 h, with correspondingly decreased RGM of up to 48%. Similarly, mussels immersed in 40 g L−1 MgCl2 suppressed HR by up to 97%, accompanied by up to 76% decrease in PCO, and a slight increase in RGM (11%) after 2 h. While responses were variable, low DO levels suppressed HR by up to 50%, yet PCO and RGM increased two- and threefold relative to control groups. The results of the present study indicated that 4 °C and 40 g MgCl2 L−1 were more effective conditions as pre-treatments than low dissolved oxygen lower the metabolism of P. canaliculus before live transport. [ABSTRACT FROM AUTHOR]

Key message: We revealed the neglected genetic relationships of resistance for six major wheat diseases and established a haploblock-based catalogue with novel forms of resistance by multi-trait haplotype characterisation. Genetic potential to improve multiple disease resistance was highlighted through haplotype stacking simulations. Wheat production is threatened by numerous fungal diseases, but the potential to breed for multiple disease resistance (MDR) mechanisms is yet to be explored. Here, significant global genetic correlations and underlying local genomic regions were identified in the Vavilov wheat diversity panel for six major fungal diseases, including biotrophic leaf rust (LR), yellow rust (YR), stem rust (SR), hemibiotrophic crown rot (CR), and necrotrophic tan spot (TS) and Septoria nodorum blotch (SNB). By adopting haplotype-based local genomic estimated breeding values, derived from an integrated set of 34,899 SNP and DArT markers, we established a novel haplotype catalogue for resistance to the six diseases in over 20 field experiments across Australia and Ethiopia. Haploblocks with high variances of haplotype effects in all environments were identified for three rusts, and pleiotropic haploblocks were identified for at least two diseases, with four haploblocks affecting all six diseases. Through simulation, we demonstrated that stacking optimal haplotypes for one disease could improve resistance substantially, but indirectly affected resistance for other five diseases, which varied depending on the genetic correlation with the non-target disease trait. On the other hand, our simulation results combining beneficial haplotypes for all diseases increased resistance to LR, YR, SR, CR, TS, and SNB, by up to 48.1%, 35.2%, 29.1%, 12.8%, 18.8%, and 32.8%, respectively. Overall, our results highlight the genetic potential to improve MDR in wheat. The haploblock-based catalogue with novel forms of resistance provides a useful resource to guide desirable haplotype stacking for breeding future wheat cultivars with MDR. [ABSTRACT FROM AUTHOR]