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Extremely severe nausea was experienced by four subjects positioned prone on a 7T scanner table with their arm extended overhead for a wrist examination and their head positioned approximately 10-20 cm above the magnet's central axis. Movement through the large static and spatial field gradients of current 7T MRI scanner magnets typically causes mild vestibular activation which is well tolerated by most individuals. However, when positioned off-axis, the head moves through regions of even larger and more rapidly changing magnetic fields which in the current study were sufficient to induce the extremely severe nausea. Ensuring the head remains on-axis mitigates this effect., (© 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Vascular leakage is a deadly complication of severe infections, ranging from bacterial sepsis to malaria. Worldwide, septicemia is among the top 10 causes of lethality because of the shock and multiorgan dysfunction that arise from the host vascular response. In the monoclonal gammopathy-associated capillary leak syndrome (MG-CLS), even otherwise mundane infections induce recurrent septic-like episodes of profound microvascular hyperpermeability and shock. There are no defined genetic risk factors for MG-CLS or effective treatments for acute crises., Methods: We characterized predicted loss-of-function mutations in PARP15 (poly[ADP-ribose] polymerase 15), a protein of unknown function that is absent in mice, in patients with MG-CLS. We analyzed barrier function in PARP15-deficient vascular endothelial cells and vascular leakage in mice engineered to express WT or loss-of-function variant human PARP15., Results: We discovered several loss-of-function PARP15 variants associated with MG-CLS. These mutations severely reduced PARP15 enzymatic function. The presence of the most frequently detected variant (G628R) correlated with clinical markers of severe vascular leakage. In human microvascular endothelial cells, PARP15 suppressed cytokine-induced barrier disruption by ADP-ribosylating the scaffold protein JIP3 (c-Jun N-terminal kinase-interacting protein 3) and inhibiting p38 MAP kinase activation. Mice expressing enzymatically inactive human PARP15(G628R) were significantly more prone to inflammation-associated vascular leakage than mice expressing WT PARP15 in a p38-dependent fashion., Conclusions: PARP15 represents a previously unrecognized genetic susceptibility factor for MG-CLS. PARP15-mediated ADP ribosylation is an essential and genetically determined mechanism of the human vascular response to inflammation.

Abstract: We describe here the impact of managing coronavirus disease 2019 (COVID-19) outbreaks, during January-August 2022, in residential aged care facilities (RACFs) in Central Queensland, Australia, following the deployment of a public health rapid response team (PHRRT, comprising a medical officer, a communicable disease nurse, and an epidemiologist) from a regional public health unit (PHU). Our existing vaccine preventable diseases surveillance framework was used in identifying any symptomatic resident, triggering a PHRRT response. We found that the Hospital in the Home (HiTH) admission and death events were significantly lower after the introduction of the PHRRT than in the outbreaks that occurred before. Based on our experience with a PHRRT-led approach in mitigating the burden of outbreaks, we recommend regular reflection on optimising resources and practices in RACFs. Effective communication from PHUs can improve the RACFs' preparedness and capacity to respond, and can inform the best practice model to protect the highly susceptible elderly residents and their staff., (© Commonwealth of Australia CC BY-NC-ND.)

The Hessian fly, Mayetiola destructor (Say) belonging to the order Diptera (family: Cecidomyiidae), is a destructive pest of host wheat (Triticum aestivum L.) causing significant economic losses. Although planting resistant wheat cultivars harboring an effective Hessian fly resistance gene (H) is the most economical and environmentally friendly pest management strategy, it imposes selection pressure on the insect populations and can lead to the evolution of Hessian fly virulence. This results in the eventual failure of the deployed H gene. New sources and novel types of resistance are urgently needed to expand the repertoire of H genes and enable strategies that are more effective and durable over the long-term. New sources of Hessian fly resistance have been identified from tetraploid (T. turgidum L., AABB) and hexaploid (T. aestivum, AABBDD) wheat species, as well as from wheat's D-genome donor (Aegilops tauschii Coss., DD). In contrast, diploid einkorn wheat (T. monococcum L., AA) has not been extensively explored for Hessian fly resistance. In this study, we phenotyped 506 T. monococcum accessions belonging to 2 subspecies, T. monococcum L. subsp. monococcum (205 accessions) and T. monococcum subsp. aegilopoides (Link) Thell. (301 accessions), for resistance against 2 predominant Hessian fly biotypes, L and GP (Great Plains). Three and 6 accessions belonging to subsp. monococcum and aegilopoides, respectively, showed > 70% resistance. These accessions provide additional resources for improving wheat cultivars as mitigating strategies for Hessian fly management., (Published by Oxford University Press on behalf of Entomological Society of America 2024.)

The octanol-air partition ratio (K OA ) is a fundamental property used for screening chemicals for concern, depending on their potential to bioaccumulate and harm living systems. With millions of chemicals used in commerce, unfortunately, less than 800 compounds currently have experimentally measured K OA values due to limitations in traditional measurement techniques. We aimed to develop a direct gas chromatography retention time (GC-RT) method using a custom-packed column, with octanol as the stationary phase, for rapidly measuring K OA . We installed the column into a GC-mass spectrometry system and isothermally measured retention times of 15 volatile organic compounds. We calculated K OA values at experimental temperatures from the retention times and extrapolated the results to values at 25 °C using the Van't Hoff equation. Our directly measured log K OA values at 25 °C spanned 3.66 log units (0.820-4.48). Except for alcohols, our measured values agree with literature log K OA values (root mean square error, RMSE = 0.50). The discrepancy probably arose from differences in how well our method versus the literature methods capture measurement artifacts, specifically, gas-phase adsorption to the octanol phase and hydrogen bonding interactions. This proof-of-concept study demonstrates that our direct GC-RT method is promising for rapidly measuring K OA to support chemical risk assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Alzheimer's disease (AD) is characterized by autobiographical memory deficits, with the ability to retrieve episodic-rich memories being particularly affected. Here, we investigated the influence of AD on a specific subtype of episodic memories known as flashbulb memories (i.e., the ability to remember the personal circumstances for the reception of important news events). We examined the frequency, characteristics, and the temporal distribution of flashbulb memories across the life span. To this aim, 28 older adults diagnosed with AD and a matched sample of 29 healthy older controls were probed for flashbulb memories for two historical events from each decade of their lives. They also estimated the subjective degree of reexperiencing for the memories reported. AD participants showed impaired access to flashbulb memories, the frequency of reported memories being lower than for healthy older adults. However, qualitative aspects of AD participants' flashbulb memories were quite similar to those of the controls, as no group differences were obtained with respect to the canonical categories or degree of reexperience. AD participants' flashbulb memories clustered during the early years of their life, consistent with a reminiscence bump, whereas healthy controls also reported memories dated to later lifetime periods. Our results suggest that probing for personal memories of important public events may serve as a powerful cue for detailed episodic memories in AD., (© 2024. The Author(s).)

Purpose: To explore the independent associations between adherence to a Mediterranean-style diet and severity of menopausal symptoms in perimenopausal and menopausal women living in Australia., Methods: Dietary adherence was assessed using the Mediterranean Diet Adherence Screener (MEDAS), the Menopause Rating Scale (MRS) was used to assess the severity of menopausal symptoms, and the 36-item short form survey instrument (SF-36) was used to assess health-related quality of life (HRQoL)., Results: A total of n = 207 participants (50.7 ± 4.3 years; BMI: 28.0 ± 7.4 kg/m2) were included in the final analyses. Participants reported low-moderate adherence to a Mediterranean-style diet (5.2 ± 1.8; range: 1-11). Adherence was not associated with severity of menopausal symptoms. However, low consumption of sugar-sweetened beverages was inversely associated with joint and muscle complaints, independent of all covariates (β = -0.149; CI: -0.118, -0.022; P = 0.042). Adherence to a Mediterranean-style diet was positively associated with the physical function subscale of HRQoL (β = 0.173, CI: 0.001, 0.029; P = 0.031) and a low intake of red and processed meat was positively associated with the general health subscale (β = 0.296, CI: 0.005, 0.014; P = < 0.001)., Conclusion: Diet quality may be related to severity of menopausal symptoms and HRQoL in perimenopausal and menopausal women. However, exploration of these findings using longitudinal analyses and robust clinical trials are needed to better elucidate these findings., (© 2024. The Author(s).)

Treatment plan quality is a crucial component for a successful outcome of radiation therapy treatments. As the complexity of radiation therapy planning and delivery techniques increases, the role of the medical physicist in assessing treatment plan quality becomes more critical. Integrating plan quality review throughout the treatment planning process allows improvements without delaying treatment or rushing to produce changes at the last minute. In this work, we aim to provide practical check items for physicists to reference when assessing treatment plan quality with a critical eye, asking questions such as "is this the best dose distribution feasible for this patient?," "could we change any planning parameters to improve plan quality?," and "could we change the planning strategy for this particular patient or for future patients?"; and to work with planners and physicians to create a multidisciplinary collaborative culture that achieves the best plan feasible for every patient. We tabulate the features that affect plan quality in each process step and check details for individual items. This report is aimed at medical physicists, planners, radiation oncologists, and other professionals who are involved in treatment planning., Competing Interests: Disclosures James A. Kavanaugh reports receiving honoraria from Varian Medical. Dustin Jacqmin reports receiving payment from ASTRO/Veteran's Health Administration and holds an unpaid leadership role as Chair of the Working Group on Treatment Planning at AAPM. Sean L. Berry reports received honoraria from RAMPS, the NYC chapter of the AAPM. The other authors have no conflicts of interest to declare., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2 , which encodes G αi2 , a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase-mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating G αi2 mutations had clinical presentations that included impaired immunity. Mutant G αi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant G αi2 influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)-activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-AKT S6 signaling to drive cellular growth and proliferation.

Background: Beginning in 2006, neuroradiologists became increasingly aware of the risk of nephrogenic system fibrosis (NSF) when patients suffering from chronic kidney disease (CKD) received gadolinium-based contrast agents (GBCAs) in conjunction with MRI scans. Radiology practices began withholding GBCAs from MRI patients with substantial CKD and instated a variety of safety measures to ensure that these individuals did not inadvertently receive GBCAs. As a result, the worldwide incidence of NSF was dramatically reduced. Since that time, a wealth of research on NSF and its etiology has found few unconfounded cases associated with those GBCAs categorized as Group II agents by the American College of Radiology., Methods: In 2023 and 2024, members of the American Society of Neuroradiology (ASNR) Standards and Guidelines Committee reviewed new research evidence on GBCA safety and its relevance to current MRI contrast administration guidelines for patients with CKD. This focused on systematic reviews and meta-analyses conducted during the past five years. Upon consideration of this literature, recommendations for administration of GBCAs to patients with CKD were formulated., Key Message: For neuroimaging applications, the ASNR recommends that Group II GBCAs no longer be withheld in patients with CKD when these agents are medically indicated for diagnosis. Moreover, if Group II GBCAs are exclusively used in an MRI practice, other safety measures such as checking renal function or querying patients about chronic kidney disease can be discontinued., Abbreviations: ACR = American College of Radiology; ASNR = American Society of Neuroradiology; CKD = chronic kidney disease; GBCA = gadolinium-based contrast agent; NSF = nephrogenic systemic fibrosis., Competing Interests: C.S. has served as an expert witness on the topic of MRI safety. K.M.W., D.J., A.W.K., D.S.L., A.M.S., N.Y., and J.E.J. declare no conflicts of interest related to the content of this article., (© 2024 by American Journal of Neuroradiology.)

Acute pulmonary embolism (PE) is a potentially life-threatening condition that causes abrupt obstruction of the pulmonary arteries, leading to acute right heart failure. Novel diagnostic methods and catheter-directed therapies are being developed rapidly, and there is an obvious need for a realistic PE animal model that can be used for pathophysiological evaluation and preclinical testing. This protocol introduces a porcine model employing large autologous pulmonary emboli. Instrumentations are performed with minimally invasive techniques, creating a close-chest model that enables the investigation of various treatment options with high reproducibility. Three hours after drawing blood to create autologous emboli ex vivo, the induction of PE caused an immediate increase in the mean pulmonary arterial pressure (17 ± 3 mmHg to 33 ± 6 mmHg, p < 0.0001) and heart rate (50 ± 9 beats·min -1 to 63 ± 6 beats·min -1 , p < 0.0003) accompanied by a decreased cardiac output (5.0 ± 0.8 L/min to 4.5 ± 0.9 L/min, p < 0.037) compared to baseline. The CT pulmonary angiography revealed multiple emboli, and the pulmonary obstruction percentage was increased compared to baseline (0% [0-0] to 57.1% [38.8-63.3], p < 0.0001). In the acute phase, the phenotype is comparable to intermediate-risk PE. The model represents a realistic and well-characterized phenotype of intermediate-risk PE and creates an opportunity to test novel diagnostic methods, interventional and pharmaceutical treatments, and hands-on training for healthcare workers in interventional procedures.

Near-fluorescent (NIR) dyes that absorb and emit light in the wavelength range of 650-1700 nm are well-suited for bioimaging due to the improved image contrast and increased penetration of the long-wavelength light through biological tissue. However, the imaging performance of NIR fluorescent dyes is limited by several inherent photophysical and physicochemical properties including, low fluorescence quantum yield, high chemical and photochemical reactivity, propensity to self-aggregate in water, non-specific association with off-target biological sites, and non-optimal pharmacokinetic profiles in living subjects. In principle, all these drawbacks can be alleviated by steric protection which is a structural process that surrounds the fluorophore with bulky groups that block undesired intermolecular interactions. The literature methods to sterically protect a long-wavelength dye can be separated into two general strategies, non-covalent dye encapsulation and covalent steric appendage. Illustrative examples of each method show how steric protection improves bioimaging performance by providing: (a) increased fluorescence brightness, (b) higher fluorophore ground state stability, (c) decreased photobleaching, and (d) superior pharmacokinetic profile. Some sterically protected dyes are commercially available and further success with future systems will require experts in chemistry, microscopy, cell biology, medical imaging, and clinical medicine to work closely as interdisciplinary teams.

Objectives: To compare in-hospital mortality and intensive care unit (ICU) length of stay for people admitted to Australian and New Zealand ICUs during 2022-23 with coronavirus disease 2019 (COVID-19) pneumonitis, incidental or exacerbating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, or without SAR-CoV-2 infections., Study Design: Retrospective cohort study; analysis of Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database data., Setting, Participants: Adults (16 years or older) admitted to participating ICUs in Australia or New Zealand, 1 January 2022 - 30 June 2023., Major Outcome Measures: The primary outcome was in-hospital mortality, the secondary outcome ICU length of stay, each by SARS-CoV-2 infection attribution classification: primary COVID-19; exacerbating SARS-CoV-2 infection (SARS-CoV-2 infection was a contributing factor to the primary cause of ICU admission); incidental SARS-CoV-2 infections (SARS-CoV-2 infection detected during ICU admission but did not contribute to admission diagnosis); no SARS-CoV-2 infection., Results: A total of 207 684 adults were admitted to 195 Australian and New Zealand ICUs during 2022-23; 2674 people (1.3%) had incidental SARS-CoV-2 infections, 4923 (2.4%) exacerbating infections, and 3620 (1.7%) primary COVID-19. Unadjusted in-hospital mortality for people with incidental SARS-CoV-2 infections (288 deaths, 10.8%) was lower than for those with exacerbating infections (928 deaths, 18.8%) or primary COVID-19 (830 deaths, 22.9%), but higher than for patients without SARS-CoV-2 infections (15 486 deaths, 7.9%). After adjusting for illness severity, frailty, geographic region, and type of hospital, mortality was higher for patients with incidental SARS-CoV-2 infections (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.10-1.50), exacerbating infections (aOR, 1.35; 95% CI, 1.22-1.48), or primary COVID-19 (aOR, 2.54; 95% CI, 2.30-2.81) than for patients without SARS-CoV-2 infections. After adjusting for diagnosis and illness severity, ICU stays were longer for people with incidental (mean difference, 3.3 hours; 95% CI, 2.4-4.2 hours) or exacerbating infections (0.8 hours; 95% CI, 0.2-1.5 hours) than for those without SARS-CoV-2 infections., Conclusion: Risk-adjusted in-hospital mortality and ICU length of stay are higher for people admitted to intensive care who have concomitant SARS-CoV-2 infections than for people who do not., (© 2024 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cunningham, Kirk, Hong, Yang, Howard, Brearley, Sáenz-Trevizo, Krawchuck, Watt, Henderson, Dokladny, DeAguero, Escobar and Wagner.)

Introduction: As the world's population ages, there has been increasing attention to developing health policies to support older adults. Engaging older adults in policy-making is one way to ensure that policy decisions align with their needs and priorities. However, ageist stereotypes often underestimate older adults' ability to participate in such initiatives. This scoping review aims to describe the characteristics and impacts of public engagement initiatives designed to help inform health policy-making for older adults., Methods: A systematic search of peer-reviewed and grey literature (English only) describing public engagement initiatives in health policy-making for older adults was conducted using six electronic databases, Google and the Participedia website. No geographical, methodological or time restrictions were applied to the search. Eligibility criteria were purposefully broad to capture a wide array of relevant engagement initiatives. The outcomes of interest included participants, engagement methods and reported impacts., Results: This review included 38 papers. The majority of public engagement initiatives were funded or initiated by governments or government agencies as a formal activity to address policy issues, compared to initiatives without a clear link to a specific policy-making process (e.g., research projects). While most initiatives engaged older adults as target participants, there was limited reporting on efforts to achieve participant diversity. Consultation-type engagement activities were most prevalent, compared to deliberative and collaborative approaches. Impacts of public engagement were frequently reported without formal evaluations. Notably, a few articles reported negative impacts of such initiatives., Conclusion: This review describes how public engagement practices have been conducted to help inform health policy-making for older adults and the documented impacts. The findings can assist policymakers, government staff, researchers and seniors' advocates in supporting the design and execution of public engagement initiatives in this policy sector., Patient or Public Contribution: Older adult partners from the McMaster University Collaborative for Health and Aging provided strategic advice throughout the key phases of this review, including developing a review protocol, data charting and synthesis and interpreting and presenting the review findings. This collaborative partnership was an essential aspect of this review, enhancing its relevance and meaningfulness for older adults., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

It is well known that inflammatory markers play an important role in the development and maintenance of healthy pregnancies. However, the literature regarding inflammation in relation to lifestyle and adverse pregnancy outcomes in twin pregnancies is remarkably uncovered. Therefore, this study aimed at evaluating the concentration of inflammatory markers in dried capillary blood spot samples from 523 women with twin pregnancies, included at a median gestational age of 21+1 weeks. The relationship between inflammatory markers and maternal lifestyle (current smoking status and pre-pregnancy body mass index) in addition to adverse pregnancy outcomes (preeclampsia, gestational diabetes mellitus, and small for gestational age) was analyzed. The study showed that active smoking at inclusion was associated with an elevated concentration of interleukin-8. Furthermore, maternal obesity was associated with an elevated concentration of C-reactive protein and monocyte chemoattractant protein-1. Analysis of the data showed no statistically significant variations in the concentration of the assessed inflammatory markers for neither preeclampsia, gestational diabetes mellitus, nor small for gestational age. The current study promotes future research on the pathophysiology of twin pregnancies in relation to adverse pregnancy outcomes, as the literature within the area remains scarce., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: Disease surveillance data was critical in supporting public health decisions throughout the coronavirus disease 2019 (COVID-19) pandemic. At the same time, the unprecedented circumstances of the pandemic revealed many shortcomings of surveillance systems for viral respiratory pathogens. Strengthening of surveillance systems was identified as a priority for the recently established Australian Centre for Disease Control, which represents a critical opportunity to review pre-pandemic and pandemic surveillance practices, and to decide on future priorities, during both pandemic and inter-pandemic periods. On 20 October 2022, we ran a workshop with experts from the academic and government sectors who had contributed to the COVID-19 response in Australia on 'The role of surveillance in epidemic response', at the University of New South Wales, Sydney, Australia. Following the workshop, we developed five recommendations to strengthen respiratory virus surveillance systems in Australia, which we present here. Our recommendations are not intended to be exhaustive. We instead chose to focus on data types that are highly valuable yet typically overlooked by surveillance planners. Three of the recommendations focus on data collection activities that support the monitoring and prediction of disease impact and the effectiveness of interventions (what to measure) and two focus on surveillance methods and capabilities (how to measure). Implementation of our recommendations would enable more robust, timely, and impactful epidemic analysis., (© Commonwealth of Australia CC BY-NC-ND.)

Objective: To evaluate the effectiveness of behavioural interventions that include motivational interviewing on physical activity outcomes in adults., Design: Systematic review and meta-analysis., Study Selection: A search of seven databases for randomised controlled trials published from inception to 1 March 2023 comparing a behavioural intervention including motivational interviewing with a comparator without motivational interviewing on physical activity outcomes in adults. Outcomes of interest were differences in change in quantitative measures of total physical activity, moderate to vigorous physical activity (MVPA), and sedentary time., Data Extraction and Synthesis: Two reviewers extracted data and assessed risk of bias. Population characteristics, intervention components, comparison groups, and outcomes of studies were summarised. For overall main effects, random effects meta-analyses were used to report standardised mean differences (SMDs) and 95% confidence intervals (CIs). Differential effects based on duration of follow-up, comparator type, intervention duration, and disease or health condition of participants were also examined., Results: 129 papers reporting 97 randomised controlled trials totalling 27 811 participants and 105 comparisons were included. Interventions including motivational interviewing were superior to comparators for increases in total physical activity (SMD 0.45, 95% CI 0.33 to 0.65, equivalent to 1323 extra steps/day; low certainty evidence) and MVPA (0.45, 0.19 to 0.71, equivalent to 95 extra min/week; very low certainty evidence) and for reductions in sedentary time (-0.58, -1.03 to -0.14, equivalent to -51 min/day; very low certainty evidence). Evidence for a difference in any outcome compared with comparators of similar intensity was lacking. The magnitude of effect diminished over time, and evidence of an effect of motivational interviewing beyond one year was lacking. Most interventions involved patients with a specific health condition, and evidence of an effect of motivational interviewing to increase MVPA or decrease sedentary time was lacking in general population samples., Conclusions: Certainty of the evidence using motivational interviewing as part of complex behavioural interventions for promoting total physical activity in adults was low, and for MVPA and sedentary time was very low. The totality of evidence suggests that although interventions with motivational interviewing increase physical activity and decrease sedentary behaviour, no difference was found in studies where the effect of motivational interviewing could be isolated. Effectiveness waned over time, with no evidence of a benefit of motivational interviewing to increase physical activity beyond one year., Systematic Review Registration: PROSPERO CRD42020219881., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research (NIHR) Biomedical Research Centres at Oxford University Hospitals and Oxford Health, and NIHR Applied Research in Collaboration Oxford and Thames Valley for the work reported; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The Data-informed Stepped Care (DiSC) study is a cluster-randomized trial implemented in 24 HIV care clinics in Kenya, aimed at improving retention in care for adolescents and youth living with HIV (AYLHIV). DiSC is a multi-component intervention that assigns AYLHIV to different intensity (steps) of services according to risk. We used the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) to characterize provider-identified adaptations to the implementation of DiSC to optimize uptake and delivery, and determine the influence on implementation outcomes., Methods: Between May and December 2022, we conducted continuous quality improvement (CQI) meetings with providers to optimize DiSC implementation at 12 intervention sites. The meetings were guided by plan-do-study-act processes to identify challenges during early phase implementation and propose targeted adaptations. Meetings were audio-recorded and analysed using FRAME to categorize the level, context and content of planned adaptations and determine if adaptations were fidelity consistent. Providers completed surveys to quantify perceptions of DiSC acceptability, appropriateness and feasibility. Mixed effects linear regression models were used to evaluate these implementation outcomes over time., Results: Providers participated in eight CQI meetings per facility over a 6-month period. A total of 65 adaptations were included in the analysis. The majority focused on optimizing the integration of DiSC within the clinic (83%, n = 54), and consisted of improving documentation, addressing scheduling challenges and improving clinic workflow. Primary reasons for adaptation were to align delivery with AYLHIV needs and preferences and to increase reach among AYLHIV: with reminder calls to AYLHIV, collaborating with schools to ensure AYLHIV attended clinic appointments and addressing transportation challenges. All adaptations to optimize DiSC implementation were fidelity-consistent. Provider perceptions of implementation were consistently high throughout the process, and on average, slightly improved each month for intervention acceptability (β = 0.011, 95% CI: 0.002, 0.020, p = 0.016), appropriateness (β = 0.012, 95% CI: 0.007, 0.027, p<0.001) and feasibility (β = 0.013, 95% CI: 0.004, 0.022, p = 0.005)., Conclusions: Provider-identified adaptations targeted improved integration into routine clinic practices and aimed to reduce barriers to service access unique to AYLHIV. Characterizing types of adaptations and adaptation rationale may enrich our understanding of the implementation context and improve abilities to tailor implementation strategies when scaling to new settings., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Abstract: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Little is known about the epidemiology, burden, and seasonality of RSV in subtropical regions of Australia like Central Queensland. This information is important to plan prevention strategies, including therapeutics, future vaccines, and health system preparedness. We collected data on laboratory-confirmed RSV cases and admissions in Central Queensland for the period 1 July 2021 to 31 December 2022. From July 2021, RSV was listed as a nationally notifiable condition on laboratory-confirmed diagnosis. During the study period, 1,142 laboratory-confirmed cases of RSV (50.0% female sex) were reported, with 169 cases (14.8%) requiring hospital admission, 12 of which (7.1%) required intensive care unit/high dependency unit admissions; two deaths occurred. Of cases requiring hospital admission, RSV was listed as the primary diagnosis in 113/169 cases (66.9%); 63/169 admitted cases (37.3%) had a major comorbidity. Of all cases, 55.4% were in children < 5 years of age (20.9% hospitalised); 35.7% in children < 2 years of age (24.3% hospitalised), and 19.1% in children < 12 months of age (27.5% hospitalised). Children under five years of age made up 78.1% of admissions, a rate of 9.0 admissions per 1,000 children over the 18-month study period, with an average age of 15.8 months (standard deviation, SD: 13.1 months) in this cohort. Indigenous children aged < 5 years were over-represented in cases (rate ratio, RR: 1.6; 95% confidence interval [95% CI]: 1.3-1.9) and admissions (RR: 1.6; 95% CI: 1.0-2.4). Antibiotics were prescribed to 48.5% of admitted cases under two years of age, despite documented bacterial infection in only 26.3% of these cases; antibiotic prescription was significantly higher in those who received a chest X-ray (p < 0.001). Of all cases, 33.5% occurred in July 2022 alone, with greater than 75.0% of cases occurring during June-August 2022. RSV showed year-round activity with a distinctive winter peak in 2022; however, this season was likely affected by coronavirus disease 2019 (COVID-19) restrictions and behaviours. Ongoing surveillance is required to better understand the epidemiology and seasonality of RSV in Central Queensland., (© Commonwealth of Australia CC BY-NC-ND.)

Rapid and accessible testing was paramount in the management of the COVID-19 pandemic. Our university established KCL TEST: a SARS-CoV-2 asymptomatic testing programme that enabled sensitive and accessible PCR testing of SARS-CoV-2 RNA in saliva. Here, we describe our learnings and provide our blueprint for launching diagnostic laboratories, particularly in low-resource settings. Between December 2020 and July 2022, we performed 158277 PCRs for our staff, students, and their household contacts, free of charge. Our average turnaround time was 16 h and 37 min from user registration to result delivery. KCL TEST combined open-source automation and in-house non-commercial reagents, which allows for rapid implementation and repurposing. Importantly, our data parallel those of the UK Office for National Statistics, though we detected a lower positive rate and virtually no delta wave. Our observations strongly support regular asymptomatic community testing as an important measure for decreasing outbreaks and providing safe working spaces. Universities can therefore provide agile, resilient, and accurate testing that reflects the infection rate and trend of the general population. Our findings call for the early integration of academic institutions in pandemic preparedness, with capabilities to rapidly deploy highly skilled staff, as well as develop, test, and accommodate efficient low-cost pipelines., (© The Author(s) 2024. Published by Oxford University Press.)

Background: One-third of people with depression do not respond to antidepressants, and, after two adequate courses of antidepressants, are classified as having treatment-resistant depression (TRD). Some case reports suggest that ketogenic diets (KDs) may improve some mental illnesses, and preclinical data indicate that KDs can influence brain reward signalling, anhedonia, cortisol, and gut microbiome which are associated with depression. To date, no trials have examined the clinical effect of a KD on TRD., Methods: This is a proof-of-concept randomised controlled trial to investigate the efficacy of a six-week programme of weekly dietitian counselling plus provision of KD meals, compared with an intervention involving similar dietetic contact time and promoting a healthy diet with increased vegetable consumption and reduction in saturated fat, plus food vouchers to purchase healthier items. At 12 weeks we will assess whether participants have continued to follow the assigned diet. The primary outcome is the difference between groups in the change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 6 weeks. PHQ-9 will be measured at weeks 2, 4, 6 and 12. The secondary outcomes are the differences between groups in the change in remission of depression, change in anxiety score, functioning ability, quality of life, cognitive performance, reward sensitivity, and anhedonia from baseline to 6 and 12 weeks. We will also assess whether changes in reward sensitivity, anhedonia, cortisol awakening response and gut microbiome may explain any changes in depression severity., Discussion: This study will test whether a ketogenic diet is an effective intervention to reduce the severity of depression, anxiety and improve quality of life and functioning ability for people with treatment-resistant depression., Competing Interests: Declaration of competing interest PA and SAJ are investigators on a publicly funded trial where Nestle have donated total diet replacement products to support the trial. All authors revised the manuscript critically for important intellectual content, and read and approved the final manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Echo planar imaging (EPI) is a fast measurement technique commonly used in magnetic resonance imaging (MRI), but is highly sensitive to measurement non-idealities in reconstruction. Point spread function (PSF)-encoded EPI is a multi-shot strategy which alleviates distortion, but acquisition of encodings suitable for direct distortion-free imaging prolongs scan time. In this work, a model-based iterative reconstruction (MBIR) framework is introduced for direct imaging with PSF-EPI to improve image quality and acceleration potential., Methods: An MBIR platform was developed for accelerated PSF-EPI. The reconstruction utilizes a subspace representation, is regularized to promote local low-rankedness (LLR), and uses variable splitting for efficient iteration. Comparisons were made against standard reconstructions from prospectively accelerated PSF-EPI data and with retrospective subsampling. Exploring aggressive partial Fourier acceleration of the PSF-encoding dimension, additional comparisons were made against an extension of Homodyne to direct PSF-EPI in numerical experiments. A neuroradiologists' assessment was completed comparing images reconstructed with MBIR from retrospectively truncated data directly against images obtained with standard reconstructions from non-truncated datasets., Results: Image quality results were consistently superior for MBIR relative to standard and Homodyne reconstructions. As the MBIR signal model and reconstruction allow for arbitrary sampling of the PSF space, random sampling of the PSF-encoding dimension was also demonstrated, with quantitative assessments indicating best performance achieved through nonuniform PSF sampling combined with partial Fourier. With retrospective subsampling, MBIR reconstructs high-quality images from sub-minute scan datasets. MBIR was shown to be superior in a neuroradiologists' assessment with respect to three of five performance criteria, with equivalence for the remaining two., Conclusions: A novel image reconstruction framework is introduced for direct imaging with PSF-EPI, enabling arbitrary PSF space sampling and reconstruction of diagnostic-quality images from highly accelerated PSF-encoded EPI data., Competing Interests: Declaration of competing interest MAB and JDT acknowledge the following interest: Mayo Clinic has licensed IP related to the compact 3T to GE Healthcare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The identification of somatic RB1 variation is crucial to confirm the heritability of retinoblastoma. We and others have previously shown that, when tumour DNA is unavailable, cell-free DNA (cfDNA) derived from aqueous humour (AH) can be used to identify somatic RB1 pathogenic variation. Here we report RB1 pathogenic variant detection, as well as cfDNA concentration in an extended cohort of 75 AH samples from 68 patients. We show cfDNA concentration is highly variable and significantly correlated with the collection point of the AH. Cell-free DNA concentrations above 5 pg/µL enabled the detection of 93% of known or expected RB1 pathogenic variants. In AH samples collected during intravitreal chemotherapy treatment (Tx), the yield of cfDNA above 5 pg/µL and subsequent variant detection was low (≤46%). However, AH collected by an anterior chamber tap after one to three cycles of primary chemotherapy (Dx1+) enabled the detection of 75% of expected pathogenic variants. Further limiting our analysis to Dx1+ samples taken after ≤2 cycles (Dx ≤ 2) provided measurable levels of cfDNA in all cases, and a subsequent variant detection rate of 95%. Early AH sampling is therefore likely to be important in maximising cfDNA concentration and the subsequent detection of somatic RB1 pathogenic variants in retinoblastoma patients undergoing conservative treatment.

Background: The 'PenCS Flu Topbar' app was deployed in Central Queensland (CQ), Australia, medical practices through a pilot programme in March 2021., Methods: We evaluated the app's user experience and examined whether the introduction of 'PenCS Flu Topbar' in medical practices could improve the coverage of NIP-funded influenza vaccinations. We conducted a mixed-method study including a qualitative analysis of in-depth interviews with key end-users and a quantitative analysis of influenza vaccine administrative data., Results: 'PenCS Flu Topbar' app users reported positive experiences identifying patients eligible for NIP-funded seasonal influenza vaccination. A total of 3606 NIP-funded influenza vaccinations was administered in the eight intervention practices, 14% higher than the eight control practices. NIP-funded vaccination coverage within practices was significantly higher in the intervention practices (31.2%) than in the control practices (27.3%) (absolute difference: 3.9%; 95% CI: 2.9%-5.0%; p < 0.001). The coverage was substantially higher in Aboriginal and Torres Strait Islander people aged more than 6 months, pregnant women and children aged 6 months to less than 5 years for the practices where the app was introduced when compared to control practices: incidence rate ratio (IRR) 2.4 (95% CI: 1.8-3.2), IRR 2.7 (95% CI: 1.8-4.2) and IRR 2.3 (1.8-2.9) times higher, respectively., Conclusions: Our evaluation indicated that the 'PenCS Flu Topbar' app is useful for identifying the patients eligible for NIP-funded influenza vaccination and is likely to increase NIP-funded influenza vaccine coverage in the eligible populations. Future impact evaluation including a greater number of practices and a wider geographical area is essential., (© 2024 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Regulators of G protein signaling (RGS) proteins constrain G protein-coupled receptor (GPCR)-mediated and other responses throughout the body primarily, but not exclusively, through their GTPase-activating protein activity. Asthma is a highly prevalent condition characterized by airway hyper-responsiveness (AHR) to environmental stimuli resulting in part from amplified GPCR-mediated airway smooth muscle contraction. Rgs2 or Rgs5 gene deletion in mice enhances AHR and airway smooth muscle contraction, whereas RGS4 KO mice unexpectedly have decreased AHR because of increased production of the bronchodilator prostaglandin E2 (PGE2) by lung epithelial cells. Here, we found that knockin mice harboring Rgs4 alleles encoding a point mutation (N128A) that sharply curtails RGS4 GTPase-activating protein activity had increased AHR, reduced airway PGE2 levels, and augmented GPCR-induced bronchoconstriction compared with either RGS4 KO mice or WT controls. RGS4 interacted with the p85α subunit of PI3K and inhibited PI3K-dependent PGE2 secretion elicited by transforming growth factor beta in airway epithelial cells. Together, these findings suggest that RGS4 affects asthma severity in part by regulating the airway inflammatory milieu in a G protein-independent manner., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Clarkson disease, or monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS), is a rare, relapsing-remitting disorder featuring the abrupt extravasation of fluids and proteins into peripheral tissues, which in turn leads to hypotensive shock, severe hemoconcentration, and hypoalbuminemia. The specific leakage factor(s) and pathways in ISCLS are unknown, and there is no effective treatment for acute flares. Here, we characterize an autonomous vascular endothelial defect in ISCLS that was recapitulated in patient-derived endothelial cells (ECs) in culture and in a mouse model of disease. ISCLS-derived ECs were functionally hyperresponsive to permeability-inducing factors like VEGF and histamine, in part due to increased endothelial nitric oxide synthase (eNOS) activity. eNOS blockade by administration of N(γ)-nitro-l-arginine methyl ester (l-NAME) ameliorated vascular leakage in an SJL/J mouse model of ISCLS induced by histamine or VEGF challenge. eNOS mislocalization and decreased protein phosphatase 2A (PP2A) expression may contribute to eNOS hyperactivation in ISCLS-derived ECs. Our findings provide mechanistic insights into microvascular barrier dysfunction in ISCLS and highlight a potential therapeutic approach.

Objective: We aimed to define the epidemiology of COVID-19 outbreaks in aged care facilities (ACFs) during the postvaccine period, including vaccine effectiveness (VE) for this high-risk group., Design: Systematic review and meta-analysis., Data Sources: Ovid Medline, Ovid Embase, Scopus, Web of Science and Cochrane databases were searched through 1 September 2023., Eligibility Criteria: Any original observational studies and trials reporting data on COVID-19 outbreaks among the partially/fully vaccinated residents from ACFs during or after the worldwide implementation of vaccine roll-out., Data Extraction and Synthesis: We estimated the attack rate, case fatality rate, mortality rate and VE during postvaccine period. Random effect model was adopted for meta-analysis. Quality assessment on all included studies was performed using the Meta Quality Appraisal Tool., Results: 38 articles were included from 12 countries reporting 79 outbreaks with 1708 confirmed cases of COVID-19 from 78 ACFs. The pooled attack rate was 28% (95% CI 20% to 37%) among the fully vaccinated residents. Two-thirds (62.5%) of the index cases were unvaccinated healthcare professionals (eg, physicians, nurses) and caregivers. Unvaccinated residents had a significantly higher rates (12%) (95% CI 7% to 19%) of mortality compared with the vaccinated residents (2%) (95% CI% 1 to 4%) and the post-COVID-19 vaccine estimates for case fatality rate (13% vs 23%) and hospitalisation rate (17% vs 37%) were substantially lower. VE in preventing disease among residents in ACFs was 73% (95% CI 49% to 86). Overall, the included studies were heterogeneous in nature, however, the risk of bias was low to moderate., Conclusions: Our study reaffirmed the impact of vaccination as a key public health measure to minimise the burden of COVID-19 in ACFs. Facilities with higher crowding indexes should be prioritised for vaccination and should advocate for higher vaccination targets among staff and residents as a critical intervention strategy to minimise disease burden in this vulnerable population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The discovery of long-range magnetic ordering in atomically thin materials catapulted the van der Waals (vdW) family of compounds into an unprecedented popularity, leading to potentially important technological applications in magnetic storage and magneto-transport devices, as well as photoelectric sensors. With the potential for the use of vdW materials in space exploration technologies it is critical to understand how the properties of such materials are affected by ionizing proton irradiation. Owing to their robust intra-layer stability and sensitivity to external perturbations, these materials also provide excellent opportunities for studying proton irradiation as a non-destructive tool for controlling their magnetic properties. Specifically, the exfoliable Cr 2 Si 2 Te 6 (CST) is a ferromagnetic semiconductor with the Curie temperature ( T C ) of ∼32 K. Here, we have investigated the magnetic properties of CST upon proton irradiation as a function of fluence (1 × 10 15 , 5 × 10 15 , 1 × 10 16 , 5 × 10 16 , and 1 × 10 18 H + /cm -2 ) by employing variable-temperature, variable-field magnetization measurements, and detail how the magnetization, magnetic anisotropy vary as a function of proton fluence across the magnetic phase transition. While the T C remains constant as a function of proton fluence, we observed that the saturation magnetization and magnetic anisotropy diverge at the proton fluence of 5 × 10 16 H + /cm -2 , which is prominent in the ferromagnetic phase, in particular.This work demonstrates that proton irradiation is a feasible method for modifying the magnetic properties and local magnetic interactions of vdWs crystals, which represents a significant step forward in the design of future spintronic and magneto-electronic applications., (© 2024 IOP Publishing Ltd.)

Ratiometric fluorescent assays have a built-in correction factor which enhances assay accuracy and reliability. We have developed fluorescent ratiometric supramolecular tandem assays for phosphatase and phytase enzymes using a mixture of three molecular components. One of the molecules is a tetra-cationic fluorescence quencher called CalixPyr which can bind and quench the polyanionic pyrene fluorophore, CMP, that emits at 430 nm. Polyphosphates can disrupt the CMP/CalixPyr complex and alter the fluorescence intensity (responsive signal). CalixPyr has no effect on the fluorescence emission of cationic pentamethine cyanine fluorophore, cCy5, which emits at 665 nm and acts as a non-responsive reference signal. The continuous ratiometric fluorescent assay for alkaline phosphatase monitored hydrolytic consumption of adenosine triphosphate (ATP). The continuous ratiometric fluorescent assay for phytase activity monitored hydrolytic consumption of phytate. With further development this latter assay may be useful for high throughput assessment of phytase activity in individual batches of fortified animal feed. It is likely that the three-molecule mixture (CMP, CalixPyr, cCy5) can become a general assay platform for other enzymes that catalyse addition/removal of phosphate groups from appropriate molecular substrates.

Objective: We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer's disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment., Design: Systematic review, Meta-Analysis., Setting: We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023., Participants and Interventions: RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included., Measurement: Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423)., Results: The systematic review included 143 studies ( n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer's Disease Assessment Scale-Cognitive Subscale (SMD = -0.96 [-1.32, -0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity., Conclusion: The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.

Purpose: Dental amalgam contains mercury and is commonly used in dental restorations. The impact of MRI on mercury excretion from dental amalgam is not well understood across clinical field strengths, especially 7T. We investigated the effects of MRI exposure on mercury excretion using fresh, lab-created dental amalgam restorations and in extracted teeth with old, pre-existing restorations., Methods: Donated, unfilled human teeth (n = 120) were restored with amalgam before being stored in saline, artificial saliva, or a dry box prior to MRI scanning. The teeth were placed in individual tubes of fresh artificial saliva and scanned at 1.5T, 3T, or 7T or left unscanned as controls. Mercury concentrations were measured 24-30 h later. Donated teeth with pre-existing restorations (n = 40) were stored in artificial saliva, scanned at 7T or left unscanned as controls, and mercury concentration tested., Results: For teeth extracted and restored in a laboratory, no significant difference was found (F = 2.42, P = 0.072) between mean mercury concentrations of unscanned teeth (13.72 μg/L) and teeth scanned at 1.5T (10.88 μg/L), 3T (12.65 μg/L), or 7T (8.88 μg/L). For teeth extracted with previously placed restorations, no significant difference (P = 0.288) was found between unscanned controls (4.28 μg/L) and teeth scanned at 7T (6.63 μg/L)., Conclusion: MRI of dental amalgam does not significantly increase mercury excretion at 1.5T, 3T, or 7T compared to unscanned teeth. This holds true for controlled laboratory restorations as well as for those placed and lived with prior to extraction and scanning, demonstrating no added risk to the clinical patient or research subject., (© 2023 International Society for Magnetic Resonance in Medicine.)

The National Immunization Survey-Child (NIS-Child) provides annual vaccination coverage estimates in the United States for children aged 19 through 35 months, nationally, for each state, and for select local areas and territories. There is a need for vaccination coverage estimates for smaller geographic areas to support local authority planning and identify counties with potentially low vaccination coverage for possible further intervention. We describe small area estimation methods using 2008-2018 NIS-Child data to generate county-level estimates for children up to two years of age born 2007-2011 and 2012-2016. We applied an empirical best linear unbiased prediction method to combine direct estimates of vaccination coverage with model-based prediction using county-level predictors regarding health and demographic characteristics. We review the predictors commonly selected for the small area models and note multiple predictors related to barriers to vaccination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry , reflectometry , sounding , interferometry , plasma characterization , and ranging . Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world., Competing Interests: Competing InterestsThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s) 2024.)

Vascular dysfunction resulting from endothelial hyperpermeability is a common and important feature of critical illness due to sepsis, trauma, and other conditions associated with acute systemic inflammation. Clarkson disease [monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS)] is a rare, orphan disorder marked by spontaneous and recurrent episodes of hypotensive shock and peripheral edema due to widespread vascular leakage in peripheral tissues. Mortality from acute flares approaches 30% due to lack of effective therapies. We evaluated a monoclonal antibody (4E2) specific for the endothelial receptor tyrosine kinase Tie2 in ISCLS models. 4E2 activated Tie2 in ISCLS patient-derived endothelial cells and reduced baseline and proinflammatory mediator-induced barrier dysfunction. 4E2 also reduced mortality and/or vascular leakage associated with systemic histamine challenge or influenza infection in the SJL/J mouse model of ISCLS. These findings support a critical role for Tie2 dysregulation in ISCLS and highlight a viable therapeutic approach to this catastrophic disorder.

Objectives: Compare two approaches to analyzing time series data-interrupted time series with segmented regression (ITS-SR) and Bayesian structural time series using the CausalImpact R package (BSTS-CI)-highlighting advantages, disadvantages, and implementation considerations., Study Design and Setting: We analyzed electronic health records using each approach to estimate the antibiotic prescribing reduction associated with an educational program delivered to Australian primary care physicians between 2012 and 2017. Two outcomes were considered: antibiotics for upper respiratory tract infections (URTIs) and antibiotics of specified formulations., Results: For URTI indication prescribing, average monthly prescriptions changes were estimated at -4,550; (95% confidence interval, -5,486 to -3,614) and -4,270; (95% credible interval, -5,934 to -2,626) for ITS-SR and BSTS-CI, respectively. Similarly for specified formulation prescribing, monthly average changes were estimated at -7,923; (95% confidence interval, -15,887 to 40) for ITS-SR and -20,269; (95% credible interval, -25,011 to -15,635) for BSTS-CI., Conclusion: Differing results between ITS-SR and BSTS-CI appear driven by divergent explanatory and outcome series trends. The BSTS-CI may be a suitable alternative to ITS-SR only if the explanatory series represent the secular trend of the outcome series before the intervention and are equally affected by exogenous or confounding factors. When appropriately applied, BSTS-CI provides an alternative to ITS with more readily interpretable Bayesian effect estimates., Competing Interests: Declaration of competing interest None of the authors have any conflicts to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Family engagement positively impacts patient and family members' experiences of care and health outcomes. While partnering with families denotes best practice in intensive care units (ICUs), its full adoption requires improvement. A better understanding of the factors that influence the implementation of family engagement practices is necessary., Aim: To investigate the factors that enable or hinder adult ICU nurse-family engagement and to explore potential international variations., Study Design: Descriptive, cross-sectional survey. Nurses from 10 countries completed the 'Questionnaire on Factors that Influence Family Engagement' (QFIFE), including five open-ended questions. We performed descriptive statistics on quantitative data and content analysis for open-ended questions, and then integrated the findings according to influencing factors and geographical patterns. This was part of a larger qualitative study where 65 nurses participated from adult intensive care units., Results: Sixty-one nurses completed the questionnaire, making a response rate of 94%. Overall, patient acuity (Md = 5.0) and nurses' attitudes (Md = 4.6) seemed to be the most influential facilitator, followed by nurse workflow (Md = 4.0) and ICU environment (Md = 3.1) (score 1-6 most influential). The open-ended question data showed a more nuanced picture of the complexity of family engagement in care around these four determinants. Adding a fifth determinant, namely Families are complex structures that respond uniquely to the ICU and patient, revealed that difficult family dynamics, miscommunication and family having difficulty in understanding the situation or health literacy, hindered family engagement. Exploring geographical variations, Africa/Middle East consistently differed from others on three of the four QFIFE subscales, showing lower median levels., Conclusions: Some determinants are perceived to be more influential than others, becoming barriers or enablers to nurse-family engagement in adult ICU. Research that investigates contextual determinants and which compares implementation and improvement initiatives tailored to address family engagement practices barriers and enablers are needed., Relevance to Clinical Practice: Knowledge of this international study expands our understanding of enablers and barriers in family engagement that may inform family engagement practice improvement efforts around the world., (© 2022 The Authors. Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.)

Multiple techniques have been developed in addition to pulmonary vein isolation (PVI) to improve the outcomes of catheter ablation in patients with persistent atrial fibrillation (AF). We sought to evaluate the long-term efficacy of alternative techniques used in our laboratory for the treatment of persistent AF, including spatiotemporal dispersion (SD) and low-voltage isolation (LVI). Consecutive patients with persistent AF who underwent catheter ablation with the studied techniques between July 2016 and December 2019 were included in the study. PVI alone was compared with PVI plus SD and PVI plus LVI in terms of long-term freedom from atrial tachycardia (AT) and AF recurrence. Follow-up data were obtained from clinical records and hospital visits, which included a 7-day Holter monitor and electrocardiograms. The study was approved by the institutional review board of Rhode Island Hospital. A total of 382 patients underwent catheter ablation at our institution during the study period. One hundred seventy-two patients had paroxysmal AF and were excluded from the study. The remaining 210 patients had persistent AF and were included in the study. One hundred and three patients underwent PVI alone, while 48 had the addition of LVI and 59 had SD. Additionally, freedom from AT/AF recurrence at 18 months was 68% in the group that underwent LVI, 49% in the SD group, and 40% in the group that underwent PVI alone (log-rank P = .014). Freedom from AF recurrence was 74% in the LVI group, 71% in the SD group, and 43% in the PVI-alone group (log-rank P = .002). On multivariate Cox regression, LVI and left atrial size were found to be independent predictors of recurrence (hazard ratio, 0.39; 95% confidence interval, 0.206-0.760; P = .005 and hazard ratio, 1.4; 95% confidence interval, 1.105-1.923; P = .008, respectively). LVI and SD in addition to PVI were associated with greater freedom from AT/AF recurrence at 18 months compared to PVI alone., Competing Interests: The authors report no conflicts of interest for the published content. No funding information was provided., (Copyright: © 2023 Innovations in Cardiac Rhythm Management.)

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)

Functional magnetic resonance imaging (fMRI) with blood oxygen level-dependent (BOLD) technique is useful for preoperative mapping of brain functional networks in tumor patients, providing reliable in vivo detection of eloquent cortex to help reduce the risk of postsurgical morbidity. BOLD task-based fMRI (tb-fMRI) is the most often used noninvasive method that can reliably map cortical networks, including those associated with sensorimotor, language, and visual functions. BOLD resting-state fMRI (rs-fMRI) is emerging as a promising ancillary tool for visualization of diverse functional networks. Although fMRI is a powerful tool that can be used as an adjunct for brain tumor surgery planning, it has some constraints that should be taken into consideration for proper clinical interpretation. BOLD fMRI interpretation may be limited by neurovascular uncoupling (NVU) induced by brain tumors. Cerebrovascular reactivity (CVR) mapping obtained using breath-hold methods is an effective method for evaluating NVU potential.

This article provides a systematic review and meta-analysis of the current evidence for universal school-based (USB) social and emotional learning (SEL) interventions for students in kindergarten through 12th grade available from 2008 through 2020. The sample includes 424 studies from 53 countries, reflecting 252 discrete USB SEL interventions, involving 575,361 students. Results endorsed that, compared to control conditions, students who participate in USB SEL interventions experienced significantly improved skills, attitudes, behaviors, school climate and safety, peer relationships, school functioning, and academic achievement. Significant heterogeneity in USB SEL content, intervention features, context, and implementation quality moderated student experiences and outcomes. Strengths and limitations of this evidence and implications for future USB SEL research, policy, and practice are discussed., (© 2023 The Authors. Child Development © 2023 Society for Research in Child Development.)

Competing Interests: Conflicts of Interest: Authors JGS, KMD, DV, and RA have no conflicts to disclose

Muramidases (also known as lysozymes) hydrolyse the peptidoglycan component of the bacterial cell wall and are found in many glycoside hydrolase (GH) families. Similar to other glycoside hydrolases, muramidases sometimes have noncatalytic domains that facilitate their interaction with the substrate. Here, the identification, characterization and X-ray structure of a novel fungal GH24 muramidase from Trichophaea saccata is first described, in which an SH3-like cell-wall-binding domain (CWBD) was identified by structure comparison in addition to its catalytic domain. Further, a complex between a triglycine peptide and the CWBD from T. saccata is presented that shows a possible anchor point of the peptidoglycan on the CWBD. A `domain-walking' approach, searching for other sequences with a domain of unknown function appended to the CWBD, was then used to identify a group of fungal muramidases that also contain homologous SH3-like cell-wall-binding modules, the catalytic domains of which define a new GH family. The properties of some representative members of this family are described as well as X-ray structures of the independent catalytic and SH3-like domains of the Kionochaeta sp., Thermothielavioides terrestris and Penicillium virgatum enzymes. This work confirms the power of the module-walking approach, extends the library of known GH families and adds a new noncatalytic module to the muramidase arsenal., (open access.)

Government investment in preparing for pandemics has never been more relevant. The COVID-19 pandemic has stimulated debate regarding the trade-offs societies are prepared to make between health and economic activity. What is not known is: (1) how much the public in different countries are prepared to pay in forgone GDP to avoid mortality from future pandemics; and (2) which health and economic policies the public in different countries want their government to invest in to prepare for and respond to the next pandemic. Using a future-focused, multi-national discrete choice experiment, we quantify these trade-offs and find that the tax-paying public is prepared to pay $3.92 million USD (Canada), $4.39 million USD (UK), $5.57 million USD (US) and $7.19 million USD (Australia) in forgone GDP per death avoided in the next pandemic. We find the health policies that taxpayers want to invest in before the next pandemic and the economic policies they want activated once the next pandemic hits are relatively consistent across the countries, with some exceptions. Such results can inform economic policy responses and government investment in health policies to reduce the adverse impacts of the next pandemic., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

The number of spinal operations performed in the United States has significantly increased in recent years. Along with these rising numbers, there has been a corresponding increase in the number of patient comorbidities. The focus of this article is to review comorbidities in Spine surgery patients and outline strategies to optimize patients and avoid complications., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: People with disability are at higher risk of severe outcomes from SARS-CoV-2 infection. Due to complex client needs and available staffing, disability support providers (DSP) were limited in their ability to mitigate the introduction of SARS-CoV-2 into disability support settings. This report describes the characteristics of a Delta variant outbreak associated with a single DSP in Canberra, Australian Capital Territory (ACT), in August 2021. We calculated attack rates for workplace exposure sites and households, using the number of people present at workplaces and households as the denominator. Thirty confirmed cases were identified, comprised of 13 support workers, six clients, and 11 household and other contacts. The median age of cases was 30.5 years (range 1 to 80 years) and 5 cases (17%) were hospitalised. No cases were admitted to an intensive care unit (ICU) or died. Twenty-two percent of people in close contact with confirmed SARS-CoV-2 cases in this cluster (23/103) subsequently tested positive to SARS-CoV-2. Investigations identified multiple primary cases, with one primary case the likely infection source for at least 17 other cases. Despite the majority being eligible for vaccination, only two cases were fully vaccinated (two doses > 14 days before exposure). The mean secondary attack rate at workplace sites (15% or 12/80 close contacts infected) was lower than the tertiary attack rate (47.8% or 11/23 close contacts infected). The overall risk of contracting SARS-CoV-2 in DSP-related work sites was lower than for household settings (relative risk: 0.42; 95% confidence interval: 0.21-0.82). These findings demonstrate the importance of ongoing collaboration between governments and the disability support sector. Development and delivery of targeted health messaging to people with disability and to disability support workers, regarding infection control in the home setting, and identification of enablers for vaccination, should be the highest priorities from this collaboration., (© Commonwealth of Australia CC BY-NC-ND.)

Circadian clocks temporally orchestrate biological processes critical for cellular/organ function. For example, the cardiomyocyte circadian clock modulates cardiac metabolism, signaling, and electrophysiology over the course of the day, such that, disruption of the clock leads to age-onset cardiomyopathy (through unknown mechanisms). Here, we report that genetic disruption of the cardiomyocyte clock results in chronic induction of the transcriptional repressor E4BP4. Importantly, E4BP4 deletion prevents age-onset cardiomyopathy following clock disruption. These studies also indicate that E4BP4 regulates both cardiac metabolism (eg, fatty acid oxidation) and electrophysiology (eg, QT interval). Collectively, these studies reveal that E4BP4 is a novel regulator of both cardiac physiology and pathophysiology., Competing Interests: This work was supported by the National Heart, Lung, and Blood Institute grants HL149159 and HL007081. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: High-frequency hospital users often present with chronic and complex health conditions and are at increased risk of serious morbidity and mortality if they contract COVID-19. Understanding where high-frequency hospital users are sourcing their information, whether they understand what they find, and how they apply the information to prevent the spread of COVID-19 is essential for health authorities to be able to target communication approaches., Methods: Cross-sectional survey of 200 frequent hospital users (115 with limited English proficiency) informed by the WHO's "Rapid, simple, flexible behavioral insights on COVID-19". Outcome measures were source of, and trust in information, and knowledge of symptoms, preventive strategies, restrictions, and identification of misinformation., Results: The most frequently cited source of information was television (n = 144, 72%) followed by the internet (n = 84, 42%). One in four television users sought their information from overseas news outlets from their country of origin, while for those using the internet, 56% relied on Facebook and other forms of social media including YouTube and WeChat. Overall, 41.2% of those surveyed had inadequate knowledge about symptoms, 35.8% had inadequate knowledge about preventative strategies, 30.2% had inadequate knowledge about government-imposed restrictions, and 69% believed in misinformation. Half of the respondents (50%) trusted all information, and only one in five (20%) were uncertain or untrusting. English-speaking participants were almost three times more likely to have adequate knowledge about symptoms (OR 2.69, 95%CI 1.47;4.91) and imposed restrictions (OR 2.10 95%CI 1.06; 4.19), and 11 times more likely to recognize misinformation (OR 11.52 95%CI 5.39; 24.60) than those with limited English., Conclusion: Within this population of high-frequency hospital users with complex and chronic conditions, many were sourcing their information from less trustworthy or locally relevant sources, including social media and overseas news outlets. Despite this, at least half were trusting all the information that they found. Speaking a language other than English was a much greater risk factor for having inadequate knowledge about COVID-19 and believing in misinformation. Health authorities must look for methods to engage diverse communities, and tailor health messaging and education in order to reduce disparities in health outcomes., (© 2023. The Author(s).)