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Purpose of Review: Pseudophakic cystoid macular edema (PCME) is the most common postoperative complication of cataract surgery, resulting in visual decline. In this review, we discuss its pathophysiology, epidemiology, clinical presentation, and the current available evidence on therapeutic management., Recent Findings: Patients with diabetes mellitus have twice the risk of developing PCME as compared to nondiabetic individuals. Recent large database studies have revealed an increased risk among young, male, and black patients. A previous history of PCME is perhaps the strongest risk factor for fellow eye involvement., Summary: PCME generally occurs around 6 weeks postoperatively and is likely a consequence of postoperative inflammation with disruption of the blood-queous and blood-retina barriers. Optical coherence tomography of the macula servers as a key diagnostic tool. There is a lack of large controlled clinical trials to guide treatment approaches. We recommend a stepwise approach for PCME that includes observation if not visually significant versus treatment with topical nonsteroidal anti-inflammatory drugs and steroids if symptomatic. Refractory cases can be treated with a periocular steroid injection, followed by intravitreal steroids if still nonresponsive., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Countries around the world are experiencing both a growing need for mental health services and major gaps in the delivery of mental healthcare. The World Health Organisation's 2022 report on mental health emphasised co-designed and systems-level innovations responsive to the voice of those with lived experience. However, evidence for implementing such methodologies is sparse. Group model building (GMB), a participatory systems-based approach, has been used in various fields, but its application is limited within mental healthcare settings. It is recognised as a valuable tool for engaging stakeholders, including those with lived experience, in understanding and redesigning health systems and services. The participatory approach aligns with the mental health sector's shift towards co-design and person-centred care. This study assessed the acceptability of GMB as a method for co-design within mental healthcare, aiming to explore its potential for meaningful collaborative improvement and systems-level insights. Participants from a regional Mental Health and Drug and Alcohol Service (MHDAS) engaged in GMB workshops and focus groups. Eighteen individuals, including lived experience workers and healthcare professionals, provided feedback that informed adjustments to the workshops' design, language, timing and facilitation techniques, enhancing GMB's relevance for mental health co-design. The findings demonstrate the value and acceptability of the adapted GMB process in acute mental healthcare, marking a significant step towards evidence-based, person-centred service improvement. This study highlights the potential effectiveness of participatory methods in identifying and addressing systemic challenges, paving the way for future mental health reforms. Future work will focus on implementing and evaluating co-designed interventions, aiming for more inclusive and effective mental healthcare and advancing innovation and reform in the field., (© 2024 The Author(s). International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Background/aims: This was a cross-sectional comparative study. We evaluated the ability of three large language models (LLMs) (ChatGPT-3.5, ChatGPT-4, and Google Bard) to generate novel patient education materials (PEMs) and improve the readability of existing PEMs on paediatric cataract., Methods: We compared LLMs' responses to three prompts. Prompt A requested they write a handout on paediatric cataract that was 'easily understandable by an average American.' Prompt B modified prompt A and requested the handout be written at a 'sixth-grade reading level, using the Simple Measure of Gobbledygook (SMOG) readability formula.' Prompt C rewrote existing PEMs on paediatric cataract 'to a sixth-grade reading level using the SMOG readability formula'. Responses were compared on their quality (DISCERN; 1 (low quality) to 5 (high quality)), understandability and actionability (Patient Education Materials Assessment Tool (≥70%: understandable, ≥70%: actionable)), accuracy (Likert misinformation; 1 (no misinformation) to 5 (high misinformation) and readability (SMOG, Flesch-Kincaid Grade Level (FKGL); grade level <7: highly readable)., Results: All LLM-generated responses were of high-quality (median DISCERN ≥4), understandability (≥70%), and accuracy (Likert=1). All LLM-generated responses were not actionable (<70%). ChatGPT-3.5 and ChatGPT-4 prompt B responses were more readable than prompt A responses (p<0.001). ChatGPT-4 generated more readable responses (lower SMOG and FKGL scores; 5.59±0.5 and 4.31±0.7, respectively) than the other two LLMs (p<0.001) and consistently rewrote them to or below the specified sixth-grade reading level (SMOG: 5.14±0.3)., Conclusion: LLMs, particularly ChatGPT-4, proved valuable in generating high-quality, readable, accurate PEMs and in improving the readability of existing materials on paediatric cataract., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the quality, reliability, and readability of online patient educational materials on leukocoria., Methods: In this cross-sectional study, the Google search engine was searched for the terms "leukocoria" and "white pupil." The first 50 search outcomes were evaluated for each search term based on predefined inclusion criteria, excluding duplicates, peer-reviewed papers, forum posts, paywalled content, and multimedia links. Sources were categorized as "institutional" or "private." Three independent raters assessed each web-site for quality and reliability using DISCERN, Health on the Net Code of Conduct (HONcode), and JAMA criteria. Readability was evaluated using seven formulas: Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG) Index, Automated Readability Index (ARI), Linsear Write (LW), Gunning Fog Index (GFI), and Coleman-Liau Index (CLI)., Results: A total of 51 websites were included. Quality, assessed by the DISCERN tool, showed a median score of 4, denoting moderate to high quality, with no significant differences between institutional and private sites or search terms. HONcode scores indicated variable reliability and trustworthiness (median: 10, range: 3 to 16), with institutional sites excelling in financial disclosure and ad differentiation. Additionally, institutional and private sites performed well in reliability and accountability, as measured by the JAMA Benchmark criteria (median: 3; range: 1 to 4). Readability, averaging an 11.3 ± 3.7 grade level, did not differ significantly between site types or search terms, consistently falling short of the recommended sixth-grade level for patient educational materials., Conclusions: The patient educational materials on leukocoria demonstrated moderate to high quality, commendable reliability, and accountability. However, the readability scores were above the recommended level for the layperson. [ J Pediatr Ophthalmol Strabismus . 2024;61(5):332-338.] .

Background and Objectives: We evaluated the performance of 3 large language models (LLMs) in generating patient education materials (PEMs) and enhancing the readability of prewritten PEMs on idiopathic intracranial hypertension (IIH)., Methods: This cross-sectional comparative study compared 3 LLMs, ChatGPT-3.5, ChatGPT-4, and Google Bard, for their ability to generate PEMs on IIH using 3 prompts. Prompt A (control prompt): "Can you write a patient-targeted health information handout on idiopathic intracranial hypertension that is easily understandable by the average American?", Prompt B (modifier statement + control prompt): "Given patient education materials are recommended to be written at a 6th-grade reading level, using the SMOG readability formula, can you write a patient-targeted health information handout on idiopathic intracranial hypertension that is easily understandable by the average American?", and Prompt C: "Given patient education materials are recommended to be written at a 6th-grade reading level, using the SMOG readability formula, can you rewrite the following text to a 6th-grade reading level: [ insert text ]." We compared generated and rewritten PEMs, along with the first 20 googled eligible PEMs on IIH, on readability (Simple Measure of Gobbledygook [SMOG] and Flesch-Kincaid Grade Level [FKGL]), quality (DISCERN and Patient Education Materials Assessment tool [PEMAT]), and accuracy (Likert misinformation scale)., Results: Generated PEMs were of high quality, understandability, and accuracy (median DISCERN score ≥4, PEMAT understandability ≥70%, Likert misinformation scale = 1). Only ChatGPT-4 was able to generate PEMs at the specified 6th-grade reading level (SMOG: 5.5 ± 0.6, FKGL: 5.6 ± 0.7). Original published PEMs were rewritten to below a 6th-grade reading level with Prompt C, without a decrease in quality, understandability, or accuracy only by ChatGPT-4 (SMOG: 5.6 ± 0.6, FKGL: 5.7 ± 0.8, p < 0.001, DISCERN ≥4, Likert misinformation = 1)., Discussion: In conclusion, LLMs, particularly ChatGPT-4, can produce high-quality, readable PEMs on IIH. They can also serve as supplementary tools to improve the readability of prewritten PEMs while maintaining quality and accuracy., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Aims: The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity ensuring safety and appropriateness of prescribing. A disruption could have significant negative implications for patient care. Using routinely collected data, our aim was first to describe codes used to record medication review activity and then to report the impact of COVID-19 on the rates of medication reviews., Methods: With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform. For each month, between April 2019 and March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months with breakdowns by regional, clinical and demographic subgroups and those prescribed high-risk medications., Results: In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity decreased (-21.1% April 2020), but the 12-month rate was not substantially impacted (-10.5% March 2021). The rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high-risk groups (care home residents 34.1%, age 90+ years 13.1%, high-risk medications 10.2%). The most used medication review code was Medication review done 314530002 (59.5%)., Conclusions: There was a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period. Structured medication reviews were prioritized for high-risk patients., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: The COVID-19 pandemic disrupted health-care delivery, including difficulty accessing in-person care, which could have increased the need for strong pharmacological pain relief. Due to the risks associated with overprescribing of opioids, especially to vulnerable populations, we aimed to quantify changes to measures during the COVID-19 pandemic, overall, and by key subgroups., Methods: For this interrupted time-series analysis study conducted in England, with National Health Service England approval, we used routine clinical data from more than 20 million general practice adult patients in OpenSAFELY-TPP, which is a a secure software platform for analysis of electronic health records. We included all adults registered with a primary care practice using TPP-SystmOne software. Using interrupted time-series analysis, we quantified prevalent and new opioid prescribing before the COVID-19 pandemic (January, 2018-February, 2020), during the lockdown (March, 2020-March, 2021), and recovery periods (April, 2021-June, 2022), overall and stratified by demographics (age, sex, deprivation, ethnicity, and geographical region) and in people in care homes identified via an address-matching algorithm., Findings: There was little change in prevalent prescribing during the pandemic, except for a temporary increase in March, 2020. We observed a 9·8% (95% CI -14·5 to -6·5) reduction in new opioid prescribing from March, 2020, with a levelling of the downward trend, and rebounding slightly after April, 2021 (4·1%, 95% CI -0·9 to 9·4). Opioid prescribing rates varied by demographics, but we found a reduction in new prescribing for all subgroups except people aged 80 years or older. Among care home residents, in April, 2020, parenteral opioid prescribing increased by 186·3% (153·1 to 223·9)., Interpretation: Opioid prescribing increased temporarily among older people and care home residents, likely reflecting use to treat end-of-life COVID-19 symptoms. Despite vulnerable populations being more affected by health-care disruptions, disparities in opioid prescribing by most demographic subgroups did not widen during the pandemic. Further research is needed to understand what is driving the changes in new opioid prescribing and its relation to changes to health-care provision during the pandemic., Funding: The Wellcome Trust, Medical Research Council, The National Institute for Health and Care Research, UK Research and Innovation, and Health Data Research UK., Competing Interests: Declaration of interests BG has received research funding from the Bennett Foundation, the Laura and John Arnold Foundation, the National Health Service (NHS), The National Institute for Health and Care Research (NIHR), the NIHR School of Primary Care Research, NHS England, the NIHR Oxford Biomedical Research Centre, the Mohn–Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK, the Health Foundation, WHO, UK Research and Innovation Medical Research Council, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme; has previously been a Non-Executive Director at NHS Digital; and has received personal income from speaking and writing for lay audiences on the misuse of science. BM is employed by NHS England working on medicines policy and is clinical lead for primary care medicines data. AM has represented the Royal College of General Practitioners in the health informatics group and the Profession Advisory Group that advises on access to GP Data for Pandemic Planning and Research, of which the latter was a paid role. AM is a former employee and interim Chief Medical Officer of NHS Digital; and has consulted for health-care vendors, the last time being in 2022. The companies consulted in the last 3 years have no relationship to OpenSAFELY., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the effect of the covid-19 pandemic on the number of patients with group A streptococcal infections and related antibiotic prescriptions., Design: Retrospective cohort study in England using OpenSAFELY-TPP., Setting: Primary care practices in England that used TPP SystmOne software, 1 January 2018 to 31 March 2023, with the approval of NHS England., Participants: Patients registered at a TPP practice at the start of each month of the study period. Patients with missing data for sex or age were excluded, resulting in a population of 23 816 470 in January 2018, increasing to 25 541 940 by March 2023., Main Outcome Measures: Monthly counts and crude rates of patients with group A streptococcal infections (sore throat or tonsillitis, scarlet fever, and invasive group A streptococcal infections), and recommended firstline, alternative, and reserved antibiotic prescriptions linked with a group A streptococcal infection before (pre-April 2020), during, and after (post-April 2021) covid-19 restrictions. Maximum and minimum count and rate for each infectious season (time from September to August), as well as the rate ratio of the 2022-23 season compared with the last comparably high season (2017-18)., Results: The number of patients with group A streptococcal infections, and antibiotic prescriptions linked to an indication of group A streptococcal infection, peaked in December 2022, higher than the peak in 2017-18. The rate ratios for monthly sore throat or tonsillitis (possible group A streptococcal throat infection), scarlet fever, and invasive group A streptococcal infection in 2022-23 relative to 2017-18 were 1.39 (95% confidence interval (CI) 1.38 to 1.40), 2.68 (2.59 to 2.77), and 4.37 (2.94 to 6.48), respectively. The rate ratio for prescriptions of first line, alternative, and reserved antibiotics to patients with group A streptococcal infections in 2022-23 relative to 2017-18 were 1.37 (95% CI 1.35 to 1.38), 2.30 (2.26 to 2.34), and 2.42 (2.24 to 2.61), respectively. For individual antibiotic prescriptions in 2022-23, azithromycin showed the greatest relative increase versus 2017-18, with a rate ratio of 7.37 (6.22 to 8.74). This finding followed a marked decrease in the recording of patients with group A streptococcal infections and associated prescriptions during the period of covid-19 restrictions where the maximum count and rates were lower than any minimum rates before the covid-19 pandemic., Conclusions: Recording of rates of scarlet fever, sore throat or tonsillitis, and invasive group A streptococcal infections, and associated antibiotic prescribing, peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed analysis of clinical and demographic subgroups., 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 Wellcome Trust, Medical Research Council (MRC), National Core Studies programme, National Institute for Health and Care Research (NIHR), UK Research and Innovation, and Health Data Research UK for the submitted work; BG has received research funding from the Laura and John Arnold Foundation, NHS NIHR, NIHR School of Primary Care Research, NHS England, NIHR Oxford Biomedical Research Centre, Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, Wellcome Trust, Good Thinking Foundation, Health Data Research UK, Health Foundation, World Health Organization, UK Research and Innovation (UKRI) MRC, Asthma UK, British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme; BG has previously been a non-executive director at NHS Digital; BG also receives personal income from speaking and writing for lay audiences on the misuse of science; BM is employed by NHS England working on medicines policy and is the clinical lead for primary care medicines data; EB is regional antimicrobial stewardship lead for NHS England-South West; KH is national pharmacy and prescribing clinical lead for antimicrobial resistance at NHS England; 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)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Elimination of restrictive practices (physical/mechanical restraint and seclusion) from adult acute mental health care services has been demanded internationally for many decades. This study aimed to: (1) Identify priority issues in the elimination of and use of alternative approaches to restrictive practices (seclusion and physical/mechanical restraint) in rural/regional acute adult mental healthcare services, as told by mental healthcare service users and practitioners, (2) identify the community-based, system-level feedback loops that enhance or reduce the use of restrictive practices and viable alternatives and, (3) identify potential action areas to improve system structures to increase regional mental healthcare services' ability to eliminate restrictive practices and use alternative approaches. Group model building (GMB) workshops were held with a small group (n = 9) of mental healthcare practitioners and service users with lived experience of restrictive practice use. This participatory approach enables exploration and visual mapping of local structures causing behaviour patterns of practitioner and service user concern over time - in this case, the barriers, and enablers to alternative approaches to restrictive practices in adult acute mental healthcare services within the Geelong-Barwon region. This is the first study that specifically applies GMB in the discussion of the elimination of restrictive practices in mental health in the non-metropolitan regional/rural context. Participants identified four key priorities in relation to eliminating restrictive practices: (1) self-advocacy, (2) continuity of care, (3) early intervention, and (4) safety for all. The study findings were distilled into a novel preliminary set of mental healthcare practitioner and service user action ideas., (© 2024 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Background: Over a quarter of children aged 2-17 years living in Australia are overweight or obese, with a higher prevalence reported in regional and remote communities. Systems thinking approaches that seek to support communities to generate and implement locally appropriate solutions targeting intertwined environmental, political, sociocultural, and individual determinants of obesity have the potential to ameliorate this. There have however been reported challenges with implementation of such initiatives, which may be strengthened by incorporating implementation science methods., Methods: This pilot randomised controlled trial protocol outlines the development and proposed evaluation of a multicomponent implementation strategy (Action-RESPOND). to increase the implementation of community-based systems thinking child obesity prevention initiatives The target of this intervention is ten rural and regional communities (or local government areas as the unit of allocation) within Northeast Victoria who were participants in a whole-of-systems intervention (RESPOND). Action-RESPOND builds on this intervention by assessing the impact of offering additional implementation strategies to five communities relative to usual care. The development of the multicomponent implementation strategy was informed by the Promoting Action on Research Implementation in Health Services (PARIHS) framework and consists of seven implementation strategies primarily delivered via 'facilitation' methods. Implementation strategies aimed to ensure initiatives implemented are i) evidence-based, ii) address community's specific needs and iii) are suitable for local context. Strategies also aimed to increase the community's capacity to implement, through iv) improving the health promotion team's implementation knowledge and skills, fostering v) leadership, vi) physical resources and vii) community culture to drive implementation. The feasibility, acceptability, potential impact, and cost of the strategy will be assessed at baseline and follow up using surveys administered to key representatives within the community and internal records maintained by the research team., Discussion: By leveraging an existing community-based whole-of-systems intervention, Action-RESPOND offers a unique opportunity to collect pilot feasibility and early empirical data on how to apply implementation and systems science approaches to support obesity prevention in rural and regional communities in Victoria., Competing Interests: S.A. is a co-inventor of the STICKE software, which is used in this study. All other authors have no conflict of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Yoong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study investigates whether disease-modifying antirheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic., Methods: A population-based cohort study was conducted using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP's SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations., Results: An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (leflunomide: +20.7 percentage points) and monitoring tests (blood pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Consistent differences were observed in overall missed monitoring rates between several groups throughout the study., Conclusion: DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions and patient groups highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should evaluate the causes of the differences identified between groups., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Food retailers can be reluctant to initiate healthy food retail activities in the face of a complex set of interrelated drivers that impact the retail environment. The Systems Thinking Approach for Retail Transformation (START) is a determinants framework created using qualitative systems modelling to guide healthy food retail interventions in community-based, health-promoting settings. We aimed to test the applicability of the START map to a suite of distinct healthy food marketing and promotion activities that formed an intervention in a grocery setting in regional Victoria, Australia., Methods: A secondary analysis was undertaken of 16 previously completed semi-structured interviews with independent grocery retailers and stakeholders. Interviews were deductively coded against the existing START framework, whilst allowing for new grocery-setting specific factors to be identified. New factors and relationships were used to build causal loop diagrams and extend the original START systems map using Vensim., Results: A version of the START map including aspects relevant to the grocery setting was developed ("START-G"). In both health-promoting and grocery settings, it was important for retailers to 'Get Started' with healthy food retail interventions that were supported by a proof-of-concept and 'Focus on the customer' response (with grocery-settings focused on monitoring sales data). New factors and relationships described perceived difficulties associated with disrupting a grocery-setting 'Supply-side status quo' that promotes less healthy food and beverage options. Yet, most grocery retailers discussed relationships that highlighted the potential for 'Healthy food as innovation' and 'Supporting cultural change through corporate social responsibility and leadership'., Conclusions: Several differences were found when implementing healthy food retail in grocery compared to health promotion settings. The START-G map offers preliminary guidance for identifying and addressing commercial interests in grocery settings that currently promote less healthy foods and beverages, including by starting to address business outcomes and supplier relationships., (© 2023. The Author(s).)

Background: Novel psychoactive substances, such as designer benzodiazepines (DBZD), are a growing public health concern. There are about 30 different DZBDs reported, which can vary widely in their effect and potential for harmful outcomes, ranging from agitation to confusion to coma. Despite the scope of this widespread phenomena, little information on the management of DBZD dependence is available in the literature., Case: In this case report, we present a patient with DBZD dependence requesting assistance tapering off the DBZD, clonazolam. He began self-medicating with clonazolam seven years prior for panic attacks to the point he was using 40 drops per day and having significant withdrawal during the day. He was prescribed gabapentin for his underlying anxiety while he tapered his clonazolam dose. Once he achieved a 75% reduction in his use of clonazolam, he had trouble managing withdrawal and anxiety symptoms and could not taper further., Discussion: We discuss the challenges of treating patients with DBZD use disorder in an outpatient setting. Switching a patient from a DZBD to a prescription benzodiazepine for the purposes of a taper can be dangerous as an outpatient due to the inability to monitor at-home DBZD usage and the resulting risk of overdose. DBZDs can also be highly potent and make it difficult to achieve success using current withdrawal guidelines.

This article proposes an event-driven solution to genotype imputation, a technique used to statistically infer missing genetic markers in DNA. The work implements the widely accepted Li and Stephens model, primary contributor to the computational complexity of modern x86 solutions, in an attempt to determine whether further investigation of the application is warranted in the event-driven domain. The model is implemented using graph-based Hidden Markov Modeling and executed as a customized forward/backward dynamic programming algorithm. The solution uses an event-driven paradigm to map the algorithm to thousands of concurrent cores, where events are small messages that carry both control and data within the algorithm. The design of a single processing element is discussed. This is then extended across multiple cores and executed on a custom RISC-V NoC cluster called POETS. Results demonstrate how the algorithm scales over increasing hardware resources and a multi-core run demonstrates a 270X reduction in wall-clock processing time when compared to a single-threaded x86 solution. Optimisation of the algorithm via linear interpolation is then introduced and tested, with results demonstrating a wall-clock reduction time of  ∼ 5 orders of magnitude when compared to a similarly optimised x86 solution.

Group model building is a participatory workshop technique used in system dynamics for developing community consensus to address complex problems by consensus building on individual assumptions. This study examines changes in individual mental models of the complex problem of childhood obesity following participation in group model building (GMB), as part of a larger community-based system dynamics project. Data are drawn from GMB participants across six community sites in the Whole of Systems Trial of Prevention Strategies for Childhood Obesity (WHO STOPS) in rural and regional Victoria, Australia. Each community participated in two GMB sessions resulting in a causal loop diagram (CLD) of drivers of childhood obesity for each community. Presurvey and postsurvey captured participants' perspectives before and after ( n = 25) participation in both GMB sessions and a blend of inductive and deductive qualitative content analysis was used to code individual responses. Three calculations were used to determine the number of responses, whether responses were a result of persuasion from others, and comparison of responses to those found in the CLD. Our study found participant mental models shifted during the course of the GMB sessions, with some responses persuaded by others and 75% of new insights identified in CLDs created by communities. The GMB process created a platform for participants to share ideas and learn from each other. In addition, participants listed new insights about childhood obesity in their community through developing CLDs.

The binaural interaction component (BIC) of the auditory brainstem response (ABR) is the difference obtained after subtracting the sum of right and left ear ABRs from binaurally evoked ABRs. The BIC has attracted interest as a biomarker of binaural processing abilities. Best binaural processing is presumed to require spectrally-matched inputs at the two ears, but peripheral pathology and/or impacts of hearing devices can lead to mismatched inputs. Such mismatching can degrade behavioral sensitivity to interaural time difference (ITD) cues, but might be detected using the BIC. Here, we examine the effect of interaural frequency mismatch (IFM) on BIC and behavioral ITD sensitivity in audiometrically normal adult human subjects (both sexes). Binaural and monaural ABRs were recorded and BICs computed from subjects in response to narrowband tones. Left ear stimuli were fixed at 4000 Hz while right ear stimuli varied over a ∼2-octave range (re: 4000 Hz). Separately, subjects performed psychophysical lateralization tasks using the same stimuli to determine ITD discrimination thresholds jointly as a function of IFM and sound level. Results demonstrated significant effects of IFM on BIC amplitudes, with lower amplitudes in mismatched conditions than frequency-matched. Behavioral ITD discrimination thresholds were elevated at mismatched frequencies and lower sound levels, but also more sharply modulated by IFM at lower sound levels. Combinations of ITD, IFM and overall sound level that resulted in fused and lateralized percepts were bound by the empirically-measured BIC, and also by model predictions simulated using an established computational model of the brainstem circuit thought to generate the BIC., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023. Published by Elsevier B.V.)

Persistent differences in wealth and power among prehispanic Pueblo societies are visible from the late AD 800s through the late 1200s, after which large portions of the northern US Southwest were depopulated. In this paper we measure these differences in wealth using Gini coefficients based on house size, and show that high Ginis (large wealth differences) are positively related to persistence in settlements and inversely related to an annual measure of the size of the unoccupied dry-farming niche. We argue that wealth inequality in this record is due first to processes inherent in village life which have internally different distributions of the most productive maize fields, exacerbated by the dynamics of systems of balanced reciprocity; and second to decreasing ability to escape village life owing to shrinking availability of unoccupied places within the maize dry-farming niche as villages get enmeshed in regional systems of tribute or taxation. We embed this analytical reconstruction in the model of an 'Abrupt imposition of Malthusian equilibrium in a natural-fertility, agrarian society' proposed by Puleston et al . (Puleston C, Tuljapurkar S, Winterhalder B. 2014 PLoS ONE 9 , e87541 (doi:10.1371/journal.pone.0087541)), but show that the transition to Malthusian dynamics in this area is not abrupt but extends over centuries This article is part of the theme issue 'Evolutionary ecology of inequality'.

Background: The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. Methods: With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,  in situ  and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. Results: Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. Conclusion: First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents., Competing Interests: Competing interests: BG has received research funding from the Laura and John Arnold Foundation, the NHS National Institute for Health Research (NIHR), the NIHR School of Primary Care Research, NHS England, the NIHR Oxford Biomedical Research Centre, the Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK, the Health Foundation, the World Health Organisation, UKRI MRC, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme; he is a Non-Executive Director at NHS Digital; he also receives personal income from speaking and writing for lay audiences on the misuse of science. BMK is also employed by NHS England working on medicines policy and clinical lead for primary care medicines data., (Copyright: © 2023 Hopcroft LE et al.)

A rich history of comparative research in the auditory field has afforded a synthetic view of sound information processing by ears and brains. Some organisms have proven to be powerful models for human hearing due to fundamental similarities (e.g., well-matched hearing ranges), while others feature intriguing differences (e.g., atympanic ears) that invite further study. Work across diverse "non-traditional" organisms, from small mammals to avians to amphibians and beyond, continues to propel auditory science forward, netting a variety of biomedical and technological advances along the way. In this brief review, limited primarily to tetrapod vertebrates, we discuss the continued importance of comparative studies in hearing research from the periphery to central nervous system with a focus on outstanding questions such as mechanisms for sound capture, peripheral and central processing of directional/spatial information, and non-canonical auditory processing, including efferent and hormonal effects., Competing Interests: Declaration of Competing Interest The authors declare no competing interests, (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Historically, diverse organisms have contributed to our understanding of auditory function. In recent years, the laboratory mouse has become the prevailing non-human model in auditory research, particularly for biomedical studies. There are many questions in auditory research for which the mouse is the most appropriate (or the only) model system available. But mice cannot provide answers for all auditory problems of basic and applied importance, nor can any single model system provide a synthetic understanding of the diverse solutions that have evolved to facilitate effective detection and use of acoustic information. In this review, spurred by trends in funding and publishing and inspired by parallel observations in other domains of neuroscience, we highlight a few examples of the profound impact and lasting benefits of comparative and basic organismal research in the auditory system. We begin with the serendipitous discovery of hair cell regeneration in non-mammalian vertebrates, a finding that has fueled an ongoing search for pathways to hearing restoration in humans. We then turn to the problem of sound source localization - a fundamental task that most auditory systems have been compelled to solve despite large variation in the magnitudes and kinds of spatial acoustic cues available, begetting varied direction-detecting mechanisms. Finally, we consider the power of work in highly specialized organisms to reveal exceptional solutions to sensory problems - and the diverse returns of deep neuroethological inquiry - via the example of echolocating bats. Throughout, we consider how discoveries made possible by comparative and curiosity-driven organismal research have driven fundamental scientific, biomedical, and technological advances in the auditory field., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Approaches to addressing unwarranted variation in health care service delivery have traditionally relied on the prospective identification of activities and outcomes, based on a hypothesis, with subsequent reporting against defined measures. Practice-level prescribing data in England are made publicly available by the National Health Service (NHS) Business Services Authority for all general practices. There is an opportunity to adopt a more data-driven approach to capture variability and identify outliers by applying hypothesis-free, data-driven algorithms to national data sets., Objective: This study aimed to develop and apply a hypothesis-free algorithm to identify unusual prescribing behavior in primary care data at multiple administrative levels in the NHS in England and to visualize these results using organization-specific interactive dashboards, thereby demonstrating proof of concept for prioritization approaches., Methods: Here we report a new data-driven approach to quantify how "unusual" the prescribing rates of a particular chemical within an organization are as compared to peer organizations, over a period of 6 months (June-December 2021). This is followed by a ranking to identify which chemicals are the most notable outliers in each organization. These outlying chemicals are calculated for all practices, primary care networks, clinical commissioning groups, and sustainability and transformation partnerships in England. Our results are presented via organization-specific interactive dashboards, the iterative development of which has been informed by user feedback., Results: We developed interactive dashboards for every practice (n=6476) in England, highlighting the unusual prescribing of 2369 chemicals (dashboards are also provided for 42 sustainability and transformation partnerships, 106 clinical commissioning groups, and 1257 primary care networks). User feedback and internal review of case studies demonstrate that our methodology identifies prescribing behavior that sometimes warrants further investigation or is a known issue., Conclusions: Data-driven approaches have the potential to overcome existing biases with regard to the planning and execution of audits, interventions, and policy making within NHS organizations, potentially revealing new targets for improved health care service delivery. We present our dashboards as a proof of concept for generating candidate lists to aid expert users in their interpretation of prescribing data and prioritize further investigations and qualitative research in terms of potential targets for improved performance., (©Lisa EM Hopcroft, Jon Massey, Helen J Curtis, Brian Mackenna, Richard Croker, Andrew D Brown, Thomas O'Dwyer, Orla Macdonald, David Evans, Peter Inglesby, Sebastian CJ Bacon, Ben Goldacre, Alex J Walker. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 19.04.2023.)

Interaural time differences (ITDs), an important acoustic cue for perceptual sound-source localization, are conventionally modeled as monotonic functions of azimuth. However, recent literature and publicly available databases from binaural manikins demonstrated ITDs conveyed by the envelopes (ENV-ITDs) of high-frequency (≥2 kHz) signals that were non-monotonic functions of azimuth. This study demonstrates using a simple, time-dependent geometric model of an elliptic head that the back-traveling (longer) sound path around the head, delayed and added to the conventionally treated front-traveling path, can account for non-monotonic ENV-ITDs. These findings have implications for spatial-hearing models in acoustic and electric (cochlear-implant) hearing.

Background: Lesbian, gay, bisexual, transgender, Queer, and people of any other minority sexuality or gender identity (LGBTQ + or "Queer") are often marginalised from accessing quality primary healthcare (PHC) in their local community. This is largely due to Queerphobic, cis-heteronormative/sexist systems pathologising Queer life and identities. The study aims were to: (1) identify key priorities for increasing Queer people's access to quality PHC as told by Queer people themselves, (2) identify the feedback loops that reduce or support Queer people's access to quality PHC in non-metropolitan, regional/rural communities, and (3) identify potential action areas to improve system structures to increase Queer people's access to quality PHC., Methods: Group Model Building (GMB) workshops were held with a small group (n = 8) of LGBTQ + people in regional Victoria with lived experience of using PHC services. This participatory approach permits exploration and visual mapping of local structures causing behaviour patterns of community concern over time - in this case, Queer people's ability to access quality PHC in the Geelong-Barwon region. This is the first study that specially applies GMB in Queer PHC in the non-metropolitan regional/rural context., Results: Key community identified PHC priorities were: (a) providers' level of Queer Literacy, (b) the responsibility of Queer Advocacy (at individual, systemic, and collective levels), (c) support from safe Queer Spaces, (d) strength from a Queer Presence, and (e) power from Intersectional Queer Life. These priorities interconnected, creating system-level feedback loops reinforcing barriers and enablers to Queer people's access to quality PHC in the Geelong-Barwon region; with potential action areas identified., Conclusions: Improving Queer people's access to quality PHC in the Geelong-Barwon region requires embedding principles of Queer Literacy, Queer Advocacy, Queer Space, Queer Presence, and Intersectional Queer Life within practices and service systems. The study findings were distilled into a novel, preliminary set of Queer Equity Principles. These need to be taken back to regional Queer communities for further co-design and planning for translation across PHC practices and systems, with potential applicability in other areas of the healthcare spectrum., (© 2023. The Author(s).)

The crowded interior of a living cell makes performing experiments on simpler in vitro systems attractive. Although these reveal interesting phenomena, their biological relevance can be questionable. A topical example is the phase separation of intrinsically disordered proteins into biomolecular condensates, which is proposed to underlie the membrane-less compartmentalization of many cellular functions. How a cell reliably controls biochemical reactions in compartments open to the compositionally-varying cytoplasm is an important question for understanding cellular homeostasis. Computer simulations are often used to study the phase behavior of model biomolecular condensates, but the number of relevant parameters increases as the number of protein components increases. It is unfeasible to exhaustively simulate such models for all parameter combinations, although interesting phenomena are almost certainly hidden in their high-dimensional parameter space. Here, we have studied the phase behavior of a model biomolecular condensate in the presence of a polymeric crowding agent. We used a novel compute framework to execute dozens of simultaneous simulations spanning the protein/crowder concentration space. We then combined the results into a graphical representation for human interpretation, which provided an efficient way to search the model's high-dimensional parameter space. We found that steric repulsion from the crowder drives a near-critical system across the phase boundary, but the molecular arrangement within the resulting biomolecular condensate is rather insensitive to the crowder concentration and molecular weight. We propose that a cell may use the local cytoplasmic concentration to assist the formation of biomolecular condensates, while relying on the dense phase to reliably provide a stable, structured, fluid milieu for cellular biochemistry despite being open to its changing environment.

Objective: Childhood obesity prevention is critical to reducing the health and economic burden currently experienced by the Australian economy. System science has emerged as an approach to manage the complexity of childhood obesity and the ever-changing risk factors, resources and priorities of government and funders. Anecdotally, our experience suggests that inflexibility of traditional research methods and dense academic terminology created issues with those working in prevention practice. Therefore, this paper provides a refined description of research-specific terminology of scale-up, fidelity, adaptation and context, drawing from community-based system dynamics and our experience in designing, implementing and evaluating non-linear, community-led system approaches to childhood obesity prevention., Design: We acknowledge the importance of using a practice lens, rather than purely a research design lens, and provide a narrative on our experience and perspectives on scale-up, fidelity, context and adaptation through a practice lens., Setting: Communities., Participants: Practice-based researcher experience and perspectives., Results: Practice-based researchers highlighted the key finding that community should be placed at the centre of the intervention logic. This allowed communities to self-organise with regard to stakeholder involvement, capacity, boundary identification, and co-creation of actions implemented to address childhood obesity will ensure scale-up, fidelity, context and adaptation are embedded., Conclusions: We need to measure beyond primary anthropometric outcomes and focus on evaluating more about implementation, process and sustainability. We need to learn more from practitioners on the ground and use an implementation science lens to further understand how actions work. This is where solutions to sustained childhood obesity prevention will be found.

Objective: To report the prevalence of healthy weight and related behaviours among Victorian Aboriginal and non-Aboriginal children and explore associations between these factors and health-related quality of life (HRQoL)., Methods: Analysis of cross-sectional data from two cluster randomised controlled trials using logistic and linear mixed models. The sample included Aboriginal (n=303) and non-Aboriginal (n=3,026) children aged 8-13 years., Results: More than two-thirds of Aboriginal children met guidelines for fruit (75.9%), sweetened drinks (66.7%), sleep (73.1%), screen time (67.7%) and objectively measured physical activity (83.6%); and 79.1% reported consuming take-away foods less than once per week. Aboriginal children were more likely to meet vegetable consumption guidelines (OR=1.42, 95%CI: 1.05, 1.93), but less likely to have a healthy weight (OR=0.66, 95%CI: 0.52, 0.85) than non-Aboriginal children. Mean HRQoL scores were significantly higher among non-Aboriginal children and both Aboriginal and non-Aboriginal children meeting health guidelines., Conclusions: Most Aboriginal children in this study met guidelines for fruit, physical activity, screen time and sleep, and those meeting these guidelines had significantly higher HRQoL., Implications for Public Health: Promoting nutrition, physical activity and sleep is likely to benefit all children. Aboriginal community-controlled organisations can use these data to design culturally-specific programs that may improve disparities in healthy weight and HRQoL., (© 2022 The Authors.)

Background: Participatory approaches to develop community-based system dynamics models to tackle complexity are promising, but research is needed in how simulation models can be developed with community stakeholders to yield significant system insights. This study presents the results of a community-based system dynamics modelling process to increase water consumption and decrease sugar sweetened beverage consumption in Portland, Victoria, a regional town in Australia., Methods: A series of group model building workshops with 11 community stakeholders addressing the topic of water and sugar sweetened beverage consumption was conducted in Portland. A simulating system dynamics model was built with stakeholders to inform action planning., Results: A system dynamics model was created to provide insight into water and sugar sweetened beverage consumption in Portland. The model included six feedback loops describing the causal effects of sugar sweetened beverage consumption habits and norms, water taste, water consumption norms, public water availability, and public health benefits. For example, the sugar sweetened beverage consumption norm loop modelled how people overestimating others' consumption may motivate an increase in their own consumption, feeding back and further amplifying an increase in sugar sweetened beverage consumption. The model contributed to the foundation of a strong partnership to improve the taste of water and educate the public on water consumption., Conclusions: Engaging stakeholders in system dynamics modelling about water and sugar sweetened beverage consumption increased engagement and collaboration to address the problem among community stakeholders., (© 2022. The Author(s).)

Introduction: Systems science methodologies have been used in attempts to address the complex and dynamic causes of childhood obesity with varied results. This paper presents a protocol for the Reflexive Evidence and Systems interventions to Prevention Obesity and Non-communicable Disease (RESPOND) trial. RESPOND represents a significant advance on previous approaches by identifying and operationalising a clear systems methodology and building skills and knowledge in the design and implementation of this approach among community stakeholders., Methods and Analysis: RESPOND is a 4-year cluster-randomised stepped-wedge trial in 10 local government areas in Victoria, Australia. The intervention comprises four stages: catalyse and set up, monitoring, community engagement and implementation. The trial will be evaluated for individuals, community settings and context, cost-effectiveness, and systems and implementation processes. Individual-level data including weight status, diet and activity behaviours will be collected every 2 years from school children in grades 2, 4 and 6 using an opt-out consent process. Community-level data will include knowledge and engagement, collaboration networks, economic costs and shifts in mental models aligned with systems training. Baseline prevalence data were collected between March and June 2019 among >3700 children from 91 primary schools., Ethics and Dissemination: Ethics approval: Deakin University Human Research Ethics Committee (HREC 2018-381) or Deakin University's Faculty of Health Ethics Advisory Committee (HEAG-H&#95;2019-1; HEAG-H 37&#95;2019; HEAG-H 173&#95;2018; HEAG-H 12&#95;2019); Victorian Government Department of Education and Training (2019&#95;003943); Catholic Archdiocese of Melbourne (Catholic Education Melbourne, 2019-0872) and Diocese of Sandhurst (24 May 2019). The results of RESPOND, including primary and secondary outcomes, and emerging studies developed throughout the intervention, will be published in the academic literature, presented at national and international conferences, community newsletters, newspapers, infographics and relevant social media., Trial Registration Number: ACTRN12618001986268p., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Applying systems science in public health trials is a recent innovation in childhood obesity prevention. This paper aims to use systems science conventions to propose a theory of change for community-based interventions aiming to build capacity and use exemplars from systems science for obesity prevention to describe how this approach works., Methods: Participants were community-based researchers. A dynamic hypothesis was created in workshops conducted in 2020 and 2021 by identifying variables critical to building community capacity for systems thinking. These were used to develop stock and flow diagrams representing individual causal relationships, feedback loops, and the overall theory of change., Results: The resultant model identified 9 stocks and 4 pairs of central balancing and reinforcing feedback loops. These represented building commitment through relationships, mutual learning, strengthening collaboration, and embedding capacity. The model is described using examples from 3 trials involving 25 communities across Victoria, Australia., Conclusions: This nonlinear and practice-based model illustrates the process of community-based obesity prevention. The model integrates >20 years of community-based intervention implementation experience, providing an overarching theory of how such interventions work to create change and prevent obesity., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Systems science approaches have demonstrated effectiveness in identifying underlying drivers of complex problems and facilitating the emergence of potential interventions that are locally tailored, feasible, sustainable and evidence informed. Despite the potential usefulness of system dynamics simulation modelling and other systems science modelling techniques in guiding implementation, time and cost constraints have limited its ability to provide strong guidance on how to implement complex interventions in communities. Guidance is required to ensure systems interventions lead to impactful systems solutions, implemented utilising strategies from the intersecting fields of systems science and implementation science. To provide cost-effective guidance on how and where to implement in systems, we offer a translation of the 'Meadows 12 places to act in a system' (Meadows 12) into language useful for public health., Methods: This translation of Meadows 12 was informed by our experience in working with 31 communities across two complex large scale randomised control trials and one large whole of community case study. These research projects utilised systems science and implementation science to co-create childhood obesity prevention interventions. The team undertaking this translation comprised research academics, implementation specialists and practitioners, practice-based researchers and a systems dynamicist. Our translation of each of the Meadows 12 levels to act in the system maintains the fidelity and nuance of the 12 distinct levels. We provide examples of each level of the Public Health 12 framework (PH12) drawn from 31 communities. All research was conducted in Victoria, Australia between 2016 and 2020., Results: PH12 provides a framework to guide both research and practice in real world contexts to implement targeted system level interventions. PH12 can be used with existing implementation science theory to identify relevant strategies for implementation of these interventions to impact the system at each of the leverage points., Conclusion: To date little guidance for public health practitioners and researchers exists regarding how to implement systems change in community-led public health interventions. PH12 enables operationalisation Meadows 12 systems theory into public health interventions. PH12 can help research and practice determine where leverage can be applied in the system to optimise public health systems level interventions and identify gaps in existing efforts., Trial Registration: WHO STOPS: ANZCTR: 12616000980437 ., Respond: ANZCTR: 12618001986268p ., (© 2022. The Author(s).)

Our ears capture sound from all directions but do not encode directional information explicitly. Instead, subtle acoustic features associated with unique sound source locations must be learned through experience. Surprisingly, aspects of this mapping process remain highly plastic throughout adulthood: Adult human listeners can accommodate acutely modified acoustic inputs ("new ears") over a period of a few weeks to recover near-normal sound localization, and this process can be accelerated with explicit training. Here we evaluated the extent of such plasticity given only transient exposure to distorted inputs. Distortions were produced via earplugs, which severely degrade sound localization performance, constraining their usability in real-world settings that require accurate directional hearing. Localization was measured over a period of ten weeks. Provision of feedback via simple paired auditory and visual stimuli led to a rapid decrease in the occurrence of large errors (responses >|±30°| from target) despite only once-weekly exposure to the altered inputs. Moreover, training effects generalized to untrained sound source locations. Lesser but qualitatively similar improvements were observed in a group of subjects that did not receive explicit feedback. In total, data demonstrate that even transient exposure to altered spatial acoustic information is sufficient for meaningful perceptual improvement (i.e., chronic exposure is not required), offering insight on the nature and time course of perceptual learning in the context of spatial hearing. Data also suggest that the large and potentially hazardous errors in localization caused by earplugs can be mitigated with appropriate training, offering a practical means to increase their usability., Competing Interests: Declaration of Competing Interest Authors report no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Phospholipid membranes surround the cell and its internal organelles, and their multicomponent nature allows the formation of domains that are important in cellular signalling, the immune system, and bacterial infection. Cytoplasmic compartments are also created by the phase separation of intrinsically disordered proteins into biomolecular condensates. The ubiquity of lipid membranes and protein condensates raises the question of how three-dimensional droplets might interact with two-dimensional domains, and whether this coupling has physiological or pathological importance. Here, we explore the equilibrium morphologies of a dilute phase of a model disordered protein interacting with an ideal-mixing, two-component lipid membrane using coarse-grained molecular simulations. We find that the proteins can wet the membrane with and without domain formation, and form phase separated droplets bound to membrane domains. Results from much larger simulations performed on a novel non-von-Neumann compute architecture called POETS, which greatly accelerates their execution compared to conventional hardware, confirm the observations. Reducing the wall clock time for such simulations requires new architectures and computational techniques. We demonstrate here an inter-disciplinary approach that uses real-world biophysical questions to drive the development of new computing hardware and simulation algorithms.

Background: The voluntary reporting of medical errors and near misses is a well-established patient safety reporting mechanism. However, studies suggest that these incident reporting systems (IRSs) detect less than 10% of all adverse events. Improving the process of reporting can facilitate more informative and timely data capture while providing more opportunities to improve health care quality and safety. The purpose of this study was to understand the barriers to incident reporting via the existing Web-based IRS and develop solutions to increase the ease and efficiency of reporting., Methods: A survey of staff in a diagnostic imaging department in St. Catharines, Ontario was performed to identify barriers to incident reporting. Based on the barriers identified, two methods of incident reporting were tested in successive phases: (1) a phone-based voice message mailbox, in the computed tomography suite; and (2) a phone-based structured interactive voice response system (IVRS), across the entire department. We measured the rate of incident reports/day and time required to complete reports., Outcomes: The three most common barriers to reporting identified were lack of time, complexity of reporting system, and lack of feedback. There was a significant difference in reports per day for the IVRS (mean [M] = 3.43, standard deviation [SD] = 2.71) compared to the IRS (M = 0.99, SD = 0.55); t(31) = 4.58, p ≤ 0.00001. There was also a significant difference in the average time to make a report for the IVRS (M = 97 seconds [s], SD = 30 s) compared to the IRS (M = 644 s, SD = 90 s); t(4) =13.55, p = 0.00025., Conclusion: IVRS is an innovative approach to incident reporting that may prove to be more efficient than Web-based approaches and encourage higher reporting rates., (Copyright © 2021 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Background: Sarcopenia, the age-related loss of skeletal muscle mass/function, has been identified as a marker of frailty. We examined the association between sarcopenia and adverse events following transcatheter aortic valve implantation (TAVI)., Methods: A retrospective cohort study was conducted at Toronto General Hospital. All patients who underwent TAVI in the time period 2007-2017 with preoperative computed tomography were included. Skeletal muscle index (SMI) was calculated radiographically using psoas muscle area at the L3 vertebral level, divided by height. Various measures of sarcopenia, including mean SMI, SMI below the sex-specific median, and SMI in the lowest sex-specific quartile were calculated. The primary outcome was postoperative adverse events, defined as a composite of in-hospital mortality and morbidity including cardiovascular, pulmonary, neurologic, access-related, and gastrointestinal complications. Univariate and multivariate logistic regression were performed to determine the association between sarcopenia and adverse events., Results: A total of 468 patients (mean age: 80.7 years) were included. Baseline comorbidity burden was high, particularly congestive heart failure (93.4%). Postoperative adverse events occurred in 62 patients (13.2%). Univariate logistic regression demonstrated that postoperative adverse events were correlated with mean SMI (odds ratio [OR] 0.81, 95% confidence interal [CI] 0.66-0.97), events were less than the SMI (OR 2.16, 95% CI 1.24-3.84), and SMI in the sex-specific lowest quartile (OR 2.34, 95% CI 1.33-4.07). On multivariate analysis, SMI in the sex-specific lowest quartile was an independent predictor of adverse events (OR 2.53, 95% CI 1.41-4.50)., Conclusions: Sarcopenia defined by radiologic psoas muscle measurements was independently associated with in-hospital mortality and morbidity following TAVI., (© 2021 The Authors.)

The interaural level difference (ILD) is a robust indicator of sound source azimuth, and human ILD sensitivity persists under conditions that degrade normally-dominant interaural time difference (ITD) cues. Nonetheless, ILD sensitivity varies somewhat with both stimulus frequency and interaural correlation (coherence). To further investigate the combined binaural perceptual influence of these variables, the present study assessed ILD sensitivity at frequencies 250-4000 Hz using stimuli of varied interaural correlation. In the first of two experiments, ILD discrimination thresholds were modestly elevated, and subjective lateralization slightly reduced, for both half-correlated and uncorrelated narrowband noise tokens relative to correlated tokens. Different from thresholds in the correlated condition, which were worst at 1000 Hz [Grantham, D.W. (1984). J. Acoust. Soc. Am. 75, 1191-1194], thresholds in the decorrelated conditions were independent of frequency. However, intrinsic envelope fluctuations in narrowband stimuli caused moment-to-moment variation of the nominal ILD, complicating interpretation of measured thresholds. Thus, a second experiment employed low-fluctuation noise tokens, revealing a clear effect of interaural decoherence per se that was strongly frequency-dependent, decreasing in magnitude from low to high frequencies. Measurements are consistent with known integration times in ILD-sensitive neurons and also suggest persistent influences of covert ITD cues in putative "ILD" tasks.

Objectives: The binaural interaction component (BIC) of the auditory brainstem response (ABR) is obtained by subtracting the sum of the monaural right and left ear ABRs from the binaurally evoked ABR. The result is a small but prominent negative peak (herein called "DN1"), indicating a smaller binaural than summed ABR, which occurs around the latency of wave V or its roll-off slope. The BIC has been proposed to have diagnostic value as a biomarker of binaural processing abilities; however, there have been conflicting reports regarding the reliability of BIC measures in human subjects. The objectives of the current study were to: (1) examine prevalence of BIC across a large group of normal-hearing young adults; (2) determine effects of interaural time differences (ITDs) on BIC; and (3) examine any relationship between BIC and behavioral ITD discrimination acuity., Design: Subjects were 40 normal-hearing adults (20 males and 20 females), aged 21 to 48 years, with no history of otologic or neurologic disorders. Midline ABRs were recorded from electrodes at high forehead (Fz) referenced to the nape of the neck (near the seventh cervical vertebra), with Fpz (low forehead) as the ground. ABRs were also recorded with a conventional earlobe reference for comparison to midline results. Stimuli were 90 dB peSPL biphasic clicks. For BIC measurements, stimuli were presented in a block as interleaved right monaural, left monaural, and binaural stimuli with 2000+ presentations per condition. Four measurements were averaged for a total of 8000+ stimuli per analyzed waveform. BIC was measured for ITD = 0 (simultaneous bilateral) and for ITDs of ±500 and ±750 µs. Subjects separately performed a lateralization task, using the same stimuli, to determine ITD discrimination thresholds., Results: An identifiable BIC DN1 was obtained in 39 of 40 subjects at ITD = 0 µs in at least one of two measurement sessions, but was seen in lesser numbers of subjects in a single session or as ITD increased. BIC was most often seen when a subject was relaxed or sleeping, and less often when they fidgeted or reported neck tension, suggesting myogenic activity as a possible factor in disrupting BIC measurements. Mean BIC latencies systematically increased with increasing ITD, and mean BIC amplitudes tended to decrease. However, across subjects, there was no significant relationship between the amplitude or latency of the BIC and behavioral ITD thresholds., Conclusions: Consistent with previous studies, measurement of the BIC was time consuming and a BIC was sometimes difficult to obtain in awake normal-hearing subjects. The BIC will thus continue to be of limited clinical utility unless stimulus parameters and measurement techniques can be identified that produce a more robust response. Nonetheless, modulation of BIC characteristics by ITD supports the concept that the ABR BIC indexes aspects of binaural brainstem processing and thus may prove useful in selected research applications, e.g. in the examination of populations expected to have aberrant binaural signal processing ability., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Age-related hearing loss (ARHL), also known as presbycusis, is a widespread and debilitating condition impacting many older adults. Conventionally, researchers utilize mammalian model systems or human cadaveric tissue to study ARHL pathology. Recently, the zebrafish has become an effective and tractable model system for a wide variety of genetic and environmental auditory insults, but little is known about the incidence or extent of ARHL in zebrafish and other non-mammalian models. Here, we evaluated whether zebrafish exhibit age-related loss in auditory sensitivity. The auditory sensitivity of adult wild-type zebrafish (AB/WIK strain) from three adult age subgroups (13-month, 20-month, and 37-month) was characterized using the auditory evoked potential (AEP) recording technique. AEPs were elicited using pure tone stimuli (115-4500 Hz) presented via an underwater loudspeaker and recorded using shielded subdermal metal electrodes. Based on measures of sound pressure and particle acceleration, the mean AEP thresholds of 37-month-old fish [mean sound pressure level (SPL) = 122.2 dB ± 2.2 dB SE re: 1 μPa; mean particle acceleration level (PAL) = -27.5 ± 2.3 dB SE re: 1 ms -2 ] were approximately 9 dB higher than that of 20-month-old fish [(mean SPL = 113.1 ± 2.7 dB SE re: 1 μPa; mean PAL = -37.2 ± 2.8 dB re: 1 ms -2 ; p = 0.007)] and 6 dB higher than that of 13-month-old fish [(mean SPL = 116.3 ± 2.5 dB SE re: 1 μPa; mean PAL = -34.1 ± 2.6 dB SE re: 1 ms -2 ; p = 0.052)]. Lowest AEP thresholds for all three age groups were generally between 800 Hz and 1850 Hz, with no evidence for frequency-specific age-related loss. Our results suggest that zebrafish undergo age-related loss in auditory sensitivity, but the form and magnitude of loss is markedly different than in mammals, including humans. Future work is needed to further describe the incidence and extent of ARHL across vertebrate groups and to determine which, if any, ARHL mechanisms may be conserved across vertebrates to support meaningful comparative/translational studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acoustic hearing listeners use binaural cues-interaural time differences (ITDs) and interaural level differences (ILDs)-for localization and segregation of sound sources in the horizontal plane. Cochlear implant users now often receive two implants (bilateral cochlear implants [BiCIs]) rather than one, with the goal to provide access to these cues. However, BiCI listeners often experience difficulty with binaural tasks. Most BiCIs use independent sound processors at each ear; it has often been suggested that such independence may degrade the transmission of binaural cues, particularly ITDs. Here, we report empirical measurements of binaural cue transmission via BiCIs implementing a common " n -of- m " spectral peak-picking stimulation strategy. Measurements were completed for speech and nonspeech stimuli presented to an acoustic manikin "fitted" with BiCI sound processors. Electric outputs from the BiCIs and acoustic outputs from the manikin's in-ear microphones were recorded simultaneously, enabling comparison of electric and acoustic binaural cues. For source locations away from the midline, BiCI binaural cues, particularly envelope ITD cues, were found to be degraded by asymmetric spectral peak-picking. In addition, pulse amplitude saturation due to nonlinear level mapping yielded smaller ILDs at higher presentation levels. Finally, while individual pulses conveyed a spurious "drifting" ITD, consistent with independent left and right processor clocks, such variation was not evident in transmitted envelope ITDs. Results point to avenues for improvement of BiCI technology and may prove useful in the interpretation of BiCI spatial hearing outcomes reported in prior and future studies.

Background: Community-based interventions have shown promise in addressing the childhood obesity epidemic. Such efforts rely on the knowledge of key community members and their engagement with the drivers of obesity in their community. This paper presents the protocol for the measurement and evaluation of knowledge and engagement among community leaders within a whole-of-community systems intervention across 10 large intervention communities in Australia., Methods: We will investigate the role of stakeholder knowledge and engagement in the implementation and effectiveness of the stepped wedge cluster randomised trial in ten communities in Victoria, Australia. Data will be collected using the Stakeholder-driven Community Diffusion Survey (SDCD) to measure levels of knowledge and engagement prior to commencement (2019), across the three separate levels of governance within the intervention at five time points. Primary outcomes will be baseline overall knowledge and engagement scores across the three levels of governance and change in overall knowledge and engagement over time., Discussion: We hypothesise there will be heterogeneity between intervention sites on levels of knowledge and engagement and that these differences will be associated with variability in implementation success., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12618001986268 . Registered on 11 December 2018.

This scoping study presents an investigation of the total and bioaccessible mercury concentrations in road dust (RD) from three international urban sites, where a one-off sampling campaign was conducted at each. This was done to address the hypothesis that the matrix in which mercury is found influences its ability to become accessible to the body once inhaled. For that purpose, the samples were analysed for total and pulmonary bioaccessible mercury and the data compared to the chemical structure of individual particles by SEM. The results obtained from this study suggest that a high mercury content does not necessarily equate to high bioaccessibility, a phenomenon which could be ascribed to the chemical character of the individual particles. It was found that the Manchester samples contained more pulmonary soluble mercury species (as determined by elemental associations of Hg and Cl) in comparison to the other two samples, Curitiba, Brazil, and Johannesburg, South Africa. This finding ultimately underlines the necessity to conduct a site-specific in-depth analysis of RD, to determine the concentration, chemical structure and molecular speciation of the materials within the complex matrix of RD. Therefore, rather than simply assuming that higher bulk concentrations equate to more significant potential human health concerns, the leaching potential of the metal/element in its specific form (for example as a mineral) should be ascertained. The importance of individual particle behaviour in the determination of human health risk is therefore highlighted.

It is well documented that a large portion of urban particulate matters is derived from road dust. Isolating particles of RD which are small enough to be inhaled, however, is a difficult process. In this study, it is shown for the first time that the < 38 µm fraction of road dust particles can be used as a proxy for road dust particles < 10 µm in bioaccessibility studies. This study probed similarities between the < 10 and < 38µm fractions of urban road dust to show that the larger of the two can be used for analysis for which larger sample masses are required, as is the case with in vitro analysis. Road dust, initially segregated to size < 38 µm using sieves, was again size segregated to < 10 µm using water deposition. Both the original < 38 µm and the separated < 10 µm fractions were then subject to single particle analysis by SEM-EDX and bulk analysis by ICP-OES for its elemental composition. Dissolution tests in artificial lysosomal fluid, representative of lung fluid, were carried out on both samples to determine % bioaccessibility of selected potentially harmful elements and thus probe similarities/differences in in vitro behaviour between the two fractions. The separation technique achieved 94.3% of particles < 10 µm in terms of number of particles (the original sample contained 90.4% as determined by SEM-EDX). Acid-soluble metal concentration results indicated differences between the samples. However, when manipulated to negate the input of Si, SEM-EDX data showed general similarities in metal concentrations. Dissolution testing results indicated similar behaviour between the two samples in a simulated biological fluid.

Objectives: (1) To characterize changes in brainstem neural activity following unilateral deafening in an animal model. (2) To compare brainstem neural activity from unilaterally deafened animals with that of normal-hearing controls., Study Design: Prospective controlled animal study., Setting: Vivarium and animal research facilities., Subjects and Methods: The effect of single-sided deafness on brainstem activity was studied in Chinchilla lanigera . Animals were unilaterally deafened via gentamycin injection into the middle ear, which was verified by loss of auditory brainstem responses (ABRs). Animals underwent measurement of ABR and local field potential in the inferior colliculus., Results: Four animals underwent chemical deafening, with 2 normal-hearing animals as controls. ABRs confirmed unilateral loss of auditory function. Deafened animals demonstrated symmetric local field potential responses that were distinctly different than the contralaterally dominated responses of the inferior colliculus seen in normal-hearing animals., Conclusion: We successfully developed a model for unilateral deafness to investigate effects of single-sided deafness on brainstem plasticity. This preliminary investigation serves as a foundation for more comprehensive studies that will include cochlear implantation and manipulation of binaural cues, as well as functional behavioral tests.

We report on the first 18 months of two communities' efforts using methods inspired by community-based participatory system dynamics for the development, implementation, and evaluation of whole of community efforts to improve the health of children. We apply Foster-Fishman's theoretical framework for characterizing systems change to describe the initiatives. Bounding the system began with defining leaders more broadly than standard health interventions to be those who had the ability to change environments to improve health, including food retailers, government, and business, and using high-quality childhood monitoring data to define the problem. Widespread access to junk food, barriers to physical activity, and efforts to promote health predominantly through programmatic approaches were identified as potential root causes. System interactions existed in the form of relationships between stakeholder groups and organizations. The approach described built new relationships and strengthened existing relationships. Willingness in taking risks, changing existing practice, and redesigning health promotion work to have a community development focus, were levers for change. This approach has resulted in hundreds of community-led actions focused on changing norms and environments. Insights from this approach may be useful to support other communities in translating systems theory into systems practice. Further empirical research is recommended to explore the observations in this paper., (© 2019 The Authors Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Generating political commitment for ending all forms of malnutrition represents a key challenge for the global nutrition community. Without commitment, the policies, programs, and resources needed to improve nutrition are unlikely to be adopted, effectively implemented, nor sustained. One essential driver of commitment is nutrition actor network (NAN) effectiveness, the web of individuals and organizations operating within a given country who share a common interest in improving nutrition and who act collectively to do so. To inform new thinking and action towards strengthening NAN effectiveness, we use a systems dynamics theoretical approach and literature review to build initial causal loop diagrams (CLDs) of political commitment and NAN effectiveness and a qualitative group model building (GMB) method involving an expert workshop to strengthen model validity. First, a "nutrition commitment system" CLD demonstrates how five interrelated forms of commitment-rhetorical, institutional, operational, embedded, and system-wide-can dynamically reinforce or diminish one another over time. Second, we present CLDs demonstrating factors shaping NAN effectiveness organized into three categories: actor features, resources, and capacities; framing strategies, evidence, and norms; and institutional, political, and societal contexts. Together, these models generate hypotheses on how political commitment and NAN effectiveness could be strengthened in future and may provide potential starting points for country-specific conversations for doing so., (© 2019 World Obesity Federation.)

The auditory brain stem response (ABR) is an evoked potential that indexes a cascade of neural events elicited by sound. In the present study we evaluated the influence of sound frequency on a derived component of the ABR known as the binaural interaction component (BIC). Specifically, we evaluated the effect of acoustic interaural (between-ear) frequency mismatch on BIC amplitude. Goals were to 1 ) increase basic understanding of sound features that influence this long-studied auditory potential and 2 ) gain insight about the persistence of the BIC with interaural electrode mismatch in human users of bilateral cochlear implants, presently a limitation on the prospective utility of the BIC in audiological settings. Data were collected in an animal model that is audiometrically similar to humans, the chinchilla ( Chinchilla lanigera ; 6 females). Frequency disparities and amplitudes of acoustic stimuli were varied over broad ranges, and associated variation of BIC amplitude was quantified. Subsequently, responses were simulated with the use of established models of the brain stem pathway thought to underlie the BIC. Collectively, the data demonstrate that at high sound intensities (≥85 dB SPL), the acoustically elicited BIC persisted with interaurally disparate stimulation (click frequencies ≥1.5 octaves apart). However, sharper tuning emerged at moderate sound intensities (65 dB SPL), with the largest BIC occurring for stimulus frequencies within ~0.8 octaves, equivalent to ±1 mm in cochlear place. Such responses were consistent with simulated responses of the presumed brain stem generator of the BIC, the lateral superior olive. The data suggest that leveraging focused electrical stimulation strategies could improve BIC-based bilateral cochlear implant fitting outcomes. NEW & NOTEWORTHY Traditional hearing tests evaluate each ear independently. Diagnosis and treatment of binaural hearing dysfunction remains a basic challenge for hearing clinicians. We demonstrate in an animal model that the prospective utility of a noninvasive electrophysiological signature of binaural function, the binaural interaction component (BIC), depends strongly on the intensity of auditory stimulation. Data suggest that more informative BIC measurements could be obtained with clinical protocols leveraging stimuli restricted in effective bandwidth.

The plainfin midshipman ( Porichthys notatus ) is an acoustically communicative teleost fish. Here, we evaluated auditory evoked potentials (AEPs) in reproductive female midshipman exposed to tones at or near dominant frequencies of the male midshipman advertisement call. An initial series of experiments characterized AEPs at behaviorally relevant suprathreshold sound levels (130-140 dB SPL re. 1 µPa). AEPs decreased in magnitude with increasing stimulus frequency and featured a stereotyped component at twice the stimulus frequency. Recording electrode position was varied systematically and found to affect AEP magnitude and phase characteristics. Later experiments employed stimuli of a single frequency to evaluate contributions of the saccule to the AEP, with particular attention to the effects of sound source azimuth on AEP amplitude. Unilateral excision of saccular otoliths (sagittae) decreased AEP amplitude; unexpectedly, decreases differed for right versus left otolith excision. A final set of experiments manipulated the sound pressure-responsive swim bladder. Swim bladder excision further reduced the magnitude of AEP responses, effectively eliminating responses at the standard test intensity (130 dB SPL) in some animals. Higher-intensity stimulation yielded response minima at forward azimuths ipsilateral to the excised sagitta, but average cross-azimuth modulation generally remained slight. Collectively, the data underscore that electrode position is an essential variable to control in fish AEP studies and suggest that in female midshipman: (1) the saccule contributes to the AEP, but its directionality as indexed by the AEP is limited, (2) a left-right auditory asymmetry may exist and (3) the swim bladder provides gain in auditory sensitivity that may be important for advertisement call detection and phonotaxis., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

The original version of this article published previously contained an error.