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Eric D Kirby,1 Katherine Jones,2 Natasha Campbell,2 Shaun D Fickling,1,2 Ryan CN D’Arcy1– 3 1Brainnet, Faculty of Applied Sciences, Simon Fraser University, Metro Vancouver, BC, Canada; 2Centre for Neurology Studies, HealthTech Connex, Metro Vancouver, BC, Canada; 3DM Centre for Brain Health, University of British Columbia, Metro Vancouver, CanadaCorrespondence: Ryan CN D’Arcy, Centre for Neurology Studies, HealthTech Connex, Metro Vancouver, BC, Canada, Email Ryan@healthtechconnex.comIntroduction: Athletic peak performance is increasingly focused on cognitive and mental factors. In the current study, cognitive performance was measured by neurophysiological responses in elite Junior-A hockey players.Methods: Neurophysiological brain vital signs were extracted from event-related potentials (ERPs) to evaluate auditory sensation (the N100), basic attention (the P300), and cognitive processing (the N400). In total, we evaluated 348 athletes, across 17 teams, throughout different hockey arenas in British Columbia, Canada. While brain vital signs were collected to help manage concussion, the current investigation focused on a retrospective performance analysis of cognitive processing differences.Results: The results revealed three interesting findings: 1) Player position differences were detectable in sensory N100 latency, with significantly faster responses for forwards compared to defense; 2) Goalies showed significantly higher attention P300 amplitude compared to all other positions; and 3) Cognitive N400 processing differences were detectable only during competitive combine testing, showing 60ms latency differences between forwards and defense on average.Discussion: The current findings suggest that neurophysiological responses, which are also sensitive to concussion, may be used to identify sensory, attentional, and cognitive processing differences to help optimize peak performance.Keywords: electroencephalography, event-related potentials, brain vital signs, performance optimization, ice hockey

A method for directly calculating the temperature derivative of two-dimensional infrared (2D-IR) spectra from simulations at a single temperature is presented. The approach is demonstrated by application to the OD stretching spectrum of isotopically dilute aqueous (HOD in H2O) solutions of urea as a function of concentration. Urea is an important osmolyte because of its ability to denature proteins, which has motivated significant interest in its effect on the structure and dynamics of water. The present results show that the temperature dependence of both the linear IR and 2D-IR spectra, which report on the underlying energetic driving forces, is more sensitive to urea concentration than the spectra themselves. Additional physical insight is provided by calculation of the contributions to the temperature derivative from different interactions, e.g., water–water, water–urea, and urea–urea, present in the system. Finally, it is demonstrated how 2D-IR spectra at other temperatures can be obtained from only room temperature simulations. [ABSTRACT FROM AUTHOR]

A daughter’s ability to inherit property is treated differently in various ancient Near Eastern cultures. This paper examines the difference between land inheritance by daughters in Israel and Babylon using the text of Numbers 27 and Babylonian Boundary Stone 9. The unique status of land and land allotment in the two societies are explored as well as the implications for the status of daughters. The conclusion from the comparison is that the biblical text excludes daughters because of limited landholdings and the desire to maintain the property inheritance from the initial land allotment event. However, Babylonian Boundary Stone 9 allows daughters to inherit more easily because of fluid landholdings and multiple (royal) land allotment events.

There was no association between antibody titres and infection episodes after two vaccine doses, but antibody titres were associated with lower BTI risk after three or four vaccine doses on multivariable analysis. B Conclusion: b Anti-S antibody titres can predict the risk of COVID-19 infection after three or more vaccine doses in patients with lymphoma. B Introduction: b Patients with B-cell lymphoma have poorer antibody responses to COVID-19 vaccines compared to patients with other malignancies. [Extracted from the article]

Purpose: Little research has focused on the potential impact that the environment plays in shaping cardiac rehabilitation (CR) patient sedentary time (ST) and physical activity (PA). To address this, the current study generated daily path areas (DPAs) based on the locations they visited during and after they completed CR., Methods: Patients in CR (n = 66) completed a survey and wore an accelerometer and Global Positioning System receiver for 7 days early (first month), late (last 2 weeks of program), and 3 months after completing CR., Results: Individual DPAs were approximately 24 km2 at baseline and remained stable over time. Location-based analyses showed that most patients' ST and PA time was spent at home, followed by other residential, commercial, work, and CR locations. However, the time spent in certain locations (eg, parks and recreation locations) fluctuated during and after CR by intensity., Conclusions: CR patient DPA was stable over time. Within this space, they primarily engaged in ST and PA at home. However, when not home, the distribution of location use varied across a number of locations that extended well beyond their neighborhoods. Therefore, proximity to home may not be a barrier for CR patients in relation to their ST and PA., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A digital adaptation of the nine-hole peg test (9HPT) was developed with the potential to provide novel disability features for patients with multiple sclerosis (PwMS)., Objectives: The objectives were to evaluate the 9HPT features based on reliability, prognosis, and discrimination between treatment groups., Methods: The MS partners Advancing Technology and Health Solutions (MS PATHS) cohort data were used to derive new features including completion time and speed. Association and reliability between features and clinical outcomes were tested by intraclass correlation coefficients (ICCs) with repeated measures. The added prognostic value of the features for a clinically meaningful decline was assessed by time-to-event analyses with likelihood ratio tests. The estimated effect size between treatment efficacy groups was acquired from linear mixed-effects models. Sample size was calculated for a hypothetical randomized clinical trial., Results: For the 10,843 PwMS, speed and completion time were associated with MS disability. Compared with time, speed showed higher reliability (ICC = 0.78 vs 0.74), added benefits in predicting disability worsening ( p < 0.001), better discrimination between high- and low-efficacy groups (effect size: 0.035 vs 0.015), and an 18% reduction in required sample size for a 1-year clinical trial., Conclusion: Integrating horizontal hand distances traveled over the 9HPT pegboard can be a more reliable measure of hand function., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.M. serving on scientific advisory boards for Genzyme and Genentech and research support from AHRQ, Biogen, NIH, and Novartis. R.B. received consultant fees for Biogen, Genentech, Genzyme, and Novartis; research support from Biogen, Genentech, and Novartis; and shares rights to intellectual property underlying the Multiple Sclerosis Performance Test, currently licensed to Qr8 Health and Biogen. D.O. received research support from Genentech, Genzyme, and Novartis and consulting fees from Biogen, Genentech-Roche, Genzyme, Novartis, and Merck. R.T.N. has consulted for Alexion Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, Genentech, Genzyme, EMD Serono, Horizon Therapeutics, Lundbeck, and TG Therapeutics. X.J. and Z.S. are the employees of and may hold stock/stock options in Biogen. N.L. is the former employee of and may hold stock/stock options in Biogen. R.H. and J.v.B are the former employees of and may hold stock/stock options in Biogen and TW1 Healthcare and consultant for International Registry for Alzheimer’s Disease and other dementias (InRAD). N.C. is the former employee of and may hold stock/stock options in Biogen and current employee of Janssen Scientific Affairs, LLC. CB. is the former employee of and may hold stock/stock options in Biogen and current employee of Novartis. J.J. and J.A. have no disclosures.

Background: The use of electronic health record (EHR) data for research is limited by a lack of structure and a standard data model. The objective of the ICAREdata (Integrating Clinical Trials and Real-World Endpoints Data) project was to structure key research data elements in EHRs using a minimal Common Oncology Data Elements (mCODE) data model to extract and transmit data., Methods: The ICAREdata project captured two EHR data elements essential to clinical trials: cancer disease status and treatment plan change. The project was implemented in clinical sites participating in Alliance for Clinical Trials in Oncology trials. Data were extracted from EHRs and sent by secure Fast Healthcare Interoperability Resource messaging (a standard for exchanging EHRs) to a database. Selected elements were compared with corresponding data from the trial's electronic data capture (EDC) system, Medidata Rave., Results: By December 2023, data were extracted and transmitted from 10 sites for 35 patients, involving 367 clinical encounters across 15 clinical trials. Data through March 2023 demonstrated that concordance for the elements treatment plan change and cancer disease status was 79% and 34%, respectively. When disease evaluation was reported by both EHR and EDC (n = 15), there was 87% agreement on cancer disease status., Conclusions: Documentation, extraction, and aggregation of structured data elements in EHRs using mCODE and ICAREdata methods is feasible in multi-institutional cancer clinical trials. EDC as a reference data set allowed assessment of the completeness of EHR data capture. Future initiatives will focus on elements with shared definitions in clinical and research environments and efficient workflows., Plain Language Summary: Clinical trials use electronic case report forms to report data, and data must be manually entered on these forms, which is costly and time consuming. ICAREdata methods use structured, organized data from clinical trials that can be more easily shared instead having to enter free text into electronic health records., (© 2024 The MITRE Corporation and The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objectives: The Integrating Clinical Trials and Real-World Endpoints (ICAREdata) project aimed to demonstrate that electronic health record (EHR) data, expressed in a standard structured format, can be extracted and transmitted to contribute to clinical research. Using the minimal Common Oncology Data Elements (mCODE), we collected standardized oncology outcome data from EHRs across 10 clinical sites and 15 trials. This report details and assesses the ICAREdata technical implementation and offers recommendations to benefit future projects with similar goals., Materials and Methods: In the ICAREdata project, we implemented tools to collect structured clinical outcome data within EHRs, then extract and transmit the mCODE-formatted data to a secure cloud storage platform. Using the socio-technical model of health information technology, we systematically assessed the technical implementations in this multi-institutional project., Results: We evaluated the ICAREdata method across the 8 inter-related dimensions of the socio-technical model. For each dimension, we identified challenges and developed recommendations that implementers of future initiatives can leverage., Discussion: The ICAREdata project successfully demonstrated the feasibility of using data standards for structured data capture and transmission in clinical trials. The lessons learned from this project can accelerate the success of similar initiatives using standards-based real-world data (RWD) capture and transmission for research., Conclusion: The ICAREdata project represents a step towards a future where researchers can access high-quality, standardized RWD leading to advances in research and improved care delivery., Competing Interests: The authors have no competing interests to report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Importance: Since 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer's Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations., Objective: To consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states., Evidence Review: PubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms "biomarker" OR "amyloid" OR "tau" OR "neurodegeneration" OR "preclinical" OR "CSF" OR "PET" OR "plasma" AND "Alzheimer's disease." The references of relevant articles were also searched., Findings: In the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease., Conclusions and Relevance: The ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.

Background: Smartphones and wearables are revolutionizing the assessment of cognitive and motor function in neurological disorders, allowing for objective, frequent, and remote data collection. However, these assessments typically provide a plethora of sensor-derived measures (SDMs), and selecting the most suitable measure for a given context of use is a challenging, often overlooked problem., Objective: This analysis aims to develop and apply an SDM selection framework, including automated data quality checks and the evaluation of statistical properties, to identify robust SDMs that describe the cognitive and motor function of people with multiple sclerosis (MS)., Methods: The proposed framework was applied to data from a cross-sectional study involving 85 people with MS and 68 healthy participants who underwent in-clinic supervised and remote unsupervised smartphone-based assessments. The assessment provided high-quality recordings from cognitive, manual dexterity, and mobility tests, from which 47 SDMs, based on established literature, were extracted using previously developed and publicly available algorithms. These SDMs were first separately and then jointly screened for bias and normality by 2 expert assessors. Selected SDMs were then analyzed to establish their reliability, using an intraclass correlation coefficient and minimal detectable change at 95% CI. The convergence of selected SDMs with in-clinic MS functional measures and patient-reported outcomes was also evaluated., Results: A total of 16 (34%) of the 47 SDMs passed the selection framework. All selected SDMs demonstrated moderate-to-good reliability in remote settings (intraclass correlation coefficient 0.5-0.85; minimal detectable change at 95% CI 19%-35%). Selected SDMs extracted from the smartphone-based cognitive test demonstrated good-to-excellent correlation (Spearman correlation coefficient, |ρ|>0.75) with the in-clinic Symbol Digit Modalities Test and fair correlation with Expanded Disability Status Scale (EDSS) scores (0.25≤|ρ|<0.5). SDMs extracted from the manual dexterity tests showed either fair correlation (0.25≤|ρ|<0.5) or were not correlated (|ρ|<0.25) with the in-clinic 9-hole peg test and EDSS scores. Most selected SDMs from mobility tests showed fair correlation with the in-clinic timed 25-foot walk test and fair to moderate-to-good correlation (0.5<|ρ|≤0.75) with EDSS scores. SDM correlations with relevant patient-reported outcomes varied by functional domain, ranging from not correlated (cognitive test SDMs) to good-to-excellent correlation (|ρ|>0.75) for mobility test SDMs. Overall, correlations were similar when smartphone-based tests were performed in a clinic or remotely., Conclusions: Reported results highlight that smartphone-based assessments are suitable tools to remotely obtain high-quality SDMs of cognitive and motor function in people with MS. The presented SDM selection framework promises to increase the interpretability and standardization of smartphone-based SDMs in people with MS, paving the way for their future use in interventional trials., (©Matthew Scaramozza, Aurélie Ruet, Patrizia A Chiesa, Laïtissia Ahamada, Emmanuel Bartholomé, Loïc Carment, Julie Charre-Morin, Gautier Cosne, Léa Diouf, Christine C Guo, Adrien Juraver, Christoph M Kanzler, Angelos Karatsidis, Claudia Mazzà, Joaquin Penalver-Andres, Marta Ruiz, Aurore Saubusse, Gabrielle Simoneau, Alf Scotland, Zhaonan Sun, Minao Tang, Johan van Beek, Lauren Zajac, Shibeshih Belachew, Bruno Brochet, Nolan Campbell. Originally published in JMIR Formative Research (https://formative.jmir.org), 08.11.2024.)

Background: Two-stage models of heterogenous treatment effects (HTE) may advance personalized medicine in multiple sclerosis (MS). Brain atrophy is a relatively objective outcome measure that has strong relationships to MS prognosis and treatment effects and is enabled by standardized MRI., Objectives: To predict brain atrophy outcomes for patients initiating disease-modifying therapies (DMT) with different efficacies, considering the patients' baseline brain atrophy risk measured via brain parenchymal fraction (BPF)., Methods: Analyses included patients enrolled in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network who started DMT and had complete baseline data and ≥ 6-month brain MRI follow-up. All brain MRIs were acquired using standardized acquisition sequences on Siemens 3T scanners. BPF change risk was derived by linear mixed effects models using baseline covariates. Model performance was assessed by predicted versus actual BPF change R 2 . Propensity score (PS) weighting was used to balance covariates between groups defined by DMT efficacy (high: natalizumab, alemtuzumab, ocrelizumab, and rituximab; moderate: dimethyl fumarate, fingolimod, and cladribine; low: teriflunomide, interferons, and glatiramer acetate). HTE models predicting 1 year change in BPF were built using a weighted linear mixed effects model with low-efficacy DMT as the reference., Results: Analyses included 581 high-, 183 moderate-, and 106 low-efficacy DMT-treated patients. The mean and median number of brain MRI observations per treatment period were 2.9 and 3.0, respectively. Risk model performance R 2 =0.55. After PS weighting, covariate standardized mean differences were <10 %, indicating excellent balance across measured variables. Changes in BPF between baseline and follow-up were found to be statistically significant (p < 0.001), suggesting a pathological change. Patients with low brain atrophy risk had a similar outcome regardless of DMT selection. In patients with high brain atrophy risk, high- and moderate-efficacy DMTs performed similarly, while a 2-fold worse BPF change was predicted for patients selecting low-efficacy DMTs (p < 0.001). Similar results were observed in a sensitivity analysis adjusting for pseudoatrophy effects in a sub-population of patients treated with natalizumab., Conclusions: The relative benefit of selecting higher efficacy treatments may vary depending on patients' baseline brain atrophy risk. Poor outcomes are predicted in individuals with high baseline risk who are treated with low-efficacy DMTs., Competing Interests: Declaration of competing interest The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Carrie M. Hersh has received speaker, consulting, and/or advisory board fees from Biogen, Novartis, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, TG Therapeutics, Alexion Pharmaceuticals, and Horizon Therapeutics; she also receives research paid directly to her institution from Biogen, Novartis, Bristol Meyers-Squibb, NIHNINDS 1U01NS111678–01A1 sub-award, and Patient Centered Outcomes Research Institute. Zhaonan Sun is an employee of Biogen and may own stock in Biogen at the time this analysis was conducted. Devon Conway, MD has received research support paid to his institution from Novartis, EMD Serono, Horizon Therapeutics, Biogen, Bristol Meyers Squibb, and the Department of Defense. He has received consulting fees from Novartis, Bristol Myers Squibb, TG Therapeutics, and Arena Pharmaceuticals and speaking fees from Biogen. Elias Sotirchos has consulted for Alexion, Horizon Therapeutics, TG Therapeutics, and Roche/Genentech, and has received speaking honoraria from Alexion and Biogen. Kathryn C. Fitzgerald has no conflicts of interest to disclose. Le H. Hua has served as a consultant to Genentech, Novartis, EMD Serono, TG Therapeutics, Horizon, and Alexion; on scientific advisory boards for Genentech, EMD Serono and Novartis; and has received non-promotional speaker honoraria for Genzyme and TG Therapeutics. She has received research funding paid directly to her institution from Biogen. Tjalf Ziemssen received grants and study funding as well as speaking and consulting fees from Biogen, BMS, Hexal, Merck, Novartis, Roche, Sanofi, TEVA and Viatris. Robert T. Naismith has consulted for Alexion Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, Genentech, Genzyme, EMD Serono, Horizon Therapeutics, Novartis, TG Therapeutics. Fabio Pellegrini was an employee of Biogen and may own stock in Biogen at the time this analysis was conducted. Cynthia Grossman was an employee of Biogen and may own stock in Biogen at the time this analysis was conducted. Nolan Campbell was an employee of Biogen and may own stock in Biogen at the time this analysis was conducted., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Monitoring cell-free plasma hemoglobin (PHb) during extracorporeal therapies allows early intervention of significant hemolysis, but timely measurements are often challenging. We thus present an analysis of a rapid benchtop device's ability to detect clinically significant hemolysis (PHb ≥50 mg/dL)., Methods: PHb was measured in 419 plasma samples from 88 pediatric patients undergoing cardiopulmonary bypass via both the benchtop device (HemoCue® Plasma/Low Hb system) and the clinical laboratory at the Children's Hospital of Pittsburgh (reference standards). Values of PHb ≥50 mg/dL as measured by the reference standard was defined as the binary outcome of clinically significant hemolysis. Analyses included Pearson correlations, logistic regression, receiver operating characteristic curves, and Bland-Altman. Because the manufacturer specifications identify the measurement range of the HemoCue® system as 30-3000 mg/dL, a secondary analysis was completed using PHb ≥30 mg/dL., Results: Using reference measurements, 66/88 subjects had at least one PHb level that fell within the range of detection (≥30 mg/dL) of the benchtop device and 46/88 had significant hemolysis as defined by PHb ≥50 mg/dL. PHb levels ≥30 mg/dL largely correlated with measurements made with the benchtop device (r = 0.82, p < .001). The device was able to predict PHb values ≥30 mg/dL (AUROC 0.9582) and ≥50 mg/dL (AUROC 0.9637). The Bland-Altman demonstrated a mean difference of 7.0 mg/dL with <5% outside the 95% limits of agreement., Conclusions: The HemoCue® system is an effective surrogate for more robust laboratory testing to identify clinically significant hemolysis during cardiopulmonary bypass., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Conflict-of-Interest Disclosures: Nnenia Campbell reports grants from Bill Anderson Fund. Betty S. Lai reports grants from The Grodman Family Foundation, grants from Canadian Institutes of Health Research, grants from WT Grant Foundation, grants from National Science Foundation, grants from Social Science and Humanities Research Council, and consulting on a grant from the Office of Head Start.

Objective: Preeclampsia (PE) is associated with hypertension (HTN) during pregnancy and activated CD4+ T cells, inflammatory cytokines, and autoantibodies to the angiotensin II type I receptor (AT1-AA). Having had COVID-19 (CV) during pregnancy is associated with an increased incidence of a PE-like phenotype. Both PE and CV have long-lasting neurological implications and studies show that nonpregnant COVID patients produce AT1-AA. We have shown that CD4+ T cells from PE women cause a PE phenotype in nude athymic rats. In this study, we sought to examine the role of CD4+ T cells from PE with a CV History (Hx) to contribute to a PE phenotype and to determine the importance of CD4+ T cells in cognitive dysfunction during pregnancy., Methods: At delivery, blood and placentas were collected, and one million placental CD4+ T cells from each PE and each normotensive patient, with (NT) or without (NP) a CV (Hx) during pregnancy, were isolated, purified, and injected i.p. into a gestational day (GD) 12 pregnant nude athymic rat (one patient/rat). At GD19, blood pressure (MAP) and circulating factors were assessed in recipient rats. Cognitive function and memory were assessed using Novel Object Recognition and Barnes Maze tests, respectively. Placental ACE-2 activity and AT1-AA were measured from COVID Hx patients. A one- or two-way ANOVA with Bonferroni's multiple comparisons test was used for statistical analysis., Results: Blood pressure was increased in patients with PE, with or without COVID, compared to NT patients. There were no significant changes in placental ACE activity in patients with COVID Hx with or without PE. AT1-AA was elevated in PE patients and in both PE and NT COVID Hx compared to control NP. In pregnant recipient rats, MAP increased in CV Hx PE (113 ± 2, n = 8) compared to CV Hx NT (101 ± 5, n = 6). PE and PE CV Hx CD4+ T Cell recipient rats exhibited impaired memory and cognitive dysfunction (p < 0.05), compared to control groups. Recipient rats of PE CV Hx CD4+ T cells had elevated AT1-AA compared to NT CV Hx recipients. Both COVID Hx groups and recipients of PE CD4+ T cells had elevated TNF alpha compared to NP., Conclusion: Our findings indicate that pregnant patients with a Hx of COVID during pregnancy produce AT1-AA, with or without PE. Recipients of CD4+ T cells from PE with or without a CV Hx during pregnancy cause HTN and elevated AT1-AA. TNF-α is elevated in PE and in CV Hx NT and PE recipients. Interestingly, recipients of T cells from PE patients with or without a Hx of CV had worse cognitive function during pregnancy, compared to recipient rats of NP CD4+ T cells. These data demonstrate the importance of CD4+ T cells in HTN and impaired neurological function during PE in the presence or absence of a prior COVID-19 infection during pregnancy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: There is a shortage of nurses, Aboriginal Health Practitioners, GPs and other staff in remote Australian health clinics. There is also high turnover of staff, leading to questions of 'who' is appropriate for remote First Nations practice? The aim of this paper was to identify the characteristics of staff who are likely to work well in remote First Nations settings, from the perspectives of remote health practitioners., Design: This is a qualitative study involving content analysis of interviews., Setting: The study is conducted in and with 11 Aboriginal Community Controlled Health Services across northern and central Australia., Participants: Eighty-four staff working in these clinics who spoke about staff qualities suited to remote practice., Results: Participants identified a range of qualities desirable in remote practitioners, which were grouped into three topics: (1) professional qualifications and experience, including cultural skills; (2) ways of working, including holisitic approach, resilience, competence, and being a team player, approachable, flexible and hard-working; and (3) specific community needs, namely the need for local First Nations staff, male practitioners and returning short-term staff. The combination of experiences, ways of working, and fit to both the team and community were emphasised., Conclusion: Identifying the characteristics of staff who are likely to work well in these settings can inform recruitment strategies. This study found that a combination of professional qualifications, skills and experience as well as ways of working, individual characteristics and needs of communities are desirable for working in remote, First Nations settings., (© 2024 The Author(s). Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)

Several clinical trials have demonstrated the effectiveness of internet-delivered psychological-based pain management programs (PMPs). However, to date, no large studies have reported the outcomes of PMPs when delivered by specialist multidisciplinary pain services in routine care. The present study reports (n = 653) the outcomes of an internet-delivered PMP provided as routine care by a specialist Australian regional pain service over a 6-year period. High levels of treatment commencement (85%) and completion (72%) were observed, with more than 80% of patients reporting they were satisfied with the intervention. Clinical improvements were observed from pretreatment to post-treatment (% change, 95% confidence intervals (CI)) in pain-related disability (8.8%; 4.5, 12.8), depression (28.4%; 23.0, 33.4), anxiety (21.9%; 14.6, 28.5), and pain intensity (7%; 3.5, 10.5), which were maintained to 3-month follow-up. At 3-month follow-up, 27% (23, 31), 46% (41, 51), 44% (39, 49), and 22% (19, 26) reported clinically meaningful (defined as ≥ 30%) improvements in pain-related disability, depression, anxiety, and pain intensity, respectively. These results were obtained with relatively little therapist time per patient (M = 30.0, (standard deviation) SD = 18.8) to deliver the intervention. The current findings highlight the potential of internet-delivered PMPs as part of the services provided by specialist pain services, particularly those servicing large geographical regions and for patients unable to travel to clinics for face-to-face care. PERSPECTIVE: This study reports the outcomes of the routine delivery of an internet-delivered psychological PMP by a specialist pain service. The findings highlight the potential of this model of care when provided by specialist pain services, particularly for patients not unable to attend and not requiring intensive face-to-face care., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Personalised Asthma Action Plans (AAPs) are a cornerstone of paediatric asthma management. We aimed to assess parental knowledge and perceptions of the use of AAPs in managing their child's asthma., Methods: In 2023 we conducted a cross-sectional survey to assess knowledge and perceptions of AAPs in parents/caregivers of children aged 0-17 years with asthma who had an AAP and attended respiratory clinics at Sydney Children's Hospital, Randwick. The questionnaire included parental perceptions on the utility of AAPs, parental asthma management self-efficacy (PAMSE), and an adapted version of the Asthma Action Plan Knowledge Interview tool (AAPKI). Descriptive statistics and regression analyses were used to assess associations between AAPKI, PAMSE and other outcomes., Results: Seventy-one parents completed the survey. Mean PAMSE score was 4.2/5 (SD 0.5). Median AAPKI score was 70.2% out of 100% (IQR 20.4%). Most parents (80.0%, n = 56) were satisfied/very satisfied with using AAPs to manage their child's asthma. Most agreed/strongly agreed that AAPs were helpful in knowing when to seek medical attention for their child's asthma (81.7%, n = 58), helped their understanding of asthma severity (81.7%, n = 58), and increased their confidence in asthma management (76.0%, n = 54). Over half of parents (55.7%, n = 39) would prefer AAPs digitally and majority (78.6%, n = 55) would like colour-coded AAPs., Conclusion: High levels of AAP knowledge and self-efficacy scores were demonstrated. Most parents expressed understanding of the benefits of AAPs. Our findings suggest parents of children with asthma prefer AAPs in colour and in digital version which may help guide standardisation of AAPs across Australia.

Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo. We find that Mir483 expression is dependent on Igf2 transcription and the regulation of the Igf2/H19 imprinting control region. Transgenic Mir483 overexpression in utero causes fetal, but not placental, growth restriction through insulin-like growth factor 1 (IGF1) and IGF2 and also causes cardiovascular defects leading to fetal death. Overexpression of Mir483 post-natally results in growth stunting through IGF1 repression, increased hepatic lipid production, and excessive adiposity. IGF1 infusion rescues the post-natal growth restriction. Our findings provide insights into the function of Mir483 as a growth suppressor and metabolic regulator and suggest that it evolved within the INS-IGF2-H19 transcriptional region to limit excessive tissue growth through repression of IGF signaling., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Aboriginal Community Controlled Health Services (ACCHSs) in Australia aim to optimise access to comprehensive and culturally safe primary health care (PHC) for Aboriginal populations. Central to quality service provision is the retention of staff. However, there is lack of published research reporting patterns of staff turnover and retention specific to ACCHSs. This study quantified staff turnover and retention in regional and remote ACCHSs in the Northern Territory (NT) and Western Australia (WA), and examined correlations between turnover and retention metrics, and ACCHSs' geographical and demographic characteristics., Methods: The study used 2017-2019 payroll data for health workers in 22 regional and remote PHC clinics managed by 11 ACCHSs. Primary outcome measures included annual turnover and 12-month stability rates, calculated at both clinic and organisation levels., Results: There was a median of five client-facing (Aboriginal health practitioners, allied health professionals, doctors, nurses/midwives, and 'other health workers' combined) and two non-client-facing (administrative and physical) staff per remote clinic, at any timepoint. Mean annual turnover rates for staff were very high, with 151% turnover rates at the clinic level and 81% turnover rates at the organisation level. Mean annual turnover rates for client-facing staff were 164% and 75%, compared to 120% and 98% for non-client-facing staff, at clinic and organisational levels, respectively. Mean 12-month stability rates were low, with clinic-level stability rates of only 49% and organisation-level stability rates of 58%. Mean annual clinic-level turnover rates were 162% for non-Aboriginal staff and 81% for Aboriginal staff. Both workforce metrics were moderately to highly correlated with the relative remoteness of clinics, size of regular clients serviced, and average annual headcount of employees in each clinic (p values < 0.01)., Conclusions: Participating ACCHSs in remote NT and WA have very high turnover and low retention of healthcare staff. Overall, clinic-level turnover rates increase as distance from regional centres increases and are lower for Aboriginal staff, suggesting that greater employment of Aboriginal staff could help stabilise staffing. Improved retention could reduce burden on ACCHSs' resources and may also support quality of service delivery due to improved cultural safety and continuity of care., (© 2024. The Author(s).)

Background: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations., Methods: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504)., Results: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10 -5 ). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10 -33 ) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10 -9 ) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts., Conclusions: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers., Funding: This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332., Competing Interests: WD, NC, NC, SA, Rd, AL, KM, SA, PS, ST, TM, KT, PM, MA, ES, GP, SA No competing interests declared, (© 2024, Deng et al.)

Background: The Konectom™ smartphone-based cognitive processing speed (CPS) test is designed to assess processing speed and account for impact of visuomotor function on performance., Objective: Evaluate reliability and validity of Konectom CPS Test, performed in clinic and remotely., Methods: Data were collected from people with multiple sclerosis (PwMS) aged 18-64 years and healthy control participants (HC) matched for age, sex, and education. Remote test-retest reliability (intraclass correlation coefficients, ICC); correlation with established clinical measures (Spearman correlation coefficients); group analyses between cognitively impaired/unimpaired PwMS; and influence of age, sex, education, and upper limb motor function on CPS Test measures were assessed., Results: Eighty PwMS and 66 HC participated. CPS Test measures from remote tests had good test-retest reliability (ICC of 0.67-0.87) and correlated with symbol digit modalities test (highest |ρ| = 0.80, p < 0.0001). Remote measures were stable (change from baseline < 5%) and correlated with MS disability (highest |ρ| = 0.39, p = 0.0004) measured by Expanded Disability Status Scale. CPS Test measures displayed sensitivity to cognitive impairment (highest d = 1.47). Demographics and motor function had the lowest impact on CPS Test substitution time, a measure accounting for visuomotor function., Conclusion: Konectom CPS Test measures provide valid, reliable remote measurements of cognitive processing speed in PwMS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MS, MR, ZS: employees of and may hold stock in Biogen. LZ, MT, EB, NC, PAC, AJ: former employees of and may hold stock in Biogen. BB: honoraria for advisory boards for Biogen, Genzyme, Merck-Serono, Novartis, and Roche; his institution (Groupe Hospitalier Pellegrin) received support for clinical trials and research activities from Actelion, Bayer HealthCare, Biogen, Genzyme, Merck-Serono, MedDay, Novartis, Roche, and Teva. LC: study funding from Biogen. AR: scientific advisory boards of Biogen and Merck; travel or speaker honoraria from Alexion, Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme; institution received research support from Biogen, Roche, and Sanofi-Genzyme. The remaining authors had nothing to disclose.

Introduction: The COVID-19 pandemic period (2020 to 2022) challenged and overstretched the capacity of primary health care services to deliver health care globally. The sector faced a highly uncertain and dynamic period that encompassed anticipation of a new, unknown, lethal and highly transmissible infection, the introduction of various travel restrictions, health workforce shortages, new government funding announcements and various policies to restrict the spread of the COVID-19 virus, then vaccination and treatments. This qualitative study aims to document and explore how the pandemic affected primary health care utilisation and delivery in remote and regional Aboriginal and Torres Strait Islander communities., Methods: Semi-structured interviews were conducted with staff working in 11 Aboriginal Community-Controlled Health Services (ACCHSs) in outer regional, remote and very remote Australia. Interviews were transcribed, inductively coded and thematically analysed., Results: 248 staff working in outer regional, remote and very remote primary health care clinics were interviewed between February 2020 and June 2021. Participants reported a decline in numbers of primary health care presentations in most communities during the initial COVID-19 lock down period. The reasons for the decline were attributed to community members apprehension to go to the clinics, change in work priorities of primary health care staff (e.g. more emphasis on preventing the virus entering the communities and stopping the spread) and limited outreach programs. Staff forecasted a future spike in acute presentations of various chronic diseases leading to increased medical retrieval requirements from remote communities to hospital. Information dissemination during the pre-vaccine roll-out stage was perceived to be well received by community members, while vaccine roll-out stage information was challenged by misinformation circulated through social media., Conclusions: The ability of ACCHSs to be able to adapt service delivery in response to the changing COVID-19 strategies and policies are highlighted in this study. The study signifies the need to adequately fund ACCHSs with staff, resources, space and appropriate information to enable them to connect with their communities and continue their work especially in an era where the additional challenges created by pandemics are likely to become more frequent. While the PHC seeking behaviour of community members during the COVID-19 period were aligned to the trends observed across the world, some of the reasons underlying the trends were unique to outer regional, remote and very remote populations. Policy makers will need to give due consideration to the potential effects of newly developed policies on ACCHSs operating in remote and regional contexts that already battle under resourcing issues and high numbers of chronically ill populations., (© 2024. The Author(s).)

Introduction: The out-of-hospital emergency medical service (EMS) care responses and the transport pathways to hospital play a vital role in patient survival following injury and are the first component of a well-functioning, optimised system of trauma care. Despite longstanding challenges in delivering equitable healthcare services in the health system of Aotearoa-New Zealand (NZ), little is known about inequities in EMS-delivered care and transport pathways to hospital-level care., Methods: This population-level cohort study on out-of-hospital care, based on national EMS data, included trauma patients <85 years in age who were injured in a road traffic crash (RTC). In this study we examined the combined relationship between ethnicity and geographical location of injury in EMS out-of-hospital care and transport pathways following RTCs in Aotearoa-NZ. Analyses were stratified by geographical location of injury (rural and urban) and combined ethnicity-geographical location (rural Māori, rural non-Māori, urban Māori, and urban non-Māori)., Results: In a two-year period, there were 746 eligible patients; of these, 692 were transported to hospital. Indigenous Māori comprised 28% (196) of vehicle occupants attended by EMS, while 47% (324) of patients' injuries occurred in a rural location. The EMS transport pathways to hospital for rural patients were slower to reach first hospital (total in slowest tertile of time 44% vs 7%, P  ≥ 0.001) and longer to reach definitive care (direct transport, 77% vs 87%, P  = 0.001) compared to urban patients. Māori patients injured in a rural location were comparatively less likely than rural non-Māori to be triaged to priority transport pathways (fastest dispatch triage, 92% vs 97%, respectively, P  = 0.05); slower to reach first hospital (total in slowest tertile of time, 55% vs 41%, P  = 0.02); and had less access to specialist trauma care (reached tertiary trauma hospital, 51% vs 73%, P  = 0.02)., Conclusion: Among RTC patients attended and transported by EMS in NZ, there was variability in out-of-hospital EMS transport pathways through to specialist trauma care, strongly patterned by location of incident and ethnicity. These findings, mirroring other health disparities for Māori, provide an equity-focused evidence base to guide clinical and policy decision makers to optimize the delivery of EMS care and reduce disparities associated with out-of-hospital EMS care., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. This project is funded by a Health Research Council of New Zealand project grant (HRC 18/465). There are no other conflicts of interest or sources of funding to declare.

Objectives: As cochlear implant (CI) criteria widen, more candidates with usable residual hearing are being considered for a CI. Unlike children, adults mostly receive only one implant. The aim of this survey was to determine bimodal-hearing and bilateral CI service provision for adults around the world. This survey offers the backdrop against which future clinical practice and service delivery can be considered., Methods: CI professionals from across the world were invited to participate in an international multicentre survey. The online questionnaire was circulated to CI professionals in 75 countries. There were 64 respondents, representing 25 countries across five world regions., Results: In this sample, adult CI users most had unilateral CI (74.5%) and only 25.5% were bilateral CI users. Some 54% of unilateral CI users used a hearing aid (HA) in the non-implanted ear. Funding for a second implant or HA was not well supported for adult unilateral CI users, and there was no clear practice guidance for fitting and maintaining the contralateral HA in most regions., Conclusions: CI professionals recognised the value of fitting contralateral HAs at CI services, with audiology departments and private HA dispensers playing an ongoing role in general maintenance and support.