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Using a learning theory is key when designing simulation-based learning linked to allied health professional placements to ensure the purposeful selection of educational methods and to understand how it may assist learners in achieving desired learning outcomes. A narrative review was undertaken to identify the learning theories reported in simulation-based learning linked to allied health professional placements and how the learning outcomes aligned with the reported theories. Only eight of the 25 reviewed studies explicitly reported a learning theory, with minimal attempt to link them to the learning experience. Educators are encouraged to develop an understanding of the breadth and depth of learning theories and how they can best align these with the desired learning outcomes to allow the best fit for purpose. As a result, the authors have developed a practical guide to assist educators in designing simulation-based learning to better understand how learning theories could be incorporated and the anticipated outcomes that could be measured.

Abstract Smartphone applications are one of the main delivery modalities in digital health. Many of these mHealth apps use gamification to engage users, improve user experience, and achieve better health outcomes. Yet, it remains unclear whether gamified approaches help to deliver effective, safe, and clinically beneficial products to users. This study examines the compliance of 69 gamified mHealth apps with the EU Medical Device Regulation and assesses the specific risks arising from the gamified nature of these apps. Of the identified apps, 32 (46.4%) were considered non-medical devices; seven (10.1%) were already cleared/approved by the regulatory authorities, and 31 (44.9%) apps were assessed as likely non-compliant or potentially non-compliant with regulatory requirements. These applications and one approved application were assessed as on the market without the required regulatory approvals. According to our analysis, a higher proportion of these apps would be classified as medical devices in the US. The level of risk posed by gamification remains ambiguous. While most apps showed only a weak link between the degree of gamification and potential risks, this link was stronger for those apps with a high degree of gamification or an immersive game experience.

Objectives: A study was undertaken to describe South African dietitians and key role players’ perceptions regarding their role in reporting food labelling legislation transgressions.Design: A multimethod study design was employed to explore a previously unstudied topic.Setting: Dietitians registered with the Health Professions Council of South Africa (HPCSA) together with key role players in food labelling in South Africa.Methods: Quantitative data were collected using a self-administered electronic questionnaire and qualitative data using a semi-structured interview guide. Quantitative data were analysed using Microsoft Excel and qualitative data using ATLAS.ti software. Data were analysed independently in the results section but integrated for interpretation of the findings.Results: In total, only 6% (n = 7) of the included dietitians (n = 126) reported food labelling transgressions, and 12% (n = 15) believed dietitians have a role to play in reporting transgressions. Interestingly, half of the included dietitians (50%, n = 63) stated they would report an identified transgression. Dietitians demonstrated a lack of awareness of the current food labelling regulations, with 43% wrongly identifying the draft regulation to consult. Almost all (99%, n = 125) of the included dietitians reported that their transgression reporting practices would improve if a clear guideline from the Department of Health: Directorate Food Control (DoH DFC) was available. Key role players (n = 8) cited enforcement issues and a perceived gap in dietitians’ understanding of legislation and reporting processes as barriers to reporting non-compliance. Key role players identified enablers such as awareness of regulations, contacts within the DoH DFC and familiarity with the reporting process for transgressions. They also provided insight on the proper procedure for reporting food labelling transgressions.Conclusion: The low prevalence of food labelling transgression reporting by dietitians stems from several barriers, including a perceived lack of confidence regarding the current regulation, awareness of the applicable legislation, uncertainty regarding the correct reporting procedure and scepticism that transgression reports will be acted upon. Regular communication regarding food and nutrition regulations and the development of an easy-to-use transgression reporting framework could support the implementation and impact of food labelling regulations in South Africa.

The sparsity of post-translocation monitoring data for rehabilitated felids leaves a pressing gap in our current understanding of their integration into and use of novel landscapes. Remote monitoring tools such as GPS collars can provide crucial insights into animal movement behavior and habitat selection following translocation and assist in the decision-making process for rehabilitation and release sites. In January 2023, a young male ocelot was released on the Osa Peninsula, Costa Rica, after eight months of rehabilitation following a vehicle strike. Six months of post-translocation monitoring using a GPS and VHF-enabled collar revealed distinctive spatial patterns between the ocelot’s initial exploratory phase (~75 days) and subsequent residential period, as well as a selection for agricultural-forest matrix habitat over primary forest. We discuss the findings in terms of learning lessons for future post-release monitoring effects and provide insight into an individual’s patterns of habitat selection in an anthropogenically modified landscape.

Marcus McMahon,1 Jeremy Goldin,2 Elizabeth Susan Kealy,3 Darrel Joseph Wicks,4 Eugene Zilberg,5 Warwick Freeman,5 Behzad Aliahmad5 1Department of Respiratory and Sleep Medicine, Epworth Hospital, Richmond, Victoria, Australia and Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Victoria, Australia; 2Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital, Parkvile, Victoria, Australia; 3Sleepmetrics Pty Ltd, Heidelberg, Victoria, Australia; 4Sleep Disorders Unit, Epworth Hospital, Richmond, Victoria, Australia; 5Medical Innovations, Compumedics Limited, Abbotsford, Victoria, AustraliaCorrespondence: Eugene Zilberg, Compumedics Limited, 30-40 Flockhart Street, Abbotsford, Victoria, 3067, Australia, Tel +61 412225842, Fax +61 3 84207399, Email ezilberg@compumedics.com.auPurpose: To investigate accuracy of the sleep staging algorithm in a new miniaturized home sleep monitoring device – Compumedics® Somfit. Somfit is attached to patient’s forehead and combines channels specified for a pulse arterial tonometry (PAT)-based home sleep apnea testing (HSAT) device with the neurological signals. Somfit sleep staging deep learning algorithm is based on convolutional neural network architecture.Patients and Methods: One hundred and ten participants referred for sleep investigation with suspected or preexisting obstructive sleep apnea (OSA) in need of a review were enrolled into the study involving simultaneous recording of full overnight polysomnography (PSG) and Somfit data. The recordings were conducted at three centers in Australia. The reported statistics include standard measures of agreement between Somfit automatic hypnogram and consensus PSG hypnogram.Results: Overall percent agreement across five sleep stages (N1, N2, N3, REM, and wake) between Somfit automatic and consensus PSG hypnograms was 76.14 (SE: 0.79). The percent agreements between different pairs of sleep technologists’ PSG hypnograms varied from 74.36 (1.93) to 85.50 (0.64), with interscorer agreement being greater for scorers from the same sleep laboratory. The estimate of kappa between Somfit and consensus PSG was 0.672 (0.002). Percent agreement for sleep/wake discrimination was 89.30 (0.37). The accuracy of Somfit sleep staging algorithm varied with increasing OSA severity – percent agreement was 79.67 (1.87) for the normal subjects, 77.38 (1.06) for mild OSA, 74.83 (1.79) for moderate OSA and 72.93 (1.68) for severe OSA.Conclusion: Agreement between Somfit and PSG hypnograms was non-inferior to PSG interscorer agreement for a number of scorers, thus confirming acceptability of electrode placement at the center of the forehead. The directions for algorithm improvement include additional arousal detection, integration of motion and oximetry signals and separate inference models for individual sleep stages.Keywords: home sleep apnea testing, polysomnography, forehead electroencephalography, deep learning, interscorer agreement

Introduction Digital health tools can be beneficial in the care of patients with chronic conditions and have the potential for widespread impact as readily scalable and cost-effective health interventions. However, benefits are often contingent on users sustaining their engagement with these tools over time. Sustained engagement with digital health tools can be challenging, and high rates of attrition from digital interventions are common. Inflammatory Bowel Disease (IBD) and irritable bowel syndrome (IBS) are prominent gastrointestinal conditions resulting in significant burdens for individuals and society. Emerging evidence suggests digital health tools can be beneficial for IBD and IBS management; however, it is not clear what barriers and enablers are experienced by people living with these conditions to sustaining their engagement with these tools, when necessary. Such knowledge could inform the tailoring of new and existing digital health tools to the needs of people living with IBD and/or IBS. This study will seek to identify the barriers and enablers of sustained engagement with digital health tools among adults living with IBD and/or IBS.Methods and analysis We will conduct semistructured interviews with a purposive sample of approximately 30 adults (>18 years) who (a) reside in Canada, (b) self-report that they have been diagnosed with IBD and/or IBS, (c) have ever used a digital health tool (ie, any application/platform) to manage their condition and (d) are capable of providing informed consent. Interviews will be audio and video recorded and transcribed verbatim. Data will be coded deductively and barriers and enablers to sustained engagement will be categorised in accordance with the Theoretical Domains Framework. Data analysis will be verified by a patient research partner.Ethics and dissemination The study has been approved by the Ottawa Health Science Network Research Ethics Board. The findings will inform the codevelopment of strategies to overcome modifiable barriers and leverage identified enablers of sustained engagement with digital health tools for IBD and IBS care. These strategies can inform the design of new, or modifications to existing, digital health tools for IBD and IBS care where sustained engagement is desirable. Strategies will be compiled into a guidebook and disseminated via the Inflammation, Microbiome and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects (IMAGINE) Strategy for Patient Oriented Research chronic disease network in Canada.

People who experience a stroke are at a higher risk of recurrent stroke when compared with people who have not had a stroke. Addressing modifiable risk factors like physical inactivity and poor diet has been shown to improve blood pressure, a leading contributor to stroke. However, survivors of stroke often experience challenges with accessing risk reduction services including long wait lists, difficulty with transportation, fatigue, impaired function, and diminished exercise capacity. Providing health interventions via a website can extend the reach when compared with programs that are only offered face to face or via real-time telehealth. Given global challenges of accessing secondary prevention programs, it is important to consider alternative ways that this information can be made available to survivors of stroke worldwide. Using the “design thinking” framework and drawing on principles of the integrated knowledge translation approach, we adapted 2 co-designed telehealth programs called i-REBOUND – Let’s get moving (physical activity intervention) and i-REBOUND – Eat for health (diet Intervention) to create the i-REBOUND after stroke website. The aim of this paper is to describe the systematic process undertaken to adapt resources from the telehealth delivered i-REBOUND – Let’s get moving and i-REBOUND – Eat for health programs to a website prototype with a focus on navigation requirements and accessibility for survivors of stroke. We engaged a variety of key stakeholders with diverse skills and expertise in areas of stroke recovery, research, and digital health. We established a governance structure, formed a consumer advisory group, appointed a diverse project team, and agreed on scope of the project. Our process of adaptation had the following 3 phases: (1) understand, (2) explore, (3) materialize. Our approach considered the survivor of stroke at the center of all decisions, which helped establish guiding principles related to our prototype design. Careful and iterative engagement with survivors of stroke together with the application of design thinking principles allowed us to establish the functional requirements for our website prototype. Through user testing, we were able to confirm the technical requirements needed to build an accessible and easy-to-navigate website catering to the unique needs of survivors of stroke. We describe the process of adapting existing content and co-creating new digital content in partnership with, and featuring, people who have lived experience of stroke. In this paper, we provide a road map for the steps taken to adapt resources from 2 telehealth-delivered programs to a website format that meets specific navigation and accessibility needs of survivors of stroke.

Summary: T cell surface CTLA4 sequesters the costimulatory ligands CD80 and CD86 on antigen-presenting cells (APCs) to prevent autoimmunity. Therapeutic immunosuppression by recombinant CTLA4-immunoglobulin (Ig) fusion proteins, including abatacept, is also attributed to CD80/CD86 blockade. Recent studies show that CTLA4-Ig binding to APC surface cis-CD80:PD-L1 complexes can release the inhibitory ligand PD-L1, but whether this contributes to T cell inhibition remains unclear. Here, we show that PD-L1 liberation by CTLA4-Ig is strictly limited, both in extent and context, relative to PD-L1-competing anti-CD80 antibodies. At APC surface CD80:PD-L1 ratios exceeding 2:1, CTLA4-Ig therapies fail to release PD-L1 regardless of their CD80 affinity. Additionally, introducing flexibility into CTLA4-Ig by modifying its rigid homodimer interface produces biologics that retain bivalent CD80 binding without dissociating cis-bound PD-L1. These findings demonstrate that CTLA4-Ig therapies liberate PD-L1 through a CD80 reorientation mechanism that imposes a strict context dependence to their PD-1 checkpoint agonism and resultant T cell inhibition.

Health care technologies have the ability to bridge or hinder equitable care. Advocates of digital mental health interventions (DMHIs) report that such technologies are poised to reduce the documented gross health care inequities that have plagued generations of people seeking care in the United States. This is due to a multitude of factors such as their potential to revolutionize access; mitigate logistical barriers to in-person mental health care; and leverage patient inputs to formulate tailored, responsive, and personalized experiences. Although we agree with the potential of DMHIs to advance health equity, we articulate several steps essential to mobilize and sustain meaningful forward progression in this endeavor, reflecting on decades of research and learnings drawn from multiple fields of expertise and real-world experience. First, DMHI manufacturers must build diversity, equity, inclusion, and belonging (DEIB) processes into the full spectrum of product evolution itself (eg, product design, evidence generation) as well as into the fabric of internal company practices (eg, talent recruitment, communication principles, and advisory boards). Second, awareness of the DEIB efforts—or lack thereof—in DMHI research trials is needed to refine and optimize future study design for inclusivity as well as proactively address potential barriers to doing so. Trials should incorporate thoughtful, inclusive, and creative approaches to recruitment, enrollment, and measurement of social determinants of health and self-identity, as well as a prioritization of planned and exploratory analyses examining outcomes across various groups of people. Third, mental health care advocacy, research funding policies, and local and federal legislation can advance these pursuits, with directives from the US Preventive Services Taskforce, National Institutes of Health, and Food and Drug Administration applied as poignant examples. For products with artificial intelligence/machine learning, maintaining a “human in the loop” as well as prespecified and adaptive analytic frameworks to monitor and remediate potential algorithmic bias can reduce the risk of increasing inequity. Last, but certainly not least, is a call for partnership and transparency within and across ecosystems (academic, industry, payer, provider, regulatory agencies, and value-based care organizations) to reliably build health equity into real-world DMHI product deployments and evidence-generation strategies. All these considerations should also extend into the context of an equity-informed commercial strategy for DMHI manufacturers and health care organizations alike. The potential to advance health equity in innovation with DMHI is apparent. We advocate the field’s thoughtful and evergreen advancement in inclusivity, thereby redefining the mental health care experience for this generation and those to come.

Abstract Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators – Caspase-8, RIPK1, RIPK3 and MLKL – in formalin-fixed mouse and human tissues. We observed surprising heterogeneity in protein expression within tissues, whereby short-lived immune barrier cells were replete with necroptotic effectors, whereas long-lived cells lacked RIPK3 or MLKL expression. Local changes in the expression of necroptotic effectors occurred in response to insults such as inflammation, dysbiosis or immune challenge, consistent with necroptosis being dysregulated in disease contexts. These methods will facilitate the precise localisation and evaluation of necroptotic signaling in vivo.

Abstract Improving the kinetics and selectivity of CO2/CO electroreduction to valuable multi-carbon products is a challenge for science and is a requirement for practical relevance. Here we develop a thiol-modified surface ligand strategy that promotes electrochemical CO-to-acetate. We explore a picture wherein nucleophilic interaction between the lone pairs of sulfur and the empty orbitals of reaction intermediates contributes to making the acetate pathway more energetically accessible. Density functional theory calculations and Raman spectroscopy suggest a mechanism where the nucleophilic interaction increases the sp 2 hybridization of CO(ad), facilitating the rate-determining step, CO* to (CHO)*. We find that the ligands stabilize the (HOOC–CH2)* intermediate, a key intermediate in the acetate pathway. In-situ Raman spectroscopy shows shifts in C–O, Cu–C, and C–S vibrational frequencies that agree with a picture of surface ligand-intermediate interactions. A Faradaic efficiency of 70% is obtained on optimized thiol-capped Cu catalysts, with onset potentials 100 mV lower than in the case of reference Cu catalysts.

IntroductionNontraumatic subarachnoid hemorrhage (ntSAH) often results from a ruptured aneurysm and correlates with significant morbidity and mortality, particularly among the older population. Despite its impact, limited comprehensive studies evaluate the longitudinal trends in ntSAH-related mortality in older adults in the United States (US).MethodsThe authors conducted a retrospective analysis using the CDC WONDER database from 1999 to 2020, analyzing Multiple Cause-of-Death Public Use death certificates to identify ntSAH as a contributing factor in the death of adults aged 65 years and older. We calculated age-adjusted mortality rates (AAMR) and annual percent change (APC) to examine trends across demographic variables such as sex, race/ethnicity, urbanization, and states/census region.ResultsA total of 78,260 ntSAH-related deaths (AAMR 8.50 per 100,000 individuals) occurred among older adults in the US from 1999 to 2020. The overall AAMR for ntSAH decreased from 9.98 in 1999 to 8.67 in 2020 with an APC of −0.7% [95% CI (−1.0, −0.3)]. However, the authors observed a noticeable rise from 2013 to 2020 with an APC of 1.7% [95% CI (0.8, 2.6)]. Sex, racial, and regional disparities were evident with higher mortality rates for ages 85 or greater (crude mortality rate 16.6), women (AAMR 9.55), non-Hispanic Asian or Pacific Islander (AAMR 12.5), and micropolitan areas (AAMR 8.99), and Western US (AAMR 8.65).ConclusionMortality from ntSAH increases with age, affects women disproportionately, and occurs more often in an inpatient setting. These findings necessitate targeted, multi-dimensional health policies and clinical interventions. Specialties beyond neurosurgery can utilize this data for improved risk stratification and early treatment. Policymakers should focus on equitable resource allocation and community-level interventions to mitigate these trends effectively.

Background PP‐007 is a polyethylene glycol (PEG)ylated bovine carboxyhemoglobin gas transfer molecule with pleotropic cytoprotective effects, vasodilatation, plasma expansion, and optimization of oxygen delivery. Rodent middle cerebral artery occlusion models have demonstrated that PP‐007 increases blood flow in the collateral circulation and reduces final infarct volumes, supporting a potential role as neuroprotective agent in acute ischemic stroke. We aim to evaluate the safety and feasibility of PP‐007 as an adjunctive treatment to mechanical thrombectomy (MT) in patients with stroke secondary to large vessel occlusion. Methods HEMERA‐1 (CarboxyHEMoglobin OxygEn delivery for Revascularization in Acute Stroke) was a multicenter, prospective, randomized, controlled phase 1 clinical trial. Anterior circulation large vessel occlusion patients were assigned in a 3:1 ratio to receive either PP‐007 (320 mg/kg: 30 min bolus followed by 2‐h infusion) plus MT or MT alone within 24 hours after symptom onset. Comprehensive safety evaluation was performed by independent Data Monitoring Safety Board and Imaging Core Lab. Results From October 1, 2021 to June 30, 2022, a total of 17 patients were recruited. Age, baseline National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT Score were 74.8±12.7 years, 17.3±4.2, and 7.9±1.8, respectively. Twelve patients were randomized to PP‐007 plus MT, 1 was randomized but not treated, 4 patients were randomized to MT alone. Recanalization of the occluded vessel was achieved in all patients. A transient systolic blood pressure increase (20–40 mm Hg) during the bolus was observed in all PP‐007 patients without any clinical consequences. There were no other safety concerns. Conclusion No significant safety concerns were identified for the adjunctive use of PP‐007 in patients undergoing MT. (The study was funded by Prolong Pharmaceuticals. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04677777.

Objective Pragmatic methodologies, often termed rapid-learning, are being pursued that can match the pace of innovation in radiotherapy and generate evidence from the real-world treatment setting. It is important to understand the feasibility of implementing such pragmatic approaches before their application in practice. This study investigated key professional stakeholders’ perceptions and opinions of rapid-learning and real-world data (RWD).Methods and analysis Twenty-three interviews were conducted with key professional stakeholders based across five UK radiotherapy cancer centres. Centres varied in size and reflected different healthcare environments. Data were collected between December 2022 and May 2023, and analysed using inductive thematic analysis.Results Four themes were generated: (1) the alignment of rapid-learning methodologies with the reality of practice, (2) concerns related to the variability of RWD, (3) the maturity of data infrastructures and capacity for rapid-learning and (4) further support, education and evidence needed to convince stakeholders to adopt rapid-learning approaches.Conclusion The potential of rapid-learning to help address evidence gaps in radiotherapy development was positively received by different professional stakeholders. However, the effectiveness of rapid-learning was viewed as being highly dependent on the collection of quality data in the routine setting, while the variable set-up at different cancer centres is also likely to be a key challenge for potential implementation. Developing data infrastructures to improve data interoperability was considered crucial for rapid-learning implementation, along with method clarity, educational support and training for radiotherapy teams.

Objective Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis.Design We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase 1, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase 2, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.Results We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen’s kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen’s kappa coefficient of 0.67 (±0.09).Conclusion We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited interobserver agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the importance of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using artificial intelligence.

Background: Mitochondria are considered the powerhouse of cells, and skeletal muscle cells are no exception. However, information regarding muscle mitochondria from different species is limited. Methods: Different muscles from cattle, pigs and chickens were analyzed for mitochondrial DNA (mtDNA), protein and oxygen consumption. Results: Bovine oxidative muscle mitochondria contain greater mtDNA (p < 0.05), protein (succinate dehydrogenase, SDHA, p < 0.01; citrate synthase, CS, p < 0.01; complex I, CI, p < 0.05), and oxygen consumption (p < 0.01) than their glycolytic counterpart. Likewise, porcine oxidative muscle contains greater mtDNA (p < 0.01), mitochondrial proteins (SDHA, p < 0.05; CS, p < 0.001; CI, p < 0.01) and oxidative phosphorylation capacity (OXPHOS, p < 0.05) in comparison to glycolytic muscle. However, avian oxidative skeletal muscle showed no differences in absolute mtDNA, SDHA, CI, complex II, lactate dehydrogenase, or glyceraldehyde 3 phosphate dehydrogenase compared to their glycolytic counterpart. Even so, avian mitochondria isolated from oxidative muscles had greater OXPHOS capacity (p < 0.05) than glycolytic muscle. Conclusions: These data show avian mitochondria function is independent of absolute mtDNA content and protein abundance, and argue that multiple levels of inquiry are warranted to determine the wholistic role of mitochondria in skeletal muscle.

Introduction: Food literacy (FL) is a rapidly emerging area of research that provides a framework to explain the interplay of food-related skills, beliefs, knowledge and practises that contribute to nutritional health and wellbeing. This review is the first to scope the current literature for FL interventions, assess their characteristics against the components provided in the most widely cited definition of FL. and describe their characteristics to identify gaps in the literature. Methods: This review scopes original articles describing FL interventions in the Medline, CINAHL, ProQuest Education, Web of Science and AMED databases up to August 2023. Results: Despite the heterogeneity between all seven included studies, they all demonstrated some improvements in their FL outcome measures alongside dietary intake (DI), with the greatest improvements seen in studies that employed a FL theoretical framework in intervention design. Populations at high risk of food insecurity, such as university students and people living in disadvantaged areas, were the main targets of FL interventions. Conclusion: The minimal inclusion of FL theory amongst interventions led to an overall poor coverage of essential FL components, indicating researchers should aim to design future FL interventions with a FL theoretical framework.

Summary: Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates cellular adaptation to decreased oxygen availability. HIF-1 recruits chromatin-modifying enzymes leading to changes in histone acetylation, citrullination, and methylation at target genes. Here, we demonstrate that hypoxia-inducible gene expression in estrogen receptor (ER)-positive MCF7 and ER-negative SUM159 human breast cancer cells requires the histone H2A/H2B chaperone facilitates chromatin transcription (FACT) and the H2B ubiquitin ligase RING finger protein 20/40 (RNF20/40). Knockdown of FACT or RNF20/40 expression leads to decreased transcription initiation and elongation at HIF-1 target genes. Mechanistically, FACT and RNF20/40 are recruited to hypoxia response elements (HREs) by HIF-1 and stabilize binding of HIF-1 (and each other) at HREs. Hypoxia induces the monoubiquitination of histone H2B at lysine 120 at HIF-1 target genes in an HIF-1-dependent manner. Together, these findings delineate a cooperative molecular mechanism by which FACT and RNF20/40 stabilize multiprotein complex formation at HREs and mediate histone ubiquitination to facilitate HIF-1 transcriptional activity.

Purpose: Metabolic vulnerabilities can exacerbate inflammatory injury and inhibit repair in multiple sclerosis (MS). The purpose was to evaluate whether blood biomarkers of inflammatory and metabolic vulnerability are associated with MS disability and neurodegeneration. Methods: Proton nuclear magnetic resonance spectra were obtained from serum samples from 153 healthy controls, 187 relapsing–remitting, and 91 progressive MS patients. The spectra were analyzed to obtain concentrations of lipoprotein sub-classes, glycated acute-phase proteins, and small-molecule metabolites, including leucine, valine, isoleucine, alanine, and citrate. Composite indices for inflammatory vulnerability, metabolic malnutrition, and metabolic vulnerability were computed. MS disability was measured on the Expanded Disability Status Scale. MRI measures of lesions and whole-brain and tissue-specific volumes were acquired. Results: Valine, leucine, isoleucine, alanine, the Inflammatory Vulnerability Index, the Metabolic Malnutrition Index, and the Metabolic Vulnerability Index differed between healthy control and MS groups in regression analyses adjusted for age, sex, and body mass index. The Expanded Disability Status Scale was associated with small HDL particle levels, inflammatory vulnerability, and metabolic vulnerability. Timed ambulation was associated with inflammatory vulnerability and metabolic vulnerability. Greater metabolic vulnerability and inflammatory vulnerability were associated with lower gray matter, deep gray matter volumes, and greater lateral ventricle volume. Conclusions: Serum-biomarker-derived indices of inflammatory and metabolic vulnerability are associated with disability and neurodegeneration in MS.

The effect of laser pulse duration on energy coupling into a planar silicon target is investigated in experiments at the OMEGA-EP facility by varying the laser pulse length τ—spanning 3 orders of magnitude from 100 ps to 10 ns—while maintaining a constant peak laser intensity, I_{0}=5×10^{14} W/cm^{2}. In theoretical models, the ablation pressure primarily scales for a given material with laser intensity and wavelength, which are all fixed variables here, allowing us to explore the specific role of laser pulse duration. Two-dimensional radiation-hydrodynamics simulations benchmarked with optical probing of the expanding plasma show that the pulse duration is critical for the ablation pressure to reach a steady state. Moreover, the pulse duration impacts shock decay and multiple wave effects, which strongly dictate the evolving shock profile that propagates within the laser-shocked target as ultimately measured by rear-surface diagnostics. The shock velocities inferred from the theoretical model, after considering shock decay, impedance matching, and shock Hugoniot, are found to be in good agreement with velocimetry measurements. However, discrepancies are observed with simulations for the shorter (0.1 ns) and longer (10 ns) pulse durations, which are respectively attributed to unaccounted contributions of kinetic absorption mechanisms and instabilities in simulations.

Background The ability of digital mental health interventions (DMHIs) to reduce mental health disparities relies on the recruitment of research participants with diverse sociodemographic and self-identity characteristics. Despite its importance, sociodemographic reporting in research is often limited, and the state of reporting practices in DMHI research in particular has not been comprehensively reviewed.Objectives To characterise the state of sociodemographic data reported in randomised controlled trials (RCTs) of app-based DMHIs published globally from 2007 to 2022.Methods A scoping review of RCTs of app-based DMHIs examined reporting frequency for 16 sociodemographic domains (eg, gender) and common category options within each domain (eg, woman). The search queried five electronic databases. 5079 records were screened and 299 articles were included.Results On average, studies reported 4.64 (SD=1.79; range 0–9) of 16 sociodemographic domains. The most common were age (97%) and education (67%). The least common were housing situation (6%), residency/location (5%), veteran status (4%), number of children (3%), sexual orientation (2%), disability status (2%) and food security (

ObjectiveHere, we demonstrate the first successful use of static neural stimulation patterns for specific information content. These static patterns were derived by a model that was applied to a subject’s own hippocampal spatiotemporal neural codes for memory.ApproachWe constructed a new model of processes by which the hippocampus encodes specific memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of targeted content into short-term memory. A memory decoding model (MDM) of hippocampal CA3 and CA1 neural firing was computed which derives a stimulation pattern for CA1 and CA3 neurons to be applied during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task.Main resultsMDM electrical stimulation delivered to the CA1 and CA3 locations in the hippocampus during the sample phase of DMS trials facilitated memory of images from the DMS task during a delayed recognition (DR) task that also included control images that were not from the DMS task. Across all subjects, the stimulated trials exhibited significant changes in performance in 22.4% of patient and category combinations. Changes in performance were a combination of both increased memory performance and decreased memory performance, with increases in performance occurring at almost 2 to 1 relative to decreases in performance. Across patients with impaired memory that received bilateral stimulation, significant changes in over 37.9% of patient and category combinations was seen with the changes in memory performance show a ratio of increased to decreased performance of over 4 to 1. Modification of memory performance was dependent on whether memory function was intact or impaired, and if stimulation was applied bilaterally or unilaterally, with nearly all increase in performance seen in subjects with impaired memory receiving bilateral stimulation.SignificanceThese results demonstrate that memory encoding in patients with impaired memory function can be facilitated for specific memory content, which offers a stimulation method for a future implantable neural prosthetic to improve human memory.

Abstract Objective: To conduct a systematic review of the published peer-reviewed articles on the biochemical assessment of nutritional status of South African infants, children and adolescents in 1997–2022. Design: Online databases (Pubmed, CINAHL, EbscoHost and SAePublications) were used to identify thirty-nine papers. Setting: South Africa, 1997–2022. Participants: Infants, children and adolescents. Results: Vitamin A deficiency prevalence was 35–67 % before 2001 and mostly below 16 % after 2008. Anaemia ranged from 5·4 to 75·0 %, with 36–54 % of infants below 1 year being anaemic. Among 0- to 6-year-olds, iron deficiency (ID) was 7·2–39·4 % in rural and 16–41·9 % in urban areas. Zn deficiency remained high, especially among 0- to 6-year-olds, at 39–48 %. Iodine insufficiency (UIC < 100 µg/l) was between 0 and 28·8 %, with excessive levels in two areas. Vitamin D deficiency was 5 % for 11- to 17-year-olds in one urban study but 33–87 % in under 10-week-old infants. The 2005 national survey reported sufficient folate status among 0- to 6-year-olds, and vitamin B12 deficiency was 0–21 %. Low-grade inflammation was between 5 % and 42 % depending on the biomarker and cut-offs. Conclusions: Vitamin A status may have improved meaningfully during the last 25 years in South Africa to below 16 %, and iodine and folate deficiency appears to be low particularly among 0- to 6-year-olds. However, confirmation is needed by a national survey. Anaemia, Fe and Zn deficiencies still pose severe problems, especially among 0- to 6-year-olds. Sufficient data on vitamin D and B12 status are lacking.

Purpose: To describe our process for returning genetic results to participants in the Colorado Center for Personalized Medicine biobank. Methods: Enrollment in the biobank is open to all adult UCHealth patients. Participants who provided a sample that was genotyped and signed the proper consent were eligible to receive results. Genetic data were generated using a custom genotyping array and confirmed via Sanger sequencing. We used 2 models for returning results and conducted interviews with participants to assess satisfaction with our process, follow-up care, and family communication. Results: As of July 2022, 73,313 participants had provided a sample and proper consent. Of these, 10,489 samples were genotyped, 137 (1.3%) had initial results, and 62 were confirmed and eligible for return. We returned results to 51 participants, 33% for cardiac risk, 31% cancer, 15% familial hypercholesterolemia, and 21% for other conditions (11 participants refused or did not respond). Less than half of participants had a relevant family history. The majority of participants were glad to receive results and satisfied with our process. Conclusion: Although array-based genotyping has known limitations that reduce its accuracy, we were able to identify persons with underlying genetic risk who were previously unaware. It is important to establish a process for returning results that follows clinical guidelines, protects participant autonomy, and is amenable to all participants.

Abstract Objectives Systemic inflammatory response syndrome (SIRS) is a frequent complication of cardiopulmonary bypass (CPB). SIRS is associated with significant morbidity and mortality, but its pathogenesis remains incompletely understood, and as a result, biomarkers are lacking and treatment remains expectant and supportive. This study aimed to understand the pathophysiological mechanisms driving SIRS induced by CPB and identify novel therapeutic targets that might reduce systemic inflammation and improve patient outcomes. Methods Twenty‐one patients undergoing cardiac surgery and CPB were recruited, and blood was sampled before, during and after surgery. SIRS was defined using the American College of Chest Physicians/Society of Critical Care Medicine criteria. We performed immune cell profiling and whole blood transcriptomics and measured individual mediators in plasma/serum to characterise SIRS induced by CPB. Results Nineteen patients fulfilled criteria for SIRS, with a mean duration of 2.7 days. Neutrophil numbers rose rapidly with CPB and remained elevated for at least 48 h afterwards. Transcriptional signatures associated with neutrophil activation and degranulation were enriched during CPB. We identified a network of cytokines governing these transcriptional changes, including granulocyte colony‐stimulating factor (G‐CSF), a regulator of neutrophil production and function. Conclusions We identified neutrophils and G‐CSF as major regulators of CPB‐induced systemic inflammation. Short‐term targeting of G‐CSF could provide a novel therapeutic strategy to limit neutrophil‐mediated inflammation and tissue damage in SIRS induced by CPB.

Precision beam pointing plays a critical role in free-space optical communications terminals in uplink, downlink and inter-satellite link scenarios. Among the various methods of beam steering, the use of fast steering mirrors (FSM) is widely adopted, with many commercial solutions employing diverse technologies, particularly focusing on small, high-bandwidth mirrors. This paper introduces a method using lightweight, commercial off-the-shelf components to construct a custom closed-loop steering mirror platform, suitable for mirror apertures exceeding 100 mm. The approach involves integrating optical encoders into two off-the-shelf open-loop actuators. These encoders read the signal reflected on purposefully diamond-machined knurled screw knobs, providing maximum contrast between light and dark lines. The resulting steering mirror has the potential to complement or replace FSM in applications requiring a larger stroke, at the expense of motion speed. In the presented setup, the mirror tilt resolution achieved based on the encoder closed-loop signal feedback is 45 μrad, with a mean slew rate of 1.5 mrad/s. Importantly, the steering assembly is self-locking, requiring no power to maintain a steady pointing angle. Using the mirror to actively correct for a constantly moving incoming beam, a 5-fold increase in concentration of the beam spot on the center of the detector was obtained compared to a fixed position mirror, demonstrating the mirrors ability to correct for satellite platform jitter and drift.

In this paper, a MEMS piezoresistive ultrathin silicon membrane-based strain sensor is presented. The sensor’s ability to capture an acoustic emission signal is demonstrated using a Hsu–Nielsen source, and shows comparable frequency content to a commercial piezoceramic ultrasonic transducer. To the authors’ knowledge, this makes the developed sensor the first known piezoresistive strain sensor which is capable of recording low-energy acoustic emissions. The improvements to the nondestructive evaluation and structural health monitoring arise from the sensor’s low minimum detectable strain and wide-frequency bandwidth, which are generated from the improved fabrication process that permits crystalline semiconductor membranes and advanced polymers to be co-processed, thus enabling a dual-use application of both acoustic emission and static strain sensing. The sensor’s ability to document quasi-static bending is also demonstrated and compared with an ultrasonic transducer, which provides no significant response. This dual-use application is proposed to effectively combine the uses of both strain and ultrasonic transducer sensor types within one sensor, making it a novel and useful method for nondestructive evaluations. The potential benefits include an enhanced sensitivity, a reduced sensor size, a lower cost, and a reduced instrumentation complexity.

People with neurological conditions may face barriers to meal preparation. Culinary nutrition interventions aim to facilitate the building of knowledge and skills for meal preparation. This scoping review aims to map the available evidence for culinary nutrition interventions for people with neurological conditions and evaluate the quality of these interventions based on program design, delivery and evaluation. After a systematic search of online databases (MEDLINE, CINAHL, Embase, Scopus and Proquest) and reference lists, a total of ten publications describing nine interventions were included. Most interventions were designed for people with stroke and/or Transient Ischemic Attack (n = 3) and Multiple Sclerosis (n = 3); others were for traumatic brain injury (n = 1), mild dementia (n = 1) and Parkinson’s Disease (n = 1). Overall, the included culinary nutrition interventions had good program delivery (inclusion of motivational experiences, delivered by appropriate health providers) but needed improvements in program design (lack of consumer engagement and neurological symptom accommodations) and evaluation (lack of complete process, outcome and impact evaluations). In conclusion, the evidence base for culinary nutrition interventions for people with neurological conditions remains sparse. To bridge the gap between theory and practice, it is important to consider the following aspects in culinary nutrition intervention planning/improvement: (I) the involvement of consumers; (II) the accommodation/tailoring for post-condition effects; and (III) the coverage of all disease-specific culinary nutrition aspects.

Objectives: A study was undertaken to describe South African dietitians and key role players' perceptions regarding their role in reporting food labelling legislation transgressions. Design: A multimethod study design was employed to explore a previously unstudied topic. Setting: Dietitians registered with the Health Professions Council of South Africa (HPCSA) together with key role players in food labelling in South Africa. Methods: Quantitative data were collected using a self-administered electronic questionnaire and qualitative data using a semi-structured interview guide. Quantitative data were analysed using Microsoft Excel and qualitative data using ATLAS.ti software. Data were analysed independently in the results section but integrated for interpretation of the findings. Results: In total, only 6% (n = 7) of the included dietitians (n = 126) reported food labelling transgressions, and 12% (n = 15) believed dietitians have a role to play in reporting transgressions. Interestingly, half of the included dietitians (50%, n = 63) stated they would report an identified transgression. Dietitians demonstrated a lack of awareness of the current food labelling regulations, with 43% wrongly identifying the draft regulation to consult. Almost all (99%, n = 125) of the included dietitians reported that their transgression reporting practices would improve if a clear guideline from the Department of Health: Directorate Food Control (DoH DFC) was available. Key role players (n = 8) cited enforcement issues and a perceived gap in dietitians' understanding of legislation and reporting processes as barriers to reporting non-compliance. Key role players identified enablers such as awareness of regulations, contacts within the DoH DFC and familiarity with the reporting process for transgressions. They also provided insight on the proper procedure for reporting food labelling transgressions. Conclusion: The low prevalence of food labelling transgression reporting by dietitians stems from several barriers, including a perceived lack of confidence regarding the current regulation, awareness of the applicable legislation, uncertainty regarding the correct reporting procedure and scepticism that transgression reports will be acted upon. Regular communication regarding food and nutrition regulations and the development of an easy-to-use transgression reporting framework could support the implementation and impact of food labelling regulations in South Africa. [ABSTRACT FROM AUTHOR]