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Telomerase elongates telomeres to maintain chromosome stability in most eukaryotes. Despite extensive studies across eukaryotic kingdoms, the telomerase holoenzyme in arthropods remains poorly understood. In this study, we purify the telomerase ribonucleoprotein complex from the lepidopteran insect Spodoptera frugiperda (fall armyworm) and identify a copurified 135-nucleotide telomerase RNA (TR) component. This miniature S. frugiperda TR (sfTR), the smallest TR known to date, retains a universal pseudoknot structure and a structurally defined template. Despite its small size, sfTR assembles with the recombinant S. frugiperda telomerase reverse transcriptase (sfTERT) protein in vivo to reconstitute telomerase activity for the synthesis of insect telomeric DNA repeats (TTAGG)n. The sfTR gene, like other animal TR genes, features an snRNA-type RNA polymerase II promoter. Uniquely, the sfTR transcript harbors a 5'-7-methylguanosine (M 7 G) cap, as opposed to the more typical snRNA-type 2,2,7-trimethylguanosine (TMG) cap. The difference in 5'-cap is likely because sfTR lacks the H/ACA snoRNA biogenesis domain necessary for cap hypermethylation. Moreover, sfTR also lacks the CR4/5 regulatory domain that is indispensable in vertebrate TRs for telomerase activity. This degenerate sfTR complements an enigmatic sfTERT that is missing certain telomerase-specific elements yet catalytically active in the absence of sfTR. Thus, insects have evolved a simplified telomerase, consisting of a small noncoding RNA that retains only minimal attributes essential for telomerase function. The simplified insect telomerase demonstrates a plausible evolutionary pathway for the emergence of telomerase ribonucleoprotein complex, arising from an ancient reverse transcriptase associated with a simple templating RNA component in early eukaryotes., Competing Interests: Competing interests statement:The authors declare no competing interest.

Purpose: Personal activity intelligence (PAI) translates heart rate during physical activity (PA) into a weekly score, which credits vigorous over low- and moderate-intensity PA. We prospectively investigated the association between PAI and fatal and nonfatal coronary heart disease (CHD) in self-reported healthy participants from Norway, with specific reference to improving the accuracy of conventional coronary risk assessment., Methods: We studied 40,961 healthy adults (56% women) from the population-based Trøndelag Health Study (the HUNT study). Individual data were linked to hospital and cause of death registries. The weekly PAI score of each participant was divided into four groups (PAI scores of 0, ≤50, 51-99, or ≥100). Adjusted hazard ratios and 95% confidence intervals for fatal and nonfatal CHD related to PAI were estimated using Cox proportional hazard regression analyses., Results: During a median follow-up period of 13.1 yr (interquartile range, 12.7-13.6), 3303 (3109 nonfatal, 194 fatal) CHD events occurred. Compared with the inactive group (0 PAI), weekly PAI scores at baseline of 51-99 and ≥100 were associated with a lower risk of CHD [0.80 (0.71-0.91) and 0.86 (0.78-0.95), respectively]. By adding PAI to traditional risk factors, the net reclassification improvement of CHD was 0.472 ( P < 0.001)., Conclusions: PAI was inversely associated with CHD risk among healthy participants at baseline, and its cardioprotective effect persisted across diverse risk factor profiles. A PAI score >50 was substantially associated with a reduced risk of CHD. These findings have implications for improving the accuracy of conventional coronary risk assessments with PAI., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Under recent reforms to the National Health Service (NHS) in England, NHS organizations have been given new objectives to contribute to social and economic development. Health systems in other high-income countries are pursuing related approaches. This paper analyses national policy documents to understand the framing of the NHS's new policy priorities on social and economic development. We focus on the role of NHS integrated care systems-area-based planning bodies responsible for managing NHS resources and coordinating local services. National policy is vague about what social and economic development means in practice. There is limited guidance on which approaches local organizations should prioritize, and which organisations are responsible for implementation. Greater clarity from national policymakers and an overarching framework to guide local action is needed to reduce the risk of inaction, poorly targeted interventions, and missed opportunities for learning and evaluation. Policymakers and health system leaders also need to be realistic about the limits of local action given the importance of national public policy choices in shaping the social determinants of health. Coordinated policy action and investment across government is needed to address underlying social and economic conditions., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: The female genital tract microbiome has become a particular area of interest in improving assisted reproductive technology (ART) outcomes with the emergence of next-generation sequencing (NGS) technology. However, NGS assessment of microbiomes currently lacks uniformity and poses significant challenges for accurate and precise bacterial population representation., Objective: As multiple NGS platforms and assays have been developed in recent years for microbiome investigation-including the advent of long-read sequencing technologies-this work aimed to identify current trends and practices undertaken in female genital tract microbiome investigations., Results: Areas like sample collection and transport, DNA extraction, 16S amplification vs. metagenomics, NGS library preparation, and bioinformatic analysis demonstrated a detrimental lack of uniformity. The lack of uniformity present is a significant limitation characterised by gap discrepancies in generation and interpretation of results. Minimal consistency was observed in primer design, DNA extraction techniques, sample transport, and bioinformatic analyses., Conclusion: With third-generation sequencing technology highlighted as a promising tool in microbiota-based research via full-length 16S rRNA sequencing, there is a desperate need for future studies to investigate and optimise methodological approaches of the genital tract microbiome to ensure better uniformity of methods and results interpretation to improve clinical impact., Competing Interests: Declarations. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing, we confirm that we have followed the regulations of our institutions concerning intellectual property. We understand that the corresponding author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the corresponding author. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Recent breakthroughs in artificial intelligence (AI) have caught the attention of many fields, including health care. The vision for AI is that a computer model can process information and provide output that is indistinguishable from that of a human and, in specific repetitive tasks, outperform a human's capability. The 2 critical underlying technologies in AI are used for supervised and unsupervised machine learning. Machine learning uses neural networks and deep learning modeled after the human brain from structured or unstructured data sets to learn, make decisions, and continuously improve the model. Natural language processing, used for supervised learning, is understanding, interpreting, and generating information using human language in chatbots and generative and conversational AI. These breakthroughs result from increased computing power and access to large data sets, setting the stage for releasing large language models, such as ChatGPT and others, and new imaging models using computer vision. Hypertension management involves using blood pressure and other biometric data from connected devices and generative AI to communicate with patients and health care professionals. AI can potentially improve hypertension diagnosis and treatment through remote patient monitoring and digital therapeutics., Competing Interests: None.

Background and Aims: Hypertension continues to be a major public health problem affecting almost half of the adults in the US. The intersection of hypertension with food insecurity has not been well-examined specifically among minority populations. We aimed to examine the influence of food insecurity on mortality among adult Hispanics., Methods and Results: Data on adult Hispanic (age≥ 20 years) respondents of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 were analyzed. Mortality was assessed by linking these data with the National Death Index through December 31, 2019. Using complex samples Cox regression analysis, the relationship between hypertension, food insecurity, and mortality was assessed. Sociodemographic (age, gender, poverty-income-ratio, marital status, and citizenship status) and health-related characteristics (COPD, diabetes, cardiovascular disease, chronic kidney disease) of the population were included as covariates in the regression analysis to assess mortality risk. The crude hazard ratio (HR) for overall mortality related to hypertension was 4.95 (95% confidence interval [CI] = 4.22-5.82, p < .001). The adjusted HR was elevated, 2.01 (95%CI = 1.50-2.70, p < .001), among individuals with both hypertension and food insecurity. However, among individuals with hypertension and no food insecurity, there was no statistically significant increase in the risk of mortality (HR = 1.09, 95%CI = 0.89-1.34, p > 0.05)., Conclusions: In adult Hispanics, food insecurity significantly increases the risk of mortality among those with hypertension compared to food-secure individuals. Clinicians should be sensitized to the need for food security among Hispanics with hypertension to effectively manage hypertension and reduce premature mortality., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Infectious coryza (IC) is a respiratory disease of chickens, including pullets, layers, and broilers, caused by the bacteria Avibacterium paragallinarum (AP), which was previously known as Hemophilus gallinarum . IC classically causes production decreases and mortality in chickens, frequently paired with swelling of the sinuses, mucoid nasal discharge, and respiratory rales. Although IC is considered an endemic disease of chickens in California, it has been unusual to rare in commercial chickens in Pennsylvania. The last reported IC case in Pennsylvania was in 2002, involving broiler breeders. However, between December 2018 and December 2019, 68 farms were affected by IC in Pennsylvania, involving approximately 14 million birds. Several farms had multiple flocks affected. Most affected farms housed layer chickens (37/68), but a smaller number of broiler farms, pullet farms, and layer breeder farms have been affected. Ages of affected birds and duration of disease were variable between flocks, as were the severity of clinical signs, pathologic lesions, and rates of mortality. PCR testing has greatly aided and sped diagnostic efforts in addition to traditional bacterial culture. In eight layer cases and five broiler cases, bacterial culture of the sinus or choanal cleft proved unrewarding, whereas culture of trachea, air sacs, lungs, heart, or liver were diagnostic. Although cases of IC in commercial Pennsylvania poultry continue, they have been greatly reduced because of implementation of a successful vaccination program. In this case series report we detail epidemiologic, clinical, and pathologic aspects of this outbreak and discuss vaccination as a control measure of IC in the state of Pennsylvania.

(1) Background: Artificial intelligence (AI) has flourished in recent years. More specifically, generative AI has had broad applications in many disciplines. While mental illness is on the rise, AI has proven valuable in aiding the diagnosis and treatment of mental disorders. However, there is little to no research about precisely how much interest there is in AI technology. (2) Methods: We performed a Google Trends search for "AI and mental health" and compared relative search volume (RSV) indices of "AI", "AI and Depression", and "AI and anxiety". This time series study employed Box-Jenkins time series modeling to forecast long-term interest through the end of 2024. (3) Results: Within the United States, AI interest steadily increased throughout 2023, with some anomalies due to media reporting. Through predictive models, we found that this trend is predicted to increase 114% through the end of the year 2024, with public interest in AI applications being on the rise. (4) Conclusions: According to our study, we found that the awareness of AI has drastically increased throughout 2023, especially in mental health. This demonstrates increasing public awareness of mental health and AI, making advocacy and education about AI technology of paramount importance.

Background: Mobile health technology's impact on cardiovascular risk factor control is not fully understood. This study evaluates the association between interaction with a mobile health application and change in cardiovascular risk factors., Methods and Results: Participants with hypertension with or without dyslipidemia enrolled in a workplace-deployed mobile health application-based cardiovascular risk self-management program between January 2018 and December 2022. Retrospective evaluation explored the influence of application engagement on change in blood pressure (BP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and weight. Multiple regression analyses examined the influence of guideline-based, nonpharmacological lifestyle-based digital coaching on outcomes adjusting for confounders. Of 102 475 participants, 49.1% were women. Median age was 53 (interquartile range, 43-61) years, BP was 134 (interquartile range, 124-144)/84 (interquartile range, 78-91) mm Hg, TC was 183 (interquartile range, 155-212) mg/dL, LDL-C was 106 (82-131) mg/dL, and body mass index was 30 (26-35) kg/m 2 . At 2 years, participants with baseline systolic BP ≥140 mm Hg reduced systolic BP by 18.6 (SEM, 0.3) mm Hg. At follow up, participants with baseline TC ≥240 mg/dL reduced TC by 65.7 (SEM, 4.6) mg/dL, participants with baseline LDL-C≥160 mg/dL reduced LDL-C by 66.6 (SEM, 6.2) mg/dL, and participants with baseline body mass index ≥30 kg/m 2 lost 12.0 (SEM, 0.3) pounds, or 5.1% of body weight. Interaction with digital coaching was associated with greater reduction in all outcomes., Conclusions: A mobile health application-based cardiovascular risk self-management program was associated with favorable reductions in BP, TC, LDL-C, and weight, highlighting the potential use of this technology in comprehensive cardiovascular risk factor control.

Fixed nitrogen species generated by the early Earth's atmosphere are thought to be critical to the emergence of life and the sustenance of early metabolisms. A previous study estimated nitrogen fixation in the Hadean Earth's N 2 /CO 2 -dominated atmosphere; however, that previous study only considered a limited chemical network that produces NO x species (i.e., no HCN formation) via the thermochemical dissociation of N 2 and CO 2 in lightning flashes, followed by photochemistry. Here, we present an updated model of nitrogen fixation on Hadean Earth. We use the Chemical Equilibrium with Applications (CEA) thermochemical model to estimate lightning-induced NO and HCN formation and an updated version of KINETICS, the 1-D Caltech/JPL photochemical model, to assess the photochemical production of fixed nitrogen species that rain out into the Earth's early ocean. Our updated photochemical model contains hydrocarbon and nitrile chemistry, and we use a Geant4 simulation platform to consider nitrogen fixation stimulated by solar energetic particle deposition throughout the atmosphere. We study the impact of a novel reaction pathway for generating HCN via HCN 2 , inspired by the experimental results which suggest that reactions with CH radicals (from CH 4 photolysis) may facilitate the incorporation of N into the molecular structure of aerosols. When the HCN 2 reactions are added, we find that the HCN rainout rate rises by a factor of five in our 1-bar case and is about the same in our 2- and 12-bar cases. Finally, we estimate the equilibrium concentration of fixed nitrogen species under a kinetic steady state in the Hadean ocean, considering loss by hydrothermal vent circulation, photoreduction, and hydrolysis. These results inform our understanding of environments that may have been relevant to the formation of life on Earth, as well as processes that could lead to the emergence of life elsewhere in the universe.

We determined δ 11 B values of green and roasted coffee beans from 20 locations worldwide and conducted laboratory experiments with the aim to investigate boron isotope fractionation during roasting. Authentic single origin roasted coffees were found to be isotopically lighter than their green bean counterparts, with an average difference of 1.5‰. This isotope fractionation can be explained as arising from partial dissociation of boric acid in capillary water of green beans, where 11 B isotopes are preferentially partitioned into molecules of undissociated boric acid and are then volatised during roasting. However, boron isotope fractionation induced by roasting was significantly smaller than between-origin variations in δ 11 B values of green coffee beans that had the range of ∼54‰. This implies that δ 11 B isotopic composition of roasted coffee retains the geographical origin information within δ 11 B values of green beans when regional differences in boron isotopic composition of coffee are considered., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A major subpopulation of midbrain 5-hydroxytryptamine (5-HT) neurons expresses the vesicular glutamate transporter 3 (VGLUT3) and co-releases 5-HT and glutamate, but the function of this co-release is unclear. Given the strong links between 5-HT and uncontrollable stress, we used a combination of c-Fos immunohistochemistry and conditional gene knockout mice to test the hypothesis that glutamate co-releasing 5-HT neurons are activated by stress and involved in stress coping. Acute, uncontrollable swim stress increased c-Fos immunoreactivity in neurons co-expressing VGLUT3 and the 5-HT marker tryptophan hydroxylase 2 (TPH2) in the dorsal raphe nucleus (DRN). This effect was localized in the ventral DRN subregion and prevented by the antidepressant fluoxetine. In contrast, a more controllable stressor, acute social defeat, had no effect on c-Fos immunoreactivity in VGLUT3-TPH2 co-expressing neurons in the DRN. To test whether activation of glutamate co-releasing 5-HT neurons was causally linked to stress coping, mice with a specific deletion of VGLUT3 in 5-HT neurons were exposed to acute swim stress. Compared to wildtype controls, the mutant mice showed increased climbing behavior, a measure of active coping. Wildtype mice also showed increased climbing when administered fluoxetine, revealing an interesting parallel between the behavioral effects of genetic loss of VGLUT3 in 5-HT neurons and 5-HT reuptake inhibition. We conclude that 5-HT-glutamate co-releasing neurons are recruited by exposure to uncontrollable stress. Furthermore, natural variation in the balance of 5-HT and glutamate co-released at the 5-HT synapse may impact stress susceptibility.

Background: Internationally, community pharmacy models of care have been moving away from a focus on dispensing to extended, clinically-focused roles for pharmacists., Objectives: To identify how community pharmacy strategies were being implemented in Aotearoa New Zealand; how changes were expected to influence health and health system outcomes; what extended services were being delivered; the responses of pharmacists, other health professionals and consumers to these developments; and the contexts and mechanisms supporting the successful implementation of new community pharmacy services., Methods: A realist evaluation methodology was employed, to explore a complex policy intervention. Realist evaluation explores the contexts (C) within which initiatives are introduced and identifies the mechanisms (M) triggered by different contexts to produce outcomes (O). Realist evaluation processes iteratively develop, test, and refine CMO configurations. In this study, initial programme theories were developed through key government and professional policy documents, then refined through key informant interviews, a survey and interviews with pharmacists and intern (pre-registration) pharmacists, and finally, 10 case studies of diverse community pharmacies., Results: Four intermediate health service outcomes were identified: development of extended community pharmacist services; consumers using extended community pharmacist services; more integrated, collaborative primary health care services; and a fit-for-purpose community pharmacy workforce. Enabling and constraining contexts are detailed for each outcome, along with the mechanisms that they trigger (or inhibit)., Conclusions: There are wide-ranging and disparate levers to support the further development of extended community pharmacy services. These include aligning funding with desired services, undergraduate educators and professional leaders setting expectations for the pharmacists' role in practice, and the availability of sufficient funding and time for both specific extended service accreditation and broader postgraduate training. However, no simple "fix" can be universally applied internationally, nor even in pharmacies within a single jurisdiction, to facilitate service development., Competing Interests: Declarations of competing interest Declarations of interest: none., (Copyright © 2023. Published by Elsevier Inc.)

Currently, assessing physical activity (PA) and cardiorespiratory fitness in healthcare settings and supporting patients on their journey toward active living is not a standard of practice in the US, although significant progress is underway. This paper summarizes the foundational as well as supporting public policies necessary to make PA assessment, prescription, and referral a standard of care in the US healthcare system to support active living for all. Measure standardization and healthcare integration will be supported by digital health and public private partnerships, as well as payer strategies and quality and performance incentives. The policy and systems change effort, currently being led by the Physical Activity Alliance's "It's Time to Move" initiative, will improve patient care and the ability to monitor PA levels across the US population, filling in gaps in current national public health surveillance systems. Having patient data available will also allow for additional research that elucidates the relationship between PA and overall health and well-being., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background: Involving patient and community stakeholders in clinical trials adds value by ensuring research prioritizes patient goals both in conduct of the study and application of the research. The use of stakeholder committees and their impact on the conduct of a multicenter clinical trial have been underreported clinically and academically. The aim of this study is to describe how Study Advisory Committee (SAC) recommendations were implemented throughout the Emergency Medicine Palliative Care Access (EMPallA) trial. EMPallA is a multi-center, pragmatic two-arm randomized controlled trial (RCT) comparing the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness., Methods: A SAC consisting of 18 individuals, including patients with palliative care experience, members of healthcare organizations, and payers was convened for the EMPallA trial. The SAC engaged in community-based participatory research and assisted in all aspects from study design to dissemination. The SAC met with the research team quarterly and annually from project inception to dissemination. Using meeting notes and recordings we completed a qualitative thematic analysis using an iterative process to develop themes and subthemes to summarize SAC recommendations throughout the project's duration., Results: The SAC convened 16 times between 2017 and 2020. Over the course of the project, the SAC provided 41 unique recommendations. Twenty-six of the 41 (63%) recommendations were adapted into formal Institutional Review Board (IRB) study modifications. Recommendations were coded into four major themes: Scientific, Pragmatic, Resource and Dissemination. A majority of the recommendations were related to either the Scientific (46%) or Pragmatic (29%) themes. Recommendations were not mutually exclusive across three study phases: Preparatory, execution and translational. A vast majority (94%) of the recommendations made were related to the execution phase. Major IRB study modifications were made based on their recommendations including data collection of novel dependent variables and expanding recruitment to Spanish-speaking patients., Conclusions: Our study provides an example of successful integration of a SAC in the conduct of a pragmatic, multi-center RCT. Future trials should engage with SACs in all study phases to ensure trials are relevant, inclusive, patient-focused, and attentive to gaps between health care and patient and family needs., Trial Registration: Clinicaltrials.gov Identifier: NCT03325985, 10/30/2017., (© 2024. The Author(s).)

Background: Cardiac rehabilitation (CR) is an evidence-based, guideline-recommended intervention for patients recovering from a cardiac event, surgery or procedure that improves morbidity, mortality, and functional status. CR is traditionally provided in-center, which limits access and engagement, most notably among underrepresented racial and ethnic groups due to barriers including cost, scheduling, and transportation access. This study is designed to evaluate the Corrie Hybrid CR, a technology-based, multicomponent health equity-focused intervention as an alternative to traditional in-center CR among patients recovering from a cardiac event, surgery, or procedure compared with usual care alone., Methods: The mTECH-Rehab (Impact of a Mobile Technology Enabled Corrie CR Program) trial will randomize 200 patients who either have diagnosis of myocardial infarction or who undergo coronary artery bypass grafting surgery, percutaneous coronary intervention, heart valve repair, or replacement presenting to 4 hospitals in a large academic health system in Maryland, United States, to the Corrie Hybrid CR program combined with usual care CR (intervention group) or usual care CR alone (control group) in a parallel arm, randomized controlled trial. The Corrie Hybrid CR program leverages 5 components: (1) a patient-facing mobile application that encourages behavior change, patient empowerment, and engagement with guideline-directed therapy; (2) Food and Drug Administration-approved smart devices that collect health metrics; (3) 2 upfront in-center CR sessions to facilitate personalization, self-efficacy, and evaluation for the safety of home exercise, followed by a combination of in-center and home-based sessions per participant preference; (4) a clinician dashboard to track health data; and (5) weekly virtual coaching sessions delivered over 12 weeks for education, encouragement, and risk factor modification. The primary outcome is the mean difference between the intervention versus control groups in distance walked on the 6-minute walk test (ie, functional capacity) at 12 weeks post randomization. Key secondary and exploratory outcomes include improvement in a composite cardiovascular health metric, CR engagement, quality of life, health factors (including low-density lipoprotein-cholesterol, hemoglobin A1c, weight, diet, smoking cessation, blood pressure), and psychosocial factors. Approval for the study was granted by the local institutional review board. Results of the trial will be published once data collection and analysis have been completed., Conclusions: The Corrie Hybrid CR program has the potential to improve functional status, cardiovascular health, and CR engagement and advance equity in access to cardiac rehabilitation., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05238103.

Study advisory committees (SACs) provide critical value to clinical trials by providing unique perspectives that pull from personal and professional experiences related to the trial's healthcare topic. The Emergency Medicine Palliative Care Access (EMPallA) study had the privilege of convening a 16-person SAC from the project's inception to completion. The study team wanted to understand the impact this project had on the SAC members. In this narrative, we use reflective dialogue to share SAC members' lived experiences and the impact the EMPallA study has had on members both personally and professionally. We detail the (1) benefits SAC members, specifically patients, and caregivers, have had through working on this project. (2) The importance of recruiting diverse SAC members with different lived experiences and leveraging their feedback in clinical research. (3) Value of community capacity building to ensure the common vision of the clinical trial is promoted., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Mobile health technologies have shown promise as delivery platforms for digital health coaching for chronic conditions. However, the impacts of such strategies on users' health beliefs, intentions and ultimately clinical outcomes are understudied., Objective: This study sought (1) to evaluate the effects of a digital health coaching intervention on participants' belief constructs; and (2) to assess relationships between these belief constructs and intentions to utilize the technological intervention, actual adherence metrics and clinical outcomes related to hypertension., Methods: Thirty-four participants with hypertension were recruited from a university community from January to May 2021. They self-measured weight and blood pressure (BP) for 30 days followed by digital coaching delivered via a mobile application for 30 days. Surveys assessed constructs from the Health Belief Model and Technology Acceptance Model, compared to intention, health belief, BP self-monitoring adherence and BP outcomes. A path analysis model was used to assess the relationships between constructs and intention, adherence metrics and clinical outcomes. A Kruskal-Wallis test was used to identify changes in beliefs., Results: Participant health beliefs significantly improved after coaching, including self-efficacy ( H (1) = 15.12, p  < 0.001), cues to action ( H (1) = 5.33, p  =   0.02), attitude ( H (1) = 10.35, p  = 0.002), perceived usefulness ( H (1) = 15.02, p  < 0.001) and decreased resistance to change ( H (1) = 4.05, p  = 0.04). Adherence to BP measurements positively correlated with perceived health threat ( β  = .033, p  = 0.007) and perceived ease of use ( β  = .0277, p  < 0.001). Self-efficacy ( β  = -2.92, p  = 0.02) and perceived usefulness ( β  = -3.75, p  = 0.01) were linked with a decrease in diastolic BP., Conclusions: A mobile health coaching intervention may help participants improve beliefs regarding hypertension self-management., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2023.)

Dust and ammonia gas (NH 3 ) are two of the most abundant pollutants suspended in the air of poultry houses. Chronic inhalation of poultry dust and NH 3 causes damage to the airways and reduces performance in broilers. Poultry dust is a mixture of organic and inorganic matter from feed, bedding material, manure, feathers, skin debris, and microorganisms. Thus, the composition and concentration of poultry dust vary among farms. This study proposes a model to assess the individual effect of a defined fraction of poultry dust derived from bedding material (wood dust) and its effects, alone or combined with NH 3 , on the performance and respiratory integrity of broilers. Ninety-six, 1-day-old broilers were randomly divided into groups of 24 and placed into four controlled environment chambers to continuously receive one of four treatments: 1) negative control; 2) exposure to airborne red oak wood dust at a concentration of 7.5 × 10 6 particles/m 3 (particulate matter 5.0 ); 3) exposure to 50 parts per million (ppm) of NH 3 ; and 4) exposure to airborne red oak wood dust and 50 ppm of NH 3 . On day 43, all birds were weighed and euthanized. Performance data were recorded. Tissue samples were collected from six birds per treatment. Histologic evaluations of the nasal turbinates, trachea, and lungs were conducted. Histologic lesion scores (0 to 3) were assigned, and tracheal mucosal thickness was measured. No significant differences among treatments were found in body weight ( P = 0.066), tracheal mucosal thickness ( P = 0.593), or tracheal lesion score ( P = 0.07). The average nasal turbinate lesion scores were higher in the wood and wood + ammonia treatments compared with the control ( P = 0.015). The lung lesion scores were higher ( P = 0.004) in all treatment groups compared with the control. In conclusion, chronic exposure to red oak wood dust, alone or in combination with NH 3 , induced important inflammatory damage to portions of the respiratory system of broilers; however, no significant effects on performance were observed.

Background: High-grade gliomas have a poor prognosis and do not respond well to treatment. Effective cancer immune responses depend on functional immune cells, which are typically absent from the brain. This study aimed to evaluate the safety and activity of two adenoviral vectors expressing HSV1-TK (Ad-hCMV-TK) and Flt3L (Ad-hCMV-Flt3L) in patients with high-grade glioma., Methods: In this dose-finding, first-in-human trial, treatment-naive adults aged 18-75 years with newly identified high-grade glioma that was evaluated per immunotherapy response assessment in neuro-oncology criteria, and a Karnofsky Performance Status score of 70 or more, underwent maximal safe resection followed by injections of adenoviral vectors expressing HSV1-TK and Flt3L into the tumour bed. The study was conducted at the University of Michigan Medical School, Michigan Medicine (Ann Arbor, MI, USA). The study included six escalating doses of viral particles with starting doses of 1×10 10 Ad-hCMV-TK viral particles and 1×10 9 Ad-hCMV-Flt3L viral particles (cohort A), and then 1×10 11 Ad-hCMV-TK viral particles and 1×10 9 Ad-hCMV-Flt3L viral particles (cohort B), 1×10 10 Ad-hCMV-TK viral particles and 1×10 10 Ad-hCMV-Flt3L viral particles (cohort C), 1×10 11 Ad-hCMV-TK viral particles and 1×10 10 Ad-hCMV-Flt3L viral particles (cohort D), 1×10 10 Ad-hCMV-TK viral particles and 1×10 11 Ad-hCMV-Flt3L viral particles (cohort E), and 1×10 11 Ad-hCMV-TK viral particles and 1×10 11 Ad-hCMV-Flt3L viral particles (cohort F) following a 3+3 design. Two 1 mL tuberculin syringes were used to deliver freehand a mix of Ad-hCMV-TK and Ad-hCMV-Flt3L vectors into the walls of the resection cavity with a total injection of 2 mL distributed as 0·1 mL per site across 20 locations. Subsequently, patients received two 14-day courses of valacyclovir (2 g orally, three times per day) at 1-3 days and 10-12 weeks after vector administration and standad upfront chemoradiotherapy. The primary endpoint was the maximum tolerated dose of Ad-hCMV-Flt3L and Ad-hCMV-TK. Overall survival was a secondary endpoint. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT01811992., Findings: Between April 8, 2014, and March 13, 2019, 21 patients were assessed for eligibility and 18 patients with high-grade glioma were enrolled and included in the analysis (three patients in each of the six dose cohorts); eight patients were female and ten were male. Neuropathological examination identified 14 (78%) patients with glioblastoma, three (17%) with gliosarcoma, and one (6%) with anaplastic ependymoma. The treatment was well-tolerated, and no dose-limiting toxicity was observed. The maximum tolerated dose was not reached. The most common serious grade 3-4 adverse events across all treatment groups were wound infection (four events in two patients) and thromboembolic events (five events in four patients). One death due to an adverse event (respiratory failure) occurred but was not related to study treatment. No treatment-related deaths occurred during the study. Median overall survival was 21·3 months (95% CI 11·1-26·1)., Interpretation: The combination of two adenoviral vectors demonstrated safety and feasibility in patients with high-grade glioma and warrants further investigation in a phase 1b/2 clinical trial., Funding: Funded in part by Phase One Foundation, Los Angeles, CA, The Board of Governors at Cedars-Sinai Medical Center, Los Angeles, CA, and The Rogel Cancer Center at The University of Michigan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cardiac rehabilitation has strong evidence of benefit across many cardiovascular conditions but is underused. Even for those patients who participate in cardiac rehabilitation, there is the potential to better support them in improving behaviors known to promote optimal cardiovascular health and in sustaining those behaviors over time. Digital technology has the potential to address many of the challenges of traditional center-based cardiac rehabilitation and to augment care delivery. This American Heart Association science advisory was assembled to guide the development and implementation of digital cardiac rehabilitation interventions that can be translated effectively into clinical care, improve health outcomes, and promote health equity. This advisory thus describes the individual digital components that can be delivered in isolation or as part of a larger cardiac rehabilitation telehealth program and highlights challenges and future directions for digital technology generally and when used in cardiac rehabilitation specifically. It is also intended to provide guidance to researchers reporting digital interventions and clinicians implementing these interventions in practice and to advance a framework for equity-centered digital health in cardiac rehabilitation.

Background: Increased hospital admissions due to COVID-19 place a disproportionate strain on inpatient general medicine service (GMS) capacity compared to other services., Objective: To study the impact on capacity and safety of a hospital-wide policy to redistribute admissions from GMS to non-GMS based on admitting diagnosis during surge periods., Design, Setting, and Participants: Retrospective case-controlled study at a large teaching hospital. The intervention included adult patients admitted to general care wards during two surge periods (January-February 2021 and 2022) whose admission diagnosis was impacted by the policy. The control cohort included admissions during a matched number of days preceding the intervention., Main Outcomes and Measures: Capacity measures included average daily admissions and hospital census occupied on GMS. Safety measures included length of stay (LOS) and adverse outcomes (death, rapid response, floor-to-intensive care unit transfer, and 30-day readmission)., Results: In the control cohort, there were 365 encounters with 299 (81.9%) GMS admissions and 66 (18.1%) non-GMS versus the intervention with 384 encounters, including 94 (24.5%) GMS admissions and 290 (75.5%) non-GMS (p < .001). The average GMS census decreased from 17.9 and 21.5 during control periods to 5.5 and 8.5 during intervention periods. An interrupted time series analysis confirmed a decrease in GMS daily admissions (p < .001) and average daily hospital census (p = .014; p < .001). There were no significant differences in LOS (5.9 vs. 5.9 days, p = .059) or adverse outcomes (53, 14.5% vs. 63, 16.4%; p = .482)., Conclusion: Admission redistribution based on diagnosis is a safe lever to reduce capacity strain on GMS during COVID-19 surges., (© 2023 Society of Hospital Medicine.)

While cyclic adenosine monophosphate (cAMP) is typically considered an intracellular signal, it has been shown to spread between adjacent cells through connexin-based gap junction channels, promoting gap junctional intercellular communication (GJIC). Gap junction-mediated signaling is critical for the coordinated function of many tissues, and have been linked with cardiovascular disease, neurogenerative disease, and cancers. In particular, it plays a complex role in tumor suppression or promotion. This work introduces a two-dimensional finite element model that can describe intercellular cAMP signaling in the presence of gap junctions on membrane interfaces. The model was utilized to simulate cAMP transfer through one and two gap junction channels on the interface of a cluster of two pulmonary microvascular endothelial cells. The simulation results were found to generally agree with what has been observed in the literature in terms of GJIC. The research outcomes suggest that the proposed model can be employed to evaluate the permeability properties of a gap junction channel if its cAMP volumetric flow rate can be experimentally measured., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Leavesley and Rich disclose financial interest in Spectracyte, LLC, a start-up company formed to commercialize spectral imaging technologies., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Hospitals have sought to increase pre-noon discharges to improve capacity, although evidence is mixed on the impact of these initiatives. Past interventions have not quantified the daily gap between morning bed supply and demand. The authors quantified this gap and applied the pre-noon data to target a pre-noon discharge initiative., Methods: The study was conducted at a large hospital and included adult and pediatric medical/surgical wards. The researchers calculated the difference between the average cumulative bed requests and transfers in for each hour of the day in 2018, the year prior to the intervention. In 2019 an intervention on six adult general medical and two surgical wards was implemented. Eight intervention and 14 nonintervention wards were compared to determine the change in average cumulative pre-noon discharges. The change in average hospital length of stay (LOS) and 30-day readmissions was also calculated., Results: The average daily cumulative gap by noon between bed supply and demand across all general care wards was 32.1 beds (per ward average, 1.3 beds). On intervention wards, mean pre-noon discharges increased from 4.7 to 6.7 (p < 0.0000) compared with the nonintervention wards 14.0 vs. 14.6 (p = 0.19877). On intervention wards, average LOS decreased from 6.9 to 6.4 days (p < 0.001) and readmission rates were 14.3% vs 13.9% (p = 0.3490)., Conclusion: The gap between daily hospital bed supply and demand can be quantified and applied to create pre-noon discharge targets. In an intervention using these targets, researchers observed an increase in morning discharges, a decrease in LOS, and no significant change in readmissions., (Copyright © 2022. Published by Elsevier Inc.)

Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses. Most vaccines induced signatures of innate immunity and plasmablasts at days 1 and 7, respectively, after vaccination. However, the yellow fever vaccine induced an early transient signature of T and B cell activation at day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at days 7 and 14-21, respectively. Thus, there was no evidence for a 'universal signature' that predicted antibody response to all vaccines. However, accounting for the asynchronous nature of responses, we defined a time-adjusted signature that predicted antibody responses across vaccines. These results provide a transcriptional atlas of immunity to vaccination and define a common, time-adjusted signature of antibody responses., (© 2022. Springer Nature America, Inc.)

Several studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. However, the generalizability and mechanisms that underlie this association remain poorly defined. Here, we sought to identify a common pre-vaccination signature and mechanisms that could predict the immune response across 13 different vaccines. Analysis of blood transcriptional profiles across studies revealed three distinct pre-vaccination endotypes, characterized by the differential expression of genes associated with a pro-inflammatory response, cell proliferation, and metabolism alterations. Importantly, individuals whose pre-vaccination endotype was enriched in pro-inflammatory response genes known to be downstream of nuclear factor-kappa B showed significantly higher serum antibody responses 1 month after vaccination. This pro-inflammatory pre-vaccination endotype showed gene expression characteristic of the innate activation state triggered by Toll-like receptor ligands or adjuvants. These results demonstrate that wide variations in the transcriptional state of the immune system in humans can be a key determinant of responsiveness to vaccination., (© 2022. The Author(s).)

Vaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern 'omic profiling techniques and computational modeling to promote rapid and transformative advances in vaccinology and vaccine discovery. The NIH/NIAID Human Immunology Project Consortium (HIPC) has leveraged systems immunology approaches to identify molecular signatures associated with the immunogenicity of many vaccines. However, comparative analyses have been limited by the distributed nature of some data, potential batch effects across studies, and the absence of multiple relevant studies from non-HIPC groups in ImmPort. To support comparative analyses across different vaccines, we have created the Immune Signatures Data Resource, a compendium of standardized systems vaccinology datasets. This data resource is available through ImmuneSpace, along with code to reproduce the processing and batch normalization starting from the underlying study data in ImmPort and the Gene Expression Omnibus (GEO). The current release comprises 1405 participants from 53 cohorts profiling the response to 24 different vaccines. This novel systems vaccinology data release represents a valuable resource for comparative and meta-analyses that will accelerate our understanding of mechanisms underlying vaccine responses., (© 2022. The Author(s).)

Monogenic forms of cerebral small vessel disease (CSVD) can be caused by both variants in nuclear DNA and mitochondrial DNA (mtDNA). Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is known to have a phenotype similar to Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy (CADASIL), and can be caused by variants in the mitochondrial genome and in several nuclear-encoded mitochondrial protein (NEMP) genes. The aim of this study was to screen for variants in the mitochondrial genome and NEMP genes in a NOTCH3-negative CADASIL cohort, to identify a potential link between mitochondrial dysfunction and CSVD pathology. Whole exome sequencing was performed for 50 patients with CADASIL-like symptomology on the Ion Torrent system. Mitochondrial sequencing was performed using an in-house designed protocol with sequencing run on the Ion GeneStudio S5 Plus (S5 +). NEMP genes and mitochondrial sequencing data were examined for rare (MAF < 0.001), non-synonymous variants that were predicted to have a deleterious effect on the protein. We identified 29 candidate NEMP variants that had links to either MELAS-, encephalopathy-, or Alzheimer's disease-related phenotypes. Based on these changes, variants affecting POLG, MTO1, LONP1, NDUFAF6, NDUFB3, and TCIRG1 were thought to play a potential role in CSVD pathology in this cohort. Overall, the exploration of the mitochondrial genome identified a potential role for mitochondrial related proteins and mtDNA variants contributing to CSVD pathologies., (© 2022. The Author(s).)

Importance: Value in health care is quality per unit cost (V = Q/C), and an emergency department-based intensive care unit (ED-ICU) model has been associated with improved quality. To assess the value of this care delivery model, it is essential to determine the incremental direct cost of care., Objective: To determine the association of an ED-ICU with inflation-adjusted change in mean direct cost of care, net revenue, and direct margin per ED patient encounter., Design, Setting, and Participants: This retrospective economic analysis evaluated the cost of care delivery to patients in the ED before and after deployment of the Joyce and Don Massey Family Foundation Emergency Critical Care Center, an ED-ICU, on February 16, 2015, at a large academic medical center in the US with approximately 75 000 adult ED visits per year. The pre-ED-ICU cohort was defined as all documented ED visits by patients 18 years or older with a complete financial record from September 8, 2012, through June 30, 2014 (660 days); the post-ED-ICU cohort, all visits from July 1, 2015, through April 21, 2017 (660 days). Fiscal year 2015 was excluded from analysis to phase in the new care model. Statistical analysis was performed March 1 through December 30, 2021., Exposures: Implementation of an ED-ICU., Main Outcomes and Measures: Inflation-adjusted direct cost of care, net revenue, and direct margin per patient encounter in the ED., Results: A total of 234 884 ED visits during the study period were analyzed, with 115 052 patients (54.7% women) in the pre-ED-ICU cohort and 119 832 patients (54.5% women) in the post-ED-ICU cohort. The post-ED-ICU cohort was older (mean [SD] age, 49.1 [19.9] vs 47.8 [19.6] years; P < .001), required more intensive respiratory support (2.2% vs 1.1%; P < .001) and more vasopressor use (0.5% vs 0.2%; P < .001), and had a higher overall case mix index (mean [SD], 1.7 [2.0] vs 1.5 [1.7]; P < .001). Implementation of the ED-ICU was associated with similar inflation-adjusted total direct cost per ED encounter (pre-ED-ICU, mean [SD], $4875 [$15 175]; post-ED-ICU, $4877 [$17 400]; P = .98). Inflation-adjusted net revenue per encounter increased by 7.0% (95% CI, 3.4%-10.6%; P < .001), and inflation-adjusted direct margin per encounter increased by 46.6% (95% CI, 32.1%-61.2%; P < .001)., Conclusions and Relevance: Implementation of an ED-ICU was associated with no significant change in inflation-adjusted total direct cost per ED encounter. Holding delivery costs constant while improving quality demonstrates improved value via the ED-ICU model of care.

Introduction: Delays in inpatient colonoscopy are commonly caused by inadequate bowel preparation and result in increased hospital length of stay (LOS) and healthcare costs. Low-volume bowel preparation (LV-BP; sodium sulfate, potassium sulfate, and magnesium sulfate ) has been shown to improve outpatient bowel preparation quality compared with standard high-volume bowel preparations (HV-BP; polyethylene glycol ). However, its efficacy in hospitalized patients has not been well-studied. We assessed the impact of LV-BP on time to colonoscopy, hospital LOS, and bowel preparation quality among inpatients., Methods: We performed a propensity score-matched analysis of adult inpatients undergoing colonoscopy who received either LV-BP or HV-BP before colonoscopy at a quaternary academic medical center. Multivariate regression models with feature selection were developed to assess the association between LV-BP and study outcomes., Results: Among 1,807 inpatients included in this study, 293 and 1,514 patients received LV-BP and HV-BP, respectively. Among the propensity score-matched population, LV-BP was associated with a shorter time to colonoscopy (β: -0.43 [95% confidence interval: -0.56 to -0.30]) while having similar odds of adequate preparation (odds ratio: 1.02 [95% confidence interval: 0.71-1.46]; P = 0.92). LV-BP was also significantly associated with decreased hospital LOS among older patients (age ≥ 75 years), patients with chronic kidney disease, and patients who were hospitalized with gastrointestinal bleeding., Discussion: LV-BP is associated with decreased time to colonoscopy in hospitalized patients. Older inpatients, inpatients with chronic kidney disease, and inpatients with gastrointestinal bleeding may particularly benefit from LV-BP. Prospective studies are needed to further establish the role of LV-BP for inpatient colonoscopies., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Variants in HECW2 have recently been reported to cause a neurodevelopmental disorder with hypotonia, seizures and impaired language; however, only six variants have been reported and the clinical characteristics have only broadly been defined., Methods: Molecular and clinical data were collected from clinical and research cohorts. Massive parallel sequencing was performed and identified individuals with a HECW2- related neurodevelopmental disorder., Results: We identified 13 novel missense variants in HECW2 in 22 unpublished cases, of which 18 were confirmed to have a de novo variant. In addition, we reviewed the genotypes and phenotypes of previously reported and new cases with HECW2 variants (n=35 cases). All variants identified are missense, and the majority of likely pathogenic and pathogenic variants are located in or near the C-terminal HECT domain (88.2%). We identified several clustered variants and four recurrent variants (p.(Arg1191Gln);p.(Asn1199Lys);p.(Phe1327Ser);p.(Arg1330Trp)). Two variants, (p.(Arg1191Gln);p.(Arg1330Trp)), accounted for 22.9% and 20% of cases, respectively. Clinical characterisation suggests complete penetrance for hypotonia with or without spasticity (100%), developmental delay/intellectual disability (100%) and developmental language disorder (100%). Other common features are behavioural problems (88.9%), vision problems (83.9%), motor coordination/movement (75%) and gastrointestinal issues (70%). Seizures were present in 61.3% of individuals. Genotype-phenotype analysis shows that HECT domain variants are more frequently associated with cortical visual impairment and gastrointestinal issues. Seizures were only observed in individuals with variants in or near the HECT domain., Conclusion: We provide a comprehensive review and expansion of the genotypic and phenotypic spectrum of HECW2 disorders, aiding future molecular and clinical diagnosis and management., Competing Interests: Competing interests: LF, KW, IMW, FZ, EAN and ET are employees of GeneDx. All other coauthors have no conflicts of interest related to the work in this manuscript., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

One synonymous nucleotide substitution in exon 2 of DQA1*05:05:01:13 results in a novel allele, HLA-DQA1*05:05:10., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The Major Histocompatibility Complex (MHC) is a hyper-polymorphic genomic region, which forms a part of the vertebrate adaptive immune system and is crucial for intra- and extra-cellular pathogen recognition (MHC-I and MHC-IIA/B, respectively). Although recent advancements in high-throughput sequencing methods sparked research on the MHC in non-model species, the evolutionary history of MHC gene structure is still poorly understood in birds. Here, to explore macroevolutionary patterns in the avian MHC architecture, we retrieved contigs with antigen-presenting MHC and MHC-related genes from available genomes based on third-generation sequencing. We identified: 1) an ancestral avian MHC architecture with compact size and tight linkage between MHC-I, MHC-IIA/IIB and MHC-related genes; 2) three major patterns of MHC-IIA/IIB unit organization in different avian lineages; and 3) lineage-specific gene translocation events (e.g., separation of the antigen-processing TAP genes from the MHC-I region in passerines), and 4) the presence of a single MHC-IIA gene copy in most taxa, showing evidence of strong purifying selection (low dN/dS ratio and low number of positively selected sites). Our study reveals long-term macroevolutionary patterns in the avian MHC architecture and provides the first evidence of important transitions in the genomic arrangement of the MHC region over the last 100 million years of bird evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Liang, Zhu, Dunn, Zhao and Minias.)

All UK H&I laboratories and transplant units operate under a single national kidney offering policy, but there have been variations in approach regarding when to undertake the pre-transplant crossmatch test. In order to minimize cold ischaemia times for deceased donor kidney transplantation we sought to find ways to be able to report a crossmatch result as early as possible in the donation process. A panel of experts in transplant surgery, nephrology, specialist nursing in organ donation and H&I (all relevant UK laboratories represented) assessed evidence and opinion concerning five factors that relate to the effectiveness of the crossmatch process, as follows: when the result should be ready for reporting; what level of donor HLA typing is needed; crossmatch sample type and availability; fairness and equity; risks and patient safety. Guidelines aimed at improving practice based on these issues are presented, and we expect that following these will allow H&I laboratories to contribute to reducing CIT in deceased donor kidney transplantation., (© 2021 The Authors. International Journal of Immunogenetics published by John Wiley & Sons Ltd.)

In 2020 Coronavirus disease (COVID-19) was identified in Australia. During the pandemic, as essential workers, hospital-based social workers have been on the frontline. This cross-sectional study examines the resilience of social workers during the COVID-19 pandemic, how the pandemic impacted on social work and lessons learnt. Hospital social workers working in three states, namely Victoria, Queensland, and New South Wales were invited to participate in an online web-based survey, providing non-identifiable demographic details and information a) relating to their proximity to COVID-19, b) their degree of resilience (CD-RISC-2), c) professional quality of life, d) perceived social support, e) physical health, f) professional and personal growth during the pandemic, and g) impacts of COVID-19 on their practice. Basic descriptive statistics were computed for variables of interest. Within group, comparisons were made using paired t-tests or one-way ANOVAs for continuous variables as appropriate to investigate possible interstate differences. Regression analyses were conducted to determine which factors contribute to resilience. Social workers, during the pandemic, whether working under the constraints of lockdown or not, demonstrated high levels of resilience. These levels were similar across the three states, unaffected by the degree of infection in the community, indicating that as a group, social workers have high innate levels of resilience. This study provides an in-depth understanding of the impact of COVID-19 on hospital social workers, the long-term impact of the pandemic on social work practice, and potentially useful lessons learnt for the future.

A crossover in exon 2 between DPA1*01:03:01:02 and DPA1*02:01:01:01 results in a novel hybrid allele, HLA-DPA1*01:58., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Changes in pharmacy models of care, services and funding have been occurring internationally, moving away from the traditional dispensing role to more extended patient-facing roles utilising pharmacists' clinical skills. This study aimed to identify the extended services offered by community pharmacy in Aotearoa New Zealand and the barriers and facilitators to extended services provision. The study is unique in that it includes intern (pre-registration) pharmacists., Methods: An online survey, conducted in 2018, of all pharmacists and intern (pre-registration) pharmacists working in a community pharmacy. Data were analysed using descriptive statistics and regression analyses., Results: The results are based on replies from 553 community pharmacists and 59 intern pharmacists (response rate: 19 and 26% respectively). Both pharmacists (83%) and interns (85%) want to work at the top of their scope of practice. Wide variation exists in the specific services individual pharmacists offer. Most pharmacists were accredited to supply the emergency contraceptive pill (95%), sildenafil for erectile dysfunction (86%) and trimethoprim for uncomplicated urinary tract infection (85%). Fewer were able to immunise (34%) or to supply selected oral contraceptives (44%). Just under a quarter could provide a Medicines Use Review (MUR) or Community Pharmacy Anticoagulation Management Service (CPAMS). Of the pharmacists not already accredited, 85% intended to gain accreditation to supply selected oral contraceptives, 40% to become vaccinators, 37% to offer CPAMS and 30% MUR. Interns expressed strong interest in becoming accredited for all extended services. Poisson regression analyses showed key factors supporting the likelihood of providing extended services were owner and management support and appropriate space and equipment. Being excited about the opportunities in community pharmacy, having employer funding and time for training and sufficient support staff were also statistically significant., Conclusions: Pharmacists need time and a supportive management structure to enable them to deliver extended services. Health policy with a greater strategic emphasis on funding services and pharmacist training, and developing technician support roles, will help to minimise or eliminate some of the barriers to role expansion both in Aotearoa New Zealand and internationally., (© 2021. The Author(s).)

Background: Stakeholder involvement in health care research has been shown to improve research development, processes, and dissemination. The literature is developing on stakeholder engagement methods and preliminarily validated tools for evaluating stakeholder level of engagement have been proposed for specific stakeholder groups and settings., Objectives: This paper describes the methodology for engaging a Study Advisory Committee (SAC) in research and reports on the use of a stakeholder engagement survey for measuring level of engagement., Methods: Stakeholders with previous research connections were recruited to the SAC during the planning process for a multicenter randomized control clinical trial, which is ongoing at the time of this writing. All SAC meetings undergo qualitative analysis, while the Stakeholder Engagement Survey instrument developed by the Patient-Centered Outcomes Research Institute (PCORI) is distributed annually for quantitative evaluation., Results: The trial's SAC is composed of 18 members from 3 stakeholder groups: patients and their caregivers; patient advocacy organizations; and health care payers. After an initial in-person meeting, the SAC meets quarterly by telephone and annually in-person. The SAC monitors research progress and provides feedback on all study processes. The stakeholder engagement survey reveals improved engagement over time as well as continued challenges., Conclusions: Stakeholder engagement in the research process has meaningfully contributed to the study design, patient recruitment, and preliminary analysis of findings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

The Mars Science Laboratory (MSL) recently discovered nitrates in Gale Crater ( e.g. , Stern et al. , 2015; Sutter et al. , 2017). One possible mechanism for ancient nitrate deposition on Mars is through HNOx formation and rain out in the atmosphere, for which lightning-induced NO is likely the fundamental source. This study investigates nitrogen (N 2 ) fixation in early Mars' atmosphere, with implications for early Mars' habitability. We consider a 1 bar atmosphere of background CO 2 , with abundance of N 2 , hydrogen, and methane varied from 1% to 10% to explore a swath of potential early Mars climates. We derive lightning-induced thermochemical equilibrium fluxes of NO and HCN by coupling the lightning-rate parametrization from the study of Romps et al. (2014) with chemical equilibrium with applications, and we use a Geant4 simulation platform to estimate the effect of solar energetic particle events. These fluxes are used as input into KINETICS, the Caltech/JPL coupled photochemistry and transport code, which models the chemistry of 50 species linked by 495 reactions to derive rain-out fluxes of HNOx and HCN. We compute equilibrium concentrations of cyanide and nitrate in a putative northern ocean at early Mars, assuming hydrothermal vent circulation and photoreduction act as the dominant loss mechanisms. We find average oceanic concentrations of ∼0.1-2 nM nitrate and ∼0.01-2 mM cyanide. HCN is critical for protein synthesis at concentrations >0.01 M ( e.g. , Holm and Neubeck, 2009), and our result is astrobiologically significant if secondary local concentration mechanisms occurred. Nitrates may act as high-potential electron acceptors for early metabolisms, although the minimum concentration required is unknown. Our study derives concentrations that will be useful for future laboratory studies to investigate the habitability at early Mars. The aqueous nitrate concentrations correspond to surface nitrate precipitates of ∼1-8 × 10 -4 wt % that may have formed after the evaporation of surface waters, and these values roughly agree with recent MSL measurements.

The COVID-19 pandemic exposed and exacerbated longstanding inefficiencies and deficiencies in chronic disease management and treatment in the United States, such as a fragmented healthcare experience and system, narrowly focused services, limited resources beyond office visits, expensive yet low quality care, and poor access to comprehensive prevention and non-pharmacological resources. It is feared that the addition of COVID-19 survivors to the pool of chronic disease patients will burden an already precarious healthcare system struggling to meet the needs of chronic disease patients. Digital health and telemedicine solutions, which exploded during the pandemic, may address many inefficiencies and deficiencies in chronic disease management, such as increasing access to care. However, these solutions are not panaceas as they are replete with several limitations, such as low uptake, poor engagement, and low long-term use. To fully optimize digital health and telemedicine solutions, we argue for the gamification of digital health and telemedicine solutions through a pantheoretical framework-one that uses personalized, contextualized, and behavioral science algorithms, data, evidence, and theories to ground treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Seixas, Olaye, Wall and Dunn.)