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Abstract Background The uptake of research findings into clinical practice is critical to providing health care that improves health outcomes for patients. This study explored how Patient-Centered Outcomes Research Institute (PCORI) awardees perceive the relationship between engagement of patients and other partners in research and three uses, or applications, of patient-centered comparative clinical effectiveness research (CER) study findings, which may lead to uptake in clinical practice: (1) Integration into clinical practice guidelines, recognized point-of-care decision tools, or documents that may inform policy; (2) Implementation beyond the study, including at sites outside of the study setting or patient populations; and (3) Active dissemination of findings to specific audiences by parties external to the study team. Methods This exploratory qualitative study examined awardee and partner perceptions of what led to each use of study findings and how engaged partners contributed. We purposively selected PCORI-funded research projects with documentation of each use and conducted virtual interviews with 42 individuals (15 PIs or project leads, 2 research team members, and 25 partners) from 17 projects. We conducted thematic analysis of individual projects or project sets, across projects within each use case, and across the three uses. Results Participants described three primary activities in which engaged partners made contributions before, during and after CER studies that facilitated the use of study findings: (1) generating relevant study findings, (2) distributing study findings strategically, and (3) making connections to people or organizations outside the study team. In addition, engagement continued to facilitate the use of study findings during subsequent PCORI-funded implementation and dissemination-specific projects, with partners adapting interventions and creating and tailoring dissemination messages and products. Finally, participants described attributes of teams’ engagement approaches that may have supported partner contributions, including early and ongoing engagement, leveraging partners’ connections and understanding of community needs, and using multiple engagement approaches. Conclusion This study identified examples of how engagement can help facilitate the use of CER study findings, especially when engagement contributions occur in meaningful ways. Findings from this study suggest a framework for future research on the relationship between engagement in research and uptake of study findings into clinical practice.

Abstract Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin atlas of the human coronary; and iv) annotation principal components representing a wide range of functional processes. We observe marked enrichment of CAD heritability for most functional annotations. These results reveal the predominant role of ultra-rare variants in low LD on the heritability of CAD. Moreover, they highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Abstract Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson’s disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is collected from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg of protein (n = 15), on average, was collected from surgical instruments. Light microscopy revealed axons, capillaries, and blood cells as the primary components of purified tissue (n = 3). ELISA assay further confirmed the presence of neuronal and glial tissue in DBS samples (n = 4). Further analysis was conducted using western blot, demonstrating that multiple αSyn antibodies are reactive in PD (n = 5) and ET (n = 3) samples; truncated αSyn (1–125 αSyn) was significantly increased in PD (n = 5) compared to ET (n = 3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that multiple forms of αSyn can be detected from living PD patients with this method.

Abstract Background As rates of obesity and overweight continue to increase in the UK, calorie labels have been introduced on menus as a policy option to provide information to consumers on the energy content of foods and to enable informed choices. This study tested whether the addition of calorie labels to items in a simulated food delivery platform may reduce the energy content of items selected. Methods UK adults (n = 8,780) who used food delivery platforms were asked to use the simulated platform as they would in real life to order a meal for themselves. Participants were randomly allocated to a control condition (no calorie labels) or to one of seven intervention groups: (1) large size calorie labels adjacent to the price (LP), (2) large size label adjacent to the product name (LN), (3) small label adjacent to price (SP), (4) small label adjacent to product name (SN), (5) LP with a calorie label switch-off filter (LP + Off), (6) LP with a switch-on filter (LP + On), or, (7) LP with a summary label of the total basket energy content (LP + Sum). Regression analysis assessed the impact of calorie labels on energy content of foods selected compared to the control condition. Results The mean energy selected in the control condition was 1408 kcal (95%CI: 93, 2719). There was a statistically significant reduction in mean energy selected in five of the seven intervention trial arms (LN labels (-60 kcal, 95%CI: -111, -6), SN (-73, 95%CI: -125, -19), LP + Off (-110, 95%CI: -161, -57), LP + On (-109, 95%CI: -159, -57), LP + Sum (-85 kcal, 95%CI: -137, -30). There was no evidence the other two conditions (LP (-33, 95%CI: -88, 24) and SP (-52, 95%CI: -105, 2)) differed from control. There was no evidence of an effect of any intervention when the analysis was restricted to participants who were overweight or obese. Conclusion Adding calorie labels to food items in a simulated online food delivery platform reduced the energy content of foods selected in five out of seven labelling scenarios. This study provides useful information to inform the implementation of these labels in a food delivery platform context.

Abstract Background The rapid start of antiretroviral therapy (RSA) model initiates antiretroviral therapy (ART) as soon as possible after a new or preliminary diagnosis of HIV, in advance of HIV-1 RNA and other baseline laboratory testing. This observational study aims to determine if RSA with a single tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) is an effective regimen for achieving viral suppression and accepted by patients at the time of diagnosis. Methods Adults newly or preliminarily diagnosed with HIV were enrolled from October 2018 through September 2021. Real world advantage, measured in days between clinical milestones and time to virologic suppression, associated with B/F/TAF RSA was compared to historical controls. Results All Study RSA participants (n = 45) accepted treatment at their first visit and 43(95.6%) achieved virologic suppression by week 48. Study RSA participants had a significantly shorter time (median 32 days) from diagnosis to ART initiation and virologic suppression, in comparison to historical controls (median 181 days) (n = 42). Qualitative feedback from study RSA participants showed high acceptance positive response to RSA. Conclusions RSA is feasible and well accepted by patients in a real-world community-based clinic setting. Promoting RSA in community-based clinics is an important tool in ending the HIV epidemic.

The objective was to explore if the regression of phenotypic performance for six milk production traits on the respective estimate of genetic merit for that trait differed by herd milking frequency; variance components for each trait in the two milking frequency environments were also estimated as well as the genetic correlation between the same trait in both environments. The data used included 12,581 lactations from 5,456 cows in 32 spring-calving once-a-day (OAD) milking herds. Each OAD herd was matched with three contemporary twice-a-day (TAD)-milking herds; 35,823 lactations from 15,188 cows in 96 TAD herds were used. Mean yield was 20% (fat yield) to 31% (milk yield) lower in OAD herds. Milk protein concentration was 11% higher in OAD herds, while milk fat concentration was 16% higher in OAD herds. The mean back-transformed somatic cell score (SCS) was 100,390 cells/mL in OAD herds and 72,493 cells/mL in TAD herds. The association between each milk production trait and its respective estimate of genetic merit differed by herd milking frequency; the estimated regression coefficients were larger in TAD for just milk yield and SCS. The genetic correlation between the same trait in OAD versus TAD was all ≥0.73 with the exception of SCS (genetic correlation of 0.48) which suggests some re-ranking of sires between environments. In conclusion, differences in the scale of the genetic variance were evident for both milking frequencies and possible re-ranking was evident for SCS.

Selection methods are commonly used in talent acquisition to predict future job performance and to find the best candidates, but questionnaire-based assessments can be lengthy and lead to candidate fatigue and poor engagement, affecting completion rates and producing poor data. Gamification can mitigate some of these issues through greater engagement and shorter testing times. One avenue of gamification is image-based tests. Although such assessments are starting to gain traction in personnel selection, few studies describing their validity and psychometric properties exist. The current study explores the potential of a five-minute, forced-choice, image-based assessment of the Big Five personality traits to be used in selection. Study 1 describes the creation of the image pairs and the selection of the 150 best-performing items based on a sample of 300 respondents. Study 2 describes the creation of machine-learning-based scoring algorithms and tests of their convergent and discriminate validity and adverse impact based on a sample of 431 respondents. All models showed good levels of convergent validity with the IPIP-NEO-120 (openness r = 0.71, conscientiousness r = 0.70, extraversion r = 0.78, agreeableness r = 0.60, and emotional stability r = 0.70) and were largely free from potential adverse impact. The implications for recruitment policy and practice and the need for further validation are discussed.

Long-term follow-up for individuals with hypospadias remains a critical area of need, yet evidence-based guidelines for such follow-up are lacking, and the role of involvement of relevant experts is not yet established. Using our hypospadias-specific health-related quality of life conceptual framework and a subsequent qualitative study of prepubertal males and parents of males with hypospadias, we identified potential priorities for long-term follow-up of youth with hypospadias. Using thematic codes from our patient and parent interviews, we searched PubMed for relevant articles and identified the specialties represented by all the authors of these articles. Our search strategy revealed consistent expertise across HRQOL themes and subthemes, including pediatric and adult urology, health psychology, psychiatry, endocrinology, genetics, and social work. Communication experts, as well as patients and families, were also represented in our literature search. Using these findings, we compiled a comprehensive list of potential stakeholders to inform the development of holistic care guidelines for individuals with hypospadias. By engaging these stakeholders, we aim to develop consensus-based, long-term follow-up guidelines and tools to address the evolving physical and psychosocial needs of people with hypospadias over a lifetime. The use of qualitatively derived thematic codes to search for relevant literature is an accessible approach to identifying relevant stakeholders. These findings underscore the importance of involving diverse, multidisciplinary expertise to ensure comprehensive, patient-centered care in complex genitourinary conditions.

IntroductionBacterial infection and biofilm formation contribute to impaired healing in chronic diabetic wounds. Staphylococcus aureus and Pseudomonas aeruginosa are found in human diabetic wound biofilms. They may develop antibiotic resistance, increasing the urgency for alternative or complementary therapies. Diabetic wound healing may be improved with the use of biomedically engineered scaffolds, which can also serve as delivery systems for antibacterial compounds. Manuka honey is a potent antibacterial and wound care agent due to its high osmolarity, low pH, and constituents (such as methylglyoxal). Honey exhibits bacteriostatic and bactericidal effects, modulates the expression of biofilm forming genes, and restores antibiotic susceptibility in previously drug resistant pathogens.MethodsIn this study, we created a dermal regeneration template (DRT) composed of polycaprolactone-gelatin (PCL-gelatin) and Manuka honey to retain honey in the wound and also provide a scaffold for tissue regeneration.Results and discussionSoluble Manuka honey inhibited the planktonic and biofilm growth of both S. aureus (UWH3) and P. aeruginosa (PA14) co-cultures. Manuka honey embedded PCL-gelatin scaffolds did not exhibit bacteriostatic or bactericidal effects on cocultures of UHW3 and PA14; however, they promoted the expression of AgrA, a gene associated with dispersal of S. aureus biofilms.

Although the intervertebral discs are the most studied region of the spinal motion segment with respect to their degeneration and contributions to back pain, it is becoming increasingly evident that degeneration of adjacent structures including the facet joints, vertebral endplates and paraspinal muscles occurs concomitant with disc degeneration. However, crosstalk between these adjacent components of the motion segment remains understudied, particularly in preclinical large animal models. In this study, intervertebral disc degeneration was induced in goat cervical discs via intradiscal injection of 2U or 5U of chondroitinase ABC (ChABC). Disc degeneration and trans-endplate small molecule diffusion into the disc were assessed at 12 weeks using in vivo MRI T2 mapping and post-contrast enhanced T1 mapping. Animals were euthanized at 12 weeks post-ChABC injection for end-term structure-function analysis of the disc, vertebral endplate and facet tissues. Intradiscal injection of ChABC yielded a spectrum of disc degeneration independent of ChABC dosage. Increasing severity of disc degeneration correlated with increased vertebral endplate bone density. In levels that did not exhibit severe degeneration or endplate resorptions, we demonstrated a significant correlation between NP T2 values and disc diffusion properties. Early-stage osteoarthritis of the facet joints was observed concomitant with disc degeneration, characterized primarily by alterations in facet cartilage mechanical properties. This work established a large animal model of whole spinal motion segment degeneration, including correlations between trans-endplate diffusion and disc health, which can be utilized to increase the translational relevance of studies evaluating strategies for disc regeneration or repair.

This article applies the Community of Inquiry (CoI) framework to a particular disciplinary context: first-year writing (FYW). Students enrolled in online FYW courses across three institutions (n = 272) completed a version of the CoI survey that was slightly modified to fit the disciplinary context of writing studies. A factor analysis was conducted to determine how well the CoI in Writing Studies data aligned with typical CoI survey research; teaching presence and cognitive presence loaded onto single factors, but the social presence items divided into multiple factors. The authors put their findings in conversation with other scholarship about social presence, especially Carlon et al. (2012) and Kreijns et al. (2014), and advocate for differentiating between survey items that relate to "social presence," "social comfort," "attitude," and "social learning." They also recommend that future disciplinary uses of the CoI Survey include survey items that ask students to report on the extent to which they engaged in the types of social learning that the discipline values.

Abstract Background Cadaveric intervertebral discs are often studied for a variety of research questions, and outcomes are interpreted in the in vivo context. Unfortunately, the cadaveric disc does not inherently represent the LIVE condition, such that the disc structure (geometry), composition (T2 relaxation time), and mechanical function (opening pressure, OP) measured in the cadaver do not necessarily represent the in vivo disc. Methods We conducted serial evaluations in the Yucatan minipig of disc geometry, T2 relaxation time, and OP to quantify the changes that occur with progressive dissection and used axial loading to restore the in vivo condition. Results We found no difference in any parameter from LIVE to TORSO; thus, within 2 h of sacrifice, the TORSO disc can represent the LIVE condition. With serial dissection and sample preparation the disc height increased (SEGMENT height 18% higher than TORSO), OP decreased (POTTED was 67% lower than TORSO), and T2 time was unchanged. With axial loading, an imposed stress of 0.20–0.33 MPa returned the disc to in vivo, LIVE disc geometry and OP, although T2 time was decreased. There was a linear correlation between applied stress and OP, and this was conserved across multiple studies and species. Conclusion To restore the LIVE disc state in human studies or other animal models, we recommend measuring the OP/stress relationship and using this relationship to select the applied stress necessary to recover the in vivo condition.

Business psychologists study and assess relevant individual differences, such as intelligence and personality, in the context of work. Such studies have informed the development of artificial intelligence systems (AI) designed to measure individual differences. This has been capitalized on by companies who have developed AI-driven recruitment solutions that include aggregation of appropriate candidates ("Hiretual"), interviewing through a chatbot ("Paradox"), video interview assessment ("MyInterview"), and CV-analysis ("Textio"), as well as estimation of psychometric characteristics through image-("Traitify") and game-based assessments ("HireVue") and video interviews ("Cammio"). However, driven by concern that such high-impact technology must be used responsibly due to the potential for unfair hiring to result from the algorithms used by these tools, there is an active effort towards proving mechanisms of governance for such automation. In this article, we apply a systematic algorithm audit framework in the context of the ethically critical industry of algorithmic recruitment systems, exploring how audit assessments on AI-driven systems can be used to assure that such systems are being responsibly deployed in a fair and well-governed manner. We outline sources of risk for the use of algorithmic hiring tools, suggest the most appropriate opportunities for audits to take place, recommend ways to measure bias in algorithms, and discuss the transparency of algorithms.

University leaders can support academic advising as an interactive process in which the adviser helps students set and achieve academic goals, acquire relevant information and services, and make responsible decisions consistent with their interests, goals, abilities, and degree requirements. The study adopted qualitative narrative inquiry research design. The data were collected via a semi-structured questionnaire administered to six faculty member on one-on-one basis and their students were also sent interview questions electronically for completion from January 25, 2019 February 25, 2019. The results revealed that Doctoral programs generally attract such students who are highly motivated to attain advanced degrees and who are willing to participate fully in the advisement process. Graduate students re-enhanced when they received appropriate academic advising at all stages of a doctoral degree program. Students were need of effective advising process at all times from being recruited, to career planning after graduation.

Abstract Background There is considerable variation in the functionality of bioethical services in different institutions and countries for children in hospital, despite new challenges due to increasing technology supports for children with serious illness and medical complexity. We aimed to understand how bioethics services address bioethical concerns that are increasingly encountered in paediatric intensive care. Methods A qualitative descriptive design was used to describe clinician’s perspectives on the functionality of clinical bioethics services for paediatric intensive care units. Clinicians who were members of formal or informal clinical bioethics groups, or who were closely involved with the process of working through ethically challenging decisions, were interviewed. Interviews took place online. Resulting transcripts were analysed using thematic analysis. Results From 33 interviews, we identified four themes that described the functionality of bioethics services when a child requires technology to sustain life: striving for consensus; the importance of guidelines; a structure that facilitates a time-sensitive and relevant response; and strong leadership and teamwork. Conclusions Clinical bioethics services have the potential to expand their role due to the challenges brought by advancing medical technology and the increasing options it brings for treatment. Further work is needed to identify where and how bioethics services can evolve and adapt to fully address the needs of the decision-makers in PICU.

Laren D Tan,1 Anthony A Hilliard,2 Ricardo L Peverini,3 Robert D Martin,4 Tamara L Thomas,5 Trevor G Wright,6 Lyndon C Edwards,6 Angela M Lalas,6 Helen M Staples-Evans,6 Barbara J Sharp,7 Stella L Ahn-Kim,7 Kent A Hansen,6 Richard H Hart8 1Department of Medicine, Pulmonary, Critical Care, Hyperbaric and Sleep Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA; 2Department of Medicine, Cardiology, Loma Linda University School of Medicine, Loma Linda, CA, USA; 3Department of Pediatrics, Neonatology, Loma Linda University School of Medicine, Loma Linda, CA, USA; 4Department of Anesthesia, Loma Linda University School of Medicine, Loma Linda, CA, USA; 5Department of Emergency Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA; 6Loma Linda University Health, Loma Linda, CA, USA; 7Loma Linda University School of Medicine, Loma Linda, CA, USA; 8Department of Preventive Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USACorrespondence: Laren D Tan, Email Latan@llu.eduAbstract: Navigating the healthcare conundrum in the Blue Zone of Loma Linda, California, requires understanding the unique factors that make this region stand out in terms of health and longevity. But more important is understanding the healthcare system sustaining the Blue Zone in Loma Linda, California. In an era marked by soaring healthcare costs and diminishing reimbursement rates, hospitals and physicians face an unprecedented challenge: providing excellent patient care while maintaining financial sustainability. This leadership perspective publication paper delves into the multifaceted struggles encountered by healthcare and hospital leaders, exploring the root causes, implications, and potential solutions for this complex issue. As we examine the evolving healthcare landscape, we aim to shed light on the critical need for innovative approaches to sustain the future of healthcare excellence in one of the five original Blue Zones.Keywords: blue zone, Loma Linda, healthcare cost, leadership healthcare, longevity, California

Although research on virtual reality (VR) as a pedagogical tool within counselor education is scarce, the parallel use of VR in health sciences education indicates VR simulations may have similar utility and effectiveness in training counselors. This conceptual piece aims to assist counselor educators in building VR simulations for counselors-in-training (CITs). The authors review the research on VR usage in counselor education and explore the practical implications of VR simulations for training counselors. The authors describe the development and utilization of VR simulations across multiple stages of training in a counselor education master’s program to support CITs’ clinical skill development during the COVID-19 pandemic. Advantages, limitations, and diversity and equity considerations of VR simulation usage in counselor training are discussed.

Abstract Brain tumours are the most common solid neoplasm in children, posing a significant challenge in oncology due to the limited range of treatment. Intraoperative magnetic resonance imaging (iMRI) has recently emerged to aid surgical intervention in neurosurgery resection with the potential to delineate tumour boundaries. This narrative literature review aimed to provide an updated evaluation of the clinical implementation of iMRI in paediatric neurosurgical resection, with an emphasis on the extent of brain tumour resection, patient outcomes and its drawbacks. Databases including MEDLINE, PubMed, Scopus and Web of Science were used to investigate this topic with key terms: paediatric, brain tumour, and iMRI. Exclusion criteria included literature comprised of adult populations and the use of iMRI in neurosurgery in the absence of brain tumours. The limited body of research evaluating the clinical implementation of iMRI in paediatric cohorts has been predominantly positive. Current evidence demonstrates the potential for iMRI use to increase rates of gross total resection (GTR), assess the extent of resection, and improve patient outcomes, such as progression‐free survival. Limitations regarding the use of iMRI include prolonged operation times and complications associated with head immobilisation devices. iMRI has the potential to aid in the achievement of maximal brain tumour resection in paediatric patients. Future prospective randomised controlled trials are necessary to determine the clinical significance and benefits of using iMRI during neurosurgical resection for clinical management of brain neoplasms in children.

Obesity, a complex condition that involves genetic, environmental, and behavioral factors, is a non-infectious pandemic that affects over 650 million adults worldwide with a rapidly growing prevalence. A major contributor is the consumption of high-fat diets, an increasingly common feature of modern diets. Maternal obesity results in an increased risk of offspring developing obesity and related health problems; however, the impact of maternal diet on the adipose tissue composition of offspring has not been evaluated. Here, we designed a generational diet-induced obesity study in female C57BL/6 mice that included maternal cohorts and their female offspring fed either a control diet (10% fat) or a high-fat diet (45% fat) and examined the visceral adipose proteome. Solubilizing proteins from adipose tissue is challenging due to the need for high concentrations of detergents; however, the use of a detergent-compatible sample preparation strategy based on suspension trapping (S-Trap) enabled label-free quantitative bottom-up analysis of the adipose proteome. We identified differentially expressed proteins related to lipid metabolism, inflammatory disease, immune response, and cancer, providing valuable molecular-level insight into how maternal obesity impacts the health of offspring. Data are available via ProteomeXchange with the identifier PXD042092.

The history of medical education scholarship is often overlooked. Moreover, although productive educational researchers are often recognized for their scholarly contributions in peer-reviewed publications, the impact of others who are not active medical education researchers may be unknown to contemporary educators and scholars. This short paper describes the contributions of Harmen Tiddens, MD PhD to Utrecht and Maastricht Universities where he established the environment and supports for scholars to undertake profoundly influential work. Through his leadership as the founding Dean of Maastricht's new medical school, Dr. Tiddens facilitated educational principles that became exemplary for generations of health professions education scholars and curriculum developers, nationally and internationally.

In a systematic scoping review, we analyzed empirical and conceptual writings on youth participatory action research (YPAR) in schools. YPAR has emerged as an empowering and youth-centered approach to group work whereby school counselors and students collaborate on researching, creating, and sharing projects about social ills impacting their lives. Reviewing YPAR literature, this article identifies knowledge gaps regarding the use and benefits of YPAR in school counseling practice.

Isolation, quarantine, and fear of the Coronavirus have led to increases in mental health concerns in adults and teens. While research has begun documenting the increased rates of mental illness resulting from the pandemic, there has been little in-depth exploration of how teens from diverse backgrounds are experiencing the COVID-19 pandemic. The present study was a focus group conducted with 5 TRIO Upward Bound high school students in a midwestern US state to explore how COVID-19 has impacted them and their communities. Results showed that while these teens reported feeling developmentally impeded and unable to follow social distancing guidelines, they also reported finding ways to cope. These results are important in understanding how teens from diverse backgrounds build resiliency, and how they face challenges during social isolation. Future research should involve longitudinal designs that follow teens into their adult lives to determine how development and resilience continue to change over time.

­Business reliance on algorithms is becoming ubiquitous, and companies are increasingly concerned about their algorithms causing major financial or reputational damage. High-profile cases include Google’s AI algorithm for photo classification mistakenly labelling a black couple as gorillas in 2015 (Gebru 2020 In The Oxford handbook of ethics of AI, pp. 251–269), Microsoft’s AI chatbot Tay that spread racist, sexist and antisemitic speech on Twitter (now X) (Wolf et al. 2017 ACM Sigcas Comput. Soc. 47, 54–64 (doi:10.1145/3144592.3144598)), and Amazon’s AI recruiting tool being scrapped after showing bias against women. In response, governments are legislating and imposing bans, regulators fining companies and the judiciary discussing potentially making algorithms artificial ‘persons’ in law. As with financial audits, governments, business and society will require algorithm audits; formal assurance that algorithms are legal, ethical and safe. A new industry is envisaged: Auditing and Assurance of Algorithms (cf. data privacy), with the remit to professionalize and industrialize AI, ML and associated algorithms. The stakeholders range from those working on policy/regulation to industry practitioners and developers. We also anticipate the nature and scope of the auditing levels and framework presented will inform those interested in systems of governance and compliance with regulation/standards. Our goal in this article is to survey the key areas necessary to perform auditing and assurance and instigate the debate in this novel area of research and practice.

Background The objectives of this study were to (1) evaluate telemetry use pre‐ and postimplementation of clinical decision support tools to support American Heart Association practice standards for telemetry monitoring and (2) understand the factors that may contribute to variation of telemetry monitoring in practice. Methods and Results First, we captured overall variability in telemetry use pre‐ and postimplementation of the clinical decision support intervention. We then conducted semistructured interviews with telemetry‐ordering providers to identify key barriers and facilitators to adoption. During the study period, 399 physicians met criteria for inclusion and were divided into excessive and nonexcessive orderers. Distribution of telemetry use was bimodal. Among nonexcessive users, 24.4% of patient days were with telemetry compared with 51.6% among excessive users. On average, both excessive (6.1% reduction) and nonexcessive users (2.8% reduction) decreased telemetry use postimplementation, and these reductions were sustained over a 16‐month period. Sixteen interviews were conducted. Physicians believed that the tool was successful because it caused them to more closely consider if telemetry was indicated for each patient. Physicians also voiced frustration with interruptions to their workflow, and some noted that they commonly use telemetry outside of practice standards to monitor patients who were acutely but not critically ill. Conclusions Embedding telemetry practice standards into the electronic health record in the form of clinical decision support is effective at reducing excess telemetry use. Although the intervention was well received, there are persistent barriers, such as preexisting views on telemetry and existing workflow habits, that may inhibit higher adoption of standards.

IntroductionLow back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain.MethodsTwenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery.ResultsDP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure).DiscussionThus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles.

In this paper we address the connections between the computational models of coupled flow and mechanical deformation in soils at the Darcy-scale and pore-scale. At the Darcy scale the Biot model requires data including permeability which is traditionally provided by experiments and empirical measurements. At the pore-scale we consider the Discrete Element Method (DEM) to generate physically realistic assemblies of the particles, and we follow up with the Stokes flow model. Next we apply upscaling to obtain the permeabilities which we find dependent on the deformation. We outline the workflow with its challenges and methods, and present results which show, e.g., hysteretic dependence of the permeability and porosity on the load. We also show how to incorporate the deformation dependent permeability in a nonlinear Biot model, and illustrate with computational results.

BackgroundAcute neurological manifestation is a common complication of acute Coronavirus Disease 2019 (COVID-19) disease. This retrospective cohort study investigated the 3-year outcomes of patients with and without significant neurological manifestations during initial COVID-19 hospitalization.Methods and findingsPatients hospitalized for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection between 03/01/2020 and 4/16/2020 in the Montefiore Health System in the Bronx, an epicenter of the early pandemic, were included. Follow-up data was captured up to 01/23/2023 (3 years post-COVID-19). This cohort consisted of 414 patients with COVID-19 with significant neurological manifestations and 1,199 propensity-matched patients (for age and COVID-19 severity score) with COVID-19 without neurological manifestations. Neurological involvement during the acute phase included acute stroke, new or recrudescent seizures, anatomic brain lesions, presence of altered mentation with evidence for impaired cognition or arousal, and neuro-COVID-19 complex (headache, anosmia, ageusia, chemesthesis, vertigo, presyncope, paresthesias, cranial nerve abnormalities, ataxia, dysautonomia, and skeletal muscle injury with normal orientation and arousal signs). There were no significant group differences in female sex composition (44.93% versus 48.21%, p = 0.249), ICU and IMV status, white, not Hispanic (6.52% versus 7.84%, p = 0.380), and Hispanic (33.57% versus 38.20%, p = 0.093), except black non-Hispanic (42.51% versus 36.03%, p = 0.019). Primary outcomes were mortality, stroke, heart attack, major adverse cardiovascular events (MACE), reinfection, and hospital readmission post-discharge. Secondary outcomes were neuroimaging findings (hemorrhage, active and prior stroke, mass effect, microhemorrhages, white matter changes, microvascular disease (MVD), and volume loss). More patients in the neurological cohort were discharged to acute rehabilitation (10.39% versus 3.34%, p < 0.001) or skilled nursing facilities (35.75% versus 25.35%, p < 0.001) and fewer to home (50.24% versus 66.64%, p < 0.001) than matched controls. Incidence of readmission for any reason (65.70% versus 60.72%, p = 0.036), stroke (6.28% versus 2.34%, p < 0.001), and MACE (20.53% versus 16.51%, p = 0.032) was higher in the neurological cohort post-discharge. Per Kaplan-Meier univariate survival curve analysis, such patients in the neurological cohort were more likely to die post-discharge compared to controls (hazard ratio: 2.346, (95% confidence interval (CI) [1.586, 3.470]; p < 0.001)). Across both cohorts, the major causes of death post-discharge were heart disease (13.79% neurological, 15.38% control), sepsis (8.63%, 17.58%), influenza and pneumonia (13.79%, 9.89%), COVID-19 (10.34%, 7.69%), and acute respiratory distress syndrome (ARDS) (10.34%, 6.59%). Factors associated with mortality after leaving the hospital involved the neurological cohort (odds ratio (OR): 1.802 (95% CI [1.237, 2.608]; p = 0.002)), discharge disposition (OR: 1.508 (95% CI [1.276, 1.775]; p < 0.001)), congestive heart failure (OR: 2.281 (95% CI [1.429, 3.593]; p < 0.001)), higher COVID-19 severity score (OR: 1.177 (95% CI [1.062, 1.304]; p = 0.002)), and older age (OR: 1.027 (95% CI [1.010, 1.044]; p = 0.002)). There were no group differences in radiological findings, except that the neurological cohort showed significantly more age-adjusted brain volume loss (p = 0.045) than controls. The study's patient cohort was limited to patients infected with COVID-19 during the first wave of the pandemic, when hospitals were overburdened, vaccines were not yet available, and treatments were limited. Patient profiles might differ when interrogating subsequent waves.ConclusionsPatients with COVID-19 with neurological manifestations had worse long-term outcomes compared to matched controls. These findings raise awareness and the need for closer monitoring and timely interventions for patients with COVID-19 with neurological manifestations, as their disease course involving initial neurological manifestations is associated with enhanced morbidity and mortality.

Abstract Nephron endowment at birth impacts long-term renal and cardiovascular health, and it is contingent on the nephron progenitor cell (NPC) pool. Glycolysis modulation is essential for determining NPC fate, but the underlying mechanism is unclear. Combining RNA sequencing and quantitative proteomics we identify 267 genes commonly targeted by Wnt activation or glycolysis inhibition in NPCs. Several of the impacted pathways converge at Acetyl-CoA, a co-product of glucose metabolism. Notably, glycolysis inhibition downregulates key genes of the Mevalonate/cholesterol pathway and stimulates NPC differentiation. Sodium acetate supplementation rescues glycolysis inhibition effects and favors NPC maintenance without hindering nephrogenesis. Six2Cre-mediated removal of ATP-citrate lyase (Acly), an enzyme that converts citrate to acetyl-CoA, leads to NPC pool depletion, glomeruli count reduction, and increases Wnt4 expression at birth. Sodium acetate supplementation counters the effects of Acly deletion on cap-mesenchyme. Our findings show a pivotal role of acetyl-CoA metabolism in kidney development and uncover new avenues for manipulating nephrogenesis and preventing adult kidney disease.