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Objectives: The purpose of this study was to examine the impact of a contact-free continuous monitoring system on clinical outcomes including unplanned intensive care unit (ICU) transfer (primary), length of stay (LOS), code blue, and mortality. A secondary aim was to evaluate the return on investment associated with implementing the contact-free continuous monitoring program during the COVID public health emergency., Methods: An interrupted time series evaluation was conducted to examine the association between the use of contact-free continuous monitoring and clinical outcomes. A cost-benefit analysis was planned to evaluate the return on investment., Results: Use of contact-free continuous monitoring was not significantly associated with unplanned ICU transfers, deaths, ICU LOS, and or rapid response team calls. However, there were significant increases in code blue events (P = 0.02) and mean hospital LOS (P = 0.01) in the postimplementation period when compared with the preimplementation period. Due to the lack of improvement, costs were calculated but a cost-benefit analysis was not conducted., Conclusions: Contact-free continuous monitoring bed use during the COVID-19 public health emergency was not associated with improvements in clinical outcomes, although there was substantial confounding. Future studies should include large randomized controlled trials to control for factors not under direct experimental control including unit staffing, staff turnover, and differences in the patient population related to surges in the COVID-19 pandemic., Competing Interests: Conflicts of interest and source of funding: Dr. Bates reports grants and personal fees from EarlySense, personal fees from CDI Negev, equity from ValeraHealth, equity from Clew, equity from MDClone, personal fees and equity from AESOP, personal fees and equity from Feelbetter, equity from Guided Clinical Solutions, and grants from IBM Watson Health, outside the submitted work. Dr. Bates has a patent pending (PHC-028564 US PCT), on intraoperative clinical decision support. This project was funded by Hillrom under a research grant. Hillrom was not involved in the conduct of the research, analysis, or development of the manuscript. For the remaining authors none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Secondary schools are important settings for promoting varied physical activity (PA) opportunities for adolescents to promote PA throughout life. However, research on the effect of secondary school-based interventions on future PA is limited. This study examined the potential impact of secondary school-based interventions on the determinants of future PA participation of Aotearoa New Zealand (NZ) adolescents using simulated modelling., Methods: We used data from a nationally representative sample of secondary school students (n = 5035) aged 12-17 between 2017 and 2020 in NZ. We modelled four secondary school-based interventions and their projected impact on five determinants of future PA. Modelled interventions were the technological augmentation of physical education (TAPE), a peer-led PA mentoring programme (PL), physically active learning (PAL) and the inclusion of a natural environment play area (NE)., Results: Total weekly PA increased the most from the NE intervention (+ 0.2 h/week), followed by TAPE (+ 0.08 h/week), PAL (+ 0.05 h/week) and PL (-0.06 h/week). Current number of PA settings increased the most in NE (+ 1.75 settings/week), followed by TAPE (+ 1.29 settings/week), PAL (+ 1.21 settings/week) and PL (+ 0.73 settings/week). Current number of PA types increased the most in NE (+ 1.57 types/week), followed by PL (+ 1.05 types/week), TAPE (+ 0.34 types/week) and PAL (+ 0.15 types/week). Physical literacy scores increased the most from PL (+ 3.6%), followed by PAL (+ 3.3%), TAPE (+ 0.43%) and NE (+ 0.12%). Social support scores increased the most from PAL (+ 5%), followed by PL (+ 1.9%), TAPE (+ 1.46%) and NE (+ 0.57%)., Conclusions: On average, all interventions benefitted determinants of future PA participation to a small degree. Results show differing magnitudes of the intervention effect by determinant, indicating the complexities surrounding the promotion of PA adherence. Future interventions could be improved through detailed consultation alongside, and involving, adolescents and stakeholders within schools. Researchers should also prioritise the collection of longitudinal PA data and explore its connection with sociodemographic differences between adolescents., (© 2024. The Author(s).)

Specialty drugs are high-cost medications often used to treat complex chronic conditions. Even with insurance coverage, patients may face very high out-of-pocket costs, which in turn may restrict access. While the Inflation Reduction Act of 2022 included policies designed to reduce specialty drug costs, relatively few policies have been enacted during the past decade. In 2022-2023, we conducted a scoping literature review to identify a range of policy options and selected a set of 9 that have been regularly discussed or recently considered to present to an expert stakeholder panel to seek consensus on (1) the feasibility of implementing each policy and (2) its likely impact on drug costs. Experts rated only 1 policy highly on both feasibility and impact: grouping originator biologics and biosimilars under the same Medicare Part B reimbursement code. They rated 3 policies focused on setting payment limits as likely to have positive (downward) impact on costs but of uncertain feasibility. They considered 4 policies as uncertain on both criteria. Experts rated capping monthly out-of-pocket costs as feasible but unlikely to reduce specialty drug costs. Based on these results, we offer 4 recommendations to policymakers considering ways to reduce specialty drug costs., Competing Interests: None of the authors have any relevant conflicts of interest. D.K. is the creator of ExpertLens which was used to collect data for this study. Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2024. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

Background: Smoking enhances plasma clozapine clearance, but the magnitude of the effect across the dose and age ranges is unclear., Methods: We audited clozapine dose and predose plasma clozapine and N -desmethylclozapine (norclozapine) concentrations by sex and smoking habit in samples submitted for clozapine TDM, 1996-2017., Results: There were 105,316/60,792 and 34,288/31,309 samples from male/female smokers/nonsmokers, respectively. There were distinct dose-median plasma concentration trajectories for male/female smokers/nonsmokers across the range <50 to >850 mg d -1 . For both sexes, the percentage difference in median plasma clozapine in nonsmokers versus smokers averaged 50% but was greatest for men (76%) and women (59%) in the 151 to 250 mg d -1 dose band. In men, the percentage difference declined steadily to 34% at doses of ≥850 mg d -1 . In women, the difference after falling initially remained relatively constant at 40% to 54%. The pattern in median plasma clozapine/norclozapine ratio by plasma clozapine concentration and dose groups was independent of sex and smoking habit, but increased with plasma clozapine concentration (higher ratio at higher concentrations) and also changed with dose. Median plasma clozapine concentration and median clozapine dose by sex and smoking habit were similar up to age 60 years. Proportional weight gain was similar over time in smokers and nonsmokers of either sex., Implications: These data explain the variations in the effect size of starting or stopping smoking on plasma clozapine concentration at constant dose reported in different studies. Changes in smoking habit in patients prescribed clozapine require prompt dose adjustment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Although the US FDA encourages manufacturers of medical devices to submit real-world evidence (RWE) to support regulatory decisions, the ability of real-world data (RWD) to generate evidence suitable for decision making remains unclear. The 2017 Medical Device User Fee Amendments (MDUFA IV), authorized the National Evaluation System for health Technology Coordinating Center (NESTcc) to conduct pilot projects, or 'Test-Cases', to assess whether current RWD captures the information needed to answer research questions proposed by industry stakeholders. We synthesized key lessons about the challenges conducting research with RWD and the strategies used by research teams to enhance their ability to generate evidence from RWD based on 18 Test-Cases conducted between 2020 and 2022. Materials & methods: We reviewed study protocols and reports from each Test-Case team and conducted 49 semi-structured interviews with representatives of participating organizations. Interview transcripts were coded and thematically analyzed. Results: Challenges that stakeholders encountered in working with RWD included the lack of unique device identifiers, capturing key data elements and their appropriate meaning in structured data, limited reliability of diagnosis and procedure codes in structured data, extracting information from unstructured electronic health record (EHR) data, limited capture of long-term study end points, missing data and data sharing. Successful strategies included using manufacturer and supply chain data, leveraging clinical registries and registry reporting processes to collect and aggregate data, querying standardized EHR data, implementing natural language processing algorithms and using multidisciplinary research teams. Conclusion: The Test-Cases identified numerous challenges working with RWD but also opportunities to address these challenges and improve researchers' ability to use RWD to generate evidence on medical devices.

Osseointegration implant (OI) surgery is the latest rehabilitation technology for amputees, where a bone-anchored implant obviates the limitations of traditional socket prostheses. The bone mineral density (BMD) in the periprosthetic and other anatomical regions can be used to assess bone remodelling following OI surgery. Currently, limited studies have used BMD measurements in reporting post-operative OI outcomes and the association between the maintenance of BMD and implant efficacy has remained elusive. This review captured and analysed all studies that have reported the BMD as an objective outcome measure in patients with trans-femoral or trans-tibial OI. The PubMed, Medline, Scopus and Web of Science databases were searched using the terms 'amputation', 'osseointegration' and 'bone mineral density'. A total of 6 studies involving human participants were included for analysis. All studies used dual X-ray absorptiometry and/or X-rays for measuring BMD. Rehabilitation of trans-femoral or trans-tibial amputation using OI may help restore healthy BMD by enabling physiological bone loading. However, there is a low correlation between the BMD around the OI and the success of OI surgery or the risk of periprosthetic fractures. This review summarises the current evidence on BMD assessment in OI for lower limb amputee rehabilitation. Despite the great variability in the results, the available evidence suggests that OI may help restore BMD following surgery. The limited evidence calls for further investigation, as well as the development of a standard BMD measurement protocol., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Carr et al.)

Background: Technology can improve care delivery, patient outcomes, and staff satisfaction, but integration into the clinical workflow remains challenging. To contribute to this knowledge area, this study examined the implementation continuum of a contact-free, continuous monitoring system (CFCM) in an inpatient setting. CFCM monitors vital signs and uses the information to alert clinicians of important changes, enabling early detection of patient deterioration., Methods: Data were collected throughout the entire implementation continuum at a community teaching hospital. Throughout the study, 3 group and 24 individual interviews and five process observations were conducted. Postimplementation alarm response data were collected. Analysis was conducted using triangulation of information sources and two-coder consensus., Results: Preimplementation perceived barriers were alarm fatigue, questions about accuracy and trust, impact on patient experience, and challenges to the status quo. Stakeholders identified the value of CFCM as preventing deterioration and benefitting patients who are not good candidates for telemetry. Educational materials addressed each barrier and emphasized the shared CFCM values. Mean alarm response times were below the desired target of two minutes. Postimplementation interview analysis themes revealed lessened concerns of alarm fatigue and improved trust in CFCM than anticipated. Postimplementation challenges included insufficient training for secondary users and impact on patient experience., Conclusion: In addition to understanding the preimplementation anticipated barriers to implementation and establishing shared value before implementation, future recommendations include studying strategies for optimal tailoring of education to each user group, identifying and reinforcing positive process changes after implementation, and including patient experience as the overarching element in frameworks for digital tool implementation., (Copyright © 2023 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Background: Some reports point to dietary caffeine intake as a cause of increased plasma clozapine concentrations in certain patients., Methods: We compared clozapine dose and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in male and female smokers and nonsmokers in relation to reported (i) coffee (caffeine) and (ii) chocolate (caffeine and theobromine) intake in samples submitted for clozapine therapeutic drug monitoring, 1993-2017., Results: There was information on coffee ingestion for 16,558 samples (8833 patients) from males and 5886 samples (3433 patients) from females and on chocolate ingestion for 12,616 samples (7568 patients) from males and 4677 samples (2939 patients) from females. When smoking was considered, there was no discernible effect of either coffee or chocolate ingestion either on the median dose of clozapine or on the median plasma clozapine and norclozapine concentrations in men and in women. However, cigarette smoking was associated with higher coffee and chocolate consumption. Although male nonsmokers who reported drinking 3 or more cups of coffee daily had significantly higher median plasma clozapine and norclozapine concentrations than those who drank less coffee, they were also prescribed a significantly higher clozapine dose. There was no clear effect of coffee ingestion on plasma clozapine and norclozapine in female nonsmokers., Implications: Inhibition of clozapine metabolism by caffeine at the doses of caffeine normally encountered in those treated with clozapine is unlikely even in male nonsmokers. Measurement of plasma caffeine in an appropriate sample should be considered in any future investigation into a presumed clozapine-caffeine interaction., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: End-stage kidney disease (ESKD) is increasingly becoming a healthcare concern in New Zealand and haemodialysis remains the most common modality of treatment. Frailty and health-related quality of life (HRQOL) are established predictors of prognosis and have already been shown to be poor in the dialyzing population. Existing data show correlation between these measures in the ESKD population, however there is little evidence for those on haemodialysis specifically. Our study aimed to assess for a correlation between frailty and HRQOL in the haemodialysis population at Palmerston North Hospital, and to assess for any differences in frailty and HRQOL scores between indigenous Māori and non-Māori subgroups., Methods: A cross-sectional study was conducted involving 93 in-centre haemodialysis patients from Palmerston North Hospital, New Zealand. Baseline demographic data was measured alongside frailty and HRQOL scores, which were measured using the Kidney Disease Quality of Life tool (KDQOL-36) and the Edmonton Frail Scale., Results: A statistically significant negative correlation was observed between frailty and all aspects of HRQOL (p < .05), with the strongest correlation observed between frailty and the physical component (r = -.64, p = <.001). Independent samples t-test showed no statistically significant difference between scores for Māori and non-Māori in frailty (M = 7.4, SD = 3.3 vs. M = 6.8, SD = 3.2; t (91) = -0.92, p = .80), or HRQOL (p values > .05 in all components)., Conclusion: A negative correlation was observed between frailty and HRQOL. This information can be beneficial in guiding discussions around treatment modality and for future patients and useful in enabling better predictions of prognosis. No statistically significant differences in frailty and HRQOL scores were observed between Māori and non-Māori groups, however the generalizability of this finding is limited due to the insufficient size of the study population., (© 2023 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Previously we identified that biomedical science students commonly misunderstand "creativity," mistaking it for "freedom." In the present study, we describe and evaluate a workshop designed to increase students' awareness of creativity as a highly sought-after employability skill and cognitive process applicable to scientific endeavors. To achieve this, we developed and introduced students to a process called the "Diamond Model," utilizing a case study to contextualize and signpost the creative processes of divergent and convergent thinking. This model was introduced to students in the first workshop of a 12-week undergraduate biochemistry unit (subject) within the Bachelor of Biomedical Science at Monash University, Australia. Students completed pre- and post-workshop surveys to gauge the impact of the workshop on their conceptions of creativity and Bloom's taxonomy of learning. In addition, reflective journals were completed by a small subset of students (n = 9) following the workshop. Following the workshop, over 65% of students indicated that their conception of creativity had changed. Thematic analysis of students' survey responses and reflections indicated that this change in the conception of creativity included broadening their definition of creativity, increased awareness of creativity as a skill and science as a creative process, and that creativity can be applied to different areas of life. Students attributed the signposting of creative elements as a contributing factor to their increased awareness. These results indicate the positive impact the workshop and our novel Diamond model had on student conception of creativity, highlighting the importance of explicit communication and signposting in skill development., (© 2023 The Authors. Biochemistry and Molecular Biology Education published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

There is evidence that men's testosterone levels decline across the transition to fatherhood and that this decline may reflect fathers' investment in the new family. There is also emerging evidence that cohabiting couples show synchrony or within-couple associations in testosterone levels during the perinatal period. Hormonal synchrony may act as a mechanism that supports fathers' biological preparation for parenthood, perhaps by facilitating perinatal declines in paternal testosterone. However, few studies have examined testosterone synchrony and change within couples. A sample of 97 U.S. couples expecting their first child provided testosterone samples during pregnancy, and of those couples, 78 couples also provided testosterone at seven months postpartum. Couples reported on relationship satisfaction both at prenatal and postpartum visits. Bayesian multilevel modeling revealed within-couple testosterone synchrony both during pregnancy and postpartum. Testosterone synchrony during pregnancy predicted a greater drop in fathers' testosterone levels from prenatal to postpartum and higher paternal postpartum relationship quality. Fathers' lower prenatal testosterone levels also subsequently predicted higher self-reported postpartum relationship quality for both parents. In sum, this study finds that couples' testosterone levels show synchrony across the transition to parenthood in ways that are associated with couple relationship quality and men's neuroendocrine preparation for fatherhood., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of chronic kidney disease. ADTKD pregnancy outcomes have not previously been described., Methods: A cross-sectional survey was sent to women from ADTKD families., Results: Information was obtained from 85 afffected women (164 term pregnancies) and 23 controls (50 pregnancies). Only 16.5% of genetically affected women knew they had ADTKD during pregnancy. Eighteen percent of ADTKD mothers had hypertension during pregnancy versus 12% in controls ( p   =  0.54) and >40% in comparative studies of chronic kidney disease in pregnancy. Eleven percent of births of ADTKD mothers were <37 weeks versus 0 in controls ( p  < 0.0001). Cesarean section occurred in 19% of pregnancies in affected women versus 38% of unaffected individuals ( p   =  0.06). Only 12% of babies required a neonatal intensive care unit stay., Conclusions: ADTKD pregnancies had lower rates of hypertension during pregnancy versus other forms of chronic kidney disease, which may have contributed to good maternal and fetal outcomes., 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) 2022.)

What Is Known on the Subject: Police and ambulance staff are increasingly asked to help people experiencing mental health crises, but they often feel under-prepared. The single frontline service approach is time-intensive and risks a coercive pathway to care. The emergency department is the default location for transfers by police or ambulance involving a person involved in a mental health crisis, despite being viewed as suboptimal., What the Paper Adds to Existing Knowledge: Police and ambulance staff struggled keeping up with the mental health demand, reporting inadequate mental health training, little enjoyment and negative experiences when trying to access help from other services. Most mental health staff had adequate mental health training and enjoyed their work, but many experienced difficulties getting help from other services. Police and ambulance staff found it hard to work with mental health services., What Are the Implications for Practice: The combination of limited training, poor interagency referral processes, and difficulties accessing support from mental health services means that when police and ambulance services attend mental health crises alone, distress may be heightened and prolonged. Enhanced mental health training for first responders and more streamlined referral processes may improve process and outcomes. Mental health nurses have key skills that could be utilized in assisting police and ambulance staff who attend 911 emergency mental health calls. New models such as co-response teams, whereby police, mental health clinicians and ambulance staff respond conjointly should be trialled and evaluated., Abstract: INTRODUCTION: First responders are increasingly called to assist people experiencing mental health crises but little research exists canvassing multi-agency perspectives of such work., Aim/question: To understand the views of police officers, ambulance and mental health staff attending mental health or suicide-related crises in Aotearoa New Zealand and to discover how they experience current models of cross-agency collaboration., Methods: A descriptive cross-sectional survey involving mixed methods. Quantitative data were analysed using descriptive statistics and free text by content analysis., Results: Participants included 57 police officers, 29 paramedics and 33 mental health professionals. Mental health staff felt adequately trained, but only 36% described good processes for accessing inter-agency support. Police and ambulance staff felt undertrained and unprepared. Accessing mental health expertise was considered difficult by 89% of police and 62% of ambulance staff., Discussion: Frontline services struggle managing mental health-related 911 emergencies. Current models are not working well. Miscommunication, dissatisfaction and distrust exist between police, ambulance and mental health services., Conclusion: The single-agency frontline response may be detrimental to service users in crisis and under-utilizes the skills of mental health staff. New ways of inter-agency cooperation are required, such as co-located police, ambulance and mental health nurses responding in partnership., (© 2023 The Authors. Journal of Psychiatric and Mental Health Nursing published by John Wiley & Sons Ltd.)

This cross-sectional study aimed to explore various determinants of future physical activity (PA) participation in adolescents across sociodemographic groups. Sociodemographic characteristics (age, gender, ethnicity, deprivation status, physical disability status) were assessed in a national sample ( n = 6906) of adolescents (12-17 years old) between 2017 and 2020 in New Zealand. The determinants of future PA participation chosen for analysis included current indicators of PA participation (i.e., total time, number of types, number of settings). We also examined widely recognised modifiable intrapersonal (i.e., physical literacy) and interpersonal (i.e., social support) determinants of current and future PA behaviour, along with indicators of PA availability issues. Older adolescents scored worse across all determinants of future PA than younger adolescents, with a key transition point appearing at 14-15 years of age. Māori and Pacific ethnicities scored best across each determinant category on average, with Asian populations scoring the worst. Gender diverse adolescents scored substantially worse than male and female adolescents across every determinant. Physically disabled adolescents scored worse than non-disabled across all determinants. Adolescents from medium and high deprivation neighbourhoods scored similarly across most determinants of future PA participation and both tended to score worse than people from low deprivation neighbourhoods. A particular focus on the improvement of future PA determinants is warranted within adolescents who are older, Asian, gender diverse, physically disabled, and from medium to high deprivation neighbourhoods. Future investigation should prioritise the longitudinal tracking of PA behaviours over time and develop interventions that affect multiple future PA determinants across a range of sociodemographic backgrounds.

Latent variable models can create a latent dementia index (LDI) using cognitive and functional ability to approximate dementia likelihood. The LDI approach has been applied across diverse cohorts. It is unclear whether sex affects its measurement properties. We use Wave A (2001-2003) of the Aging, Demographics, and Memory Study ( n  = 856). Multiple group confirmatory factor analysis (CFA) was used to test measurement invariance (MI) using informant-reported functional ability and cognitive performance tasks, which we group into verbal, nonverbal, and memory. Partial scalar invariance was found, allowing for testing sex differences in LDI means ( M Diff  = 0.38). The LDI correlated with consensus panel dementia diagnosis, Mini-Mental State Examination (MMSE), and dementia risk factors (low education, advanced age, and apolipoprotein ε4 [APOE-ε4] status) for men and women. The LDI validly captures dementia likelihood to permit estimation of sex differences. LDI sex differences indicate higher dementia likelihood in women, potentially due to social, environmental, and biological factors., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Three-dimensional printing (3DP) is a popular manufacturing technique with versatile potential for materials processing in tissue engineering and regenerative medicine. In particular, the repair and regeneration of significant bone defects remain as substantial clinical challenges that require biomaterial implants to maintain mechanical strength and porosity, which may be realized using 3DP. The rapid progress in 3DP development in the past decade warrants a bibliometric analysis to gain insights into its applications in bone tissue engineering (BTE). Here, we performed a comparative study using bibliometric methods for 3DP in bone repair and regeneration. A total of 2,025 articles were included, and the results showed an increase in the number of publications and relative research interest on 3DP annually worldwide. China was the leader in international cooperation in this field and also the largest contributor to the number of citations. The majority of articles in this field were published in the journal Biofabrication . Chen Y was the author who made the highest contribution to the included studies. The keywords included in the publications were mainly related to BTE and regenerative medicine (including "3DP techniques," "3DP materials," "bone regeneration strategies," and "bone disease therapeutics") for bone regeneration and repair. This bibliometric and visualized analysis provides significant insights into the historical development of 3DP in BTE from 2012 to 2022, which will be beneficial for scientists to conduct further investigations into this dynamic field., Competing Interests: The authors declare no conflicts of interest., (Copyright:© 2023, Yang Z, Li H, Lin J, et al.)

Objective: Mental health-related calls to emergency services made via 111 (New Zealand) or 000 (Australia) often represent critical junctures for the person in crisis. Traditionally, police, ambulance and mental health services work separately to manage such emergencies. Sequential agency responses may be protracted and cause escalation. This study tests multi-agency co-response aiming for more integrated, faster, safer and less coercive management of mental health crises., Methods: Immediate and 1-month outcomes of mental health emergency calls made to police and ambulance were compared according to whether they occurred on days with co-response availability. Outcomes measured included emergency department admission and waiting times, psychiatric admissions, compulsory treatment, use of force, detention in police cells and the time to resolution of the event. Relative risk estimates were constructed., Results: A total 1273 eligible mental health emergency callouts occurred between March 2020 and March 2021 (38% coded 'mental health' emergencies, 48% suicide risk and 14% as 'other'), 881 on days with co-response availability and 392 on days without. Co-response interventions were resolved faster and were more likely to be community-based. Fewer than one-third (32%) led to emergency department admissions, compared with close to half (45%) on days without co-response (risk ratio: 0.7 [0.6, 0.8]). In the following month, the number of emergency department and mental health admissions reduced ( p  < 0.01 and 0.05, respectively). There were no statistically significant differences in use of force and few people were detained in police custody., Conclusion: Co-response intervention increased the likelihood of mental health crises being resolved in the community and reduced hospitalisations. Benefits were sustained at 1 month.

Objective: To identify barriers and facilitators to the use of formal dementia services among underserved and minority groups (UMG) in the United States and Germany., Method: Semi-structured qualitative interviews with caregivers ( N  = 18) of persons with dementia in the United States and Germany. Data were analyzed using thematic analysis., Results: Caregivers described their experiences in three stages of seeking, initiating, and utilizing care, and different factors served to hinder or enable the use of care services in each stage. The most important factors included limited knowledge about dementia, challenges interacting with healthcare systems, and how closely formal services met the expectations and needs of caregivers, particularly with regard to accommodating cultural or ethnic/racial identity. Caregivers preferred interacting with service care providers who shared a similar identity to receive information or services., Conclusion: Barriers and facilitators to using dementia care services vary by stage of engaging services and may be shared across different healthcare contexts. Targeting specific barriers and strengthening facilitators could help reduce disparities in dementia care among UMG.

The liver is the largest internal organ in the human body with largest mass of glandular tissue. Modeling the liver has been challenging due to its variety of major functions, including processing nutrients and vitamins, detoxification, and regulating body metabolism. The intrinsic shortfalls of conventional two-dimensional (2D) cell culture methods for studying pharmacokinetics in parenchymal cells (hepatocytes) have contributed to suboptimal outcomes in clinical trials and drug development. This prompts the development of highly automated, biomimetic liver-on-a-chip (LOC) devices to simulate native liver structure and function, with the aid of recent progress in microfluidics. LOC offers a cost-effective and accurate model for pharmacokinetics, pharmacodynamics, and toxicity studies. This review provides a critical update on recent developments in designing LOCs and fabrication strategies. We highlight biomimetic design approaches for LOCs, including mimicking liver structure and function, and their diverse applications in areas such as drug screening, toxicity assessment, and real-time biosensing. We capture the newest ideas in the field to advance the field of LOCs and address current challenges., (© 2022 Author(s).)

Deep neural networks (DNNs) show promise in image-based medical diagnosis, but cannot be fully trusted since they can fail for reasons unrelated to underlying pathology. Humans are less likely to make such superficial mistakes, since they use features that are grounded on medical science. It is therefore important to know whether DNNs use different features than humans. Towards this end, we propose a framework for comparing human and machine perception in medical diagnosis. We frame the comparison in terms of perturbation robustness, and mitigate Simpson's paradox by performing a subgroup analysis. The framework is demonstrated with a case study in breast cancer screening, where we separately analyze microcalcifications and soft tissue lesions. While it is inconclusive whether humans and DNNs use different features to detect microcalcifications, we find that for soft tissue lesions, DNNs rely on high frequency components ignored by radiologists. Moreover, these features are located outside of the region of the images found most suspicious by radiologists. This difference between humans and machines was only visible through subgroup analysis, which highlights the importance of incorporating medical domain knowledge into the comparison., (© 2022. The Author(s).)

Objectives: To enhance the generalizability of the evidence it reviews, the US Food and Drug Administration (FDA) has encouraged manufacturers to expand the submission of real-world evidence (RWE). The extent to which this evidence, which is generated outside of research settings, can support decision making remains unclear. We described the current use of RWE for medical devices, assessed manufacturers' challenges in generating and using it for regulatory and coverage decisions, and identified opportunities to expand its use., Methods: We conducted 27 solo and group interviews with FDA officials and representatives of device manufacturers, payers, and health technology assessment organizations. All interviews used a semistructured protocol and were transcribed to allow thematic analysis., Results: Accessing and linking real-world data sources, identifying unique devices, capturing longitudinal data, limited staff expertise, and uncertain return on investment have hampered efforts to use real-world data. Many companies in our sample were conducting research using real-world data, but none had submitted RWE as the primary evidence supporting a premarket approval. FDA guidance was helpful, but regulatory requirements remained ambiguous and examples of successful regulatory decisions based on RWE were limited. Payers mainly used RWE to supplement experimental evidence in coverage decisions, evaluated both types of evidence in similar ways, and had concerns about the rigor of RWE., Conclusions: Technical challenges may slow efforts to generate and use RWE in the near term. Additional regulatory guidance and examples, greater use of rigorous study designs and analytic methods, and continued stakeholder engagement could accelerate the use of RWE., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Although several studies have shown small longitudinal associations between baseline loneliness and subsequent dementia risk, studies rarely test whether change in loneliness predicts dementia risk. Furthermore, as both increase with advancing age, genetic and environmental selection processes may confound the putative causal association between loneliness and dementia risk. We used a sample of 2,476 individual twins from three longitudinal twin studies of aging in the Swedish Twin Registry to test the hypothesis that greater positive change in loneliness predicts greater dementia risk. We then used a sample of 1,632 pairs of twins to evaluate the hypothesis that effects of change in loneliness on dementia risk would remain after adjusting for effects of genetic and environmental variance. Phenotypic model results suggest that mild levels of baseline loneliness predict greater dementia risk. Contrary to our hypothesis, change in loneliness did not correlate with dementia risk, regardless of whether genetic and environmental selection confounds were taken into account. Worsening loneliness with age may not confer greater dementia risk., 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 Kim, Gold, Fenton, Pilgrim, Lynch, Climer, Penichet, Kam and Beam.)

Because of limited free diffusion in the cytoplasm, viruses must use active transport mechanisms to move intracellularly. Nevertheless, how the plant single-stranded DNA begomoviruses hijack the host intracytoplasmic transport machinery to move from the nucleus to the plasmodesmata remains enigmatic. Here, we identified nuclear shuttle protein (NSP)-interacting proteins from Arabidopsis (Arabidopsis thaliana) by probing a protein microarray and demonstrated that the cabbage leaf curl virus NSP, a facilitator of the nucleocytoplasmic trafficking of viral (v)DNA, interacts in planta with an endosomal vesicle-localized, plant-specific syntaxin-6 protein, designated NSP-interacting syntaxin domain-containing protein (NISP). NISP displays a proviral function, unlike the syntaxin-6 paralog AT2G18860 that failed to interact with NSP. Consistent with these findings, nisp-1 mutant plants were less susceptible to begomovirus infection, a phenotype reversed by NISP complementation. NISP-overexpressing lines accumulated higher levels of vDNA than wild-type. Furthermore, NISP interacted with an NSP-interacting GTPase (NIG) involved in NSP-vDNA nucleocytoplasmic translocation. The NISP-NIG interaction was enhanced by NSP. We also showed that endosomal NISP associates with vDNA. NISP may function as a docking site for recruiting NIG and NSP into endosomes, providing a mechanism for the intracytoplasmic translocation of the NSP-vDNA complex toward and from the cell periphery., (© American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Palliative care has expanded rapidly in recent years. Hence, there has been a growing awareness of and emphasis on the importance of developing quality measures specific to palliative care. This article describes information-gathering activities conducted by RAND to develop two measures of palliative care quality for patients receiving such care in outpatient, clinic-based settings. The authors describe the consensus that has developed for measurement priorities in the palliative care community, provide a summary of clinical practice guidelines, and review the evidence base for palliative care. The authors also review current relevant regulations, existing measures of patient and caregiver experience, findings from a gap analysis on palliative care assessment, and findings from provider focus groups and interviews with patients and caregivers or family members., (Copyright © 2021 RAND Corporation.)

To combat racial/ethnic and socioeconomic health disparities associated with COVID-19 in our surrounding communities, the Cleveland Clinic Community Health & Partnership team developed a comprehensive program focused on connecting and communicating with local officials, faith-based organizations, and individual community members. Since March of 2020, our team has donated resources (e.g., personal protective equipment) to local organizations, referred thousands of community members to community or clinical resources, and partnered with federally-qualified health centers to support community COVID-19 testing. Future work will include the use of these networks to deploy the COVID-19 vaccine., (Copyright © 2021 The Cleveland Clinic Foundation. All Rights Reserved.)

Bamlanivimab and casirivimab-imdevimab are novel virus-neutralizing monoclonal antibodies authorized to treat mild to moderate COVID-19 in outpatients at risk for progression to severe disease. Treatment early in the disease may show efficacy in reducing progression to severe disease, although safety and efficacy data are limited. They are not authorized for hospitalized patients with more advanced disease., (Copyright © 2021 The Cleveland Clinic Foundation. All Rights Reserved.)

Background: We developed a novel intervention that uses behavioral economics incentives and mobile-health text messages to increase HIV knowledge and testing frequency among Latinx sexual minority men and Latinx transgender women. Here we provide a theoretically-grounded assessment regarding the intervention's acceptability and feasibility., Methods: We conducted 30-min exit interviews with a stratified sample of participants (n = 26 Latinx sexual minority men, 15 Latinx transgender women), supplemented with insights from study staff (n = 6). All interviews were recorded, transcribed, and translated for a content analysis using Dedoose. Cohen's Kappa was 89.4% across coded excerpts. We evaluated acceptability based on how participants cognitively and emotionally reacted to the intervention and whether they considered it to be appropriate. We measured feasibility based on resource, scientific and process assessments (e.g., functionality of text messaging service, feedback on study recruitment procedures and surveys)., Results: Regarding acceptability, most participants clearly understood the intervention as a program to receive information about HIV prevention methods through text messages. Participants who did not complete the intervention shared they did not fully understand what it entailed at their initial enrollment, and thought it was a one-time engagement and not an ongoing program. Though some participants with a higher level of education felt the information was simplistic, most appreciated moving beyond a narrow focus on HIV to include general information on sexually transmitted infections; drug use and impaired sexual decision-making; and differential risks associated with sexual positions and practices. Latinx transgender women in particular appreciated receiving information about Pre-Exposure Prophylaxis. While participants didn't fully understand the exact chances of winning a prize in the quiz component, most enjoyed the quizzes and chance of winning a prize. Participants appreciated that the intervention required a minimal time investment. Participants shared that the intervention was generally culturally appropriate. Regarding feasibility, most participants reported the text message platform worked well though inactive participants consistently said technical difficulties led to their disengagement. Staff shared that clients had varying reactions to being approached while being tested for HIV, with some unwilling to enroll and others being very open and curious about the program. Both staff and participants relayed concerns regarding the length of the recruitment process and study surveys., Conclusions: Our theoretically-grounded assessment shows the intervention is both acceptable and feasible., Trial Registration: The trial was registered on May 5, 2017 with the ClinicalTrials.gov registry [ NCT03144336 ].

Traditional Asian fermented soy food products are associated with reduced cardiovascular disease risk in prospective studies, but few randomized controlled trials have been conducted in at-risk populations. The aim of this study was to investigate the effect of a commercial non-probiotic fermented soy product on blood lipids in adults with cardiovascular risk biomarkers. In a randomized, crossover, intervention study, 27 men and women (aged 29-75 y) exhibiting at least two risk factors, consumed two packets (12.5 g each) daily of a fermented powdered soy product, or an isoenergic control powder made from germinated brown rice for 12 weeks each. The consumption of the fermented soy product resulted in a significantly greater mean change from baseline (compared to the germinated rice, all p < 0.05) in total cholesterol of -0.23 mmol/L (CI: -0.40, -0.06) compared with 0.14 mmol/L (CI: -0.03, 0.31), respectively; and low density lipoprotein (LDL) cholesterol -0.18 mmol/L (CI: -0.32, -0.04) compared with 0.04 mmol/L (CI: -0.01, 0.018) respectively. This was accompanied by an increase in high density lipoprotein (HDL) cholesterol in the germinated rice group, a decrease in apolipoprotein B (ApoB) in the fermented soy group, and a between-treatment effect in apolipoprotein A1 (ApoA1); however, the ratio of the LDL:HDL and of Apo B:ApoA1 did not differ between the groups. The ratio of total cholesterol:LDL decreased in men in the fermented soy group ( p < 0.001). Twenty-four-hour urine collection at the end of each treatment period resulted in an increased excretion expressed as a ratio in μmol/d between treatments of 10.93 (CI: 5.07, 23.54) for daidzein; 1.24 (CI: 1.14, 4.43) for genistein; and, 8.48 (CI: 4.28, 16.80) for glycitein, all p < 0.05. The fermented soy powder consumed by participants in this study without implementing other changes in their typical diets, decreased the total and LDL cholesterol, and may serve as a dietary strategy to manage blood lipids. The trial was registered at ClinicalTrials.gov as NCT03429920.

Background: Family caregivers of people living with dementia benefit from supportive service use to address care needs associated with caregiving. Yet, research consistently demonstrates low rates of service use. Existing research has focused on barriers and facilitators to service use, with few studies examining the influence of caregivers' environmental context which often patterns social advantage and health services accessibility., Objective: To describe the perspectives of caregivers residing in socially disadvantaged areas have in regards to utilizing supportive services., Methods: Ten informal caregivers residing in socially disadvantaged areas participated in in-depth interviews that were analyzed using thematic analysis., Results: Across all interviews, caregivers spontaneously described common precedents of service use (crisis or accumulation of unmet needs) and a distinct sequence of stages (seeking, initiating, and utilizing) surrounding service engagement. Major themes characterizing caregivers' experiences throughout service engagement highlight the varied influence of personal, familial, health, and social system-related factors. Findings demonstrate that caregivers may have different service needs as dementia progresses and that gerontological social work practice can facilitate service use., Conclusion: While preliminary, these findings provide important insights into new domains that can be further examined in future research and intervention efforts to improve supportive service use in socially disadvantaged and underserved communities.

Objective: Higher levels of loneliness in older adulthood predict cognitive decline, but research on mediating mechanisms is sparse. We examine multisystemic physiological risk, functional ability, self-rated health, depressive symptoms, and social participation as mediating processes for the association between loneliness and general cognitive ability over a 10-year follow-up in an older adult sample., Methods: Three waves of data from 3,005 individuals (mean intake age: 69.30 (SD: 7.85) years; female = 51.61%) recruited during Wave 1 of the National Social Life, Health, and Aging Project were used to test whether hypothesized mediators collected at the 5-year follow-up explained effects of baseline loneliness on 10-year general cognitive ability., Results: The relationship between baseline loneliness and 10-year general cognitive ability was not mediated by multisystemic physiological risk. Functional ability (b = -0.24, SE = 0.05, p <0.001), self-rated health (b = -0.08, SE = 0.02, p <0.001), depressive symptoms (b= -0.20, SE = 0.05, p <0.001), and social participation (b = -0.03, SE = 0.01, p = 0.016) significantly mediated effects. Indirect effects remained significant after adjusting for demographic covariates and 5-year general cognitive ability, except social participation., Discussion: Loneliness may influence cognitive ability indirectly, signaling waning physical and psychiatric health more proximally correlated with cognitive ability. These mechanisms may serve as targets of intervention for cognitive maintenance in lonely older adults., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To determine how weekly text messages and small incentives impact HIV knowledge and frequency of HIV testing among Latinx sexual minority men (LSMM) and transgender women (LTGW)., Design: Prospectively randomized participants into 2 intervention arms compared with a nonrandomized comparison group., Setting: Bienestar, a primarily Latinx focused HIV service provider located across Los Angeles County., Subjects, Participants: Two hundred eighteen participants self-identifying as LSMM or LTGW, HIV negative, having regular mobile phone access, ≥18 years, and fluent in English or Spanish., Intervention: The "information only" (IO) group received text messages with HIV prevention information. The "information plus" (IP) group additionally could win incentives by answering weekly quiz questions correctly and testing for HIV once every 3 months. We followed participants for 12 months., Main Outcome Measure(s): HIV knowledge and frequency of HIV testing., Results: We found no effect on HIV knowledge in the IO group but a statistically significant improvement in the IP group (79.2%-88.1%; P = 0.007). The frequency of HIV testing was higher in both intervention groups relative to the comparison group: On average, 22.0% of IO participants and 24.9% of IP participants tested at a Bienestar site within a given 3-month period, compared with 13.0% in the comparison group. This represents unadjusted relative risk ratios of 1.69 for the IO group (95% CI: 1.25 to 2.1; P < 0.01) and 1.91 for the IP group (95% CI: 1.51 to 2.31; P < 0.01), respectively., Conclusions: This study demonstrates that a simple, low-cost intervention may help increase HIV testing frequency among LSMM and LTGW, 2 groups at high HIV risk.

As the spread of COVID-19 has led to global efforts to social distance, concerns about the negative psychological effects of social isolation and loneliness have grown. The purpose of this commentary is to draw attention to 2 populations across the life span at risk for the psychological sequelae of social isolation and loneliness: young adults and old-old adults. We present data from three population-based longitudinal studies from two nations (United States and Sweden) to support this view. We then provide recommendations for the prevention of loneliness during social distancing as well as after social distancing measures are eased through implementation of programs that match young adults with older adults to foster intergenerational connection and group-based psychotherapy. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Introduction: Residence in a disadvantaged neighborhood associates with adverse health exposures and outcomes, and may increase risk for cognitive impairment and dementia. Utilization of a publicly available, geocoded disadvantage metric could facilitate efficient integration of social determinants of health into models of cognitive aging., Methods: Using the validated Area Deprivation Index and two cognitive aging cohorts, we quantified Census block-level poverty, education, housing, and employment characteristics for the neighborhoods of 2119 older adults. We assessed relationships between neighborhood disadvantage and cognitive performance in domains sensitive to age-related change., Results: Participants in the most disadvantaged neighborhoods (n = 156) were younger, more often female, and less often college-educated or white than those in less disadvantaged neighborhoods (n = 1963). Disadvantaged neighborhood residence associated with poorer performance on tests of executive function, verbal learning, and memory., Discussion: This geospatial metric of neighborhood disadvantage may be valuable for exploring socially rooted risk mechanisms, and prioritizing high-risk communities for research recruitment and intervention., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Cleveland Clinic recognized the importance of mitigating community transmission of COVID-19 by keeping people at home. Patient-care activities quickly pivoted to remote touches, preserving continuity through a variety of digital and telephonic modalities. As the number of confirmed cases grew, standardizing home-based care became critical to managing high-risk patients, moderating the risk of exposure for healthcare workers, and reducing the amount of community spread through appropriate education on home-based care for exposed or infected individuals. This novel, team-based approach to caring for patients with COVID-19 incorporates a self-monitoring app for patient engagement, monitors symptoms for early intervention, and promotes a holistic view of care., (Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.)

Importance: Identifying risk factors for brain atrophy during the aging process can help direct new preventive approaches for dementia and cognitive decline. The association of neighborhood socioeconomic disadvantage with brain volume in this context is not well known., Objective: To test whether neighborhood-level socioeconomic disadvantage is associated with decreased brain volume in a cognitively unimpaired population enriched for Alzheimer disease risk., Design, Setting, and Participants: This study, conducted from January 6, 2010, to January 17, 2019, at an academic research neuroimaging center, used cross-sectional data on 951 participants from 2 large, ongoing cohort studies of Alzheimer disease (Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center clinical cohort). Participants were cognitively unimpaired based on National Institute on Aging-Alzheimer's Association workgroup diagnostic criteria for mild cognitive impairment and Alzheimer disease, confirmed through a consensus diagnosis panel. The cohort was enriched for Alzheimer disease risk based on family history of dementia. Statistical analysis was performed from April 3 to September 27, 2019., Main Outcomes and Measures: The Area Deprivation Index, a geospatially determined index of neighborhood-level disadvantage, and cardiovascular disease risk indices were calculated for each participant. Linear regression models were fitted to test associations between relative neighborhood-level disadvantage (highest 20% based on state of residence) and hippocampal and total brain tissue volume, as assessed by magnetic resonance imaging., Results: In the primary analysis of 951 participants (637 women [67.0%]; mean [SD] age, 63.9 [8.1] years), living in the 20% most disadvantaged neighborhoods was associated with 4.1% lower hippocampal volume (β = -317.44; 95% CI, -543.32 to -91.56; P = .006) and 2.0% lower total brain tissue volume (β = -20 959.67; 95% CI, -37 611.92 to -4307.43; P = .01), after controlling for intracranial volume, individual-level educational attainment, age, and sex. Robust propensity score-matched analyses determined that this association was not due to racial/ethnic or demographic characteristics. Cardiovascular risk score, examined in a subsample of 893 participants, mediated this association for total brain tissue but not for hippocampal volume., Conclusions and Relevance: For cognitively unimpaired individuals, living in the most disadvantaged neighborhoods was associated with significantly lower cerebral volumes, after controlling for maximal premorbid (total intracranial) volume. This finding suggests an association of community socioeconomic context, distinct from individual-level socioeconomic status, with brain volume during aging. Cardiovascular risk mediated this association for total brain tissue volume but not for hippocampal volume, suggesting that neighborhood-level disadvantage may be associated with these 2 outcomes via distinct biological pathways.

Background: The US health care system is the most expensive in the world, but it lags behind many other industrialized nations on multiple measures of effectiveness and quality. This poor performance may have played a role in the push to incentivize health care organizations to achieve high performance over a range of domains. Research is needed to understand the determinants of health system performance., Methods: To identify key attributes of health systems associated with performance, a literature review was conducted. The characteristics identified were compiled into a Web-based rating instrument for use with a Technical Expert Panel composed of leaders in health systems and health services research. A modified Delphi process was initiated using three rounds to develop group consensus., Results: The expert panel reached consensus on nine broad areas important to health system performance. Panelists also rated which specific attributes within those domains were predictive of performance. Panelists tended to rate the kind of characteristics used in past research (such as size, ownership, and profit status) as only somewhat or not at all important, while rating aspects of culture, leadership, and business execution as very important., Conclusion: There is limited empirical evidence and understanding of factors associated with health system performance. This study illustrates the value of using a modified Delphi process to bring experiential evidence to the task. These findings may help researchers refine their data collection efforts, policy makers craft better policies to incentivize high performance, and health leaders build better systems., (Copyright © 2019 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Background: As the proportion of older people with migration background (PwM) increases, the proportion of older PwM with dementia might also increase. Dementia is underdiagnosed in this group and a large proportion of PwM with dementia and family caregivers are not properly supported. Healthcare utilization is lower among older migrant populations. Thus, a better understanding of how PwM and family caregivers perceive their situation and how they experience healthcare services is needed to improve utilization of the healthcare system., Objective: Analyze how family caregivers of PwM with dementia experience their situation, why healthcare services are utilized less often, and what can be done to reverse this., Methods: Eight semi-structured interviews were conducted with people with Turkish migration background caring for PwM with dementia. Qualitative content analysis was used for data analysis., Results: Daily care was performed by one family member with the support of others. Healthcare services were used by most participants. Participants identified a need for better access to relevant information and incorporation of Turkish culture into healthcare services., Conclusion: PwM face similar challenges in taking care of persons with dementia as those without migration background. There is a willingness to use services, and services embracing Turkish culture would help to reduce hesitance and make affected people feel more comfortable, thereby increasing utilization and satisfaction. A limitation of this study is that participants were already connected to health services, which may not reflect the help-seeking behavior of those in the Turkish community who are not involved in healthcare.

Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy 1-8 . However, the reason some tumours have high CD8 T cell infiltration while others do not remains unclear. Here we investigate the requirements for maintaining a CD8 T cell response against human cancer. We find that CD8 T cells within tumours consist of distinct populations of terminally differentiated and stem-like cells. On proliferation, stem-like CD8 T cells give rise to more terminally differentiated, effector-molecule-expressing daughter cells. For many T cells to infiltrate the tumour, it is critical that this effector differentiation process occur. In addition, we show that these stem-like T cells reside in dense antigen-presenting-cell niches within the tumour, and that tumours that fail to form these structures are not extensively infiltrated by T cells. Patients with progressive disease lack these immune niches, suggesting that niche breakdown may be a key mechanism of immune escape.

Creativity is a uniquely human trait and it is the force behind many modern advancements. Due to the rapid changes seen across the economy and society, creativity has become highly valued and is in increasing demand by employers. To prepare students to meet this demand, many education stakeholders (such as Monash University) have incorporated creativity into their ethos. However, preliminary analysis of the learning objectives of the Bachelor of Biomedical Science degree (program) at Monash University identified little reference to creativity, even though one of its Graduate Attributes is to become a "creative scholar." The aims of this study were to ascertain the biomedical science students' perception of creativity in the program and to evaluate the program's core units (subjects) for creative learning opportunities. The data shows that students perceived a lack of creativity in the program. However, using Bloom's taxonomy's definition of create, an evaluation of the creative learning opportunities in the core Biomedical Science units identified the presence of a variety of creative opportunities. This discrepancy between student perceptions and learning opportunities lead to the question: Why do not students recognize creative learning opportunities? From the survey responses and mapping data, three reasons were identified: students' lack of awareness of a Graduate attribute, a lack of explicit reference to creativity at the program and unit level, and students' lack of understanding of creativity. © 2019 International Union of Biochemistry and Molecular Biology, 47(6):656-668, 2019., (© 2019 International Union of Biochemistry and Molecular Biology.)

The traditional teaching style in higher education is didactic. However, the current literature states that student learning improves when they are active players in the process, triggering the move to implement active learning within the curriculum. In accordance, Monash University (an Australian research-intensive university) introduced the "Better Teaching Better Learning" agenda to deliver a more student-centered learning experience but its implementation has been inconsistent across its different schools. Interviews and an online survey were conducted to evaluate the teaching practices in lectures of Biomedical Science academics, identify barriers preventing them from implementing active learning in their teaching, and identify possible strategies to overcome said barriers. The two main teaching groups use a variety of teaching styles in lectures, with education-focused academics employing more active learning practices. Many academics were in the process of changing their teaching style, mainly to improve the overall student learning experience. However, complex barriers prevent them from doing so. Possible strategies were identified that would help academics adopt a more student-centered teaching style. © 2018 International Union of Biochemistry and Molecular Biology, 47(1):29-40, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)

Improving quality and delivery of care for people with Alzheimer disease and related dementias (ADRD) requires a comprehensive research agenda that encompasses the entire care continuum. Logistical and ethical challenges of informed consent for research participation of persons with ADRD include determination of capacity to consent, surrogate consent when capacity to consent is compromised, timely identification of the legally authorized representative (LAR) providing surrogate consent, and balancing residual autonomy with surrogate consent. Short stays; limited access to patients, caregivers, and LARs; and fluctuating influences of acute illness on capacity determination compound these challenges in the acute care setting. To address these challenges, we worked with the University of Wisconsin Health Sciences Institutional Review Board to develop a procedural framework for obtaining informed consent from hospitalized individuals with ADRD and their caregivers to participate in a minimal risk care intervention. The framework is specially designed for minimal risk situations in which rapid enrollment is a necessity and uses rapid identification of surrogates to consent for patients who lack legal capacity to make medical decisions, indicated by an activated healthcare power of attorney, and individualized formal assent procedures for patients who lack capacity to consent. These methods were proven effective in facilitating hospital-based recruitment in an ongoing randomized controlled trial and provide a basis for increasing access to acute care clinical research for persons with ADRD. Bolstering research participation through more easily used consent procedures during acute illness is critical to fostering improvements in the delivery of high-quality care to persons with ADRD. J Am Geriatr Soc 66:2243-2248, 2018., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Analyzing health care reimbursement is a dynamic process. Infectious Diseases (ID) physicians have careers in diverse practice models. With current compensation models focusing on value and quality metrics, ID physicians are poised to be at the forefront of these delivery models. Monitoring and disseminating the current status of ID physician compensation are priorities of the Infectious Diseases Society (IDSA). In 2015, the IDSA conducted the largest ID physician compensation survey to date. The data were analyzed and disseminated, and the society subsequently responded with a plan to continue to develop and collect the most comprehensive and accurate data on ID physician compensation. Therefore, from May to June 2017, the IDSA conducted a follow-up compensation survey of its members. This survey resulted in the largest number of respondents of any ID compensation survey. It revealed that compensation across the different practice demographics had increased since the 2015 survey and is generally higher than salaries published in other comparable surveys. These data and the subsequent analyses focus on physicians who report patient care as their primary responsibility; they are presented by members of the IDSA's Clinical Affairs Committee.

Background: Mobile Technology and Incentives (MOTIVES) is a randomized pilot study of a mobile technology-based and behavioral economics-supported HIV prevention intervention. Behavioral economics (BE) uses financial incentives in a way that departs from the traditional focus on large monetary payments. Instead, BE suggests that relatively small "nudges" can effectively initiate and sustain behavior change. This pilot study examines the feasibility and acceptability of an HIV prevention intervention that uses text messages in combination with BE incentives to improve retention of HIV prevention information and increase frequency of HIV testing among Latino/a men who have sex with men (MSM) and transgender women (TGW). The pilot will also estimate mission-critical design parameters with point and confidence interval estimates of the intervention to inform a future, fully powered effectiveness study., Methods: The project will be conducted in collaboration with Bienestar Human Services, Inc. (Bienestar), a non-profit community-based service organization. The intervention is being tested in a small, randomized controlled trial to pilot the intervention's feasibility and acceptability among 200 Latino/a MSM and TGW from Bienestar's HIV testing sites. Information on feasibility will include recruitment, refusal, and retention rates as well as message sending success rates; acceptability will include perceived appropriateness based on responses to the intervention. Participants will be randomized into either the "information only" control group (e.g. receiving text messages with HIV prevention information) or the "information plus" intervention group (e.g. additionally receiving quiz questions that provide the possibility of winning prizes). Participants will be followed for 12 months from enrollment. In addition to using data abstracted from Bienestar's routine data collection mechanisms, we will also collect survey data (blinded outcome assessment) from participants at 0, 6, and 12 months to provide an initial assessment of whether incentives affect their level of HIV knowledge and testing frequency., Discussion: If shown to be acceptable, feasible, and resource-efficient, MOTIVES will provide an innovative way to communicate the latest HIV prevention information and support trimestral HIV screening among Latino/a MSM and TGW., Trial Registration: ClinicalTrials.gov, NCT03144336 . Registered on 5 May 2017.

Objectives: Although the spacing effect has been investigated extensively in a variety of populations, few studies have focused on individuals with hippocampal amnesia and none, to our knowledge, have investigated differences in performance as a function of spacing schedule in these cases. In the current study, we investigated the benefit of expanding and equal-interval, compared to massed, spacing schedules in a developmental amnesic person, H.C., who shows congenitally based abnormal development of the hippocampal memory system., Methods: Given the possibility of plasticity and reorganization in the developing brain, we investigated whether H.C. would benefit more from an expanding versus equal-interval schedule using a continuous recognition paradigm, even though this task has been shown to recruit structures within the medial temporal lobe, including the hippocampus., Results: H.C. and matched controls both showed a clear spacing effect, although neither group benefited more from an equal-interval or expanding spacing schedule., Conclusions: The results of the current study show that the spacing effect is an effective and clinically meaningful memory intervention technique that may be applied to clinical conditions known to affect hippocampal function and episodic memory early in life. (JINS, 2018, 24, 1003-1012).

Before 2011 rates of hospitalization for heart attacks were about the same in San Diego County as they were in the rest of California. In 2011 a multistakeholder population health collaborative consisting of partners at the federal, state, and local levels launched Be There San Diego. The collaborative's goal was to reduce cardiovascular events through the spread of best practices aimed at improving control of hypertension, lipid levels, and blood sugar and through patient and medical community activation. Using hospital discharge data for the period 2007-16, we compared acute myocardial infarction (AMI) hospitalization rates in San Diego County and the rest of the state before and after the demonstration project started. AMI hospitalization rates decreased by 22 percent in San Diego County versus 8 percent in the rest of the state, with an estimated 3,826 AMI hospitalizations avoided and $86 million in savings in San Diego. Results show that a science-based health collaborative can improve outcomes while lowering costs, and efforts are under way to ensure the collaborative's sustainability.

Physical interactions between proteins and other molecules can be evaluated at a proteome scale using protein arrays, a type of high-throughput pulldown assay. We developed a modified in situ protein array known as the nucleic acid programmable protein assay (NAPPA) that allows the screening of thousands of open reading frames (ORFs) at a lower cost, with less labor, and in less time than conventional protein arrays. The HaloTag-NAPPA protein array can efficiently capture proteins expressed in situ on a glass slide using the Halo high-affinity capture tag. Here, we describe the fabrication of the array using publicly available resources and detection of protein-protein interactions (PPIs) that can be used to generate a protein interactome map. The Basic Protocol includes procedures for preparing the plasmid DNA spotted on glass slides, in situ protein expression, and PPI detection. The supporting protocols outline the construction of vectors and preparation of ORF clones. © 2018 by John Wiley & Sons, Inc., (© 2018 John Wiley & Sons, Inc.)

Cathepsin S (CTSS) activity is elevated in Sjögren's Syndrome (SS) patient tears. Here we tested whether protease inhibition and cystatin C (Cys C) levels are reduced in SS tears, which could lead to enhanced CTSS-driven degradation of tear proteins. CTSS activity against Cys C, LF and sIgA was tested in SS or healthy control tears. Tears from 156 female subjects (33, SS; 33, rheumatoid arthritis; 31, other autoimmune diseases; 35, non-autoimmune dry eye (DE); 24, healthy controls) were analyzed for CTSS activity and Cys C, LF, and sIgA levels. Cys C and LF showed enhanced degradation in SS tears supplemented with recombinant CTSS, but not supplemented healthy control tears. CTSS activity was significantly increased, while Cys C, LF and sIgA levels were significantly decreased, in SS tears compared to other groups. While tear CTSS activity remained the strongest discriminator of SS in autoimmune populations, combining LF and CTSS improved discrimination of SS beyond CTSS in DE patients. Reductions in Cys C and other endogenous proteases may enhance CTSS activity in SS tears. Tear CTSS activity is reconfirmed as a putative biomarker of SS in an independent patient cohort while combined LF and CTSS measurements may distinguish SS from DE patients.

Purpose This study demonstrates a standardized approach to measuring retinal thickness (RT) using spectral domain optical coherence tomography (SD-OCT) in commonly used animal models of disease and reports a normative data set for future use. Materials and Methods Twenty normal eyes of 4 adult animal models (5 rats, 5 rabbits, 5 canines, and 5 mini-pigs) were used. Manual measurements were made on the commercially available Heidelberg Spectralis™ SD-OCT to determine the total, inner, and outer retinal thickness (RT) at fixed distances from the optic nerve head (ONH) (1, 2, 3, 4, 5, and 6 mm away) in order to control for normal variation in retinal thickness. Analysis of variance (ANOVA) with P value <0.05 indicated statistical significance. Results Total RT significantly decreased with increasing distance from the ONH for the canine, mini-pig, and rabbit vascular models. Inner RT significantly decreased for the canine, mini-pig, rabbit vascular, and rabbit avascular models; and outer RT significantly decreased for only the canine model. Among the animal models, RT at similar distances from the ONH were significantly different for total, inner, and outer RT. Conclusion There are significant differences in the total, inner, and outer RT of normal canine, mini-pig, rabbit, and rat retinas with SD-OCT using a standardized approach. These measurements provide a normative reference for future studies and illustrate a standardized method of assessing RT.