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A popular focus in affective neuroscience research has been to map the relationships between individual differences (e.g. personality and environmental experiences) and psychophysiological responses, in order to further understand the effect of individual differences upon neurobehavioral systems that support affect and arousal. Despite this trend, there have been a lack of practical examples demonstrating how the quantification of individual differences (e.g. categorical or continuous) impacts the observed relationships between different units of analysis (e.g. self-report > psychophysiological responses). To address this gap, we conducted a two-stage aggregated meta-analysis of self-reported intolerance of uncertainty (IU) and skin conductance responses during threat extinction (k = 18, n = 1006) using different quantification choices for individual differences in self-reported intolerance of uncertainty (continuous, categorical via median split, and categorical via extremes - one standard deviation above/below). Results from the meta-analyses revealed that the different quantification techniques produced some consistent (e.g. higher IU was significantly associated with skin conductance responding during late extinction training) and inconsistent IU-related effects. Furthermore, the number of statistically significant effects and effect sizes varied based on the quantification of individual differences in IU (e.g. categorical, compared to continuous was associated with more statistically significant effects, and larger effect sizes). The current study highlights how conducting different quantification methods for individual differences may help researchers understand the individual difference construct of interest (e.g. characterisation, measurement), as well as examine the stability and reliability of individual difference-based effects and correspondence between various units of analysis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hospital-acquired pneumonia (HAP) also known as non-ventilator associated pneumonia, is one of the most common infections acquired in hospitalised patients. Improving oral hygiene appears to reduce the incidence of HAP. This study aimed to describe current practices, barriers and facilitators, knowledge and educational preferences of registered nurses performing oral health care in the Australian hospital setting, with a focus on the prevention of HAP. We present this as a short research report., Methods: We undertook a cross sectional online anonymous survey of Australian registered nurses. Participants were recruited via electronic distribution through existing professional networks and social media. The survey used was modified from an existing survey on oral care practice., Results: The survey was completed by 179 participants. Hand hygiene was considered a very important strategy to prevent pneumonia (n = 90, 58%), while 45% (n = 71) felt that oral care was very important. The most highly reported barriers for providing oral care included: an uncooperative patient; inadequate staffing; and a lack of oral hygiene requisite. Patients' reminders, prompts and the provision of toothbrushes were common ways believed to help facilitate improvements in oral care., Conclusion: Findings from this survey will be used in conjunction with consumer feedback, to help inform a planned multi-centre randomised trial, the Hospital Acquired Pneumonia PrEveNtion (HAPPEN) study, aimed at reducing the incidence of HAP. Findings may also be useful for informing studies and quality improvement initiatives aimed at improving oral care to reduce the incidence of HAP., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The policymaking process is largely opaque, especially regarding the actual writing of the policy. To attempt to better understand this complex process, we utilized mixed methods in our evaluation of an intervention. However, the process of mixing methods can be messy, and thus may require recalibration during the evaluation itself. Yet, in comparison to reporting results, relatively little attention is paid to the effects of mixing methods on the evaluation process. In this article, we take a reflexive approach to reporting a mixed methods evaluation of an intervention on the use of research evidence in U.S. federal policymaking. We focus on the research process in a qualitative coding team, and the effects of mixing methods on that process. Additionally, we report in general terms how to interpret multinomial logistic regressions, an underused analysis type applicable to many evaluations. Thus, this reflexive piece contributes (1) findings from evaluation of the intervention on the policymaking process, (2) an example of mixing methods leading to unexpected findings and future directions, (3) a report about the evaluation process itself, and (4) a tutorial for those new to multinomial logistic regressions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Modifications to opioid regimens for persistent pain are typically made after an initial period of short-acting opioid (SAO) use. Regimen changes may include an escalation of the SAO dosage or an initiation of a long-acting opioid (LAO) as a switch or add-on therapy. This study evaluates the comparative effectiveness between these alternative regimens in nursing home residents., Design: A retrospective observational cohort analysis of US long-stay nursing home residents., Setting and Participants: Nursing home resident data were obtained from the national Minimum Dataset (MDS) version 3.0 and linked Medicare data, 2011-2016., Methods: Opioid regimen changes were identified using Part D dispensing claims to identify dosage escalation of SAOs, initiation of an LAO, or a switch to an LAO. Outcomes included indices of pain occurrence, frequency, and severity reported on the earliest MDS assessment within 3 months following the opioid regimen change. Resident attributes were described by opioid regimen cohort. Prevalence ratios of pain and depression indices were quantified using doubly robust inverse probability of treatment (IPT)-weighted log-binomial regression., Results: The study cohorts included 2072 SAO dose escalations, 575 LAO add-on initiations, and 247 LAO switch initiations. After IPT weighting, we observed comparable effects on pain and mood across the opioid regimen cohorts. A substantial number of residents continued to report frequent/constant pain (36% in SAO Escalation Cohort, 42% in LAO Add-on Cohort, 42% in the LAO Switch Cohort). The distribution of depressive symptoms was similar regardless of the opioid regimen change., Conclusions and Implications: Initiation of an LAO as an add-on to SAO or a switch from SAO had comparable effects on pain and mood to SAO dose escalation without initiation of an LAO. Although fewer residents reported any pain after the regimen change, persistent pain was reported by most residents., Competing Interests: Disclosure K.L.L. is a consultant for Exponent. A.P.N. is a consultant for Optum Epidemiology. The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: An inclusive residency program is crucial to the recruitment and retention of competitive and diverse applicants. The radiology lesbian, gay, bisexual, transgender, queer or questioning, or another diverse gender identity (LGBTQ+) inclusion audit was published in 2022, which provided a road map for assessing the inclusivity of a program's policies, facilities, culture, and engagement. In this multi-institutional trial, we detail the results of the LGBTQ+ inclusion audit for nine US radiology residency programs., Methods: A volunteer cohort of academic radiology programs was recruited through the Radiology Residency Education Research Alliance. The LGBTQ+ inclusion audit was modified to apply to a multi-institutional study. Participating programs performed the audit from December 2023 to February 2024. Pre- and postaudit surveys were distributed to capture participants subjective assessment of inclusivity at their programs., Results: Nine US radiology residency programs completed the audit. Audit scores ranged from 6 out of 10 to 9 out of 10; no program received a perfect 10 out of 10 score. Inclusive facilities and institutional culture scored highly, with eight of nine programs reporting all milestones met in these areas. The lowest-performing areas were department culture and community engagement with only three of nine and four of nine programs reporting "all milestones met." After the audit, programs overall reported improved self-perceived inclusivity, with postaudit survey scores increasing in areas related to department policy, inclusive facilities, and LGBTQ+ community outreach., Discussion: Participating radiology residency programs demonstrated an overall high level of LGBTQ+ inclusivity; however, all programs identified inclusion shortcomings in department policy and practice. Intentional review of a department can be a helpful tool to promote a welcoming and healthy environment for a diverse radiology practice., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: Extracurricular activities (EAs) listed on radiology residency applications can signal traits and characteristics desired in holistic reviews. The authors conducted an objective analysis to determine the influence of EAs on resident selection decisions., Methods: A discrete-choice experiment was designed to model radiology resident selection and determine the relative weights of EAs among academic and demographic application factors. Faculty members involved in resident selection at 30 US radiology programs chose between hypothetical pairs of applicant profiles between October 2021 and February 2022. Each applicant profile included one of 22 EAs chosen for study. A conditional logistic regression model assessed the relative weights of the attributes and odds ratios (ORs) were calculated., Results: Two hundred forty-four participants completed the exercise. Community-service EAs were ranked most highly by participants. LGBTQ Pride Alliance (OR, 1.56; 95% confidence interval [CI], 1.14-2.15; P = .006) and Young Republicans (OR, 0.60; 95% CI, 0.43-0.82; P = .001) significantly influenced decisions. The highest ranked EAs were significantly preferred over the lowest ranked EAs (OR, 1.916; 95% CI, 1.671-2.197; P < .001). Participants preferred EAs that reflected active over passive engagement (OR, 1.154; 95% CI, 1.022-1.304; P = .021) and progressive over conservative ideology (OR, 1.280; 95% CI, 1.133-1.447; P < .001). Participants who ranked progressive EAs more highly preferred applicants with progressive EAs (P < .05 for all)., Conclusions: The influence of EAs on resident selection decisions is significant and likely to gain importance in resident selection as medical student performance metrics are further eliminated. Applicants and selection committees should consider this influence and the bias that EAs can bring to resident selection decisions., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Introduction: Integration of hospice and palliative care principles within pharmacy curricula is essential to fill the need of pharmacist training in this growing specialty. A formalized assessment tool to evaluate skill development does not exist for student pharmacists specific to palliative care. The objective of this study was to develop a valid and reliable, palliative care-focused, performance-based assessment tool for student pharmacists., Methods: Eight academic palliative care (PC) pharmacists were recruited for the workgroup to perform domain development, validation, tool creation, and reliability testing for this performance-based assessment tool. Hospice and palliative care clinical pharmacist entrustable professional activities (EPAs) served as the framework. Content validity testing utilized content validity index and scale universal agreement (S-CVI/UA) to determine level of agreement for activities included in the tool. Student volunteers completed a standardized patient case and workgroup members served as raters during the reliability testing phase. Interrater reliability was measured through calculation of Fleiss Kappa scores for each activity., Results: Out of 14 EPAs, nine were deemed "essential" to include in the tool. Thirty-four supporting activities for the nine essential EPAs were drafted. Two rounds of content validity testing were necessary to achieve S-CVI/UA of 0.9593. Consensus was reached from workgroup members for activities deemed necessary to include in the tool after questionnaire distribution utilizing a Fleiss Kappa cutoff >0.6., Conclusions: This validated tool will afford colleges and schools of pharmacy with PC curricula an opportunity to assess student achievement of PC-specific skills and evaluate curricular effectiveness., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Social media platforms such as Twitter are home ground for rapid COVID-19-related information sharing over the Internet, thereby becoming the favorable data resource for many downstream applications. Due to the massive pile of COVID-19 tweets generated every day, it is significant that the machine-learning-supported downstream applications can effectively skip the uninformative tweets and only pick up the informative tweets for their further use. However, existing solutions do not specifically consider the negative effect caused by the imbalanced ratios between informative and uninformative tweets in training data. In particular, most of the existing solutions are dominated by single-view learning, neglecting the rich information from different views to facilitate learning. In this study, a novel deep imbalanced multi-view learning approach called D-SVM-2K is proposed to identify the informative COVID-19 tweets from social media. This approach is built upon the well-known multiview learning method SVM-2K to incorporate different views generated from different feature extraction techniques. To battle against the class imbalance problem and enhance its learning ability, D-SVM-2K stacks multiple SVM-2K base classifiers in a stacked deep structure where its base classifiers can learn from either the original training dataset or the shifted critical regions identified using the well-known k-nearest neighboring algorithm. D-SVM-2K also realises a global and local deep ensemble learning on the multiple views' data. Our empirical experiments on a real-world labeled tweet dataset demonstrate the effectiveness of D-SVM-2K in dealing with the real-world multi-view class imbalance issues., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objectives: Impostor syndrome (IS) is prevalent in medical professionals. However, little is known about the prevalence of IS among medical trainees and those who are underrepresented in medicine (UiM). Even less is known about the experiences of UiM students at predominantly white institutions (PWIs) and historically black colleges/universities (HBCUs) relative to their non-UiM peers. The purpose of this study is to investigate differences in impostor syndrome among UiM and non-UiM medical students at a PWI and a HBCU. We additionally explored gender differences in impostor syndrome among UiM and non-UiM students at both institutions., Method: Medical students (N = 278) at a PWI (N = 183, 107 (59%) women) and a HBCU (N = 95, 60 (63%) women), completed an anonymous, online two-part survey. In part one, students provided demographic information, and in part two, students completed the Clance Impostor Phenomenon Scale, a 20-item self-report questionnaire that assessed feelings of inadequacy and self-doubt surrounding intelligence, success, achievements, and one's inability to accept praise/recognition. Based on the student's score, the level of IS was measured and placed into one of two levels: few/moderate IS feelings, or frequent/intense IS feelings. We conducted a series of chi-square tests, binary logistic regression, independent sample t-tests, and analysis of variance to test the main aim of the study., Results: The response rate was 22% and 25% at the PWI and HBCU, respectively. Overall, 97% of students reported moderate to intense feelings of IS, and women were 1.7 times more likely than men to report frequent or intense feelings of IS (63.5% vs 50.5%, p = 0.03). Students at PWI were 2.7 times more likely to report frequent or intense IS than HBCU students (66.7% vs 42.1%, p< 0.01). In addition, UiM students at PWI were 3.0 times more likely to report frequent or intense IS compared to UiM students at HBCU (68.6 % vs 42.0%, p = 0.01). Computation of a three-way ANOVA with gender, minority status, and school type revealed a two-way interaction indicating that UiM women scored higher on impostor syndrome than UiM men at the PWI and HBCU. This trend was not observed among non-UiM students., Conclusions: Impostor syndrome is informed by gender, UiM status, as well as environmental context. Efforts to provide supportive professional development for medical students should be directed towards understanding and combatting this phenomenon at this critical juncture of their medical career., Competing Interests: Declaration of Competing Interest I do not have conflicts of interest to disclose. The authors of this paper do not have conflicts of interest to disclose., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

The goal of Working Group 1 in the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to outline factors influencing biological processes governing human milk secretion and to evaluate our current knowledge of these processes. Many factors regulate mammary gland development in utero, during puberty, in pregnancy, through secretory activation, and at weaning. These factors include breast anatomy, breast vasculature, diet, and the lactating parent's hormonal milieu including estrogen, progesterone, placental lactogen, cortisol, prolactin, and growth hormone. We examine the effects of time of day and postpartum interval on milk secretion, along with the role and mechanisms of lactating parent-infant interactions on milk secretion and bonding, with particular attention to the actions of oxytocin on the mammary gland and the pleasure systems in the brain. We then consider the potential effects of clinical conditions including infection, pre-eclampsia, preterm birth, cardiovascular health, inflammatory states, mastitis, and particularly, gestational diabetes and obesity. Although we know a great deal about the transporter systems by which zinc and calcium pass from the blood stream into milk, the interactions and cellular localization of transporters that carry substrates such as glucose, amino acids, copper, and the many other trace metals present in human milk across plasma and intracellular membranes require more research. We pose the question of how cultured mammary alveolar cells and animal models can help answer lingering questions about the mechanisms and regulation of human milk secretion. We raise questions about the role of the lactating parent and the infant microbiome and the immune system during breast development, secretion of immune molecules into milk, and protection of the breast from pathogens. Finally, we consider the effect of medications, recreational and illicit drugs, pesticides, and endocrine-disrupting chemicals on milk secretion and composition, emphasizing that this area needs much more research attention., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Midwives have a pivotal role in screening for risk factors for mental illness and psychosocial vulnerabilities in women during the perinatal period. They also have a key responsibility to provide women with the appropriate resources to support their mental wellbeing. Midwives can lack confidence and/or feelings of competence regarding these skills. Care of women in the context of their perinatal mental health is a core midwifery skill that deserves practical learning during pre-registration education, just as the more 'hands on' skills such as abdominal palpation, labour and birth support or newborn examination. However, there is limited opportunity for students to gain clinical placement experiences that are specific to perinatal mental health (PMH). This discussion paper describes an innovative teaching and learning project that aimed to improve confidence in students' ability to conduct screening, support, and referral of women experiencing mental ill health. The project involved the development of an Objective Structured Clinical Examination (OSCE) and audio visual resources to support learning and teaching and clinical placement. Feedback was collected to inform the refinement of the first OSCE, and to assist in the design of the audio visual resources that are now displayed publicly on the Australian College of Midwives website at https://www.midwives.org.au/Web/Web/Professional-Development/Resources.aspx?hkey=12c2360e-d8b9-4286-8d0a-50aeaeca9702., (Copyright © 2023 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: Smoking is associated with health inequalities and is the most important modifiable risk factor for poor outcome in pregnancy., Aim: To explore women's experiences of smoking during pregnancy, examine their attitudes and barriers to smoking cessation, and to discover what support they feel might enable them to have a smoke-free pregnancy in future., Methods: A qualitative study was conducted with nineteen women in the United Kingdom who had smoked at some stage in pregnancy during the last five years. Data were collected through in-depth telephone interviews between June and August 2021. The interviews were audio-recorded, transcribed verbatim, and thematically analysed., Findings: Four key themes were identified: the complex relationship with smoking, being ready to quit, the need for support and understanding, and ideas to support a smoke free pregnancy. The findings revealed that there were two distinct avenues for enabling the support process: encouraging a readiness to quit through identifying individual context, personalised support, and educational risk perception, and, supporting the process of quitting, and offering a range of options, underpinned by a personalised, non-judgemental approach., Conclusion: Smoking in pregnancy is a complex issue resulting from a combination of social, emotional, and physical factors. The findings from this study suggest that a combination of approaches should be made available to enable pregnant women who smoke to select the best options for their individual needs. Irrespective of the practical support offered, there is a need for informed, sensitive, individualised support system that women can identify with., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Extracorporeal membrane oxygenation (ECMO) is an invasive procedure used to support critically ill patients with the most severe forms of cardiac or respiratory failure in the short term, but long-term effects on incidence of death and disability are unknown. We aimed to assess incidence of death or disability associated with ECMO up to 6 months (180 days) after treatment., Methods: This prospective, multicentre, registry-embedded cohort study was done at 23 hospitals in Australia from Feb 15, 2019, to Dec 31, 2020. The EXCEL registry included all adults (≥18 years) in Australia who were admitted to an intensive care unit (ICU) in a participating centre at the time of the study and who underwent ECMO. All patients who received ECMO support for respiratory failure, cardiac failure, or cardiac arrest during their ICU stay were eligible for this study. The primary outcome was death or moderate-to-severe disability (defined using the WHO Disability Assessment Schedule 2.0, 12-item survey) at 6 months after ECMO initiation. We used Fisher's exact test to compare categorical variables. This study is registered with ClinicalTrials.gov, NCT03793257., Findings: Outcome data were available for 391 (88%) of 442 enrolled patients. The primary outcome of death or moderate-to-severe disability at 6 months was reported in 260 (66%) of 391 patients: 136 (67%) of 202 who received veno-arterial (VA)-ECMO, 60 (54%) of 111 who received veno-venous (VV)-ECMO, and 64 (82%) of 78 who received extracorporeal cardiopulmonary resuscitation (eCPR). After adjustment for age, comorbidities, Acute Physiology and Chronic Health Evaluation (APACHE) IV score, days between ICU admission and ECMO start, and use of vasopressors before ECMO, death or moderate-to-severe disability was higher in patients who received eCPR than in those who received VV-ECMO (VV-ECMO vs eCPR: risk difference [RD] -32% [95% CI -49 to -15]; p&lt;0·001) but not VA-ECMO (VA-ECMO vs eCPR -8% [-22 to 6]; p=0·27)., Interpretation: In our study, only a third of patients were alive without moderate-to-severe disability at 6 months after initiation of ECMO. The finding that disability was common across all areas of functioning points to the need for long-term, multidisciplinary care and support for surviving patients who have had ECMO. Further studies are needed to understand the 180-day and longer-term prognosis of patients with different diagnoses receiving different modes of ECMO, which could have important implications for the selection of patients for ECMO and management strategies in the ICU., Funding: The National Health and Medical Research Council of Australia., Competing Interests: Declaration of interests CLH leads the bi-national EXCEL registry, with funding from the Australian National Health and Medical Research Council (NHMRC) and the Heart Foundation of Australia (HFA), holds an NHMRC investigator grant, and is on the executive committee of the International ECMO Network (ECMONet). AMH, AJCB, and DJC receive research support from NHMRC. AMH, MJB, SB, BJF, NJL, DJC, DJG, IKH, DVP, TVT, and AAU received funding for the EXCEL registry from NHMRC and HFA. DB is Chair of the Executive Committee of ECMONet and President-elect of ELSO, receives research support from ALung Technologies, and has been on medical advisory boards for Abiomed, Xenios, Medtronic, and Cellenkos. DJC holds an NHMRC practitioner fellowship. EF is on the executive committee of ECMONet and the steering committee of the Extracorporeal Life Support Organization (ELSO). JFF and VAP are on the Executive Committee of ECMONet. JFF is President of the Asia-Pacific Chapter of ELSO, Chair of the Queensland Cardiovascular Research Network, co-founder of BiVACOR, and receives research support from Xenios, Mallenkrodt Getinge, and MERA (all ECMO companies). DS received research support from a HFA fellowship. AAU is on the executive committee of the Australian and New Zealand Intensive Care Society Clinical Trials Group. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Peripheral artery disease (PAD) disproportionately affects nonwhite, Hispanic/Latino, and low socioeconomic status patients, who are less likely to have insurance and routine healthcare visits. Medicaid expansion (ME) has improved insurance rates and access to care, potentially benefitting these patients. We sought to assess the impact of ME on disparities in outcomes after peripheral vascular intervention (PVI) for PAD., Methods: A retrospective analysis of prospectively-collected Vascular Quality Initiative PVI procedures between 2011 and 2019 was conducted. The sample was restricted to first-record procedures in adults under the age 65 in states that expanded Medicaid on January 1, 2014 (ME group) or had not expanded before January 1, 2019 (non-expansion [NE] group). ME and NE groups were compared between pre-expansion (2011-2013) and post-expansion (2014- 2019) time periods to assess baseline demographic and operative differences. We used difference-in-differences multivariable logistic regression adjusted for patient factors and clinical center and year fixed effects. Our primary outcome was 1-year major amputation. Secondary outcomes included trends in presentation, 30-day mortality, 1-year mortality, and 1-year primary and secondary patency. Outcomes were stratified by race and ethnicity., Results: We examined 34,313 PVI procedures, including 20,378 with follow-up data. Rates of Medicaid insurance increased post-expansion in ME and NE states (ME 16.7% to 23.0%, P < 0.001; NE 10.0% to 11.9%, P = 0.013) while rates of self-pay decreased in ME states only (ME 4.6% to 1.8%, P < 0.001; NE 8.1% to 8.4%, P = 0.620). Adjusted difference-in-differences analysis revealed lower odds of urgent/emergent PVI among all patients and all nonwhite patients in ME states post-expansion compared to NE states (all: odds ratio [OR] 0.53 [95% confidence interval 0.33-0.87], P = 0.011; nonwhite: OR 0.41 [0.19-0.88], P = 0.023). No differences were observed for 1-year major amputation (OR 0.70 [0.43-1.14], P = 0.152), primary patency (OR 0.93 [0.63-1.38], P = 0.726), or secondary patency (OR 1.29 [0.69-2.41], P = 0.431). Odds of 1-year mortality were higher in ME states post-expansion compared to NE states (OR 2.50 [1.07-5.87], P = 0.035), although 30-day mortality was not different (OR 2.04 [0.60-6.90], P = 0.253). Notably, odds of 1-year major amputation among Hispanic/Latino patients decreased in ME states post-expansion compared to NE states (OR 0.11 [0.01-0.86], P = 0.036)., Conclusions: ME was associated with lower odds of 1-year major amputation among Hispanic/Latino patients who underwent PVI for PAD. ME was also associated with lower odds of urgent/emergent procedures among patients overall and nonwhite patients specifically. However, 1-year mortality increased in the overall cohort. Further study is needed to corroborate our findings that ME may have benefits for certain underserved populations with PAD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Delirium, poor performance status, and dyspnea predict short survival in the palliative care setting., Objective: Our goal was to determine whether these three conditions, which we refer to as a "triple threat," also predict mortality among patients with advanced cancers in the emergency department (ED)., Methods: The study sample included 243 randomly selected, clinically stable patients with advanced cancer who presented to our ED. The analysis included patients who had delirium (Memorial Delirium Assessment Scale score ≥ 7), poor performance status (Eastern Cooperative Oncology Group performance status score of 3 or 4), or dyspnea as a presenting symptom. We obtained survival data from medical records. We calculated predicted probability of dying within 30 days and association with number of symptoms after the ED visit using logistic regression analysis., Results: Twenty-eight patients died within 30 days after presenting to the ED. Death within 30 days occurred in 36% (16 of 44) of patients with delirium, 28% (17 of 61) of patients with poor performance status, and 14% (7 of 50) of patients with dyspnea, with a predicted probability of 30-day mortality of 0.38 (95% confidence interval [CI] 0.25-0.53), 0.28 (95% CI 0.18-0.40), and 0.15 (95% CI 0.07-0.29), respectively. The predicted probability of death within 30 days for patients with two or three of the conditions was 0.49 (95% CI 0.34-0.66) vs. 0.05 (95% CI 0.02-0.09) for patients with none or one of the conditions., Conclusions: Patients with advanced cancers who present to the ED and have at least two triple threat conditions have a high probability of death within 30 days., (Published by Elsevier Inc.)

Checking behaviour has been described as a form of preventative behaviour used by an individual to establish control over the environment and avoid future misfortune. However, when compulsive, checking behaviours can become disabling and distressing and have been linked to the maintenance of anxiety and obsessive-compulsive disorders. Despite this, there is limited literature across the field that has assessed the impact of dimensional measures of anxiety and obsessive-compulsive features (i.e., negative affect, uncertainty, and perfectionism) in driving checking behaviour. As such, the present study examined the impact of individual differences in self-reported anxiety and obsessive-compulsive features on subjective, behavioural, and physiological indices during a visual discrimination and checking task (n = 87). Higher self-reported anxiety and obsessive-compulsive features were associated with higher subjective ratings of unpleasantness and the urge to check during the task. Moreover, higher self-reported anxiety and obsessive-compulsive features related to general negative affect, uncertainty, and perfectionism were associated with greater checking frequency during the task. Lastly, stronger obsessional beliefs about perfectionism and the need for certainty were found to predict poorer accuracy, slower reaction times, and higher engagement of the corrugator supercilii during the task. In sum, these findings demonstrate how different anxiety and obsessive-compulsive features, in particular perfectionism and the need for certainty, may relate to and maintain checking behaviour in low threat contexts, which likely has implications for models of excessive and persistent checking in anxiety and obsessive-compulsive disorders., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: CMV viremia is associated with increased mortality in persons with HIV. We previously demonstrated that CMV viremia was a risk factor for 10-week mortality in antiretroviral therapy (ART)-naïve persons with cryptococcal meningitis. We investigated whether similar observations existed over a broader cohort of patients with HIV-associated meningitis at 18 weeks., Methods: We prospectively enrolled Ugandans with cryptococcal or TB meningitis into clinical trials in 2015-2019. We quantified CMV DNA concentrations from stored baseline plasma or serum samples from 340 participants. We compared 18-week survival between those with and without CMV viremia., Results: We included 308 persons with cryptococcal meningitis and 32 with TB meningitis, of whom 121 (36%) had detectable CMV DNA. Baseline CD4 + T-cell counts (14 vs. 24 cells/µl; P = 0.07) and antiretroviral exposure (47% vs. 45%; P = 0.68) did not differ between persons with and without CMV viremia. The 18-week mortality was 50% (61/121) in those with CMV viremia versus 34% (74/219) in those without (P = 0.003). Detectable CMV viremia (adjusted hazard ratio [aHR] 1.60; 95% confidence interval [CI] 1.13-2.25; P = 0.008) and greater viral load (aHR 1.22 per log 10 IU/ml increase; 95% CI 1.09-1.35; P <0.001) were positively associated with all-cause mortality through 18 weeks., Conclusion: CMV viremia at baseline was associated with a higher risk of death at 18 weeks among persons with HIV-associated cryptococcal or TB meningitis, and the risk increased as the CMV viral load increased. Further investigation is warranted to determine whether CMV is a modifiable risk contributing to deaths in HIV-associated meningitis or is a biomarker of immune dysfunction., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Most Australian women access contraception through general practitioners (GPs) but choose oral methods rather than long-acting reversible contraceptives (LARCS). The Australian Contraceptive ChOice pRoject (ACCORd) successfully tested a complex intervention for LARC uptake. We aimed to explore the critical elements of this intervention to increase LARC uptake., Design: ACCORd was a cluster randomised control trial conducted in 57 GP clinics in Melbourne, Australia. To explore intervention impact, fidelity checks (n=21 GPs) and interviews with 37 GPs and 40 patients were undertaken 12 months after initial consultations. Data were inductively coded, thematically analysed and mapped to Normalization Process Theory constructs., Results: Doctors understood the importance of effectiveness-based contraceptive counselling (EBCC). GPs demonstrated cognitive engagement in the promotion of LARC and some appreciated the rapid referral pathways. GPs and women valued the effectiveness approach. GPs held varying views about having a rapid referral pathway, with many already having established pathways in place. Some GPs viewed intrauterine device insertion costs or insertion training as barriers to ongoing practice. Most GPs and women saw the ACCORD model as effective and sustainable., Conclusions: GP training in EBCC and the use of rapid referral pathways were critical features of an effective sustainable model for successful uptake of LARCs in primary care., Implications for Public Health: Improving Australian women's access to and use of LARCs is sustainable with EBCC training and support for general practitioners., (© 2022 The Authors.)

Individuals who score high in self-reported Intolerance of Uncertainty (IU) tend to find uncertainty unacceptable and aversive. In recent years, research has shed light on the role of IU in modulating subjective (i.e. expectancy ratings) and psychophysiological responses (i.e. skin conductance) across different classical fear conditioning procedures. In particular, during immediate extinction higher IU is associated with disrupted safety learning. However, there remain gaps in understanding how IU, in comparison to other negative emotionality traits (STAI-T), impact different types of subjective and psychophysiological measures during different classical fear conditioning procedures. In our exploratory study, we analyzed IU, STAI-T, subjective (i.e. fear ratings) and psychophysiological (i.e. skin conductance, auditory startle blink) data recorded during fear acquisition training and 24 h-delayed extinction training (n = 66). Higher IU, controlled for STAI-T, was: (1) significantly associated with greater fear ratings to the learned fear cue during fear acquisition training, and (2) at trend associated with greater fear ratings to the learned fear versus safe cue during delayed extinction training. Null results were observed for both IU and STAI-T in relation to skin conductance and auditory startle blink during fear acquisition training and delayed extinction training. These results add to and extend our current understanding of the role of IU on subjective and physiological measures during different fear conditioning procedures particularly that of subjective fear ratings during acquisition and delayed extinction training. Implications of these findings and future directions are discussed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Individuals who score high in self-reported Intolerance of Uncertainty (IU) tend to find uncertainty aversive. Prior research has demonstrated that under uncertainty individuals with high IU display difficulties in updating learned threat associations to safety associations. Importantly, recent research has shown that providing contingency instructions about threat and safety contingencies (i.e. reducing uncertainty) to individuals with high IU promotes the updating of learned threat associations to safety associations. Here we aimed to conceptually replicate IU and contingency instruction-based effects by conducting a secondary analysis of self-reported IU, ratings, skin conductance, and functional magnetic resonance imaging (fMRI) data recorded during uninstructed/instructed blocks of threat acquisition and threat extinction training (n = 48). Generally, no significant associations were observed between self-reported IU and differential responding to learned threat and safety cues for any measure during uninstructed/instructed blocks of threat acquisition and threat extinction training. There was some tentative evidence that higher IU was associated with greater ratings of unpleasantness and arousal to the safety cue after the experiment and greater skin conductance response to the safety cue during extinction generally. Potential explanations for these null effects and directions for future research are discussed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To compare time to incidence, extent of incidence and severity of heel pressure injury with a heel off-loading boot (intervention) or pillows (control)., Research Methodology/design: Multi-centre, single-blinded randomised controlled trial of 394 critically ill patients. Patients were randomised to the intervention or control for heel offloading., Setting: Three hospital intensive care units; two in greater Sydney, Australia and one in regional New South Wales, Australia., Main Outcome Measures: Time to intensive care unit-acquired pressure injury in heels of patients without pre-existing heel pressure injury within 28 days from intensive care unit admission., Secondary Outcomes: incidence of heel pressure injury within 28 days of intensive care unit admission; severity of intensive care unit-acquired heel pressure injuries; occurrence of plantar contractures (a change in ankle dorsiflexion of 5° or greater) within 28 days of admission., Results: Within 28 days of admission, one pressure injury was recorded in the intervention group and 11 in the control group. Hazard of pressure injury incidence within 28 days of admission was significantly lower (p = 0.0239) in heels assigned to the intervention (hazard ratio 0.0896 [95% CI 0.0110, 0.727]). Odds of pressure injury incidence within 28 days of admission were significantly lower (p = 0.0261) in the intervention group (odds ratio 0.0883 [95% CI 0.0104, 0.749]). The pressure injury recorded in the intervention group was superficial (stage 1) whereas those recorded in the control group were more severe (stage 2 to 4)., Conclusion: The heel-offloading boot used in this study significantly reduced heel pressure injury occurrence compared with heel offloading using pillows., (Copyright © 2022. Published by Elsevier Ltd.)

Legacy mining facilities pose significant risks to aquatic resources. From March 30th to April 9th, 2021, 814 million liters of phosphate mining wastewater and marine dredge water from the Piney Point facility were released into lower Tampa Bay (Florida, USA). This resulted in an estimated addition of 186 metric tons of total nitrogen, exceeding typical annual external nitrogen load estimates to lower Tampa Bay in a matter of days. An initial phytoplankton bloom (non-harmful diatoms) was first observed in April. Filamentous cyanobacteria blooms (Dapis spp.) peaked in June, followed by a bloom of the red tide organism Karenia brevis. Reported fish kills tracked K. brevis concentrations, prompting cleanup of over 1600 metric tons of dead fish. Seagrasses had minimal changes over the study period. By comparing these results to baseline environmental monitoring data, we demonstrate adverse water quality changes in response to abnormally high and rapidly delivered nitrogen loads., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: The increased COVID-19 mortality for Black individuals over White individuals may be explained by the known racial disparities in access to insurance., Objective: To determine whether racial disparities in COVID-19 mortality still exist when Blacks and Whites are equally insured., Design: Routinely collected data on race, mortality, type of insurance, known risk factors, and lab results from the EPIC Patient Management System were analyzed using a multivariable logistic regression model., Setting: Piedmont Healthcare is the largest hospital system in Georgia. Due to its multiple locations across the state of Georgia, it receives a relatively equitably insured population., Participants: All patients hospitalized with a positive COVID-19 status between March 1 and November 30, 2020., Main Outcomes: We hypothesized that Black patients would not have higher odds of mortality than White patients, and that type of insurance would predict COVID-19 mortality., Results: 6,881 (3,674 Black, 3,207 White; 48% male, mean age = 60) patients were included. Race was not a significant predictor of COVID-19 mortality (p>0.05). When controlling for age and insurance, the mortality rate for Black patients was not statistically significant from that for White patients (p>0.05). Compared to those relying on Medicare, patients with commercial (OR=0.68, 95% CI: 0.48-0.96) or out-of-pocket (self-pay) insurance (OR=0.22, 95% CI: 0.03-0.88) had lower odds of mortality., Conclusions: National trends of racial disparities in COVID-19 mortality may be partially explained by disparities in insurance., Competing Interests: Declaration of Competing Interest To: The Journal of the National Medical Association Date: August 27, 2021 Dear Whomever It May Concern: I have no conflicts of interest in the following paper submitted for publication: Assessing the Impact of Insurance Type on COVID-19 Mortality in Black and White Patients in the Largest Healthcare System in the State of Georgia My research team and all authors also have no conflict of interest. Thank you. Best Regards, Jayne Morgan, M.D. Corresponding Author, (Copyright © 2022 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological evidence in multiple jurisdictions has shown an association between nitrate exposure in drinking water and an increased risk of colorectal cancer (CRC)., Objective: We aimed to review the extent of nitrate contamination in New Zealand drinking water and estimate the health and financial burden of nitrate-attributable CRC., Methods: We collated data on nitrate concentrations in drinking water for an estimated 85% of the New Zealand population (∼4 million people) who were on registered supplies. We estimated nitrate levels for the remaining population (∼600,000 people) based on samples from 371 unregistered (private) supplies. We used the effective rate ratio from previous epidemiological studies to estimate CRC cases and deaths attributable to nitrate in drinking water., Results: Three-quarters of New Zealanders are on water supplies with less than 1 mg/L NO 3 -N. The population weighted average for nitrate exposure for people on registered supplies was 0.49 mg/L NO 3 -N with 1.91% (95%CI 0.49, 3.30) of CRC cases attributable to nitrates. This correlates to 49.7 cases per year (95%CI 14.9, 101.5) at a cost of 21.3 million USD (95% 6.4, 43.5 million USD). When combining registered and unregistered supplies, we estimated 3.26% (95%CI 0.84, 5.57) of CRC cases were attributable to nitrates, resulting in 100 cases (95%CI 25.7, 171.3) and 41 deaths (95%CI 10.5, 69.7) at a cost of 43.2 million USD (95%CI 10.9, 73.4)., Conclusion: A substantial minority of New Zealanders are exposed to high or unknown levels of nitrates in their drinking water. Given the international epidemiological studies showing an association between cancer and nitrate ingestion from drinking water, this exposure may cause an important burden of preventable CRC cases, deaths, and economic costs. We consider there is sufficient evidence to justify a review of drinking water standards. Protecting public health adds to the strong environmental arguments to improve water management in New Zealand., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Carotid blowout syndrome (CBS) is an infrequent but dangerous oncologic emergency that must be recognized due to a mortality rate that approaches 40% and neurologic morbidity that approaches 60%. Patients present with a variety of symptoms ranging from asymptomatic to frank hemorrhage, and appropriate recognition and management may improve their outcomes., Case Report: A man in his late 60s with squamous cell carcinoma of the oropharynx presented to the emergency department (ED) with hemoptysis and several episodes of post-tussive emesis with large clots. He had been cancer free for multiple years after treatment with chemotherapy and radiation to the neck. Evaluation revealed a necrotic tumor on the posterior pharynx on bedside laryngoscopy and an external carotid pseudoaneurysm that was stented by interventional radiology. The patient experienced recurrent hemorrhage several months later and opted for palliative measures and expired of massive hemorrhage in the ED on a subsequent visit. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: CBS can be fatal, and early suspicion and recognition are key to ensure that a threatened or impending carotid blowout are appropriately managed. Once carotid blowout is suspected, early resuscitation and consultation with interventional radiology and vascular surgery is warranted., (Copyright © 2021. Published by Elsevier Inc.)

Background: Studies in separate cohorts suggest possible discrepancies between inhaled medicines supplied (median 50-60%) and medicines used (median 30-40%). We performed the first study that directly compares CF medicine supply against use to identify the cost of excess medicines supply., Methods: This cross-sectional study included participants from 12 UK adult centres with ≥1 year of continuous adherence data from data-logging nebulisers. Medicine supply was measured as medication possession ratio (MPR) for a 1-year period from the first suitable supply date. Medicine use was measured as electronic data capture (EDC) adherence over the same period. The cost of excess medicines was calculated as whole excess box(es) supplied after accounting for the discrepancy between EDC adherence and MPR with 20% contingency., Results: Among 275 participants, 133 (48.4%) were females and mean age was 30 years (95% CI 29-31 years). Median EDC adherence was 57% (IQR 23-86%), median MPR was 74% (IQR 46-96%) and the discrepancy between measures was median 14% (IQR 2-29%). Even with 20% contingency, mean potential cost of excess medicines was £1,124 (95% CI £855-1,394), ranging from £183 (95% CI £29-338) for EDC adherence ≥80% to £2,017 (95% CI £1,507-2,526) for EDC adherence <50%., Conclusions: This study provides a conservative estimate of excess inhaled medicines supply cost among adults with CF in the UK. The excess supply cost was highest among those with lowest EDC adherence, highlighting the importance of adherence support and supplying medicine according to actual use. MPR provides information about medicine supply but over-estimates actual medicine use., (Copyright © 2021. Published by Elsevier B.V.)

Fixation of distal femoral fractures is often challenging due to the fracture configuration and associated poor bone quality. Dual plating (lateral and medial) has become an acceptable option to provide improved stability versus a single plate fixation. Though there are several commercially available anatomically designed plates for the lateral femoral condyle, there is no anatomic plate available in UK specifically for medial fixation of distal femur fractures. Our aim is to determine the best suited pre-contoured plate for stabilising the medial femoral condyle (MFC). Right sided femur sawbones were used to determine how well 18 different pre-contoured anatomical plates (Depuy Synthes, Leeds, UK) fit the medial femoral condyle. Some of these had variable angle (VA) option. Lift off, fit and notch penetration were assessed and recorded independently by 4 orthopaedic trauma surgeons. The number and distribution of screws in the MFC that each plate allowed was also determined. To do this the MFC was divided into quadrants: Proximal anterior (PA), distal anterior (DA), proximal posterior (PP) and distal posterior (DP). The ipsilateral anterolateral proximal tibial (VA and 4.5 mm non-VA), PHILOS, posteromedial proximal tibial and ipsilateral lateral extra-articular distal humeral plate offered good sagittal fit, less than 2 mm lift off at the condyles and no diaphyseal lift off. Plate positioning in the PA quadrant offered the best fit. The ipsilateral anterolateral proximal tibial plates (VA) and PHILOS allowed at least 4 screws to be placed in the PA and 2 in the PP quadrant with no notch penetration. The Tomofix provided good fit, but all 4 screws were in PA quadrant, with distal screws causing notch penetration. The non-VA and PHILOS plates did not offer the VA advantage. The ipsilateral anterolateral proximal tibial VA plates provided the best anatomical fit for the MFC with the greatest number of screws in the condylar quadrants with the option of variable angle screw placement., Competing Interests: Declaration of Competing Interest None of the authors have received any personal fees, or have any conflict of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Distal femoral fractures occur in patients with osteoporotic bone and also as a consequence of high energy trauma. The recognised treatment options include closed or open reduction of the fracture and fixation using a locking plate or a femoral nail. Both these fixation modalities have some drawbacks. There is a risk of metalwork failure with single lateral locking plates and limited distal fixation with intramedullary nails. Since January 2018, we started using augmented fixation of distal femoral fractures using a combination of a retrograde femoral nail and a lateral locking plate. This study compares the outcomes of single lateral femoral plating (SLP) and combined nail-plate fixation (NPF)., Methods: This is a single centre retrospective case control study including all patients who sustained distal femoral fractures (OTA 33-A2, 33-A3, 33-C, 33-V3B and 33-V3D) over the study period. Outcomes for SLP were compared to NPF. The principal outcome measure was fracture union. Secondary outcome measures were reoperation rate, mortality and post-operative weight bearing status., Results: 67 distal femoral fractures were included in the study. 19 patients had peri‑prosthetic fractures. 40 were treated by SLP, 27 were managed with NPF.  23 (58%) patients in the SLP group were given instructions to non-weight bear or Toe touch weight bear for 6 weeks post-surgery compared to 1 (4%) in the NPF group (p = 0.000004). 7 (18%) patients treated with SLP had metalwork failure due to a non-union compared to none treated with NPF (p = 0.04). 11 fractures in the SLP group failed to unite compared to no non-unions in the NPF group (p = 0.01). These differences were magnified when assessing older (>50 years old) patients., Conclusions: Augmented fixation of distal femoral fractures using a nail plate fixation provided significantly higher union and enabled early weightbearing compared to single plate fixation. We recommend nail plate fixation for the treatment of distal femoral fractures, particularly in osteoporotic fractures., Competing Interests: Declaration of Competing Interest There are no conflicts of interest (from any author) with regards to this publication. No funding was received for this project If accepted all authors agree for copyright to be transferred to the Bone and Joint journal, (Copyright © 2021. Published by Elsevier Ltd.)

Competing Interests: Declaration of interests We declare no competing interests.

A series of complexes of the type rac-cis-β-[Ru(N 4 -T L )(N 2 -bidentates)] 2+ (where N 4 -T L  = 1,6-di(2'-pyridyl)-2,5-dibenzyl-2,5-diazahexane (picenBz 2 , N 4 -T L -2) and N 2 -bidentates = 1,10-phenanthroline (phen, Ru-2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, Ru-3), 7,8-dimethyl-dipyrido[3,2-a:2',3'-c] phenazine (dppzMe 2, Ru-4), 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline (phenpyrBz, Ru-5), 2-(p-tolyl)-1H-imidazo[4,5-f][1,10]phenanthroline (phenpyrBzMe, Ru-6), 2-(4-nitrophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (phenpyrBzNO 2, Ru-7), were synthesised and characterised and X-ray crystallography of Ru-5 obtained. The in vitro cytotoxicity assays revealed that Ru-6 was 5, 2 and 19-fold more potent than oxaliplatin, cisplatin, and carboplatin, respectively displaying an average GI 50 value of ≈ 0.76 μM against a panel of 11 cancer cell lines., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To investigate associations between long-term exposure to PM 2.5 , NO 2 , mortality and morbidity in New Zealand, a country with low levels of exposure., Design: Retrospective cohort study., Setting: The New Zealand resident population., Method: The main analyses included all adults aged 30 years and over with complete data on covariates: N = 2,223,507. People who died, or were admitted to hospital, (2013-2016) were linked anonymously to the 2013 census, and to estimates of ambient PM 2.5 , and NO 2 concentration. We fitted Poisson regression models of mortality and morbidity in adults (≥30) for all natural causes of death, and by sub- group of major cause. Person-time of exposure, censored at the time of death, was included as an offset. We adjusted for confounding by age, sex, ethnicity, income, education, smoking status and ambient temperature. Further analyses stratified by ethnic group, and investigated respiratory hospital admissions in children., Results: There were statistically significant positive associations between pollutants and natural causes of death: RR (per 10 μg/m 3 ) for PM 2.5 1.11 (1.07 to 1.15) and for NO 2 1.10 (1.07 to 1.12). For morbidity, the strongest associations were for PM 2.5 and ischaemic heart disease in adults, RR: 1.29 (1.23 to 1.35) and for NO 2 and asthma in children, RR: 1.18 (1.09 to 1.28). In models restricted to specific ethnic groups, we found no consistent differences in any of the associations., Conclusions: The results for NO 2 are higher than those published previously. Other studies have reported that the dose-response for PM 2.5 may be higher at low concentrations, but less is known about NO 2 . It is possible NO 2 is acting as a proxy for other traffic-related pollutants that are causally related to health impacts. This study underlines the importance of controlling pollution caused by motor vehicles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition., Methods: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable., Results: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were predicted to induce premature protein truncation leading to a loss of PCDHGC4 function. The three detected missense variants were located in extracellular cadherin (EC) domains EC5 and EC6 of PCDHGC4, and in silico analysis of the affected residues showed that two of these substitutions were predicted to influence the Ca 2+ -binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4., Conclusion: We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans., (© 2021. The Author(s).)

Copper ion (Cu 2+ ) is an important cofactor for many enzymes in human body. Either excessive or deficient Cu 2+ in the body may cause serious dysfunctions and diseases. So sensitive determination of Cu 2+ in environmental samples is of more significance for evaluation and control of Cu 2+ intake. Based on a low-cost gold-plated coplanar electrode array, a disposable aptasensor is developed with an ultra-sensitive indicator of interfacial capacitance. Modified with a specially isolated DNA aptamer for Cu 2+ , this sensor achieves a high selectivity of 1207: 1 against non-target ions. To realize real-time response, alternating-current electrothermal effect is integrated into the capacitance measuring process to efficiently enrich the trace Cu 2+ . This sensor reaches a limit of detection of 2.97 fM, with a linear range from 5.0 fM to 50 pM. The response time is only 15 s, which can meet the real-time detection requirement. On-site test of practical samples is also realized using the disposable sensor combined with a handheld inductance/capacitance/resistance meter. This sensor with its portable test system provides a cost-efficient solution for on-site, real-time and sensitive detection of Cu 2+ , showing great application value in environment monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory., Methods: A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure., Results: A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557-0.664], p = 0.0015) and 0.516 [0.443-0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume., Conclusions: SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification., (Copyright © 2021 International Association for the Study of Lung Cancer. All rights reserved.)

Background: The SARS CoV-2 virus has caused one of the deadliest pandemics in recent history, resulting in over 170 million deaths and global economic disruption. There remains an urgent need for clinical trials to test therapies for treatment and prevention., Design: An online research platform was created to support a registry community of healthcare workers (HCWs) to understand their experiences and conduct clinical studies to address their concerns. The first study, HERO-HCQ, was a double-blind, multicenter, randomized, pragmatic trial to evaluate the superiority of hydroxychloroquine (HCQ) vs placebo for pre-exposure prophylaxis (PrEP) of COVID-19 clinical infection in HCWs. Secondary objectives were to assess the efficacy of HCQ in preventing viral shedding of COVID-19 among HCWs and to assess the safety and tolerability of HCQ., Methods: HCWs joined the Registry and were pre-screened for trial interest and eligibility. Trial participants were randomized 1:1 to receive HCQ or placebo. On-site baseline assessment included a COVID-19 nasopharyngeal PCR and blood serology test. Weekly follow-up was done via an online portal and included screening for symptoms of COVID-19, self-reported testing, adverse events, and quality of life assessments. The on-site visit was repeated at Day 30., Discussion: The HERO research platform offers an approach to rapidly engage, screen, invite and enroll into clinical studies using a novel participant-facing online portal interface and remote data collection, enabling limited onsite procedures for conduct of a pragmatic clinical trial. This platform may be an example for future clinical trials of common conditions to enable more rapid evidence generation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Peripheral artery disease (PAD) is associated with an increased risk of ischemic events following percutaneous coronary intervention (PCI). More aggressive antiplatelet therapy may mitigate this risk. The present study evaluates the efficacy of cangrelor in patients with PAD undergoing PCI., Methods and Results: This is a pooled analysis from the CHAMPION PCI, CHAMPION PLATFORM, AND CHAMPION PHOENIX trials, evaluating cangrelor versus either clopidogrel or placebo in PCI patients. The occurrence of the primary endpoint of death, myocardial infarction, or ischemia-driven revascularization (IDR) was assessed in patients with and without PAD. GUSTO severe bleeding at 48 h was also evaluated. There were 1720 (7%) patients with PAD and 22,802 (93%) without PAD. After adjustment for differences in baseline variables, PAD patients, compared with those without PAD, experienced increased odds of the primary endpoint (OR [95% CI] = 1.27 [0.91, 1.77], P = 0.16) and GUSTO severe bleeding (OR [95% CI] = 3.24 [1.28, 8.21], P = 0.01). In PAD patients, the primary endpoint was 4.7% with cangrelor vs. 7.2% with clopidogrel (OR [95% CI] = 0.64 [0.42,0.96]); in patients without PAD the primary endpoint was 3.5% with cangrelor vs. 4.2% with clopidogrel (OR [95% CI] = 0.83 [0.72,0.95]), P-interaction 0.23. Among patients with or without PAD, there was no significant difference in the rate of GUSTO severe bleeding with cangrelor compared with control, P-interaction 0.86., Conclusions: In a pooled analysis of the CHAMPION studies, PAD was associated with increased rates of ischemic and bleeding complications. Cangrelor reduced the odds of ischemic events, without increasing GUSTO severe bleeding., Clinical Trial Registration: clinicaltrials.gov identifiers: CHAMPION PCI (NCT00305162), CHAMPION PLATFORM(NCT00385138), CHAMPION PHOENIX (NCT01156571)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. J. Antonio Gutierrez discloses the following – personal fees from Janssen Pharmaceuticals. Dr. Robert A. Harrington discloses the following relationships – personal fees from Amgen Inc., Daiichi-Lilly, GILEAD Sciences, Gilead Sciences Inc., Janssen R and D, Medtronic, Merk, Novartis Corporation, The Medicines Company, Vida Health, Vox Media, and WebMD; Grants from AstraZeneca, BMS, CSL Behring, GSK, Merk, Portola, Sanofi-aventis, and The Medicines Company; ownership in Element Science and Myokardia; Advisory role in Evidint and Scandu. Dr. Gregg W. Stone discloses personal fees from Boston Scientific, InspireMD, Atrium, Daiichi-Lilly, and Astra Zeneca. Dr. Ph Gabriel Steg discloses the following relationships – Institutional research grant from Merck, Sanofi, and Servier; speaking or consulting fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, CSL-Behring, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Lilly, Merck Novartis, Pfizer, Regeneron, Sanofi, Servier, and The Medicines Company. Dr. Charles Michael Gibson discloses personal fees from The Medicines Company. Dr. Christian W. Hamm discloses the following relationships – Advisory board and speaking fees from AstraZeneca, Boehringer Ingelheim; speaking fees from Bayer, Daiichi Sankyo, Lilly, and Sanofi Aventis. Dr. Matthew J. Price reports personal fees from The Medicines Company, during the conduct of the study, AstraZeneca, Merck & Co., Accriva Diagnostics, Boston Scientific, Medtronic, and Terumo. Dr. Renato D. Lopes discloses the following relationships - Institutional research grant and consulting fees from Bristol-Myers Squibb; institutional research grant from GlaxoSmithKline; consulting fees from Bayer, Boehringer Ingleheim, Pfizer, Merck, Portola. Dr. Sergio Leonardi discloses the following relationships - Advisory Board: The Medicine Company, AstraZeneca, and Eli Lilly. Dr. Jayne Prats discloses the following relationships — was an employee of the Medicines Company at the time of the study and is a consultant for Chiesi USA. Dr. Efthymios N. Deliagyris discloses the following relationships — was an employee of the Medicines Company. Dr. Mahaffey discloses personal fees from American College of Cardiology, grants from Amgen, personal fees from AstraZeneca, personal fees from Bayer, personal fees from Boehringer Ingelheim, personal fees from Bristol Myers Squibb, personal fees from Cubist, grants from Daiichi, personal fees from Eli Lilly, personal fees from Epson, personal fees from Forest, personal fees from Glaxo Smith Kline, grants and personal fees from Johnson & Johnson, grants and personal fees from Medtronic, personal fees from Merck, personal fees from Mt. Sinai, personal fees from Myokardia, personal fees from Omthera, personal fees from Portola, personal fees from Purdue Pharma, personal fees from Spring Publishing, grants from St. Jude, grants from Tenax, personal fees from Vindico, personal fees from WebMD, outside the submitted work. Dr. White discloses grants from Sanofi-Aventis, grants from Eli Lilly, grants from National Institute of Health, grants from GSK, grants from Merck Sharpe & Dohme, grants and personal fees from AstraZeneca, outside. Dr. Deepak L. Bhatt discloses the following relationships - Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi (including for serving as co-Chair and co-PI of the CHAMPION trials), Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company (including for serving as co-Chair and co-PI of the CHAMPION trials); Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St. Jude Medical (now Abbott); Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, PLx Pharma, Takeda., (© 2021 The Authors.)

Intolerance of uncertainty (IU), the tendency to find uncertainty aversive, is an important transdiagnostic dimension in mental health disorders. Over the last decade, there has been a surge of research on the role of IU in classical threat conditioning procedures, which serve as analogues to the development, treatment, and relapse of anxiety, obsessive-compulsive, and trauma- and stressor-related disorders. This review provides an overview of the existing literature on IU in classical threat conditioning procedures. The review integrates findings based on the shared or discrete parameters of uncertainty embedded within classical threat conditioning procedures. Under periods of unexpected uncertainty, where threat and safety contingencies change, high IU, over other self-reported measures of anxiety, is specifically associated with poorer threat extinction learning and retention, as well as overgeneralisation. Under periods of estimation and expected uncertainty, where the parameters of uncertainty are being learned or have been learned, such as threat acquisition training and avoidance learning, the findings are mixed for IU. These findings provide evidence that individual differences in IU play a significant role in maintaining learned fear and anxiety, particularly under volatile environments. Recommendations for future research are outlined, with discussion focusing on how parameters of uncertainty can be better defined to capture how IU is involved in the maintenance of learned fear and anxiety. Such work will be crucial for understanding the role of IU in neurobiological models of uncertainty-based maintenance of fear and anxiety and inform translational work aiming to improve the diagnosis and treatment of relevant psychopathology., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

A critical need exists to address structural racism within academic and community medicine and surgery and determine methods that will serve to repair its long-standing effects and alleviate the associated negative consequences. Because of our broad skillset and the populations we serve, vascular surgeons are uniquely positioned to identify and address the effects of structural racism in our places of work and for the populations we treat. Our goal is to discuss the effects of racism on healthcare outcomes and provide recommendations on how to combat these through equitable practices such as the diversification of the vascular surgery workforce, inclusivity as partners and leaders, and the promotion of improved outcomes among our most vulnerable patients from racial and ethnic minority groups. It is imperative that we stand for antiracism within our field through our societies, journals, clinical trials, training programs, clinical practice groups, and leadership., (Published by Elsevier Inc.)

Abstract: Food manufacturers often use squeegees as a tool to remove condensation from overhead surfaces. This practice is done to reduce the likelihood of environmental pathogen contamination by eliminating condensed-water droplets that could fall from overhead surfaces during production. However, this practice may actually spread environmental pathogens across these surfaces, defeating its purpose and further increasing the risk for contamination in the processing area. To understand the risk associated with this common practice, test pipes inoculated with Listeria innocua ATCC 33090 were exposed to steam to produce condensation, which was then removed by squeegees. The pipe surfaces, droplets, and squeegees were subsequently analyzed for Listeria to determine the distance the organism spread across the pipe and how many organisms were transferred to the droplets and the squeegees. Results showed that Listeria traveled as far as 16 in. across the surface of the pipe, and bacterial transfer to the droplets decreased as the squeegee traveled further from the contaminated area. Sanitizers alone were able to remove about 1 to 2 log CFU of Listeria per in2 from the squeegee blades when materials were contaminated with Listeria (>6 log CFU/in2). Among the cleaning protocols evaluated, an extensive cleaning regimen was able to remove 3 to 4 log CFU/in2, which would be recommended to reduce the risk associated with environmental pathogen transfer. This study provides evidence that supports recommendations for minimizing the cross-contamination risk associated with condensation management practices., (Copyright ©, International Association for Food Protection.)

Background and Objectives: Self-reported Intolerance of Uncertainty (IU) is the tendency to find uncertainty aversive. There is a lack of empirical research on how IU modulates anticipatory responding during threatening contexts with different parameters of uncertainty., Methods: Exploratory secondary analyses were conducted on an existing data set (n = 45) to examine whether IU is related to a particular parameter of uncertainty during instructed threat of shock (i.e. certain shock, certain safety from shock, outcome uncertainty of shock, temporal uncertainty of shock)., Results: Analyses revealed that IU was associated with larger auditory startle blink during the anticipatory period for the certain safety from shock condition relative to the certain shock condition., Limitations: The sample was relatively small., Conclusions: Individuals with higher self-reported IU may be more inclined to generalize threat to safety cues in the context of instructed threat of shock., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Problem: The Edinburgh Postnatal Depression Scale (EPDS) is considered the gold standard in perinatal mental health screening and the Australian Clinical Practice Guidelines recommend universal use. However, screening rates are four times lower with Indigenous Australian women compared to non-Indigenous women. Difficulties have been reported using the EPDS in this context., Background: Evidence demonstrates the link between perinatal mental health and maternal and child outcomes. Indigenous Australian maternal and child health and wellbeing outcomes remain unacceptably poor across all measured parameters and reported psychological distress and child removal rates are increasing., Methods: A systematic literature review was conducted to assess the effectiveness, validity, reliability, and cultural safety of the EPDS in the Indigenous Australian context and identify the availability and suitability of any adaptations., Findings: The EPDS has not been validated for use with Indigenous Australian women., Discussion: The findings and limitations identified in this review are consistent with concerns in other countries about the cross-cultural use of the EPDS and its sensitivity in predicting risk for postnatal depression amongst Indigenous women. Where adaptations of the EPDS have been used there has been no psychometric and cultural validation beyond the remote communities in which they were developed., Conclusions: There is no evidence to demonstrate that the EPDS in its current form and application is suitable for screening with Indigenous Australian women. Urgent work is required to evaluate and/or develop culturally meaningful screening tools that are predictive of risk for social and emotional wellbeing and perinatal mental distress in this context., (Copyright © 2020 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate the pattern of tuberculosis (TB) care initiation and risk factors for TB diagnostic delay in The Gambia., Methods: In this cross-sectional study, adult patients diagnosed with pulmonary TB (pTB) in public facilities in the Greater Banjul Area of The Gambia were consecutively recruited from October 2016 to March 2017. Diagnostic delay was defined as >21 days from the onset of at least one symptom suggestive of pTB to diagnosis. Logistic regression analyses were used to investigate risk factors for diagnostic delay., Results: Overall, 216 pTB patients were included in the study; the median (Interquartile Range (IQR)) age was 30 (23-39) years and 167 (77%) were male patients. Of the 216 patients, 110 (50.9%) of them initiated care-seeking in the formal and informal private sector and 181/216 (83.8%) had TB diagnostic delay. The median (IQR) duration from the onset of symptoms to TB diagnosis was 34 (28-56) days. Age groups 18-29 years (aOR 3.2; 95% CI 1.2-8.8 [p = 0.02]) and 30-49 years (aOR 5.1; 95% CI 1.6-16.2 [p = 0.006]) and being employed (aOR 4.2; 95% CI 1.7-10.5 [p = 0.002]) were independent risk factors for TB diagnostic delay., Conclusion: There is considerable TB diagnostic delay in The Gambia, and this is likely to be worsened by the COVID-19 pandemic., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Individuals who score high in Intolerance of Uncertainty (IU) have a tendency to find uncertainty and the unknown aversive. However, there is a dearth of literature on the extent to which the known vs. the unknown during threatening contexts induce fear and anxiety in individuals with high IU. In the following registered report we attempted to address this question by manipulating the known and unknown in the threat of predictable and unpredictable aversive events task. Throughout the task, we measured a variety of self-report (ratings of valence and arousal) and physiological indices (skin conductance, pupil dilation, orbicularis oculi, corrugator supercilii). We collected data from 93 participants. Higher IU, relative to lower IU was associated with: (1) less discriminatory orbicularis oculi activity between cue and interstimulus interval periods across conditions, and (2) larger corrugator supercilii activity to the known predictable shock condition and smaller corrugator supercilii activity to the known unpredictable shock condition, compared to the other conditions. These findings provide evidence that IU-related biases manifest differently depending on the physiological marker of fear and anxiety and the type of known-unknown threat i.e. orbicularis oculi activity was related to generalisation across conditions, whilse corrugator supercilii activity reflected distress/relief during conditions with known threat. Ultimately, this research will inform future models of IU in relation to anxiety and stress disorders., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Individuals who score high in self-reported Intolerance of Uncertainty (IU) display difficulties updating threat associations to safe associations. Here we sought to determine whether individuals who score high in IU can learn and retain new safety associations if given more exposure. We recorded skin conductance response, pupil dilation and expectancy ratings during an associative threat learning task with acquisition, same-day extinction and next-day extinction phases. Participants (n = 144) were assigned to either a regular exposure (32 trials of same-day and next-day extinction) or extended exposure condition (48 trials of same-day and next-day extinction). We failed to replicate previous work showing that IU is associated with poorer safety-learning indexed via SCR. We found preliminary evidence for promoted safety-retention in individuals with higher Inhibitory IU in the extended exposure condition, relative to individuals with higher Inhibitory IU in the regular exposure condition, indexed via SCR. These findings further our current understanding of the role of IU in safety-learning and -retention, informing models of IU and exposure-based treatments., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)