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Breast cancer risk reduction strategies have been well-validated, but barriers remain for high-risk individuals to adopt them. We performed a study among participants with high risk of breast cancer to validate whether a virtual breast health decision tool impacted a participant's willingness to start risk-reducing activities, identify barriers to adopting these strategies, and understand if it affects breast cancer anxiety. The study sample was 318 participants in the personalized (investigational) arm of the Women Informed to Screen Depending on Measures of risk (WISDOM) clinical trial. After reviewing the tool, these participants completed a feedback survey. We demonstrated that 15 (4.7%) women were taking endocrine risk reduction, 123 (38.7%) were reducing alcohol intake, and 199 (62.6%) were exercising. In the three-month follow-up survey of 109 respondents, only 8 of 61 (13.1%) women who considered endocrine risk reduction pursued it. In contrast, 11 of 16 (68%) participants who considered alcohol reduction pursued the activity, and 14 of 24 (58%) women who considered exercise followed through. Participants listed fear of side effects as the most common barrier to endocrine risk reduction. We also present further steps to be taken to improve the effectiveness of the Breast Health Decisions tool., (© 2024. The Author(s).)

Objective: Hospital-based labor and delivery units are closing at increasing rates in the rural US, significantly impacting maternal and newborn health. The objective of this study to determine if rurality-measured as distance from the hospital-and socioeconomic status-measured as insurance payor-impact both spontaneous and medically indicated preterm birth incidence at a single rural academic institution., Methods: This was a retrospective cohort study using electronic medical records of patients with singleton pregnancies delivering at a single rural academic institution between 2016-2018. The primary outcome was preterm delivery (PTD) and secondary outcomes included low birth weight (LBW) and intensive care nursery (ICN) admission. The primary exposures included (1) travel time from a patient's address to the hospital and (2) insurance carrier as a proxy for socioeconomic status. Bivariate analyses indicated that travel time, insurance status, race, ethnicity, marital status, number of prenatal visits, gravida and para, and smoking status were significant predictors of all outcomes (LBW, ICN admission, and PTD). Therefore, these predictors were included in the multivariable logistic models., Results: Within the multivariable logistic model, patients traveling 1-1.5 hours had approximately twice the odds of PTD (Odds Ratio, OR: 2.08, 95% Confidence Interval CI, 1.32, 3.29, p = .002), birth of a LBW neonate (OR: 2.15; 95% CI: 1.29-3.58, p = .005), and infant admission to the ICN (OR 1.83, 95% CI: 1.22-2.76, p = .004) compared to patients traveling under 30 minutes,. Insurance carrier status was not associated with increased odds of PTD, LBW, or ICN admission., Conclusion: Patients living 1-to-1.5 hours from the hospital had an increased risk for LBW, ICN admission, and PTD, despite living in zip codes with less social deprivation than zip codes further away from the hospital., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Darivemula et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: -22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models., Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case-control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions., Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: -17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: -17.9% to 89.6%), and further increased to 80.9% (95% CI: -17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker., Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen., Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV., Competing Interests: Declaration of interests TvdK has a patent application with Johnson & Johnson and has stocks in Johnson & Johnson. BK received internal support for the present manuscript from her employer (Los Alamos National Laboratory). In the past 36 months, she received support for attending meetings and/or travel from NIH NIAID and from the Gates foundation. Her institution (LANL) had a patent on this work, although she did not receive any personal funds through this patent and was not involved with the licensing of the design to Johnson & Johnson. DHB has a patent on the mosaic HIV vaccine, but no royalties. FT was an employee of Janssen/Johnson & Johnson at the time the work was conducted and owns stock in Johnson & Johnson. LL received support from Janssen Infectious Diseases BV, Beerse, Belgium for travel expenses to attend HIV conferences and has stock or stock options in Johnson & Johnson. JvD, MGP, WW, TvdK and JHen are employees of Janssen/Johnson & Johnson and hold stock or stock options in Johnson & Johnson. WW has a patent planned, issued, or pending with Johnson & Johnson. SCDR had contracts in the past 36 months to perform immunogenicity testing for Janssen, Sanofi, and Moderna. HS and DJS were employees of Janssen Vaccines & Prevention BV and had stock and/or stock options in Johnson & Johnson at the time the work was conducted. SN was an employee of Janssen Infectious Diseases BV and had stock and/or stock options in Johnson & Johnson at the time the work was conducted. LP was an employee of Janssen Vaccines & Prevention BV at the time the work was conducted. GDT has received consulting fees for a scientific consulting session. All other authors have no potential competing interests to disclose. Funding for the Imbokodo Study and Correlates Group is the same as listed in “Acknowledgments” for the current work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To describe the unique challenges faced by rural pregnant women with intersecting substance use disorder (SUD) and unmet social needs., Design: Secondary qualitative data analysis with an analytic expansion approach., Setting: Hospital system in northern New England., Participants: Four rural women with food insecurity who were in recovery for SUD (three were pregnant and one had given birth in the past 15 weeks)., Methods: In the primary qualitative descriptive study, we interviewed 14 women about their experience of food insecurity during the perinatal period, including facilitators and barriers to being screened and accessing referrals for food insecurity and other social needs during prenatal care. This secondary analysis centered on the perspectives of four participants who reflected specifically on receiving material and mental health support through the integration of prenatal care and SUD treatment., Results: Rural women with SUD who experience social needs during pregnancy have difficulty accessing appropriate prenatal care and maintaining treatment engagement due to intersecting factors (e.g., food and housing insecurity and transportation) and psychological (e.g., mental health challenges, social isolation, and stigma) factors. Participants emphasized the importance of integrating social support within prenatal and substance use care to promote physical and mental health and engagement in SUD treatment., Conclusion: In line with The Joint Commission's 2022 policy recommendations for universal social determinants of health screening, we support one-stop clinical and social care for pregnant women who face intersecting barriers to health, such as SUD and unmet social needs. Nurses can play an important role in care coordination for people with complex medical and social determinants of health screening needs. This approach is especially relevant to rural areas, where food, housing, and transportation insecurity rates are greater than nonrural areas., Competing Interests: Conflict of Interest The authors report no conflicts of interest or relevant financial relationships., (Copyright © 2024 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Aim: To study COVID-19 vaccination status in kidney transplant recipients (KTRs), reasons for incomplete vaccination and the clinical impact of vaccination on patient outcomes., Methods: A single-centre retrospective analysis of KTR (n = 543) conducted between 1970 and December 2022. Data included baseline demographics, number of vaccinations, reason for incomplete vaccination and patient outcomes following COVID-19 infection. A completed course of COVID-19 vaccination was defined as four or more vaccine doses., Exclusion Criteria: those deceased prior December 2019, managed by another health service, failed graft, or deceased secondary to non-COVID cause., Results: 273 of 543 patients met inclusion criteria. Mean age was 58.1 ± 12.2 years, 66% were male. 58.2% of patients were fully vaccinated, 22.7% received three doses, 7.7% received two doses, 0.7% received one dose, 0.7% received zero doses, and 10% incomplete records. The most common reasons for incomplete vaccination were COVID-19 infection, concern for side effects, and patient unawareness of booster recommendations. Vaccination uptake was greater in Australian born patients compared with those born overseas, odds ratio 0.40 (95% CI 0.23-0.69). KTR with incomplete vaccination had poorer outcomes, higher rate of AKI, long COVID, and increased hospitalization., Conclusion: The majority of KTR were fully vaccinated. KTR with incomplete vaccination status had poorer outcomes with COVID-19 infection and other issues. Patient education is a major area for improvement targeting patients born overseas and better information regarding side effects. Potential interventions need to address improved communication, cultural relevancy, and language., (© 2024 Asian Pacific Society of Nephrology.)

In order to advance our understanding of precancers in the pancreas, 69 pancreatic intraductal papillary neoplasms (IPNs), including 64 intraductal papillary mucinous neoplasms (IPMNs) and 5 intraductal oncocytic papillary neoplasms (IOPNs), 32 pancreatic cyst fluid samples, 104 invasive pancreatic ductal adenocarcinomas (PDACs), 43 normal adjacent tissues (NATs), and 76 macro-dissected normal pancreatic ducts (NDs) were analyzed by mass spectrometry. A total of 10,246 proteins and 22,284 glycopeptides were identified in all tissue samples, and 756 proteins with more than 1.5-fold increase in abundance in IPMNs relative to NDs were identified, 45% of which were also identified in cyst fluids. The over-expression of selected proteins was validated by immunolabeling. Proteins and glycoproteins overexpressed in IPMNs included those involved in glycan biosynthesis and the immune system. In addition, multiomics clustering identified two subtypes of IPMNs. This study provides a foundation for understanding tumor progression and targets for earlier detection and therapies., Significance: This multilevel characterization of intraductal papillary neoplasms of the pancreas provides a foundation for understanding the changes in protein and glycoprotein expression during the progression from normal duct to intraductal papillary neoplasm, and to invasive pancreatic carcinoma, providing a foundation for informed approaches to earlier detection and treatment.

Background: Human papillomavirus (HPV) status plays a major role in predicting oropharyngeal squamous cell carcinoma (OPSCC) survival. This study assesses the accuracy of a fully automated 3D convolutional neural network (CNN) in predicting HPV status using CT images., Methods: Pretreatment CT images from OPSCC patients were used to train a 3D DenseNet-121 model to predict HPV-p16 status. Performance was evaluated by the ROC Curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score., Results: The network achieved a mean AUC of 0.80 ± 0.06. The best-preforming fold had a sensitivity of 0.86 and specificity of 0.92 at the Youden's index. The PPV, NPV, and F1 scores are 0.97, 0.71, and 0.82, respectively., Conclusions: A fully automated CNN can characterize the HPV status of OPSCC patients with high sensitivity and specificity. Further refinement of this algorithm has the potential to provide a non-invasive tool to guide clinical management., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing, yet it protected mice and cynomolgus macaques from severe disease. The mechanisms of NTD non-neutralizing antibody-mediated protection are unknown. Here we show that Fc effector functions mediate NTD non-neutralizing antibody (non-nAb) protection against SARS-CoV-2 MA10 viral challenge in mice. Though non-nAb prophylactic infusion did not suppress infectious viral titers in the lung as potently as neutralizing antibody (nAb) infusion, disease markers including gross lung discoloration were similar in nAb and non-nAb groups. Fc functional knockout substitutions abolished non-nAb protection and increased viral titers in the nAb group. Fc enhancement increased non-nAb protection relative to WT, supporting a positive association between Fc functionality and degree of protection from SARS-CoV-2 infection. For therapeutic administration of antibodies, non-nAb effector functions contributed to virus suppression and lessening of lung discoloration, but the presence of neutralization was required for optimal protection from disease. This study demonstrates that non-nAbs can utilize Fc-mediated mechanisms to lower viral load and prevent lung damage due to coronavirus infection., Competing Interests: KOS, DL, and BFH have patents related to the antibodies described in this manuscript., (Copyright: © 2024 Pierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The application of artificial intelligence (AI) systems in ophthalmology is rapidly expanding. Early detection and management of keratoconus is important for preventing disease progression and the need for corneal transplant. We review studies regarding the utility of AI in the diagnosis and management of keratoconus and other corneal ectasias., Methods: We conducted a systematic search for relevant original, English-language research studies in the PubMed, Web of Science, Embase, and Cochrane databases from inception to October 31, 2023, using a combination of the following keywords: artificial intelligence, deep learning, machine learning, keratoconus, and corneal ectasia. Case reports, literature reviews, conference proceedings, and editorials were excluded. We extracted the following data from each eligible study: type of AI, input used for training, output, ground truth or reference, dataset size, availability of algorithm/model, availability of dataset, and major study findings., Results: Ninety-three original research studies were included in this review, with the date of publication ranging from 1994 to 2023. The majority of studies were regarding the use of AI in detecting keratoconus or subclinical keratoconus (n=61). Among studies regarding keratoconus diagnosis, the most common inputs were corneal topography, Scheimpflug-based corneal tomography, and anterior segment-optical coherence tomography. This review also summarized 16 original research studies regarding AI-based assessment of severity and clinical features, 7 studies regarding the prediction of disease progression, and 6 studies regarding the characterization of treatment response. There were only three studies regarding the use of AI in identifying susceptibility genes involved in the etiology and pathogenesis of keratoconus., Discussion: Algorithms trained on Scheimpflug-based tomography seem promising tools for the early diagnosis of keratoconus that can be particularly applied in low-resource communities. Future studies could investigate the application of AI models trained on multimodal patient information for staging keratoconus severity and tracking disease progression., 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 © 2024 Goodman and Zhu.)

Objectives: Phenobarbital (PB) is a long-acting GABA A-agonist with favorable pharmacokinetics (long half-life and duration of effect) that allows effective treatment of alcohol withdrawal (AW) after administration of a single loading dose. Current evidence suggests that in the setting of AW, PB administration may be associated with decreased hospital admissions and hospital length of stay. The aim of this study was to evaluate the safety outcomes of AW patients who were treated and discharged from the emergency department (ED) after receiving PB for AW., Methods: This retrospective chart review included a convenience sample of 33 AW patients who presented to four EDs within an 18-month span. Descriptive statistics (frequencies and percentages) were used to describe demographics, distribution of resources and referrals, and the safety outcomes of PB administration for low-risk AW patients. Patients were selected for inclusion in consultation with a medical toxicologist, treated with PB, and discharged from the ED. Electronic medical records were utilized to gather information on the patient cohort., Results: All patients were treated with at least a single loading dose of 5‒10 mg/kg (ideal body weight) of intravenous or per os PB during their ED stay. Only one patient had an unanticipated event after discharge, which was related to driving against advice. Two additional patients had ED revisits for recurrent alcohol use within 72 h, and 16 patients had recurrent alcohol use within 30 days. All 33 patients were provided with resources for linkage to treatment. None required hospital admission., Conclusion: ED PB "load and go" may be a safe, effective AW treatment that could help treat AW, facilitate linkage to specific rehabilitation treatments, and decrease hospital admissions., Competing Interests: The authors declare they have no conflicts of interest., (© 2024 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Background: Health care providers are a key source of reports of infants to child welfare related to birthing people's substance use. Many of these reports are overreports, or reports that exceed what is legally mandated, and reflect racial bias. We developed and evaluated a webinar for health professionals to address overreporting related to birthing people's substance use., Methods: This evaluation study collected data from health professionals registering to participate in a professional education webinar about pregnancy, substance use, and child welfare reporting. It collected baseline data upon webinar registration, immediate post-webinar data, and 6 month follow-up data. Differences in both pre-post-and 6 month follow-up data were used to examine changes from before to after the webinars in beliefs, attitudes, and practices related to pregnant and birthing people who use drugs and child welfare reporting., Results: 592 nurses, social workers, physicians, public health professionals, and other health professionals completed the baseline survey. More than half of those completing the baseline survey (n = 307, 52%) completed one or both follow-up surveys. We observed statistically significant changes in five of the eleven opioid attitudes/beliefs and in four of the nine child welfare attitudes/beliefs from baseline to follow-ups, and few changes in "control statements," i.e. beliefs we did not expect to change based on webinar participation. All of the changes were in the direction of less support for child welfare reporting. In particular, the proportion agreeing with the main evaluation outcome of "I would rather err on the side of overreporting to child welfare than underreporting to child welfare" decreased from 41% at baseline to 28% and 31% post-webinar and at 6-month follow up (p = 0.001). In addition, fewer participants endorsed reporting everyone at the 6 month follow-up than at baseline (12% to 22%) and more participants endorsed reporting no one at the 6-month follow-up than at baseline (28% to 18%), p = 0.013., Conclusions: Webinars on the legal, scientific, and ethical aspects of reporting that are co-developed with people with lived experience may be a path to reducing health professional overreporting to child welfare related to birthing people's substance use., (© 2024. The Author(s).)

Competing Interests: Competing interests: None declared.

A recent article in the BJD postulated that it may be "Time to reconsider skin cancer-related follow-up visits". In our unit, we too have been seeing too many patient's unnecessarily and we put in place measures to reduce the numbers of outpatient appointments thereby diverting the resources saved into professional development., Competing Interests: None to declare., (© 2024 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Purpose: Long-term patient satisfaction may influence patients' perspectives of the quality of care and their relationship with their providers. This is a follow up to a comparative effectiveness study investigating oral to intravenous sedation (OIV study). The OIV study found that oral sedation was noninferior in patient satisfaction to standard intravenous (IV) sedation for anterior segment and vitreoretinal surgeries. This study aims to determine if patient satisfaction with oral sedation remained noninferior long term., Patients and Methods: Patients were re-interviewed using the same satisfaction survey given during the OIV study. Statistical analysis involved t-tests for noninferiority of the long-term mean satisfaction score of oral and IV sedation. We also compared the original mean satisfaction score and the follow-up mean satisfaction score for each type of sedation and for both groups combined., Results: Participants were interviewed at a median of 1225.5 days (range 754-1675 days) from their surgery. The original mean satisfaction score was 5.26 ± 0.79 for the oral treatment group (n = 52) and 5.27 ± 0.64 for the intravenous treatment group (n = 46), demonstrating noninferiority with a difference in mean satisfaction score of 0.015 (p < 0.0001). The follow-up mean satisfaction score was 5.23 ± 0.90 for oral sedation and 5.60 ± 0.61 for IV sedation, with a difference in the mean satisfaction score of 0.371 (p = 0.2071). Satisfaction scores did not differ between the original mean satisfaction score and the follow-up mean satisfaction score for the oral treatment group alone (p = 0.8367), but scores in the intravenous treatment group increased longitudinally (p = 0.0004)., Conclusion: In this study, long-term patient satisfaction with oral sedation was not noninferior to satisfaction with IV sedation, unlike our findings with short-term patient satisfaction in our original study. Patient satisfaction also remained unchanged over time for the oral treatment group, but patients in the intravenous treatment group reported higher long-term satisfaction with their anesthesia experience compared to the immediate post-operative period., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Prasad et al.)

Adoptive T cell therapies have produced exceptional responses in a subset of patients with cancer. However, therapeutic efficacy can be hindered by poor T cell persistence and function 1 . In human T cell cancers, evolution of the disease positively selects for mutations that improve fitness of T cells in challenging situations analogous to those faced by therapeutic T cells. Therefore, we reasoned that these mutations could be co-opted to improve T cell therapies. Here we systematically screened the effects of 71 mutations from T cell neoplasms on T cell signalling, cytokine production and in vivo persistence in tumours. We identify a gene fusion, CARD11-PIK3R3, found in a CD4 + cutaneous T cell lymphoma 2 , that augments CARD11-BCL10-MALT1 complex signalling and anti-tumour efficacy of therapeutic T cells in several immunotherapy-refractory models in an antigen-dependent manner. Underscoring its potential to be deployed safely, CARD11-PIK3R3-expressing cells were followed up to 418 days after T cell transfer in vivo without evidence of malignant transformation. Collectively, our results indicate that exploiting naturally occurring mutations represents a promising approach to explore the extremes of T cell biology and discover how solutions derived from evolution of malignant T cells can improve a broad range of T cell therapies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The current US addiction treatment system does not effectively meet the needs of pregnant and parenting women with substance use disorder (SUD). The aim of this research was to identify barriers and facilitators to engagement and retention in SUD residential treatment for pregnant and parenting women. This research was part of a co-design process to collaboratively create a more patient-centered long-term residential program., Design and Methods: The study conducted semi-structured individual interviews with both parenting women with lived experience (WWLE) in residential SUD treatment and SUD treatment providers. Interviews aimed to elicit participants' experiences either receiving or providing care. The study team analyzed data in NVivo-12 using a deductive codebook based on the six principles of trauma informed care (TIC)., Results: We conducted a total of 32 interviews (WWLE =13, SUD providers =19). The study identified four major themes: 1) peer relationships provide inspiration and diminish shame; 2) providing individuals safe space to stumble in recovery creates opportunities for growth and builds self-efficacy; 3) reasonable, clear boundaries create a structured, protective environment for early recovery; 4) nonjudgmental connections facilitate engagement and build trust. We identified small pivotal moments along the continuum of care that showed how the elements in the four themes enhanced engagement and retention in treatment. These interactions, along the care continuum, are either structural (workflow process) or relational (interpersonal)., Conclusion: This research increases understanding of the interplay of the structural and relational barriers and facilitators to engagement and retention in treatment. These seemingly minor positive or negative interactions along the care continuum are pivotal to fully operationalizing TIC and optimizing women's engagement in treatment. Improvement strategies that integrate the voices of WWLE and collaboratively co-design a more patient-centered system are critical steps to improving engagement in SUD treatment and more equitable SUD treatment services., Competing Interests: Declaration of competing interest None to Declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pregnant and parenting women have low engagement and poor retention in substance use disorder (SUD) treatment. The aim of this study was to analyse the implementation of an adapted experience-based codesign (EBCD) process involving SUD treatment staff and pregnant or parenting women with lived experience (WWLE) of SUD to launch a residential treatment service where women could coreside with their children and receive long term comprehensive treatment for dual diagnosis of SUD and mental illness., Methods: A process evaluation was conducted utilising five data sources: two sets of semistructured interviews with WWLE and SUD treatment staff, ethnographic observation and transcripts from group events, and meeting minutes. Based on the Integrated Promoting Action on Research in Health Services framework constructs (context, recipients, facilitation, innovation) researchers applied thematic analysis to determine main themes within each construct., Results: The full sample across the implementation totalled 34 individuals (WWLE = 13 and SUD staff = 21). The EBCD process engaged both cohorts and supported group cohesion and collaborative brainstorming. WWLE felt respected, emotionally safe to share, and empowered by participation. A cohesive, multidisciplinary codesign planning group, inclusive of WWLE, supported a more equitable codesign process. The need for a virtual platform due to the COVID-19 pandemic impeded human connection and relationship building. The complex environment of residential regulations and uncertainties during start-up phase of an organisation presented implementation challenges., Conclusion: These results highlight the feasibility of, and challenges to, effectively engaging WWLE in a codesign process. The findings also demonstrated a positive influence on WWLE's feelings of empowerment. Identified themes reinforce the purposeful components within EBCD that enhance participation, along with new insights to inform successful codesign with a vulnerable population. The author's team included a WWLE who collaborated throughout the full scope of the research process, enriching the overall research and ensuring the authenticity of the presentation of women in recovery's perspective. Utilising the codesign approach to design and implement new services should improve health equity by enhancing patient engagement and retention in care., Patient Contribution: Parenting WWLE of residential SUD treatment were involved in the full scope of the research process and the implementation being evaluated. For the actual codesign work WWLE were key members of the codesign planning team that met weekly throughout the implementation to plan, implement, problem solve and adapt the process over an 18 month timeframe. As is appropriate for codesign the actual ongoing workgroup participants had average 50% WWLE participation. For the research team, this research is a culmination of the lead author's doctoral dissertation. One member of the five-person dissertation committee was a recovery coach and a WWLE. She was an active participant across the entire research process overseeing and influencing the research design, conduct of the study, analysis, interpretation of findings and approval of the final manuscript. The findings were member checked with the larger codesign planning group that had additional WWLE members., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

The Tumor Combination Guide was created at the request of the U. S. Food and Drug Administration (FDA) by a Working Group of biopharmaceutical experts from international societies of toxicologic pathology, the Food and Drug Administration (FDA), and members of the Standard for Exchange of Nonclinical Data (SEND) initiative, to assist pharmacology/toxicology reviewers and biostatisticians in statistical analysis of nonclinical tumor data. The guide will also be useful to study and peer review pathologists in interpreting the tumor data. This guide provides a higher-level hierarchy of tumor types or categories correlating the tumor names from the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) publications with those available in the NEOPLASM controlled terminology (CT) code list in SEND. The version of CT used in a study should be referenced in the nonclinical study data reviewer's guide (SDRG) (section 3.1) of electronic submissions to the FDA. The tumor combination guide instructions and examples are in a tabular format to make informed decisions for combining tumor data for statistical analysis. The strategy for combining tumor types for statistical analysis is based on scientific criteria gleaned from the current scientific literature; as SEND and INHAND terminology and information evolve, this guide will be updated., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Metabolic syndrome (MetS) is defined by clustering of cardiometabolic components, which may be present in different combinations. The authors evaluated clustering in individuals and extended families within and across ancestry groups., Methods: The prevalence of different combinations of MetS components (high fasting glucose, low high-density lipoprotein cholesterol, high triglycerides, high blood pressure, and abdominal obesity) was estimated in 1651 individuals (340 families) self-reporting as European American (EA), Hispanic/Mexican American (MA), African American (AA), and Japanese American (JA). Odds ratios were estimated using logistic regression with generalized estimating equations comparing individual MetS components, number, and combinations of components for each ancestry group versus EA., Results: Clustering of all five components (Combination #16) was more prevalent in EA (29.9%) and MA (25.2%) individuals than in AA (18.7%) and JA (15.5%) individuals. Compared with EA individuals, AA individuals were 64% and 66% less likely to have high triglycerides and low high-density lipoprotein cholesterol, whereas JA individuals were 85% and 56% less likely to have abdominal obesity and high blood pressure, respectively. Compared with EA individuals, the odds of having two, four, or five components were at least 77% lower in JA individuals, whereas the odds of having three, four, or five components were at least 3.79 times greater in MA individuals., Conclusions: Understanding heterogeneity in MetS clustering may identify factors important in reducing health disparities., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Abstract: Pregnant and parenting people with substance use disorders are a highly stigmatized group. Structural and interpersonal bias contribute to reluctance to engage in prenatal, postpartum, and well-child care for this population. Two studies described in this issue of the Journal of Addiction Medicine explore the implications of health care provider-family relationships on experience of care for birthing people with substance use disorders and their infants. Patient voices describe how intensive monitoring of infants for sequelae of substance exposure and that being scrutinized as caregivers undermined their confidence as parents, contributed to self-blame, and damaged their trust in health care teams. Data from these studies suggest that the voices of pregnant and parenting individuals need to be present at local, regional, and national levels to mitigate harm when redesigning programs for this population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P<0.001), indicating that a combination of Fc-FcR parameters contribute to overall inter-species functional differences. These data strongly support the importance of multi-parameter analyses of Fc-FcR NK-mediated functions when evaluating efficacy of passive and active immunizations in pre- and clinical trials and identifying correlates of protection. The results also suggest that pre-screening animals for multiple FcR-mediated NK function would ensure even distribution of animals among treatment groups in future preclinical trials., 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 © 2023 Tuyishime, Spreng, Hueber, Nohara, Goodman, Chan, Barfield, Beck, Jha, Asdell, Wiehe, He, Easterhoff, Conley, Hoxie, Gurley, Jones, Adhikary, Villinger, Thomas, Denny, Moody, Tomaras, Pollara, Reeves and Ferrari.)

Background: Human papillomavirus (HPV) status influences prognosis in oropharyngeal cancer (OPC). Identifying high-risk patients are critical to improving treatment. We aim to provide a noninvasive opportunity for managing OPC patients by training multiple machine learning pipelines to determine the best model for characterizing HPV status and survival., Methods: Multi-parametric algorithms were designed using a 492 OPC patient database. HPV status incorporated age, sex, smoking/drinking habits, cancer subsite, TNM, and AJCC 7th edition staging. Survival considered HPV model inputs plus HPV status. Patients were split 4:1 training: testing. Algorithm efficacy was assessed through accuracy and area under the receiver operator characteristic curve (AUC)., Results: From 31 HPV status models, ensemble yielded 0.83 AUC and 78.7% accuracy. From 38 survival models, ensemble yielded 0.91 AUC and 87.7% accuracy., Conclusion: Results reinforce artificial intelligence's potential to use tumor imaging and patient characterizations for HPV status and outcome prediction. Utilizing these algorithms can optimize clinical guidance and patient care noninvasively., (© 2023 Wiley Periodicals LLC.)

Background: Breast density is an important risk factor for breast cancer and is known to be associated with characteristics such as age, race, and hormone levels; however, it is unclear what factors contribute to changes in breast density in postmenopausal women over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and facilitate potential strategies for prevention., Methods: This study investigated potential associations between personal factors and changes in mammographic density in a cohort of 3,392 postmenopausal women with no personal history of breast cancer between 2011 and 2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and breast imaging reporting and database system (BI-RADS) mammographic density scores were obtained from electronic medical records. Factors associated with a longitudinal increase or decrease in mammographic density were identified using Fisher's exact test and multivariate conditional logistic regression., Results: 7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were correlated with age, race/ethnicity, and age at menopause in the univariate analysis. In the multivariate analysis, Asian women were more likely to exhibit a longitudinal increase in mammographic density and less likely to exhibit a decrease compared to White women. On the other hand, obese women were less likely to exhibit an increase and more likely to exhibit a decrease compared to normal weight women. Women who underwent menopause at age 55 years or older were less likely to exhibit a decrease in mammographic density compared to women who underwent menopause at a younger age. Besides obesity, lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density., Conclusions: The associations we observed between Asian race/obesity and longitudinal changes in BI-RADS density in postmenopausal women are paradoxical in that breast cancer risk is lower in Asian women and higher in obese women. However, the association between later age at menopause and a decreased likelihood of decreasing in BI-RADS density over time is consistent with later age at menopause being a risk factor for breast cancer and suggests a potential relationship between greater cumulative lifetime estrogen exposure and relative stability in breast density after menopause. Our findings support the complexity of the relationships between breast density, BMI, hormone exposure, and breast cancer risk., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Hannah Lui Park et al.)

Objective: To assess whether prevalence of treatment for ADHD varies by location of mental healthcare among US college students aged 18 to 25 with professionally diagnosed ADHD., Method: Our analysis uses cross-sectional data from the National College Health Assessment (NCHA) and evaluated the relationship between types of care received and location of mental health services received in the past year (dichotomized into "use of any on-campus services" and "use of off-campus services only"). We generated unadjusted and adjusted logistic regression models of each type of treatment., Results: Students who reported receiving mental healthcare on campus were less likely to receive any medication (aOR 0.66, 95% CI [0.60, 0.72]), any therapy (aOR 0.82, 95% CI [0.75, 0.89]), and any medication or therapy for ADHD (aOR 0.63, 95% CI [0.57, 0.70])., Conclusion: Future research should evaluate the causes of lower prevalence of ADHD treatment among students receiving mental healthcare from campus-based clinics.

Objective: To describe the experience of food insecurity and food access among women in northern New England during the perinatal period., Design: Qualitative descriptive., Setting: Hospital system in northern New England., Participants: Twelve pregnant women and two women who gave birth., Methods: We interviewed participants during pregnancy and the postpartum period about their experiences of food insecurity, including screening, their willingness and ability to access food programs, and the extent to which their food needs were met through referrals. We analyzed interview transcripts to identify themes related to participants' experiences of food insecurity; food support, including screening and referral; and opportunities for improvement in current food support interventions., Results: Most participants accepted being screened for food insecurity and were satisfied with the food distributed in their perinatal care settings. Food insecurity consistently occurred alongside general financial strain, housing insecurity, and transportation needs, which affirmed the interconnectedness of social determinants of health. Other co-occurring risks included intimate partner violence, substance use, and mental health challenges. Food receipt was facilitated by care team members who were knowledgeable about food distribution programs. Barriers to food receipt included challenges with enrolling in public assistance programs, poor awareness among participants of available resources, the persistence and unpredictability of food insecurity, and stigma. We identified three distinct themes that described participants' experiences with food insecurity during pregnancy and the postpartum period: Experience of Being Screened for Food Insecurity, Intersecting Social Needs, and Experience of Accessing Resources., Conclusion: These findings can be used to inform comprehensive food support programs that reflect the needs and values of women during the perinatal period. Interventions to screen and intervene for food insecurity during and after pregnancy align with the quality standards of The Joint Commission and should be integrated into nursing practice., Competing Interests: Conflict of Interest The authors report no conflicts of interest or relevant financial relationships., (Copyright © 2023 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Background: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF., Methods: BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488)., Findings: Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48)., Interpretation: Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation., Funding: Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter., Competing Interests: Declaration of interests MGC has received research support from Baxter Healthcare, the manufacturer of Plasma-Lyte 148, via a Baxter Investigator-Initiated Research grant that provided fluids for the BEST-Fluids trial (commercial value of US$36 270). DWJ has received consultancy fees, research grants, speaker's honoraria, and travel sponsorships from Baxter Healthcare and Fresenius Medical Care; consultancy fees from AstraZeneca and AWAK; speaker's honoraria and travel sponsorships from ONO; and travel sponsorships from Amgen. DR, LEH, LAV, EMP, CK, and JV are employees of the sponsor, The University of Queensland. KBD's salary was funded by a Better Evidence and Translation in Chronic Kidney Disease (BEAT-CKD) grant' and she is an employee of the ANZDATA Registry. PAC is the Deputy Executive Officer of the ANZDATA Registry. CMH has received fees for research committee activities from Janssen and GlaxoSmithKline paid to her institution; personal fees from Otsuka; research grants from Fresenius, Shire, and PKD Australia outside the submitted work; and research grants from Baxter and the National Health and Medical Research Council of Australia related to the current project. LW works in the Department of Anaesthesia at Austin Health, which has received funding from Baxter Healthcare for investigator-initiated clinical research. PFM has received honoraria for presentations on behalf of AstraZeneca and consultancy fees from Vifor. LW has received honoraria from Baxter Healthcare for consulting activities. All LW's fluid-related research, including study design, execution, data collection, analysis, and reporting, has been conducted independently of Baxter Healthcare and other commercial entities. ZHE has received consultancy fees and travel sponsorships from AstraZeneca. WHL has received honoraria from Alexion and education or research grants from Astellas. SJC has received research support, travel support, speaker fees, or honoraria from AstraZeneca, Bayer, CSL-Behring, Novartis, and Takeda. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Children with bronchopulmonary dysplasia (BPD) who require invasive home mechanical ventilation (IHMV) are medically vulnerable and experience high caregiving and healthcare costs. Predictors for duration of IHMV in children with BPD remain unclear, which can make prognostication and decision-making challenging., Methods: A retrospective cohort study of children with BPD requiring IHMV was conducted from independent children's hospital records (2005-2021). The primary outcome was IHMV duration, defined as time from initial discharge home on IHMV until cessation of positive pressure ventilation (day and night). Two new variables were included: discharge age corrected for tracheostomy (DACT) (chronological age at discharge minus age at tracheostomy) and level of ventilator support at discharge (minute ventilation per kg per day). Univariable Cox regression was performed with variables of interest compared to IHMV duration. Significant nonlinear factors (p < 0.05) were included in the multivariable analysis., Results: One-hundred-and-nineteen patients used IHMV primarily for BPD. Patient median index hospitalization lasted 12 months (interquartile range [IQR] 8.0,14.4). Once home, half of the patients were weaned off IHMV by 36.0 months and 90% by 52.2 months. Being Hispanic/Latinx ethnicity (hazard ratio [HR] 0.14 (95% confidence interval [CI] 0.04, 0.53), p < 0.01) and having a higher DACT were associated with increased IHMV duration (HR 0.66 (CI 0.43, 0.98), p < 0.05)., Conclusions: Disparity in IHMV duration exists among patients using IHMV after prematurity. Prospective multisite studies that further investigate new analytic variables, such as DACT and level of ventilator support, and address standardization of IHMV care are needed to create more equitable IHMV management strategies., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Animal and epidemiologic studies suggest that there may be adverse health effects from exposure to glyphosate, the most highly used pesticide in the world, and its metabolite aminomethylphosphonic acid (AMPA). Meanwhile, consumption of organic foods (presumably grown free of chemical pesticides) has increased in recent years. However, there have been limited biomonitoring studies assessing the levels of human glyphosate and AMPA exposure in the United States. We examined urinary levels of glyphosate and AMPA in the context of organic eating behavior in a cohort of healthy postmenopausal women residing in Southern California and evaluated associations with demographics, dietary intake, and other lifestyle factors. 338 women provided two first-morning urine samples and at least one paired 24-h dietary recall reporting the previous day's dietary intake. Urinary glyphosate and AMPA were measured using LC-MS/MS. Participants reported on demographic and lifestyle factors via questionnaires. Potential associations were examined between these factors and urinary glyphosate and AMPA concentrations. Glyphosate was detected in 89.9% of urine samples and AMPA in 67.2%. 37.9% of study participants reported often or always eating organic food, 30.2% sometimes, and 32.0% seldom or never. Frequency of organic food consumption was associated with several demographic and lifestyle factors. Frequent organic eaters had significantly lower urinary glyphosate and AMPA levels, but not after adjustment for covariates. Grain consumption was significantly associated with higher urinary glyphosate levels, even among women who reported often or always eating organic grains. Soy protein and alcohol consumption as well as high frequency of eating fast food were associated with higher urinary AMPA levels. In conclusion, in the largest study to date examining paired dietary recall data and measurements of first-void urinary glyphosate and AMPA, the vast majority of subjects sampled had detectable levels, and significant dietary sources in the American diet were identified., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier GmbH.)

Objective: The aim of this study was to determine the discharge destinations and associated patient-specific factors among patients hospitalized with COVID-19., Design: A retrospective cohort study was carried out at a single-site tertiary acute care hospital., Results: Among 2872 patients, discharge destination included home without services ( n = 2044, 71.2%), home with services ( n = 379, 13.2%), skilled nursing facility (117, 4.1%), long-term acute care hospital ( n = 39, 1.3%), inpatient rehabilitation facility ( n = 97, 3.4%), acute care facility ( n = 23, 0.8%), hospice services ( n = 20, 0.7%), or deceased during hospitalization ( n = 153, 5.3%). Adjusting by covariates, patients had higher odds of discharge to a rehabilitation facility (skilled nursing facility, long-term acute care hospital, or inpatient rehabilitation facility) than home (with or without services) when they were older (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.80-3.11; P < 0.001), had a higher Charlson Comorbidity Index score (3-6: OR, 2.36; 95% CI, 1.34-4.15; P = 0.003; ≥7: OR, 2.76; 95% CI, 1.56-4.86; P < 0.001), were intubated or required critical care (OR, 2.15; 95% CI, 1.48-3.13; P < 0.001), or had a longer hospitalization (3-7 days: OR, 12.48; 95% CI, 3.77-41.32; P < 0.001; 7-14 days: OR, 28.14; 95% CI, 8.57-92.43; P < 0.001). Patients were less likely to be discharged to a rehabilitation facility if they received remdesivir (OR, 0.44; 95% CI, 0.31-0.64; P < 0.001)., Conclusions: Patient-specific factors associated with COVID-19 hospitalization should be considered by physicians when prognosticating patient rehabilitation., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Through case studies of two early nineteenth-century French geologists, this article shows how relations of family and friendship were integral to determining where science took place. Digging up the traces of what I call the "affective geographies" of individual scientists that are entangled with their intellectual itineraries, I show how the practice of science is embedded in such affective relations and thus in everyday life.

The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% vaccine efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates of decreased infection risk. New strategies to increase magnitude and durability of protective immunity are critically needed. The RV305 HIV-1 clinical trial evaluated the immunological impact of a follow-up boost of HIV-1-uninfected RV144 recipients after 6-8 years with RV144 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 alone, or ALVAC-HIV + AIDSVAX B/E gp120). Previous reports demonstrated that this regimen elicited higher binding, antibody Fc function, and cellular responses than the primary RV144 regimen. However, the impact of the canarypox viral vector in driving antibody specificity, breadth, durability and function is unknown. We performed a follow-up analysis of humoral responses elicited in RV305 to determine the impact of the different booster immunogens on HIV-1 epitope specificity, antibody subclass, isotype, and Fc effector functions. Importantly, we observed that the ALVAC vaccine component directly contributed to improved breadth, function, and durability of vaccine-elicited antibody responses. Extended boosts in RV305 increased circulating antibody concentration and coverage of heterologous HIV-1 strains by V1V2-specific antibodies above estimated protective levels observed in RV144. Antibody Fc effector functions, specifically antibody-dependent cellular cytotoxicity and phagocytosis, were boosted to higher levels than was achieved in RV144. V1V2 Env IgG3, a correlate of lower HIV-1 risk, was not increased; plasma Env IgA (specifically IgA1), a correlate of increased HIV-1 risk, was elevated. The quality of the circulating polyclonal antibody response changed with each booster immunization. Remarkably, the ALVAC-HIV booster immunogen induced antibody responses post-second boost, indicating that the viral vector immunogen can be utilized to selectively enhance immune correlates of decreased HIV-1 risk. These results reveal a complex dynamic of HIV-1 immunity post-vaccination that may require careful balancing to achieve protective immunity in the vaccinated population. Trial registration: RV305 clinical trial (ClinicalTrials.gov number, NCT01435135). ClinicalTrials.gov Identifier: NCT00223080., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Given the expanding elderly population in the United States and the world, it is important to understand the processes underlying both natural and pathological age-related changes in the eye. Both the anterior and posterior segment of the eye undergo changes in biological, chemical, and physical properties driven by oxidative stress. With advancing age, changes in the anterior segment include dermatochalasis, blepharoptosis, thickening of the sclera, loss of corneal endothelial cells, and stiffening of the lens. Changes in the posterior segment include lowered viscoelasticity of the vitreous body, photoreceptor cell loss, and drusen deposition at the macula and fovea. Age-related ocular pathologies including glaucoma, cataracts, and age-related macular degeneration are largely mediated by oxidative stress. The prevalence of these diseases is expected to increase in the coming years, highlighting the need to develop new therapies that address oxidative stress and slow the progression of age-related pathologies.

Purpose  The H-index (H i ), an author-level metric of scholarly impact, is predictive of future scientific achievement. We sought to analyze the scholarly impact of student authorship on the H i of corresponding authors (CAs) within a major academic journal in the specialty of ophthalmology. Materials and Methods  We compared the H i of all unique CAs for manuscripts published in Ophthalmology (Journal of the American Academy of Ophthalmology) in 2008, 2012, and 2016. Data abstraction was completed twice: in October 2018 and March 2021. We further grouped published articles for CAs into those with student authors (StA) and those without (nStA). Primary analysis involved a linear regression analysis with change in H i from October 2018 to March 2021 as the outcome variable, CA groups as the predictor variable, adjusting for the covariates of baseline H i , the year when the CA published his or her article, number of research items published in October 2018, and the academic appointment of the CAs. Secondary analysis involved a linear regression analysis with change in H i from October 2018 to March 2021 as the outcome variable, total number of student authors per CA as the predictor variable, adjusting for the covariates of baseline H i , the year CA published his or her article, number of research items published in October 2018, and the academic appointment of the CAs. Results  The number of student authors increased from 168 in 2008 to 192 in 2016. Of the 902 articles, 316 articles were co-authored by one or more student authors. The average change in H i of CAs publishing with student authors (StA, 11.0 ± 14.7) was significantly greater ( p  < 0.0001) than the change in H i of CAs publishing without student authors (nStA, 6.2 ± 6.2). As the total number of student authors increased, the change in H i of CAs increased linearly for all years combined (regression coefficient = 1.70, p -value < 0.0001). Conclusion  CAs publishing with students in the field of ophthalmology have a higher scholarly impact than those publishing without students. The development of programs to integrate students into ophthalmology research early on may encourage their pursuit of a career in ophthalmology, while advancing the careers of their mentors., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Over the last half-century, left ventricular assist device (LVAD) technology has progressed from conceptual therapy for failed cardiopulmonary bypass weaning to an accepted destination therapy for advanced heart failure. The history of LVAD engineering is defined by an initial development phase, which demonstrated the feasibility of such an approach, to the more recent three major generations of commercial devices. In this review, we explore the engineering challenges of LVADs, how they were addressed over time, and the clinical outcomes that resulted from each major technological development. The first generation of commercial LVADs were pulsatile devices, which lacked the appropriate durability due to their number of moving components and hemocompatibility. The second generation of LVADs was defined by replacement of complex, pulsatile pumps with primarily axial, continuous-flow systems with an impeller in the blood passageway. These devices experienced significant commercial success, but the presence of excessive trauma to the blood and in-situ bearing resulted in an unacceptable burden of adverse events. Third generation centrifugal-flow pumps use magnetically suspended rotors within the pump chamber. Superior outcomes with this newest generation of devices have been observed, particularly with respect to hemocompatibility-related adverse events including pump thrombosis, with fully magnetically levitated devices. The future of LVAD engineering includes wireless charging foregoing percutaneous drivelines and more advanced pump control mechanisms, including synchronization of the pump flow with the native cardiac cycle, and varying pump output based on degree of physical exertion using sensor or advanced device-level data triggers., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Crossover youth (COY) are involved with child welfare and/or the justice system and experience multifaceted challenges in their transition into adulthood. A literature review identified eight critical indicators of successful transitions for COY and the absence of a validated comprehensive assessment that is youth informed and culturally sensitive., Objective: To develop a Successful Transitions Assessment Tool (STAT) that is informed by research, Critical Race Theory, and subject matter experts., Participants and Setting: Field experts were approached to review the initial STAT, developed from literature findings, using the Delphi approach; 13 experts completed the first round and nine completed the second round. Child welfare youth participated in a focus group and youth justice youth completed interviews; 10 youth aged 16 to 24 provided feedback., Methods: A two-round Delphi study with experts used a survey link. The focus groups and interviews with youth experts were conducted virtually. Expert rankings in the examined areas were aggregated and qualitative data were thematically analyzed., Results: Responding experts in both rounds of the Delphi process ranked the STAT highly, achieving scores of 16.8 and 16.4 of 20 possible points, respectively (consensus >80 %). No additional rounds were deemed necessary. All suggested tool clarifications were incorporated. Additional questions were added based on suggestions relevant to the eight critical domains., Conclusions: This innovative study created a single, brief, yet comprehensive assessment tool of eight key domains for successful transitions out of care settings, informed by experts through the Delphi approach and youth themselves., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors have no conflicts of interest to declare

Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content. Better Evidence for Selecting Transplant Fluids (BEST-Fluids), a pragmatic, registry-based, double-blind, randomized trial, sought to determine whether using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce DGF. We sought to evaluate the generalizability of the trial cohort by reporting the baseline characteristics and representativeness of the trial participants in detail., Methods: We compared the characteristics of BEST-Fluids participants with those of a contemporary cohort of deceased donor kidney transplant recipients in Australia and New Zealand using data from the Australia and New Zealand Dialysis and Transplant Registry. To explore potential international differences, we compared trial participants with a cohort of transplant recipients in the United States using data from the Scientific Registry of Transplant Recipients., Results: During the trial recruitment period, 2373 deceased donor kidney transplants were performed in Australia and New Zealand; 2178 were eligible' and 808 were enrolled in BEST-Fluids. Overall, trial participants and nonparticipants were similar at baseline. Trial participants had more coronary artery disease (standardized difference [d] = 0.09; P = 0.03), longer dialysis duration (d = 0.18, P < 0.001), and fewer hypertensive (d = -0.11, P = 0.03) and circulatory death (d = -0.14, P < 0.01) donors than nonparticipants. Most key characteristics were similar between trial participants and US recipients, with moderate differences (|d| ≥ 0.2; all P < 0.001) in kidney failure cause, diabetes, dialysis duration, ischemic time, and several donor risk predictors, likely reflecting underlying population differences., Conclusions: BEST-Fluids participants had more comorbidities and received slightly fewer high-risk deceased donor kidneys but were otherwise representative of Australian and New Zealand transplant recipients and were generally similar to US recipients. The trial results should be broadly applicable to deceased donor kidney transplantation practice worldwide., Competing Interests: M.G.C. has received research support from Baxter Healthcare Pty Ltd, the manufacturer of Plasma-Lyte 148, through a Baxter Investigator-Initiated Research grant that provided fluids for the BEST-Fluids trial (commercial value of US $36 270). D.W.J. has received consultancy fees, research grants, speaker’s honoraria, and travel sponsorships from Baxter Healthcare and Fresenius Medical Care; consultancy fees from AstraZeneca and AWAK; speaker’s honoraria and travel sponsorships from ONO; and travel sponsorships from Amgen. D.R., L.E.H. L.A.V., E.M.P., C.K., and J.V. are employees of the sponsor, The University of Queensland. K.B.D.’s salary was funded by a BEAT-CKD grant‚ and she is an employee of the ANZDATA Registry. P.A.C. is the deputy executive officer of the ANZDATA Registry. C.M.H. has received fees for research committee activities from Janssen and GlaxoSmithKline paid to her institution; personal fees from Otsuka; research grants from Fresenius, Shire, and PKD Australia outside the submitted work; and research grants from Baxter and NHMRC related to the current project. L.W. works in the Department of Anaesthesia at Austin Health, which has received funding from Baxter Healthcare for investigator-initiated clinical research. L.W. has received honoraria from Baxter Healthcare for consulting activities. All L.W.’s fluid-related research, including study design, execution, data collection, analysis, and reporting, has been conducted independently of Baxter Healthcare and other commercial entities. Z.H.E. has received consultancy fees and travel sponsorships from AstraZeneca. W.H.L. has received honoraria from Alexion and education/research grants from Astellas. S.J.C. has received research support, travel support, speaker fees, or honoraria from AstraZeneca, Bayer, CSL-Behring, Novartis, and Takeda. The other authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Over the past decade, states have passed several laws on prenatal drug use, including "maltreatment laws" deeming prenatal drug use child maltreatment, "reporting laws" requiring providers to report prenatal drug use to Child Protective Services (CPS) and "criminalization laws" that criminalize prenatal drug use., Method: We examined the association between a 2012 Utah maltreatment law, a 2013 Alabama maltreatment and criminalization law, and a 2014 Maryland reporting law on the rate of infant CPS reports using 2010-2017 National Child Abuse and Neglect Data System data. We conducted an event study comparing CPS reporting pre/post law in each treatment state with reporting in a pool of control states over the same period. Regression models included state and year fixed effects and state-level demographics. We triangulated quantitative results with qualitative interviews of 11 state leaders whose professional responsibilities included implementation of the state law., Results: We found no association between Alabama's simultaneous maltreatment and criminalization laws and infant reporting. Maryland's reporting law (28.2 fewer reports per 1000 infants, 95%CI: [-42.9, -13.6], 4-years post-law) and Utah's maltreatment laws (31.0 fewer CPS reports per 1000 infants, 95%CI: [-61.2, -0.8], 6-years post-law) were associated with declines in infant CPS reports. Qualitative results suggest that the reduced reporting associated with Maryland's reporting and Utah's maltreatment laws may be due to increased perceived stigma resulting from the law, and health providers' distrust of CPS and/or confusion about reporting to CPS., Conclusion: Future research should characterize differential policy implementation across states and counties and identify policy impacts on treatment seeking behavior., Competing Interests: Declarations of 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 © 2022. Published by Elsevier B.V.)

Background: Although male breast cancer (MBC) is a rare disease, accounting for <1% of all breast cancers, it has significant oncological, survival and psychosocial implications for patients. The aim of this study is to assess the latest literature in the diagnosis, management, oncological outcomes, and psychosocial impact of MBC., Methods: A systematic literature review was conducted using the PRISMA guidelines (Moher et al., 2009) [1] to explore the management of MBC, with particular focus on investigative imaging, surgical management, oncological outcomes, survival, genetic screening and psychosocial effects. Electronic databases were searched for randomised control trials, cohort studies and case series involving more than 10 patients. Imaging and surgical techniques, local and distant disease recurrence, survival, genetic screening and psychosocial implications in the setting of MBC were assessed., Results: The search criteria identified 199 articles, of which 59 met the inclusion criteria. This included 39,529 patients, with a mean age of 64.5 years (55-71), and a mean follow-up of 66.3 months (26.2-115). Mastectomy remains the most frequently used surgical technique, with an average of 89.6%. Loco-regional and distant recurrence rate was 10.1% and 21.4% respectively. Disease-free survival (DFS) at 5 and 10 years was 66.8% and 54.5% respectively. Disease-specific survival (DSS) at 5 and 10 years was 87.1% and 67.1% respectively. Overall survival (OS) at 5 and 10 years was 72.7% and 50.7% respectively. Genetic screening was conducted in 38.6% of patients of which 4.8% and 15.8% were found to be BRCA1 and BRCA2 carriers respectively. Psychosocial studies were conducted mainly using questionnaire and interview-based methodology focusing primarily on awareness of breast cancer in men, support available and impact on gender identity., Conclusions: This review demonstrates that men present with later stage disease with subsequent impact on survival outcomes. There remains a paucity of high-level evidence and prospective studies are required. There is a need for increasing awareness amongst the public and health care professionals in order to improve outcomes and reduce stigma associated with MBC., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Social Determinants of Health (SDOH) consider social, political, and economic factors that contribute to health disparities in patients and populations. The most common health-related SDOH exposures are food and housing insecurity, financial instability, transportation needs, low levels of education, and psychosocial stress. These domains describe risks that can impact health outcomes more than health care. Epidemiologic and translational research demonstrates that SDOH factors represent exposures that predict harm and impact the health of individuals. International and national guidelines urge health professionals to address SDOH in clinical practice and public health. The further implementation of these recommendations into basic and translational research, however, is lagging. Herein, we consider a precision health framework to describe how SDOH contributes to the exposome and exacerbates physiologic pathways that lead to chronic disease. SDOH factors are associated with various forms of stressors that impact physiological processes through epigenetic, inflammatory, and redox regulation. Many SDOH exposures may add to or potentiate the pathologic effects of additional environmental exposures. This overview aims to inform basic life science and translational researchers about SDOH exposures that can confound associations between classic biomedical determinants of disease and health outcomes. To advance the study of toxicology through either qualitative or quantitative assessment of exposures to chemical and biological substances, a more complete environmental evaluation should include SDOH exposures. We discuss common approaches to measure SDOH factors at individual and population levels and review the associations between SDOH risk factors and physiologic mechanisms that influence chronic disease. We provide clinical and policy-based motivation to encourage researchers to consider the impact of SDOH exposures on study results and data interpretation. With valid measures of SDOH factors incorporated into study design and analyses, future toxicological research may contribute to an evidence base that can better inform prevention and treatment options, to improve equitable clinical care and population health. © 2022 Wiley Periodicals LLC., (© 2022 Wiley Periodicals LLC.)

Adjuvants can alter the magnitude, characteristics, and persistence of the humoral response to protein vaccination. HIV vaccination might benefit from tailored adjuvant choice as raising a durable and protective response to vaccination has been exceptionally challenging. Analysis of trials of partially effective HIV vaccines have identified features of the immune response that correlate with decreased risk, including high titers of V1V2-binding IgG and IgG3 responses with low titers of V1V2-binding IgA responses and enhanced Fc effector functions, notably antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). However, there has been limited opportunity to compare the effect of different adjuvants on these activities in humans. Here, samples from the AVEG015 study, a phase 1 trial in which participants (n = 112) were immunized with gp120 SF-2 and one of six different adjuvants or combinations thereof were assessed for antibody titer, biophysical features, and diverse effector functions. Three adjuvants, MF59 + MTP-PE, SAF/2, and SAF/2 + MDP, increased the peak magnitude and durability of antigen-specific IgG3, IgA, FcγR-binding responses and ADCP activity, as compared to alum. While multiple adjuvants increased the titer of IgG, IgG3, and IgA responses, none consistently altered the balance of IgG to IgA or IgG3 to IgA. Linear regression analysis identified biophysical features including gp120-specific IgG and FcγR-binding responses that could predict functional activity, and network analysis identified coordinated aspects of the humoral response. These analyses reveal the ability of adjuvants to drive the character and function of the humoral response despite limitations of small sample size and immune variability in this human clinical trial., (© 2022. The Author(s).)

Background: Lactate hydrogenase (LDH) is a common biomarker utilized in the detection and monitoring of left ventricular assist device (LVAD) hemolysis and thrombosis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are common laboratory tests that can be used to calculate the De Ritis ratio and the De Ritis adjusted AST., Methods: A retrospective review of LVAD patients was performed to identify three cohorts of patients: those with confirmed pump thrombosis after device exchange, those with LVAD-related hemolysis who were medically managed without pump exchange, and those who did not meet these criteria and served as the control cohort. Evaluation of AST, AST/ALT ratio (referred to as the De Ritis ratio) as well as AST x (AST/ALT) or the De Ritis-adjusted AST (DRA) was performed., Results: There were 29 patients who underwent device exchange for thrombosis, 25 patients who were diagnosed with hemolysis and treated medically (clopidogrel (N = 6), heparin (N = 13), tirofiban (N = 8), eptifibatide (N = 2), and some received more than one of these treatments), and 425 control patients. A qualitatively comparable relative and absolute rise in DRA and LDH were found in both surgically managed pump thrombosis and suspected device-related hemolysis., Conclusions: Both AST and LDH as well DRA are significantly associated with pump thrombosis (p < 0.0001 for each). DRA is a potential screening biomarker for hemolysis and device thrombosis in stable left ventricular assist device patients., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)