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Peripheral blood lymphocyte phenotyping panels typically include CD45 for discrimination of the lymphocyte population, and fluorophore-conjugated monoclonal antibodies to identify T, B, and Natural Killer (NK) cells. While CD45 combined with side scatter is generally sufficient to clearly distinguish lymphocytes from monocytes in the majority of peripheral blood samples, it is challenging to accurately gate lymphocytes in samples from patients with monocytosis or significant lymphopenia, or from very young infants. Addition of a monocyte marker to lymphocyte phenotyping panels for monocyte exclusion has previously been evaluated for improved discrimination of lymphocytes, albeit largely in healthy donor adult samples. Here we evaluate the effect of the addition of CD14 to a standard lymphocyte phenotyping panel on total lymphocyte, T, B, and NK cell percentages in a predominantly pediatric population of patients under evaluation chiefly for immunodeficiency, immune-depletion, or immune reconstitution. Addition of CD14 to the standard lymphocyte phenotyping improved discrimination of lymphocytes from monocytes, resulted in decreased NK cell percentages, likely because CD16+ and/or CD56+ monocytes were included in the CD56+CD16+ NK cell gate with conventional gating, and although less significant, resulted in an increased percentage of B cells, since relatively larger B cells were likely gated out by more restrictive light scatter gating used with the conventional gating approach. The change in NK and B cell percentages were more pronounced in samples from patients below a year of age, and in patients who were relatively lymphopenic. These data suggest that addition of CD14 to conventional lymphocyte phenotyping panels that utilize CD45 versus side scatter gating results in significant improvement in the accuracy of lymphocyte gating, and accurate quantification of NK and B cells particularly in samples from infants and lymphopenic individuals., (© 2024 International Clinical Cytometry Society.)

Purpose: Compared with lower field strengths, DWI at 7 T faces the combined challenges of increased distortion and blurring due to B 0 inhomogeneity, and increased signal dropouts due to B 1 + inhomogeneity. This study addresses the B 1 + limitations using slice-specific static parallel transmission (pTx) in a multi-shot, readout-segmented EPI diffusion imaging sequence., Methods: DWI was performed in 7 healthy subjects using MRI at 7 T and readout-segmented EPI. Data were acquired with non-pTx circular-polarized (CP) pulses (CP-DWI) and static pTx pulses (pTx-DWI) using slice-specific B 1 + shim coefficients. Each volunteer underwent two scan sessions on the same day, with two runs of each sequence in the first session and one run in the second. The sequences were evaluated by assessing image quality, flip-angle homogeneity, and intrasession and intersession repeatability in ADC estimates., Results: pTx-DWI significantly reduced signal voids compared with CP-DWI, particularly in inferior brain regions. The use of pTx also improved RF uniformity and symmetry across the brain. These effects translated into improved intrasession and intersession repeatability for pTx-DWI. Additionally, re-optimizing the pTx pulse between repeat scans did not have a negative effect on ADC repeatability., Conclusion: The study demonstrates that pTx provides a reproducible image-quality increase in multishot DWI at 7 T. The benefits of pTx also extend to quantitative ADC estimation with regard to the improvement in intrasession and intersession repeatability. Overall, the combination of multishot imaging and pTx can support the development of reliable, high-resolution DWI for clinical studies at 7 T., (© 2024 International Society for Magnetic Resonance in Medicine.)

There is a dearth of evidence indicating the effectiveness of psychological interventions targeting depression and/or posttraumatic stress disorder (PTSD) for Black women in the United States (US) exposed to intimate partner violence (IPV). We searched PubMed, MEDLINE, PsycINFO, EBSCOhost, Social Sciences, Social Sciences Full Text, Social Work Abstracts, and Cochrane databases between September 2021 and October 2022, for original studies of randomized control trials (RCTs) reporting depression and/or PTSD interventions delivered to US Black women with histories of IPV. Of the 1,276 articles, 46 were eligible and 8 RCTs were ultimately included in the review; interventions for depression (four interventions, n  = 1,518) and PTSD (four interventions, n  = 477). Among Depression and PTSD interventions (one intervention, n  = 208), Beck's Depression Inventory II indicated M  = 35.2, SD  = 12.6 versus M  = 29.5, SD  = 13.1, <.01, and Davidson Trauma Scale indicated M  = 79.4, SD  = 31.5 versus M  = 72.1, SD  = 33.5, <.01, at pre- and post-intervention respectively. Also, some interventions reported severity of depression M  = 13.9 ( SD  = 5.4) versus M  = 7.9 ( SD  = 5.7) < 0.01, and PTSD ( M  = 8.08 vs. M  = 14.13, F (1,117) = 9.93, p  < .01) at pre- and post-intervention respectively. Publication bias was moderate and varied between 12 and 17 via the Downs and Black Checklist for Methodological Rigor for RCTs. Psychological interventions targeting depression and/or PTSD for Black women with histories of IPV reflect moderate improvement. Interventions that account for cultural nuances specific to Black women are fundamental for improving outcomes for survivors presenting with depression and/or PTSD., 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.

In 2021, the National Ambulatory Medical Care Survey Health Center (NAMCS HC) Component modernized its data collection and began collecting clinical visit data from health centers using transmission of electronic health record (EHR) data. With this redesign, there are potential cost implications for a health center to participate. Beginning in 2021, a one-time set-up fee (i.e., payment) of up to $10,000 was offered to centers who participated in the NAMCS HC Component. Starting in 2022, a Set-up Fee Questionnaire was used to capture data on the use of this money. Results show on average the fee appeared adequate in covering participation costs, with the fee most often used to cover costs of health center and EHR vendor information technology staff. Although this fee was offered only during the initial year of participation, retention rates for centers appeared high. Implications from the findings of this case study on use of a set-up fee in establishment surveys are also briefly discussed.

Health communication has relevance for virtually every aspect of health and well-being, including disease prevention. This review explored the effectiveness of communications in enhancing the adoption of or adherence to behavioural interventions (non-pharmaceutical interventions (NPIs)) related to COVID-19. The review takes the UK as a case study and focuses on self-reported behaviours (e.g. social distancing). It also reviews the psychosocial determinants of adherence. Searches were conducted using PubMed, Scopus, CINAL, ASSIA and iCite databases. Eleven thousand five hundred records were identified and 13 were included in the final sample. Included studies suggest that NPI adoption or adherence was generally high, and communication had significant impacts, with key themes including clarity and consistency, trust and control. Based on the evidence in this review, features of effective communication in the context of NPI adoption or adherence are (i) information should be conveyed clearly and conflicting (mixed) messages should be avoided; (ii) information should be conveyed by trusted sources (e.g. health authorities) and (iii) communication should strike a balance between being authoritative but avoiding language seen as controlling (e.g. 'you must'). Future research should prioritize quantitative, experimental and longitudinal study designs, that focus specifically on communication as an intervention, and which measure behaviour. This article is part of the theme issue 'The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence'.

Background and Aims: The aim of the study was to investigate the role and mechanisms of tuberous sclerosis complex 1 (TSC1) and mechanistic target of rapamycin complex 1 (mTORC1) in alcohol-associated liver disease., Approach and Results: Liver-specific Tsc1 knockout (L- Tsc1 KO) mice and their matched wild-type mice were subjected to Gao-binge alcohol. Human alcoholic hepatitis (AH) samples were also used for immunohistochemistry staining, western blot, and quantitative real-time PCR (q-PCR) analysis. Human AH and Gao-binge alcohol-fed mice had decreased hepatic TSC1 and increased mTORC1 activation. Gao-binge alcohol markedly increased liver/body weight ratio and serum alanine aminotransferase levels in L- Tsc1 KO mice compared with Gao-binge alcohol-fed wild-type mice. Results from immunohistochemistry staining, western blot, and q-PCR analysis revealed that human AH and Gao-binge alcohol-fed L- Tsc1 KO mouse livers had significantly increased hepatic progenitor cells, macrophages, and neutrophils but decreased HNF4α-positive cells. Gao-binge alcohol-fed L- Tsc1 KO mice also developed severe inflammation and liver fibrosis. Deleting Tsc1 in cholangiocytes but not in hepatocytes promoted cholangiocyte proliferation and aggravated alcohol-induced ductular reactions, fibrosis, inflammation, and liver injury. Pharmacological inhibition of mTORC1 partially reversed hepatomegaly, ductular reaction, fibrosis, inflammatory cell infiltration, and liver injury in alcohol-fed L- Tsc1 KO mice., Conclusions: Our findings indicate that persistent activation of mTORC1 due to the loss of cholangiocyte TSC1 promotes liver cell repopulation, ductular reaction, inflammation, fibrosis, and liver injury in Gao-binge alcohol-fed L- Tsc1 KO mice, which phenocopy the pathogenesis of human AH., (Copyright © 2023 American Association for the Study of Liver Diseases.)

As part of modernization efforts, in 2021 the National Ambulatory Medical Care Survey (NAMCS) began collecting electronic health records (EHRs) for ambulatory care visits in its Health Center (HC) Component. As a result, the National Center for Health Statistics (NCHS)needed to adjust the approaches used in the sampling design for the HC Component. This report provides details on these changes to the 2021-2022 NAMCS., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Purpose: To investigate the effects of using different parallel-transmit (pTx) head coils and specific absorption rate (SAR) supervision strategies on pTx pulse design for ultrahigh-field MRI using a 3D-MPRAGE sequence., Methods: The PTx universal pulses (UPs) and fast online-customized (FOCUS) pulses were designed with pre-acquired data sets (B 0 , B 1 + maps, specific absorption rate [SAR] supervision data) from two different 8 transmit/32 receive head coils on two 7T whole-body MR systems. For one coil, the SAR supervision model consisted of per-channel RF power limits. In the other coil, SAR estimations were done with both per-channel RF power limits as well as virtual observation points (VOPs) derived from electromagnetic field (EMF) simulations using three virtual human body models at three different positions. All pulses were made for nonselective excitation and inversion and evaluated on 132 B 0 , B 1 + , and SAR supervision datasets obtained with one coil and 12 from the other. At both sites, 3 subjects were examined using MPRAGE sequences that used UP/FOCUS pulses generated for both coils., Results: For some subjects, the UPs underperformed when simulated on a different coil from which they were derived, whereas FOCUS pulses still showed acceptable performance in that case. FOCUS inversion pulses outperformed adiabatic pulses when scaled to the same local SAR level. For the self-built coil, the use of VOPs showed reliable overestimation compared with the ground-truth EMF simulations, predicting about 52% lower local SAR for inversion pulses compared with per-channel power limits., Conclusion: FOCUS inversion pulses offer a low-SAR alternative to adiabatic pulses and benefit from using EMF-based VOPs for SAR estimation., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: To explore UK public decisions around whether or not to get COVID-19 vaccines, and the facilitators and barriers behind participants' decisions., Design: This qualitative study consisted of six online focus groups conducted between 15th March and 22nd April 2021. Data were analysed using a framework approach., Setting: Focus groups took place via online videoconferencing (Zoom)., Participants: Participants (n = 29) were a diverse group (by ethnicity, age and gender) UK residents aged 18 years and older., Results: We used the World Health Organization's vaccine hesitancy continuum model to look for, and explore, three main types of decisions related to COVID-19 vaccines: vaccine acceptance, vaccine refusal and vaccine hesitancy (or vaccine delay). Two reasons for vaccine delay were identified: delay due to a perceived need for more information and delay until vaccine was "required" in the future. Nine themes were identified: three main facilitators (Vaccination as a social norm; Vaccination as a necessity; Trust in science) and six main barriers (Preference for "natural immunity"; Concerns over possible side effects; Perceived lack of information; Distrust in government;; Conspiracy theories; "Covid echo chambers") to vaccine uptake., Conclusion: In order to address vaccine uptake and vaccine hesitancy, it is useful to understand the reasons behind people's decisions to accept or refuse an offer of a vaccine, and to listen to them and engage with, rather than dismiss, these reasons. Those working in public health or health communication around vaccines, including COVID-19 vaccines, in and beyond the UK, might benefit from incorporating the facilitators and barriers found in this study., Competing Interests: CJA is supported by NIHR Manchester Biomedical Research Centre and NIHR Greater Manchester Patient Safety Translational Research Centre. This does not alter our adherence to PLOS ONE policies on sharing data and materials. JD sits on SAGE SPI-B subgroup, and Independent Sage. TT currently works for the World Health Organization, but contributed to this paper as an independent researcher. This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests The authors have no other relationships or activities that could appear to have influenced the submitted work., (Copyright: © 2023 Williams 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.)

This paper reviews the field of multiple or parallel radiofrequency (RF) transmission for magnetic resonance imaging (MRI). Currently the use of ultra-high field (UHF) MRI at 7 tesla and above is gaining popularity, yet faces challenges with non-uniformity of the RF field and higher RF power deposition. Since its introduction in the early 2000s, parallel transmission (pTx) has been recognized as a powerful tool for accelerating spatially selective RF pulses and combating the challenges associated with RF inhomogeneity at UHF. We provide a survey of the types of dedicated RF coils used commonly for pTx and the important modeling of the coil behavior by electromagnetic (EM) field simulations. We also discuss the additional safety considerations involved with pTx such as the specific absorption rate (SAR) and how to manage them. We then describe the application of pTx with RF pulse design, including a practical guide to popular methods. Finally, we conclude with a description of the current and future prospects for pTx, particularly its potential for routine clinical use., (Creative Commons Attribution license.)

Mechanistic target of rapamycin (mTOR) is a serine-threonine kinase and a cellular sensor for nutrient and energy status, which is critical in regulating cell metabolism and growth by governing the anabolic (protein and lipid synthesis) and catabolic process (autophagy). Alcohol-associated liver disease (ALD) is a major chronic liver disease worldwide that carries a huge financial burden. The spectrum of the pathogenesis of ALD includes steatosis, fibrosis, inflammation, ductular reaction, and eventual hepatocellular carcinoma, which is closely associated with metabolic changes that are regulated by mTOR. In this review, we summarized recent progress of alcohol consumption on the changes of mTORC1 and mTORC2 activity, the potential mechanisms and possible impact of the mTORC1 changes on autophagy in ALD. We also discussed the potential beneficial effects and limitations of targeting mTORC1 against ALD.

Introduction: The objective of this manuscript is to outline the process involved in the development and validation of a survey that is optimal for assessing the impact of a substance use disorder (SUD) elective course., Methods: Face validation was performed once the initial survey was developed. Additionally, field validation was performed by surveying a small population of pharmacy students enrolled in the elective course. Non-parametric chi-square test and factor analysis were performed to analyze survey results and measure survey validity, while Cronbach alpha (CA) was performed to measure reliability., Results: Student survey responses showed a significance of P < .05 using one sample chi-square test for statements 1, 5, 6, 7, 8, 11, 12, 13, and 15. Factor analysis identified five factors; however, only three factors were identified as having good correlation. Factor 1 related to students' beliefs about patients with SUD, factor 2 related to attitudes about patients with SUD, and factor 3 related to beliefs about SUD. Factors 1, 2, and 3 have a calculated CA > 0.7, indicating strong internal consistency and reliability., Conclusions: Some of the original statements loaded as expected and assessed the impact of the course in shaping students' beliefs and attitudes regarding SUD. However, some statements did not load as expected, and the survey was modified in order to better assess the desired endpoints., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: This qualitative study explored public attitudes to COVID-19 vaccines in children, including reasons for support or opposition to them., Study Design: This was a qualitative study using online focus groups and interviews., Methods: Group and individual online interviews were conducted with a diverse sample of 24 adults in the United Kingdom to explore their views on the issue of COVID-19 vaccination in children. Data were analysed using a framework approach., Results: COVID-19 vaccination in children was framed as a complex problem (a 'minefield'). Six themes emerged to explain participants views: (1) uncertainty over whether children can catch, transmit or be severely harmed by COVID-19; (2) lower risk tolerance for unknown longer term effects of the vaccine in children; (3) association of the vaccine programme with government's handling of the pandemic; (4) local social norms as a driver of hesitancy; (5) vaccinating children as a way to protect vulnerable adults; and (6) children's vaccination as parental choice., Conclusions: COVID-19 vaccination in children is perceived by members of the public as a complex issue, and many are torn or hesitant about the idea. Public health communications will need to combat this hesitancy if vaccine uptake for children is to be pursued as a public health policy., (Copyright © 2022 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Neutrophil trafficking is a key component of the inflammatory response. Here, we have investigated the role of the immunomodulatory lectin Galectin-9 (Gal-9) on neutrophil recruitment. Our data indicate that Gal-9 is upregulated in the inflamed vasculature of RA synovial biopsies and report the release of Gal-9 into the extracellular environment following endothelial cell activation. siRNA knockdown of endothelial Gal-9 resulted in reduced neutrophil adhesion and neutrophil recruitment was significantly reduced in Gal-9 knockout mice in a model of zymosan-induced peritonitis. We also provide evidence for Gal-9 binding sites on human neutrophils; Gal-9 binding induced neutrophil activation (increased expression of β2 integrins and reduced expression of CD62L). Intra-vital microscopy confirmed a pro-recruitment role for Gal-9, with increased numbers of transmigrated neutrophils following Gal-9 administration. We studied the role of both soluble and immobilized Gal-9 on human neutrophil recruitment. Soluble Gal-9 significantly strengthened the interaction between neutrophils and the endothelium and inhibited neutrophil crawling on ICAM-1. When immobilized, Gal-9 functioned as an adhesion molecule and captured neutrophils from the flow. Neutrophils adherent to Gal-9 exhibited a spread/activated phenotype that was inhibited by CD18 and CD44 neutralizing antibodies, suggesting a role for these molecules in the pro-adhesive effects of Gal-9. Our data indicate that Gal-9 is expressed and released by the activated endothelium and functions both in soluble form and when immobilized as a neutrophil adhesion molecule. This study paves the way for further investigation of the role of Gal-9 in leukocyte recruitment in different inflammatory settings., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Novel viral pandemics present significant challenges to global public health. Non-pharmaceutical interventions (e.g. social distancing) are an important means through which to control the transmission of such viruses. One of the key factors determining the effectiveness of such measures is the level of public adherence to them. Research to date has focused on quantitative exploration of adherence and non-adherence, with a relative lack of qualitative exploration of the reasons for non-adherence., Objective: To explore participants' perceptions of non-adherence to COVID-19 policy measures by self and others in the UK, focusing on perceived reasons for non-adherence., Methods: Qualitative study comprising 12 focus groups conducted via video-conferencing between 25th September and 13th November 2020. Participants were 51 UK residents aged 18 and above, reflecting a range of ages, genders and race/ethnicities. Data were analysed using a thematic approach., Results: Participants reported seeing an increase in non-adherence in others over the course of the pandemic. Reports of non-adherence in self were lower than reports of non-adherence in others. Analysis revealed six main themes related to participants' reported reasons for non-adherence in self and others: (1) 'Alert fatigue' (where people find it difficult to follow, or switch off from, information about frequently changing rules or advice) (2) Inconsistent rules (3) Lack of trust in government (4) Learned Helplessness (5) Resistance and rebelliousness (6)The impact of vaccines on risk perception. Participants perceived a number of systemic failures (e.g. unclear policy, untrustworthy policymakers) to strongly contribute to two forms non-adherence-violations and errors., Conclusion: Findings suggest that latent and systemic failures-in the form of policy decisions that are commonly experienced as too changeable, inconsistent and confusing, and policy makers that are commonly perceived as untrustworthy-may play a significant role in creating the conditions that enable or encourage non-adherence., Competing Interests: CJA is supported by NIHR Manchester Biomedical Research Centre and NIHR Greater Manchester Patient Safety Translational Research Centre. This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). The authors have no other relationships or activities that could appear to have influenced the submitted work.

Purpose: Explore if and how American Samoan cultural norms influence caregivers' knowledge, attitudes, and care choices for person's living with Alzheimer's Dementia (AD). Design: This pilot study used mixed methods. Methods: 1) Quantitative survey: measuring knowledge/attitudes towards AD (n = 80); 2) Qualitative techniques: a) Focus groups (n= 54) with caregivers; b) Semi-structured interviews (n=26) with health professionals; and c) In-depth interviews (n=3) with key informants. Emergent themes were created using data from all methods. Findings: Quantitative analyses revealed 50% of participants identified AD as normal aging, 83% as mental illness. The majority of participants believed elders with AD do not experience pain (70%) and should be cared for solely at home (74%). Qualitative evidence showed dissonance between cultural norms of respect for elders, familial caregiving duty, shame in others observing elders' dementia-related behaviours, and the current language used to describe AD. Conclusions: Our findings show a need for developing and disseminating culturally sensitive terminology for AD to destigmatize and transmute attitudes, knowledge and care choices for elders living with AD. Clinical Evidence: American Samoan terminology for dementia is discordant with its cultural norms, thus shaping caregivers' perceptions of AD and influencing care choices for managing AD symptoms.

Objective-This report demonstrates the ability of the National Hospital Care Survey (NHCS) to examine delivery hospitalizations involving severe maternal morbidity (SMM). These data are unweighted and not nationally representative, so the results are intended to illustrate the unique capability of NHCS to track patients across hospitalizations and emergency department (ED) visits rather than provide nationally representative estimates of these outcomes., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Bloodstream infections (BSI) are significant causes of morbidity and mortality in cancer patients. These patients often receive 10 to 14 days of intravenous (IV) antibiotics. The objective of this study was to compare the outcomes of cancer patients transitioned from IV to oral (PO) therapy compared to continuation of IV treatment., Methods: This was a single-center, retrospective cohort study of hospitalized adult cancer patients with gram-negative bacteremia. Patients transitioned to a PO fluoroquinolone (FQ) within 5 days were allocated to the IV-to-PO group, while the remaining patients comprised the IV group. The primary outcome was the composite of treatment failure, defined as infection-related readmission, infection recurrence, or inpatient mortality. A multivariable logistic regression model was constructed to account for confounding variables. Secondary outcomes assessed included infection-related length of stay (LOS), hospital LOS, and adverse events, such as Clostridioides difficile infection and catheter-related complications., Results: The IV-to-PO group included 78 patients, while the remaining 133 patients were allocated to the IV group. Differences at baseline included more hematologic malignancy, neutropenia, ICU admissions, and higher Pitt bacteremia scores in the IV group. The rate of treatment failure was significantly higher in the IV group (24% vs 9%; p < 0.01), which persisted in the logistic regression (aOR 3.5, 95% CI 1.3-9.1). The IV-to-PO group had decreased infection-related and hospital length of stay, as well as fewer catheter-related complications., Conclusions: The use of PO FQ may be considered for the definitive treatment of uncomplicated Enterobacterales BSI in cancer patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Competing Interests: Competing interests: SW declares none. GY declares that he is a signatory to the People’s Vaccine Campaign and is a funding member of Amnesty International, one of the members of the People’s Vaccine Alliance. He was a member of the Covid-19 Vaccine Development Taskforce, hosted by the World Bank, and participated as an academic unpaid adviser in the consultation process that led to the launch of Covax, a global covid-19 vaccine sharing mechanism. He has received grant funding from WHO; Gavi, the Vaccine Alliance; and the Bill & Melinda Gates Foundation.

Background: During the 2020 COVID-19 pandemic, one of the key components of many countries' strategies to reduce the spread of the virus is contact tracing., Objective: To explore public attitudes to a COVID-19 contact tracing app in the United Kingdom., Setting: Online video-conferencing., Participants: 27 participants, UK residents aged 18 years and older., Methods: Qualitative study consisting of six focus groups carried out between 1st-12th May, 2020 (39-50 days into the UK 'lockdown')., Results: Participants were divided as to whether or not they felt they would use the app. Analysis revealed five themes: (1) lack of information and misconceptions surrounding COVID-19 contact tracing apps; (2) concerns over privacy; (3) concerns over stigma; (4)concerns over uptake; and (5) contact tracing as the 'greater good'. Concerns over privacy, uptake and stigma were particularly significant amongst those stated they will not be using the app, and the view that the app is for the 'greater good' was particularly significant amongst those who stated they will be using the app. One of the most common misconceptions about the app was that it could allow users to specifically identify and map COVID-19 cases amongst their contacts and in their vicinity., Conclusions: Our participants were torn over whether digital contact tracing is a good idea or not, and views were heavily influenced by moral reasoning., Patient or Public Contribution: No patients were involved in this study. The public were not involved in the development of the research questions, research design or outcome measures. A pilot focus group with participants not included in the present paper was used to help test and refine the focus group questions. Summary results were disseminated via email to participants prior to publication for feedback and comment., (© 2020 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Objective: This study explored UK public perceptions and experiences of social distancing and social isolation related to the COVID-19 pandemic., Design: This qualitative study comprised five focus groups, carried out online during the early stages of the UK's stay at home order ('lockdown'), and analysed using a thematic approach., Setting: Focus groups took place via online videoconferencing., Participants: Participants (n=27) were all UK residents aged 18 years and older, representing a range of gender, ethnic, age and occupational backgrounds., Results: Qualitative analysis revealed four main themes: (1) loss-participants' loss of (in-person) social interaction, loss of income and loss of structure and routine led to psychological and emotional 'losses' such as loss of motivation, loss of meaning and loss of self-worth; (2) criticisms of government communication-participants reported a lack of trust in government and a lack of clarity in the guidelines around social distancing and isolation; (3) adherence-participants reported high self-adherence to social distancing guidelines but reported seeing or hearing of non-adherence in others; (4) uncertainty around social reintegration and the future-some participants felt they would have lingering concerns over social contact while others were eager to return to high levels of social activity.Most participants, and particularly those in low-paid or precarious employment, reported feeling that the social distancing and isolation associated with COVID-19 policy has had negative impacts on their mental health and well-being during the early stages of the UK's 'lockdown'., Conclusions: A rapid response is necessary in terms of public health programming to mitigate the mental health impacts of COVID-19 social distancing and isolation. Social distancing and isolation 'exit strategies' must account for the fact that, although some individuals will voluntarily or habitually continue to socially distance, others will seek high levels of social engagement as soon as possible., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Spectrally selective "prewinding" radiofrequency pulses can counteract B0 inhomogeneity in steady-state sequences, but can only prephase a limited range of off-resonance. We propose spectral-spatial small-tip angle prewinding pulses that increase the off-resonance bandwidth that can be successfully prephased by incorporating spatially tailored excitation patterns., Theory and Methods: We present a feasibility study to compare spectral and spectral-spatial prewinding pulses. These pulses add a prephasing term to the target magnetization pattern that aims to recover an assigned off-resonance bandwidth at the echo time. For spectral-spatial pulses, the design bandwidth is centered at the off-resonance frequency for each spatial location in a field map. We use these pulses in the small-tip fast recovery steady-state sequence, which is similar to balanced steady-state free precession. We investigate improvement of spectral-spatial pulses over spectral pulses using simulations and small-tip fast recovery scans of a gel phantom and human brain., Results: In simulation, spectral-spatial pulses yielded lower normalized root mean squared excitation error than spectral pulses. For both experiments, the spectral-spatial pulse images are also qualitatively better (more uniform, less signal loss) than the spectral pulse images., Conclusion: Spectral-spatial prewinding pulses can prephase over a larger range of off-resonance than their purely spectral counterparts. Magn Reson Med 79:1377-1386, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

This review examines the role of nutritional strategies to improve lifetime performance in ruminants. Strategies to increase ruminants' productive longevity by means of nutritional interventions provide the opportunity not only to increase their lifetime performances and their welfare, but also to decrease their environmental impact. This paper will also address how such nutritional interventions can increase herd efficiency and farm profitability. The key competencies reviewed in this article are redox balance, skeletal development and health, nutrient utilization and sustainability, which includes rearing ruminants without antibiotics and methane mitigation. While the relationships between these areas are extremely complex, a multidisciplinary approach is needed to develop nutritional strategies that would allow ruminants to become more resilient to the environmental and physiological challenges that they will have to endure during their productive career. As the demand of ruminant products from the rapidly growing human world population is ever-increasing, the aim of this review is to present animal and veterinary scientists as well as nutritionists a multidisciplinary approach towards a sustainable ruminant production, while improving their nutrient utilization, health and welfare, and mitigation of their carbon footprint at the same time., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Suicide risk and protective factors function for prisoners within the context of incarceration. The Culture and Protective Suicide Scale for Incarcerated Persons (CAPSSIP) is a tool designed to assess protective factors and cultural barriers to suicide for inmates. We present initial findings on the reliability, validity, factor structure, and utility of the CAPSSIP based on a trial conducted with inmates sent to an inpatient psychiatric program. Implications for suicide risk assessment processes in correctional settings are discussed. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Improvement in the proportion of underrepresented racial and ethnic minorities (URMs) in academic positions has been unsatisfactory. Although this is a complex problem, one key issue is that graduate students often rely on research mentors for career-related support, the effectiveness of which can be variable. We present results from a novel academic career "coaching" intervention, one aim of which was to provide supplementary social support for PhD students, particularly those from underrepresented backgrounds. Coaching was delivered both within small groups and on an individual basis, with a diverse group of coaches and students coming from many universities. Coaches were provided with additional diversity training. Ninety-six semistructured interviews with 33 URM students over 3 years were analyzed using a qualitative framework approach. For most of the URM PhD students, coaching provided social support in the form of emotional, informational, and appraisal support. Coaching groups provided a noncompetitive environment and "community of support" within which students were able to learn from one another's experiences and discuss negative and stressful experiences related to their graduate school, lab, or career plans. This coached peer group model is capable of providing the social support that many URM students do not find at their home universities., (© 2017 S. N. Williams et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

The Human antigen R protein (HuR) is an RNA-binding protein that recognizes U/AU-rich elements in diverse RNAs through two RNA-recognition motifs, RRM1 and RRM2, and post-transcriptionally regulates the fate of target RNAs. The natural product dihydrotanshinone-I (DHTS) prevents the association of HuR and target RNAs in vitro and in cultured cells by interfering with the binding of HuR to RNA. Here, we report the structural determinants of the interaction between DHTS and HuR and the impact of DHTS on HuR binding to target mRNAs transcriptome-wide. NMR titration and Molecular Dynamics simulation identified the residues within RRM1 and RRM2 responsible for the interaction between DHTS and HuR. RNA Electromobility Shifts and Alpha Screen Assays showed that DHTS interacts with HuR through the same binding regions as target RNAs, stabilizing HuR in a locked conformation that hampers RNA binding competitively. HuR ribonucleoprotein immunoprecipitation followed by microarray (RIP-chip) analysis showed that DHTS treatment of HeLa cells paradoxically enriched HuR binding to mRNAs with longer 3'UTR and with higher density of U/AU-rich elements, suggesting that DHTS inhibits the association of HuR to weaker target mRNAs. In vivo, DHTS potently inhibited xenograft tumor growth in a HuR-dependent model without systemic toxicity., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: To understand the role of hypoxia in prostate tumor progression and to evaluate the ability of the novel unidirectional hypoxia-activated prodrug OCT1002 to enhance the antitumor effect of bicalutamide. Experimental Design: The effect of OCT1002 on prostate cancer cells (LNCaP, 22Rv1, and PC3) was measured in normoxia and hypoxia in vitro In vivo , tumor growth and lung metastases were measured in mice treated with bicalutamide, OCT1002, or a combination. Dorsal skin fold chambers were used to image tumor vasculature in vivo Longitudinal gene expression changes in tumors were analyzed using PCR. Results: Reduction of OCT1002 to its active form (OCT1001) decreased prostate cancer cell viability. In LNCaP-luc spheroids, OCT1002 caused increased apoptosis and decreased clonogenicity. In vivo , treatment with OCT1002 alone, or with bicalutamide, showed significantly greater tumor growth control and reduced lung metastases compared with controls. Reestablishment of the tumor microvasculature following bicalutamide-induced vascular collapse is inhibited by OCT1002. Significantly, the upregulation of RUNX2 and its targets caused by bicalutamide alone was blocked by OCT1002. Conclusions: OCT1002 selectively targets hypoxic tumor cells and enhances the antitumor efficacy of bicalutamide. Furthermore, bicalutamide caused changes in gene expression, which indicated progression to a more malignant genotype; OCT1002 blocked these effects, emphasizing that more attention should be attached to understanding genetic changes that may occur during treatment. Early targeting of hypoxic cells with OCT1002 can provide a means of inhibiting prostate tumor growth and malignant progression. This is of importance for the design and refinement of existing androgen-deprivation regimens in the clinic. Clin Cancer Res; 23(7); 1797-808. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Purpose: The Academy for Future Science Faculty (the Academy) is a novel coaching intervention for biomedical PhD students designed to address limitations in previous efforts to promote faculty diversity. Unlike traditional research mentoring, the Academy includes both group and individual coaching, coaches have no research or evaluation roles with the students, and it is based on social science theories. The authors present a qualitative case study of one of the coaching groups and provide statistical analyses indicating whether one year in the Academy effects students' perceptions of the achievability and desirability of an academic career., Method: The authors tested (July 2012-July 2013), with Northwestern University ethical approval, the Academy via a longitudinal randomized controlled trial. Participants were 121 latter-stage biomedical PhD students. The authors collected data via questionnaires, interviews, and meeting recordings., Results: The case study shows how group career coaching can effectively supplement traditional one-to-one research mentoring; provide new role models for underrepresented minority students; and provide theory-based lenses through which to engage in open conversations about race, gender, and science careers. Repeated-measures analysis of variance showed that perceived achievability increased in the Academy group from baseline to one-year follow-up (mean, 5.75 versus 6.39) but decreased in the control group (6.58 versus 5.81). Perceived desirability decreased significantly less (P < .05) in the Academy group (7.00 versus 6.36) than in the control group (7.83 versus 5.97)., Conclusions: Early results suggest that an academic career coaching model can effectively supplement traditional research mentoring and promote persistence toward academic careers.

Introduction: Many recent mentoring initiatives have sought to help improve the proportion of underrepresented racial and ethnic minorities (URMs) in academic positions across the biomedical sciences. However, the intractable nature of the problem of underrepresentation suggests that many young scientists may require supplemental career development beyond what many mentors are able to offer. As an adjunct to traditional scientific mentoring, we created a novel academic career "coaching" intervention for PhD students in the biomedical sciences., Objective: To determine whether and how academic career coaches can provide effective career-development-related learning experiences for URM PhD students in the biomedical sciences. We focus specifically on vicarious learning experiences, where individuals learn indirectly through the experiences of others., Method: The intervention is being tested as part of a longitudinal randomized control trial (RCT). Here, we describe a nested qualitative study, using a framework approach to analyze data from a total of 48 semi-structured interviews from 24 URM PhD students (2 interviews per participant, 1 at baseline, 1 at 12-month follow-up) (16 female, 8 male; 11 Black, 12 Hispanic, 1 Native-American). We explored the role of the coach as a source of vicarious learning, in relation to the students' goal of being future biomedical science faculty., Results: Coaches were resources through which most students in the study were able to learn vicariously about how to pursue, and succeed within, an academic career. Coaches were particularly useful in instances where students' research mentors are unable to provide such vicarious learning opportunities, for example because the mentor is too busy to have career-related discussions with a student, or because they have, or value, a different type of academic career to the type the student hopes to achieve., Implications: Coaching can be an important way to address the lack of structured career development that students receive in their home training environment.

We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-feet degeneration and perivascular edema; damaged motor neurons, swollen axons with unraveled myelin in ascending and descending tracts and astrogliosis were also observed. Evans Blue dye extravasation was maximal at 7 days. There was immunofluorescence evidence of reduction of microvascular expression of tight junction occludin, upregulation of Beclin-1 and LC3B immunoreactivities at 7 days and a reduction of the latter at 30 days post-ischemia. These novel pathological alterations on the cervical spinal cord microvasculature in rats after tMCAO suggest pervasive and long-lasting BSCB damage after focal cerebral ischemia, and that spinal cord ischemic diaschisis should be considered in the pathophysiology and therapeutic approaches in patients with ischemic cerebral infarction., (© 2016 American Association of Neuropathologists, Inc. All rights reserved.)

The mesolimbic dopamine system plays a major role in psychostimulant-induced ultrasonic vocalization (USV) behavior in rodents. Within this system, psychostimulants elevate synaptic concentrations of dopamine thereby leading to exaggerated activation of postsynaptic dopamine receptors within the D1-like and D2-like subfamilies. Dopamine receptor stimulation activate several transmembrane signaling systems and cognate intracellular mediators; downstream activation of transcription factors then conveys the information from receptor activation to appropriate modulation of cellular and physiologic functions. We previously showed that cocaine-induced USV behavior was associated with enhanced expression of the neurotrophin BDNF. Like cocaine, amphetamine also increases synaptic dopamine levels, albeit primarily through facilitating dopamine release. Therefore, in the present study we investigated whether amphetamine and cocaine similarly activate dopamine-linked signaling cascades to regulate intracellular mediators leading to induction of USV behavior. The results show that amphetamine increased the emission of 50 kHz USVs and this effect was blocked by SCH23390, a D1 receptor antagonist. Similar to cocaine, amphetamine increased BDNF protein expression in discrete brain regions, while pretreatment with K252a, a trkB neurotrophin receptor inhibitor, significantly reduced amphetamine-induced USV behavior. Inhibition of cyclic-AMP/PKA signaling with H89 or inhibition of PLC signaling with U73122 significantly blocked both the acute and subchronic amphetamine-induced USV behavior. In contrast, pharmacologic inhibition of either pathway enhanced cocaine-induced USV behavior. Although cocaine and amphetamine similarly modulate neurotrophin expression and USV, the molecular mechanisms by which these psychostimulants differentially activate dopamine receptor subtypes or other monoaminergic systems may be responsible for the distinct aspects of behavioral responses., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The power of genome-wide association studies (GWAS) for mapping complex traits with single-SNP analysis (where SNP is single-nucleotide polymorphism) may be undermined by modest SNP effect sizes, unobserved causal SNPs, correlation among adjacent SNPs, and SNP-SNP interactions. Alternative approaches for testing the association between a single SNP set and individual phenotypes have been shown to be promising for improving the power of GWAS. We propose a Bayesian latent variable selection (BLVS) method to simultaneously model the joint association mapping between a large number of SNP sets and complex traits. Compared with single SNP set analysis, such joint association mapping not only accounts for the correlation among SNP sets but also is capable of detecting causal SNP sets that are marginally uncorrelated with traits. The spike-and-slab prior assigned to the effects of SNP sets can greatly reduce the dimension of effective SNP sets, while speeding up computation. An efficient Markov chain Monte Carlo algorithm is developed. Simulations demonstrate that BLVS outperforms several competing variable selection methods in some important scenarios., (© 2015 WILEY PERIODICALS, INC.)

In 2010, total knee replacement was the most frequently performed inpatient procedure on adults aged 45 and over. In the 11-year period from 2000 through 2010, an estimated 5.2 million total knee replacements were performed. Adults aged 45 and over comprised 98.1% of those surgeries. This report uses data from the National Hospital Discharge Survey (NHDS) to present trends in the rate of hospitalizations for total knee replacement, mean age at hospitalization, and discharge status for inpatients aged 45 and over from 2000 through 2010., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Posttraumatic stress disorder (PTSD) is of great concern in veterans. PTSD usually occurs after a person is exposed to death, threatened death, actual or threatened serious injury, or actual or threatened sexual violence. Active duty soldiers deployed to war zones are at risk for PTSD. Psychoneuroimmunological theory predicts that PTSD, depression, and stress can lead to low-grade, chronic inflammation. We asked whether there were relationships between PTSD symptoms and chronic stress, depression and inflammation in active duty U.S. soldiers. We enrolled 52 active duty enlisted and reservist soldiers in a cross-sectional study while they participated in a week of military training in fall 2011. They completed a demographic questionnaire, the Center for Epidemiological Studies-Depression Scale, the Combat Exposure Scale, and the PTSD symptom Checklist-Military version (PCL-M). Blood samples were taken for analysis of cytokines and C-reactive protein (CRP). Hair samples shaved from the forearm were measured for cortisol. Of the soldiers, 11 had PCL-M scores in the moderate to severe range. Regression analysis demonstrated that depression and war zone deployment were strong predictors of PTSD symptoms. CRP and hair cortisol were correlated with each other and with depression and PTSD symptoms. These results suggest relationships among war zone deployment, depression, and PTSD. Chronic stress associated with depression, PTSD, and war zone experiences may be related to inflammation in active duty soldiers., (© The Author(s) 2014.)

Implementation lessons: (1) The development and testing of a culturally appropriate palliative care navigation curriculum for countries facing high cancer and non-communicable diseases burden requires collaboration with the local Ministry of Health. (2) Lay volunteers from non-governmental and faith-based organizations are potential candidates to provide patient navigation services., (Copyright © 2014 Elsevier Inc. All rights reserved.)