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PhD students' experiences in graduate school and associated outcomes vary by field of study, learning environment conditions, and support structures. In the context of the COVID-19 pandemic specifically, PhD students' individual educational trajectories were potentially rendered more uncertain, as disruptive conditions for learning and research have continued over the past several years. We compared the reports of 422 PhD students at 12 U.S. institutions in terms of their experiences of support or marginalization and educational plans from the summer of 2020 with follow-up data gathered during the summer of 2021. We then examined factors related to PhD students' changes in their estimated times to degree. We found lower, but still on average moderate, levels of depression symptoms compared to the previous year and continued experiences of emotional, financial, educational, and career stressors. Findings point to the importance of institutional material and psychological structural supports over time.

Despite the breadth of scientific literature on micro- and nanoplastics (MNPs), a standardized procedure for detecting MNPs is still lacking so far, leading to incomparable results between published studies. This work innovatively proposed the combination of machine learning with advanced optical photothermal infrared (O-PTIR) spectroscopy to develop an efficient and reliable detection framework for MNPs. Spectra of MPs and non-MPs were first collected and inputted to build a classification model, based on which four important wavenumbers were selected. A simplified support vector machine (SVM) model was subsequently developed using the selected four wavenumbers. Good predictive ability was evidenced by a high accuracy of 0.9133. The developed method can improve speed as well as the reliability of results, having a great potential for routine analysis of MNPs, ultimately leading to the standardization of detection methods.

Symmetry studies in autism are inconclusive possibly due to different types of stimuli used which depend on either local or global cues. Therefore, this study compared symmetry detection between 20 autistic and 18 non-autistic adults matched on age, IQ, gender and handedness, using contour integration tasks containing open and closed contours that rely more on local or global processing respectively. Results showed that the autistic group performed equally well with both stimuli and outperformed the non-autistic group only for the open contours, possibly due to a different strategy used in detecting symmetry. However, there were no group differences for the closed contour. Results explain discrepant findings in previous symmetry studies suggesting that symmetry tasks that favour a local strategy may be advantageous for autistic individuals. Implications of the findings towards understanding visual sensory issues in this group are discussed.

Cis-regulatory elements (CREs) interact with trans regulators to orchestrate gene expression, but how transcriptional regulation is coordinated in multi-gene loci has not been experimentally defined. We sought to characterize the CREs controlling dynamic expression of the adjacent costimulatory genes CD28, CTLA4 and ICOS, encoding regulators of T cell-mediated immunity. Tiling CRISPR interference (CRISPRi) screens in primary human T cells, both conventional and regulatory subsets, uncovered gene-, cell subset- and stimulation-specific CREs. Integration with CRISPR knockout screens and assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling identified trans regulators influencing chromatin states at specific CRISPRi-responsive elements to control costimulatory gene expression. We then discovered a critical CCCTC-binding factor (CTCF) boundary that reinforces CRE interaction with CTLA4 while also preventing promiscuous activation of CD28. By systematically mapping CREs and associated trans regulators directly in primary human T cell subsets, this work overcomes longstanding experimental limitations to decode context-dependent gene regulatory programs in a complex, multi-gene locus critical to immune homeostasis.

Background & aims: Communicative and sensory differences are core autistic traits, yet speech-perception abilities and difficulties among autistic individuals remain poorly understood. Laboratory studies have produced mixed and inconclusive results, in part because of the lack of input from autistic individuals in defining the hypotheses and shaping the methods used in this field of research. Little in-depth qualitative research on autistic experiences of speech perception has been published, yet such research could form the basis for better laboratory research, for improved understanding of autistic experiences, and for the development of interventions. Existing qualitative research describes widespread autistic listening differences with significant impacts, but these results rely on data gathered via oral interviews in a small sample. The present study addresses these limitations and employs a mixed-methods approach to explore autistic listening experiences. Methods: We gathered survey data from 79 autistic individuals aged 18-55 without diagnosed hearing loss. The questionnaire included 20 closed-set questions on listening abilities and difficulties and three free-text questions on listening experiences. The free-text questions underwent deductive content analysis using a framework composed of themes from previous interview data on listening experiences (including auditory differences, contributing factors, impacts, and coping strategies). Concepts in the free-text data that were not part of the analysis framework were analyzed inductively. Results: In the closed-set data, participants reported listening difficulties in most specified environments, but complex background sounds and particularly background voices caused the most difficulty. Those who reported listening difficulties expressed having substantially greater difficulties than other people the same age. Participants indicated multiple impacts from listening difficulties, most prominently in their social lives. Concepts in the free-text data strongly supported previous interview data on listening differences and factors that affect listening ability, especially the diversity of types of listening difficulties. Consistent with the closed-set data, background-sound complexity and concurrent voices were especially troubling. Some concepts in the free-text data were novel, particularly difficulties with remote, broadcast, and recorded audio, prompting the creation of new themes. Conclusions: Both forms of data indicate widespread listening differences--predominantly listening difficulties--affecting most autistic adults. Diverse types of listening difficulty are evident, potentially indicating heterogeneous underlying mechanisms, and complexity of background noise is consistently identified as an important factor. Listening difficulties are said to have substantial and varied impacts. Autistic adults are keen to share coping strategies, which are varied and usually self-devised. Implications: Based on both the quantitative and qualitative results, we provide recommendations to improve future research and support the autistic community. The data-revealing types of listening difficulties can guide better quantitative research into underlying mechanisms. Such research should take into account potential heterogeneity in listening difficulties. Suggestions for optimized collection of self-report data are also offered. Additionally, our results could be used to improve societal understanding of autistic listening differences and to create beneficial interventions for and with autistic individuals. Moreover, given the willingness of the autistic community to share coping strategies, systematic collation of these strategies could form the basis for self-help and clinical guidance.

Background Many children and young people in England provide support to family members who are disabled, have mental or physical ill health, or misuse drugs or alcohol. Providing care can negatively impact children and young people’s education, employment, health and social participation, with associated costs. Support is needed to prevent and reduce these negative impacts. The study sought to provide new knowledge and address prior research gaps regarding how best to support young carers from their perspective and that of the people they care for. Objectives To address the following questions: What types, components or features of services and other support are seen as helpful, valued, and acceptable to young people who look after someone at home and the people they support? Conversely, what is found to be less or unhelpful? What additional support is perceived as needed? What are the barriers experienced by young and young adult carers in seeking and accessing services for themselves or the person they support? What are the barriers and facilitators for practitioners in providing support and services perceived as valued, helpful and needed by young and young adult carers and the people they support? Design and setting In-depth qualitative methodology using focus groups, in-depth semistructured interviews and workshops in four localities in England. Participants One hundred and thirty-three carers aged 9–25 years with a range of caring and life circumstances and sociodemographic characteristics. Seventeen adult care recipients (parents) with a range of physical and/or mental healthcare and support needs. Nineteen practitioners from schools, colleges, young carers organisations, voluntary sector services, mental health services, the National Health Service, adult social care and local authority adult and children’s social care commissioners. Results The types and aspects of support that young carers and their families need, and value when received, include: support that reduces or removes their practical and emotional caring responsibilities; support to mitigate the negative impacts of care and help with other life issues; information and advice about services and wider resources and support; someone trusted available to talk to; greater awareness, recognition and understanding; and choice, flexibility, and co-development of plans and solutions. We found a great deal of unmet need for support, and variation in type and quality of support received, including geographically. Limitations Potential limitations are that we were not able to engage with, or recruit, young carers from some intended subgroups, meaning some perspectives are missing. Partly because of COVID-19 measures during the study, we mainly recruited through young carers organisations and their family projects, although this was balanced by recruitment through schools and extensive outreach and engagement by the collaborating organisations prior to the project starting. Conclusions Action is now needed to consistently and sustainably implement the types of support that young carers and the people they care for say they need and value. Future work Future work should include more research from the perspectives of young carers and the people they care for, especially from particularly marginalised groups; and research to understand what works and how to improve implementation of the support needed and valued. Study registration This study is registered as Current Controlled Trials ISRCTN13478876. https://doi.org/10.1186/ISRCTN13478876 Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR129645) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 36. See the NIHR Funding and Awards website for further award information. Plain language summary Many children and young people in England provide support to family members who are disabled, have mental or physical ill health, or misuse drugs or alcohol. They are sometimes called young or young adult carers. Providing care often brings satisfaction and a sense of pride but can also have negative effects on young people’s lives. The study aimed to find out their views about what would best support them and the people they care for. The study asked two important questions: (1) What are the difficulties faced by young carers and the people they support in seeking, accessing and receiving the right type of support at the right times? (2) What services and support do they find helpful, what support would they like, and what needs would it meet? To answer these questions, we held group discussions (focus groups) and in-depth interviews with 133 young carers with a range of caring and life circumstances and 17 parents receiving help from a young carer. We also held workshops with 19 practitioners who are involved in identifying, supporting and funding services for young carers and their families. They told us that the types of support that they and their families need, and value when received, include: support for the people they care for, so they are providing less practical and emotional care support to help with any negative impacts of providing care and with other life issues information and advice about services, wider resources and support someone trusted to talk to greater awareness, recognition and understanding choice, flexibility and working together to develop plans and solutions We found a great deal of unmet need for support, and variation in the type and quality of support received, including across geographical areas. Action is now needed to consistently and sustainably implement the types of support that young carers and their families say they need and value. Scientific summary Background Providing care can negatively impact children and young people’s education, employment, health and social participation, with associated costs to individuals and the government. Transition to adulthood can be particularly challenging. Recent years have seen improved legal rights for young carers, aiming to increase support provided and avoiding excessive or inappropriate care that might risk their emotional or physical health or life chances. However, there are substantial knowledge gaps regarding how best to support young carers in the current service and rights context and from the perspective of young carers and the people they care for. Objectives To explore the following questions: What types, components or features of services and other support are seen as helpful, valued and acceptable to young people who look after someone at home and the people they support? Conversely, what is found to be less or unhelpful? What additional support is perceived as needed? What are the barriers experienced by young and young adult carers in seeking and accessing services for themselves or the person they support? What are the barriers and facilitators for practitioners in providing support and services perceived as valued, helpful and needed by young and young adult carers and the people they support? Methods The study used in-depth qualitative methods including focus groups and semistructured interviews with young and young adult carers aged 9–25 years and parent care recipients and workshops with practitioners. Data collection methods in focus groups included group and paired discussions, use of flipchart and stickers, drawing, writing and annotation. Focus groups and interviews were structured around topic guides to explore perceptions of: what is helpful, unhelpful or could be improved about existing services; what additional support is needed and what needs would it cover; and barriers to accessing support. We recruited participants in four localities in England, representing different young carer and marginalised groups and different geographical and sociodemographic areas. The inclusion criteria for young carers were that they be aged between 9 and 25 years and providing unpaid care and, for care recipients, that they be aged 16 years or older and cared for by a young carer (not necessarily a young carer involved in the study). Participants were recruited through young carers organisations, schools and colleges in the four localities. Workshops were held with practitioners from each locality, recruited through partner organisations and their networks. Workshops were informed by preliminary findings from the focus groups and interviews and structured around key findings and questions about barriers and facilitators to their implementation. Data included transcripts, fieldnotes and other written and drawn material and annotations. Data were analysed using deductive and inductive thematic analysis with the aid of NVivo 12 (QSR International, Warrington, UK) software. We set out with particular research questions, seeking to discover what acceptable intervention or support looked like, and for whom, how this related to what was currently on offer and what the barriers to access were perceived to be. Initial codes and themes were also informed by the theoretical frameworks and existing literature described elsewhere in this report. Coding also took place inductively, with categories not pre-set but drawn from the data, allowing the development of unanticipated themes. Analysis of the focus groups and interviews with carers and care recipients took place prior to the practitioner workshops, so that preliminary results could be discussed with the advisory groups and used to inform workshop discussions. Results The study sample was 150 participants of which 17 were care recipients. Young carer participants had varied caring and life circumstances and sociodemographic characteristics. Care recipients were parents with a range of physical and/or mental care and support needs. We found seven key areas of support and services that were perceived by young carers and the people they care for as needed, valued when received, but often lacking. Young carers and the people they care for valued having someone they trust to talk to. This person would listen, understand and be non-judgemental and would not share private information inappropriately and without consulting with them first. Trusted relationships were highly valued where they occurred. The trusted person could be a named person or named role in school or college or a school counsellor; a key worker in a young carers organisation; a social worker or family support worker; or their general practitioner. Young carers and their families also wanted clear, early, accessible information about what to expect and not expect from a service or person. This might include information about the length of the waiting list for that service; how a service or person can and cannot help; expected number of sessions; and when and why information might need to be shared with others. Being transparent, and consulting with the young person about the sharing of information, helped build trust. Clear and well-managed endings mattered, including clarity about why support was ending, what would happen next and where to go should similar help be needed in future. Linking to other support, or new workers when existing staff leave, was also needed, and valued when received. A wide range of support might be required. Accessible and multiformat information and advice about wider resources, and formal and informal support that might be available, were therefore needed. However, information alone was rarely enough. Support to access services was sometimes perceived as needed and valued by young carers and care recipients when received. Practitioners felt that linking to other services by an already-trusted practitioner could increase likelihood of take-up and engagement. Valued practice included helping with introductions, attending sessions or appointments with the young carer or care recipient, and checking in after first sessions to address barriers and concerns. Specific or generalised information about the care recipient’s health conditions and treatment was also valued by young carers, although care recipients in the study did not always want this information shared. The heterogeneity of the young carer population and their caring experiences means that support needed and valued will vary. Choice, flexibility and co-development of plans and solutions are key. This entails involving young carers in decisions and plans; a flexible approach to support; and allowing young carers and their families repeated chances to accept support from services. Timing is important to the young carers and their families; they are not always ready to access support when it is offered, or they need to return to support as circumstances or life stage changed. Support that reduces young people’s practical and emotional caring responsibilities was needed. It was valued when received, but was often absent or insufficient, resulting in considerable unmet need. Reduced caring responsibilities would enable young people to have more time for other things in their lives, such as education, social participation and hobbies, and to have less stress and sense of responsibility. In some cases, it was also perceived that support provided by others would improve the health, happiness and independence of the care recipient. Support needed varied but could come, it was felt, from paid caregivers, adult mental health services, other family members, community groups, social connections and activities or aids and adaptations. It could involve long-term reductions, short breaks and/or emergency or crisis support for the person with care needs. Support to reduce the need for children and young people to provide excessive or inappropriate care by providing more support for the person they care for should consider the whole family. While practitioners recognised the value of whole-family working, both practitioners and young people felt effective support could be given working with specific individuals only, and some young people valued having a practitioner who was ‘just for them’. Practitioners also recognised the challenges involved in providing support for the whole family, such as eligibility criteria mismatches, differences of opinion within the family and different commissioning systems for children’s and adult services. In the absence of support that reduced or removed caring responsibilities, or in addition to it, support that helps with impacts of caring and/or young carers’ other life issues was identified as needed and was valued when received. This included timely, helpful, accessible and young carer-aware mental health support and greater understanding at school, such as flexibility of deadlines for schoolwork and homework, although there was a recognition of the difficult balance between making allowances for the home situation and supporting the young person’s educational progress. Opportunities to take a break at school were valued, as were systems where breaks could be taken without publicly having to give an explanation. Peer support from other young carers was usually valued, along with activities that were ‘fun’ and gave them a break, which were often provided by young carers organisations or sometimes young carer clubs in schools. Greater awareness, recognition and understanding of young carers, what young carers do, and about disability and mental and physical illness, would be helpful to young carers. Although there were some examples where schools, particular school staff, or other students, had shown good awareness and understanding, this was often felt to be lacking. Children’s mental health services needed to be more understanding of the interaction between mental ill health and caring responsibilities. Young carers and the people they care for expressed numerous barriers to accessing the support they needed and valued: the support needed may not have been available and/or services were sometimes not accessible or approachable; there may not have been enough information about a service and how it worked and/or information may not have been communicated in accessible, user-friendly formats. Other perceived barriers identified in the study were service boundaries and lack of links between services. Young carers’ and care recipients’ lack of time and competing priorities such as school or caring responsibilities (for the young carers) and their mental or physical health could get in the way of support. Feelings of fear, mistrust, nervousness, embarrassment, fear of judgement or lack of confidence in seeking help were further barriers and ones that services could help overcome. Lack of transport prevented some carers and care recipients from accessing services, exacerbated by centralised, rather than local, hubs. The findings have economic implications. Provision of care by young adult carers aged 16–25 years costs the state an estimated £1B annually. Recent, relevant and high-quality economic evidence on interventions supporting young carers, and which might alleviate impacts, is limited. In the extant studies found ion the scoping review, estimated costs of interventions per person ranged widely from £121 to £778 for co-developed support planning and review; £1200 to more than £15,000 for family interventions; £265 to £385 for social prescribing; and £1100 for having a designated person at school. Return-on-investment estimates [calculated by dividing estimated benefits (‘returns’) by the cost of the intervention or support provided] ranged from £5 to £91 per £1 spent on whole-family approaches; and £8 per £1 spent for a designated person at school. Most of the ‘returns’ related to a societal perspective, including benefits to the government and to individuals (such as in the form of income gains). Conclusions In-depth listening to young and young adult carers and their families has shown the types, aspects and range of support that young and young adult carers need, and value when received. The study shows much unmet need for support, and variation in type and quality of support received, including geographically. Many of the valued and needed aspects of support are already recognised and embedded in current legislation. Action is now needed to implement this legislation and to sustain and extend the areas of good practice that currently exist. Other aspects of good and needed support we identified are not currently reflected in legal rights, and are not consistently reflected in commissioning, service tenders or practice. Implications for social care commissioners, practitioners and policy-makers There needs to be more funding overall, and more targeted funding and allocation of resources nationally and locally, for adult social care and mental health services to fulfil the requirements of the 2014 Care Act, to prevent children undertaking inappropriate or excessive caring roles, which impact young carers’ wellbeing, education and life prospects. Funding needs to be directed at practitioners and organisations working with young carers and the people they care for to have time to provide the support young carers say they need and value and to allow time for building trusting relationships. Commissioning of services and support in schools, adult and children’s social care, young carers organisations and mental health services could be done in ways that enable continuity of valued support; flexibility of support is needed that responds to changes in needs and strengths over time, and as people’s readiness to access support, and their circumstances, change. There should be wider implementation of whole-family agreements, assessment and practice across and within adult and children’s social care, mental health and the voluntary and community sector. Policy or guidance should recommend a designated person(s) available in schools for young carers to talk to about their caring situation or if they are in need of extra help. Wider roll-out of good practice is needed. Greater use should be made of active linking to wider support, such as accompanying people to meetings or appointments. More, and more accessible and multiformat, information about remit, eligibility, nature and how to access the support available needs to be provided. Advocacy to help people negotiate the system might be beneficial, but better communication is key. Young carers are young people first and the impacts of the care they provide, the context in which they provide it, and the support they need and value varies; their views and individual experiences need to be taken into account. Recommendations for research (numbered in priority order) More research is needed from the perspectives of young and young adult carers and the people they care for, including those from marginalised groups of young and young adult carers, such as those from Roma and Traveller communities and refugee and migrant communities. There are key roles for peer researchers in this type of research. Research is needed to identify and understand the good practice that exists, and how to improve wider implementation of the support needed and valued by young carers and the people they care for. Future research could also valuably include economic evaluation of the support needed set against the costs of not providing it. Study registration This study is registered as Current Controlled Trials ISRCTN13478876. https://doi.org/10.1186/ISRCTN13478876 Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR129645) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 36. See the NIHR Funding and Awards website for further award information.

The aim of this study is to classify seven types of Irish milk (butter, fresh, heart active, lactose free, light, protein, and slimline), supplied by a specific company, using vibrational spectroscopy methods: Near infrared (NIR), mid infrared (MIR), and Raman spectroscopy. In this regard, chemometric methods were used, and the impact of spectral data fusion on prediction accuracy was evaluated. A total of 105 samples were tested, with 21 used in the test set. The study assessed principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), and sequential and orthogonalized partial least squares linear discriminant analysis (SO-PLS-LDA) for classifying different milk types. The prediction accuracy, when applying PLS-DA on individual blocks of data and low-level fused data, did not exceed 85.71 %. However, implementing the SO-PLS-LDA strategy significantly improved the accuracy to 95 %, suggesting a promising method for the development of classification models for milk using data fusion strategies.

BACKGROUND: Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination there is significant variability between individuals in protective antibody levels against SARS-CoV-2, and within individuals against different virus variants. However, host demographic or clinical characteristics that predict variability in cross-reactive antibody levels are not well-described. These data could inform clinicians, researchers, and policymakers on the populations most likely to require vaccine booster shots. METHODS: In an institutional review board-approved prospective observational cohort study of staff at St. Jude Childrens Research Hospital, we identified participants with plasma samples collected after SARS-CoV-2 infection, after mRNA vaccination, and after vaccination following infection, and quantitated immunoglobulin G (IgG) levels by enzyme-linked immunosorbent assay to the spike receptor binding domain (RBD) from 5 important SARS-CoV-2 variants (Wuhan Hu-1, B.1.1.7, B.1.351, P.1, and B.1.617.2). We used regression models to identify factors that contributed to cross-reactive IgG against 1 or multiple viral variants. RESULTS: Following infection, a minority of the cohort generated cross-reactive antibodies, IgG antibodies that bound all tested variants. Those who did had increased disease severity, poor metabolic health, and were of a particular ancestry. Vaccination increased the levels of cross-reactive IgG levels in all populations, including immunocompromised, elderly, and persons with poor metabolic health. Younger people with a healthy weight mounted the highest responses. CONCLUSIONS: Our findings provide important new information on individual antibody responses to infection/vaccination that could inform clinicians on populations that may require follow-on immunization.

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions. Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar−/−, and AG129 mice. Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar−/− mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar−/− mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus. Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile.

SARS-CoV-2 infection causes diverse outcomes ranging from asymptomatic infection to respiratory distress and death. A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoVs) impacts susceptibility to SARS-CoV-2 infection or immunity following infection and vaccination. Therefore, we analyzed samples from the same individuals before and after SARS-CoV-2 infection or vaccination. We found hCCCoV antibody levels increase after SARS-CoV-2 exposure, demonstrating cross-reactivity. However, a case-control study indicates that baseline hCCCoV antibody levels are not associated with protection against SARS-CoV-2 infection. Rather, higher magnitudes of pre-existing betacoronavirus antibodies correlate with more SARS-CoV-2 antibodies following infection, an indicator of greater disease severity. Additionally, immunization with hCCCoV spike proteins before SARS-CoV-2 immunization impedes the generation of SARS-CoV-2-neutralizing antibodies in mice. Together, these data suggest that pre-existing hCCCoV antibodies hinder SARS-CoV-2 antibody-based immunity following infection and provide insight on how pre-existing coronavirus immunity impacts SARS-CoV-2 infection, which is critical considering emerging variants.

Five New World mammarenaviruses (NWMs) cause life-threatening hemorrhagic fever (HF). Cellular entry by these viruses is mediated by human transferrin receptor 1 (hTfR1). Here, we demonstrate that an antibody (ch128.1/IgG1) which binds the apical domain of hTfR1, potently inhibits infection of attenuated and pathogenic NWMs in vitro. Computational docking of the antibody Fab crystal structure onto the known structure of hTfR1 shows an overlapping receptor-binding region shared by the Fab and the viral envelope glycoprotein GP1 subunit that binds hTfR1, and we demonstrate competitive inhibition of NWM GP1 binding by ch128.1/IgG1 as the principal mechanism of action. Importantly, ch128.1/IgG1 protects hTfR1-expressing transgenic mice against lethal NWM challenge. Additionally, the antibody is well-tolerated and only partially reduces ferritin uptake. Our findings provide the basis for the development of a novel, host receptor-targeted antibody therapeutic broadly applicable to the treatment of HF of NWM etiology.

Introduction: Little research on the association of neighborhood environment with physical activity in resource-poor communities has been done. This study assessed changes in perceptions of the neighborhood environment and the association between those perceptions and physical activity in Mexican Americans on the Texas–Mexico border in an area where there would be community efforts to enhance pedestrian and cycling infrastructure and programming. Methods: We analyzed data from a population-based cohort of Mexican American individuals on the Texas–Mexico border. From 2008 to 2018, interviewer-administered questionnaires were used to collect perceptions of neighborhood environment and physical activity at baseline, 5- and 10-year follow-ups, and at other ancillary study visits, with an average of 3 data points per participant. We conducted multivariable longitudinal logistic regression analyses to assess if the changes in odds of positive perceptions of the neighborhood environment over the study years differed by physical activity patterns. Results: The sample (n = 1036) was mostly female (71%), born in Mexico (70%), and had no health insurance (69%). We saw improvements in the perceptions of several neighborhood environment attributes from 2008 to 2018, though we saw different longitudinal trajectories in these perceptions based on an individual's longitudinal physical activity patterns. By 2014–2018, we saw significantly higher positive perceptions of the neighborhood environment for those who consistently met physical activity guidelines compared with those who did not (adjusted rate ratio = 1.12, P =.049). Discussion: We found that perceptions of many neighborhood environment attributes improved between 2008 and 2018, and that overall positive perceptions were associated with consistently meeting physical activity guidelines over time. [ABSTRACT FROM AUTHOR]

Abstract The zoonotic Rift Valley fever virus (RVFV) can cause severe disease in humans and has pandemic potential, yet no approved vaccine or therapy exists. Here we describe a dual-mechanism human monoclonal antibody (mAb) combination against RVFV that is effective at minimal doses in a lethal mouse model of infection. We structurally analyze and characterize the binding mode of a prototypical potent Gn domain-A-binding antibody that blocks attachment and of an antibody that inhibits infection by abrogating the fusion process as previously determined. Surprisingly, the Gn domain-A antibody does not directly block RVFV Gn interaction with the host receptor low density lipoprotein receptor-related protein 1 (LRP1) as determined by a competitive assay. This study identifies a rationally designed combination of human mAbs deserving of future investigation for use in humans against RVFV infection. Using a two-pronged mechanistic approach, we demonstrate the potent efficacy of a rationally designed combination mAb therapeutic.

BackgroundSafely and effectively discharging a patient from the hospital requires working within a multidisciplinary team. However, little is known about how perceptions of responsibility among the team impact discharge communication practices.ObjectiveOur study attempts to understand residents' perceptions of who is primarily responsible for discharge education, how these perceptions affect their own reported communication with patients, and how residents envision improving multidisciplinary communication around discharges.DesignA multi-institutional cross-sectional survey.ParticipantsInternal medicine (IM) residents from seven US residency programs at academic medical centers were invited to participate between March and May 2019, via email of an electronic link to the survey.Main measuresData collected included resident perception of who on the multidisciplinary team is primarily responsible for discharge communication, their own reported discharge communication practices, and open-ended comments on ways discharge multidisciplinary team communication could be improved.Key resultsOf the 613 resident responses (63% response rate), 35% reported they were unsure which member of the multidisciplinary team is primarily responsible for discharge education. Residents who believed it was either the intern's or the resident's primary responsibility had 4.28 (95% CI, 2.51-7.30) and 3.01 (95% CI, 1.66-5.71) times the odds, respectively, of reporting doing discharge communication practices frequently compared to those who were not sure who was primarily responsible. To improve multidisciplinary discharge communication, residents called for the following among team members: (1) clarifying roles and responsibilities for communication with patients, (2) setting expectations for communication among multidisciplinary team members, and (3) redefining culture around discharges.ConclusionsResidents report a lack of understanding of who is responsible for discharge education. This diffusion of ownership impacts how much residents invest in patient education, with more perceived responsibility associated with more frequent discharge communication.

IntroductionMotor Imagery (MI) is when an individual imagines performing an action without physically executing that action and is thought to involve similar neural processes used for execution of physical movement. As motor coordination difficulties are common in autistic individuals it is possible that these may affect MI ability. The aim of this systematic review was to assess the current knowledge around MI ability in autistic individuals.MethodsA systematic search was conducted for articles published before September 2023, following PRISMA guidance. Search engines were PsycINFO, PubMed, Web of Science, Scopus, Wiley Online Library and PsyArXiv. Inclusion criteria included: (a) Original peer-reviewed and pre-print publications; (b) Autistic and a non-autistic group (c) Implicit or explicit imagery tasks (d) Behavioral, neurophysiological or self-rating measures, (e) Written in the English language. Exclusion criteria were (a) Articles only about MI or autism (b) Articles where the autism data is not presented separately (c) Articles on action observation, recognition or imitation only (d) Review articles. A narrative synthesis of the evidence was conducted.ResultsSixteen studies across fourteen articles were included. Tasks were divided into implicit (unconscious) or explicit (conscious) MI. The implicit tasks used either hand (6) or body (4) rotation tasks. Explicit tasks consisted of perspective taking tasks (3), a questionnaire (1) and explicit instructions to imagine performing a movement (2). A MI strategy was apparent for the hand rotation task in autistic children, although may have been more challenging. Evidence was mixed and inconclusive for the remaining task types due to the varied range of different tasks and, measures conducted and design limitations. Further limitations included a sex bias toward males and the hand rotation task only being conducted in children.DiscussionThere is currently an incomplete understanding of MI ability in autistic individuals. The field would benefit from a battery of fully described implicit and explicit MI tasks, conducted across the same groups of autistic children and adults. Improved knowledge around MI in autistic individuals is important for understanding whether MI techniques may benefit motor coordination in some autistic people.

Globally, many children and young people provide support to family members who have poor physical or mental health, are disabled, or misuse drugs and alcohol. These young carers are at higher risk of poorer education, employment, health, and social participation outcomes compared to their peers without caring responsibilities. In the UK, awareness of the challenges faced by young carers, and a framework of their legal rights, are relatively well-developed. However, it is unclear how support can most effectively be provided. Taking a qualitative approach we explored experiences and views of young carers (aged 9-25), conducting focus groups or interviews with 133 young carers and 17 parent care recipients. We explored what aspects of services and support are seen as helpful, valued, and acceptable to young people, and what could be improved. A reflexive, thematic analysis was conducted. Valued support came from: young carers groups (including peer support), school-based and mental health support, and support for the care recipient. Helpful aspects of support included someone who listens and understands, and can be trusted not to break confidentiality; involving the young person in information, decision-making and planning (sometimes including regarding the care recipient); and finding and linking to other services. There was a difficult balance for practitioners between being perceived as proactive, persistent or intrusive when offering support to a young carer, but it was important to allow opportunities for young carers, and those they care for, to change their minds about when and whether to access support. Many interactions were perceived as unhelpful or threatening to the family, and there was often not enough of the type of support that was valued. Sharing of positive experiences can be beneficial for both people seeking support and those delivering it; key messages on what is helpful from the perspective of young carers can help support and shape practice approaches.