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Abstract Background Emerging evidence has demonstrated the unfavourable cardiovascular risk of individuals with lean type 2 diabetes mellitus (T2DM). Our study aims to investigate the prognostic value of lean T2DM in patients with acute myocardial infarction (AMI), stratified by sex. Methods The study cohort examines the clinical characteristics and long-term outcomes of individuals with AMI, stratified by four phenotypes based on T2DM and lean body category—lean T2DM, non-lean T2DM, lean non-T2DM and non-lean non-T2DM. The primary outcome was long-term all-cause mortality. Cox regression model was constructed to investigate the associations of lean and non-lean T2DM phenotypes with mortality, adjusted for age, ethnicity, previous AMI, AMI type, chronic kidney disease, angiotensin converting enzyme inhibitor or angiotensin receptor blockers, beta-blockers, and smoking status. Results A cohort of 9545 AMI patients was examined, with a mean follow-up duration of 3.4 ± 2.4 years. Majority had the non-lean T2DM phenotype (40.4%), followed by non-lean non-T2DM (29.8%), lean non-T2DM (15.9%), and lean T2DM (13.9%). In the T2DM group, one-quarter was lean (N = 1324), while the vast majority (74.5%) was non-lean. Individuals with lean T2DM tended to be female and older. Patients with lean T2DM had the highest rates of heart failure (23.3%, p

Background One million people in England and Wales experience sexual violence and abuse each year, with nearly half experiencing serious sexual offences; around 30,000 survivors access sexual assault referral centres. Objectives This research was commissioned by National Institute for Health and Care Research to evaluate access, interventions and care pathways for survivors, especially those provided through sexual assault referral centres. Design, setting, participants The sexual assault referral centres care pathway was investigated through six sub-studies. There were two Cochrane Reviews (4274 participants). Seventy-two providers and 5 survivors were interviewed at eight sites; the children and young people study involved 12 participants from two sexual assault referral centres. A cohort study involving three-wave data collection over 1 year (21 sites; 2602 service users screened, 337 recruited) used a multilevel modelling framework to explore risk factors for burden of post-traumatic stress disorder symptoms at baseline and change at 1 year. We analysed costs and outcomes and conducted a narrative analysis (41 survivors). We worked closely with survivors and prioritised the safety/welfare of participants and researchers. Results Cochrane Reviews identified large effects from psychosocial interventions for post-traumatic stress disorder and depression. Sexual assault referral centres delivered a high-quality frontline service for survivors but groups experiencing domestic abuse and some ethnic and cultural minorities were under-represented. The qualitative research emphasised inter-agency collaboration for survivor benefit. The cohort study identified a risk ‘triad’ of adverse childhood experiences, poor mental health and economic deprivation, which was associated with baseline trauma burden. There were important improvements in trauma symptoms a year later. These improvements were unrelated to different sexual assault referral centre models. Costs and other outcomes were also similar across models. Harmful policing and justice practices/procedures were identified by 25% of participants. In this context, trauma-competent interviewing techniques, regular/timely updates and conveying case decisions with care signalled good practice. Limitations The cohort study lacked a comparison group, reducing confidence in the finding that access to sexual assault referral centres explained the reduction observed in post-traumatic stress disorder. Conclusions and future work Barriers to access call for concerted efforts to implement trauma-informed universal health services. The risk ‘triad’ underscores the value of holistic approaches to care at sexual assault referral centres and timely follow-on care. Poor mental health was the main barrier to service access beyond sexual assault referral centres. The persistence of trauma symptoms a year after accessing sexual assault referral centres signals urgent need for tackling counselling wait-lists, expanding support options and commitment to lifelong care. Multidisciplinary evaluation of sexual assault referral centres for better health provides a foundation for advancing trauma-informed practices in the context of sexual violence and abuse. Study registration This study is registered as ISRCTN30846825 https://doi.org/10.1186/ISRCTN30846825 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: 16/117/04) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 35. See the NIHR Funding and Awards website for further award information. Plain language summary What was the question? Around 30,000 survivors of rape, sexual assault and sexual abuse access sexual assault referral centres in England each year. Sexual assault referral centres provide support, health care and, if people wish, can gather evidence for a criminal investigation. Sexual assault referral centres also open routes to other care/support. We intended to understand the benefits of sexual assault referral centres and ways to improve care. What did we do? We interviewed 72 professionals to understand how they worked together. We followed up 335 survivors over 1 year after visiting a sexual assault referral centre. We gathered the views of 12 children and young people and 41 people from minority and disadvantaged backgrounds. We examined existing research to gather evidence of the benefit of care/support. We worked with survivors to confirm the safety and relevance of our research. What did we find? Participants were positive about sexual assault referral centres and Independent Sexual Violence Advisors, reporting very low harms (1% viewed sexual assault referral centre services as harmful to them). They were also satisfied with charities offering counselling, helplines and advocacy (4% harms). The research gathered mixed feedback about the National Health Service and police, with more harm being reported (15% and 25%, respectively). We found gaps in NHS care for those with complex trauma and long-term mental health problems. Post-traumatic stress disorder affected 70% of participants, with the highest being observed for those with adverse childhood experiences, poor mental health and economic struggles (a risk ‘triad’). Improvements occurred 1 year later, although half of participants still had trauma symptoms. We identified new treatments (e.g. yoga) as potential alternatives to traditional interventions. What does this mean? Sexual assault referral centres offer excellent care to survivors but should be accessible to a wider group of people. Identifying, supporting and careful referral of those with the risk triad mentioned may aid recovery after sexual violence and abuse. The research suggests that the NHS and policing/justice needs to ensure that they provide good care more often. Scientific summary Background Approximately 30,000 victims and survivors of rape, sexual assault and sexual abuse access sexual assault referral centres (SARCs) each year; therefore, there has been an urgent need to assess the experiences of these services. There is also a need to improve options for care; the visibility of and access to SARCs; and collaboration within frontline specialist services to serve people of all ages and genders exposed to sexual assault and rape in England. This research was commissioned by the National Institute for Health and Care Research (NIHR) to evaluate the provision of SARCs. We intended to determine the extent to which SARCs meet the needs of victims and survivors of recent and non-recent sexual violence and abuse, including children, young people and other survivors who may be silenced across different communities in Britain. Objectives The multidisciplinary evaluation of sexual assault referral centres for better health (MESARCH) project addressed a range of research questions, allowing for the evaluation of SARCs and expanding evidence for different services and interventions across SARC care pathways. The questions are as follows: For individuals who have had exposure to sexual violence and abuse, do psychosocial interventions reduce post-traumatic stress disorder (PTSD) and other poor health outcomes? What are providers’ experiences of delivering such psychosocial interventions? What are the experiences of survivors and supporters in accessing such psychosocial interventions? What are the implications of inter-related aspects of SARCs – the everyday work they do, the workforce, the technology and the organisation – for the delivery of SARC services? To what extent are SARCs embedded within the overall response by statutory and voluntary sector organisations to meet the needs of survivors? What are the health and cost trajectories of those who attend SARCs? How can these be compared for different SARC models of service delivery and access to health and Sexual Assault and Abuse Services (SAAS)? What is the effect of different sectors where survivors receive care, including any advantages or disadvantages of accessing post-crisis counselling in the voluntary sector compared with the NHS? What are the experiences of children and young people (CYP) in receiving care and support from SARCs? What do CYP’s recovery journeys look like after receiving support from SARCs? What are the experiences of access to SARCs by survivors with additional vulnerabilities such as chronic mental health problems and survivors from racially and other minoritised populations such as lesbian, gay, bisexual, transgender and/or queer survivors and those with socio-economic deprivation? Methods An innovative focus on patient and public involvement prioritised the safety and welfare of participants and researchers, largely through experts-by-experience embedded across the project lifecycle. A range of mixed-methods was employed: Systematic review, meta-analysis and qualitative evidence synthesis for two Cochrane Reviews For the SARC process evaluation, we mapped out service delivery, undertook thematic analysis of data collected from professionals from a range of SARCs and partners and integrated qualitative data on survivors’ experiences from the cohort study The cohort study interviewed survivors about their health, well-being and service use at baseline, 6 months and 12 months post-SARC. A multilevel modelling framework was used to explore risk factors for PTSD symptoms [Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5)] (primary outcome) at baseline and reduction in symptoms during the subsequent year; and determine whether SARC service models, service experience and participant-level factors influenced the outcome An economic evaluation based on the costs and changes in health-related quality of life, examining cost per quality-adjusted life-year (QALY) gained at 6 and 12 months Thematic analysis was used in the CYP study A life-narrative method with dialogical narrative analysis was applied in a qualitative study embedded within the cohort study to explore access and recovery experiences of racially minoritised survivors or those disadvantaged by other minoritised identities. Settings of studies in the Cochrane Reviews were health (emergency, primary care) and clinical/therapeutic (mental health), medico-legal (similar to SARCs), universities and community (charity-provided services) and most studies were from the USA. For our primary research, our process evaluation study included eight SARC sites and their inward and onwards partners/professionals; the cohort study followed-up survivors attending 21 SARCs; the CYP study was conducted at two SARCs; the qualitative study included cohort participants and a community (non-SARC) setting. Overall, 24 voluntary sector agencies, a local authority and an NHS sexual health clinic referred people into the sub-studies as our main model of recruitment. The study participants included 72 professionals and 5 survivors from service providers in the process evaluation; 2602 adult service users screened for eligibility through SARCs, 337 of whom joined the cohort study; 34 cohort participants and 7 people from the community (qualitative study); and 12 CYP. Two Cochrane Reviews reported on 4274 survivors, 19 family members and 60 providers. Results A comparative analysis of psychosocial interventions with inactive controls in our Cochrane Review suggests a beneficial effect at post-treatment favouring psychosocial interventions in reducing PTSD [standardised mean difference (SMD) −0.83, 95% confidence interval (CI) −1.22 to −0.44; 16 studies, 1130 participants; low‐certainty evidence; large effect size based on Cohen’s d] and depression (SMD −0.82, 95% CI −1.17 to −0.48; 12 studies, 901 participants; low‐certainty evidence; large effect size). The main comparative analysis did not detect unwanted effects from interventions. Our complementary Cochrane Review revealed that interventions helped survivors to better understand trauma and its effects, re-engage in many areas of life and improve interpersonal functioning. ‘Readiness’ was vital for engagement and may be as important as intervention content. Empowering survivors (and supporters) to make decisions about their interventions, for instance, having control over when they start and end interventions, was an important step in recovery. Our process evaluation study showed that SARCs remain an underutilised care pathway for survivors, exacerbated by lack of awareness in the general public, and thus survivors. Routes to SARC care are well-established among police forces, but poorly developed across some other professional groups (e.g. general practitioners [GPs]). Statutory and voluntary sector organisations working in partnership provides enhanced care for survivors, but SARCs and other organisations are hampered by a range of organisational and commissioning structures and processes. Service users joined the cohort study (with a baseline interview) 100 days after they had accessed a SARC (median = 104 days). They met the inclusion criteria of being ≥ 18 years and having sought assistance from a SARC after sexual violence and abuse (index exposure). This abuse was perpetrated by acquaintances (40%), strangers (20%) and partners (25%) and during childhood (13%). Forty-four per cent of the participants accessed a SARC within 10 days of trauma exposure; 38% underwent a forensic medical examination, and 85% had accessed Independent Sexual Violence Advisor (ISVA) care at baseline. Cohort participants were mainly women (90%), belonged to non-minoritised ethnicities (85%), had a mean age of 32 years (range: 18–75 years) and reported a high burden of lifetime trauma [77% indicated four or more adverse childhood experiences (ACEs) and 80% had prior exposure to domestic abuse]. Seventeen per cent of the users faced major daily financial problems. Nearly half of them had pre-existing mental health problems at the point of accessing SARC, and more than half had attempted suicide. Between SARC access and baseline, 56% had been prescribed psychotropic medications and had an average of 20 contacts with health/social/third-sector care [21 contacts at 6 months (a longer timeframe), dropping to 13 at 12 months]. At baseline, 71% of participants had ‘probable PTSD’, decreasing to 55% at 1 year. This reflected an unadjusted mean reduction of 9 points on PCL-5 (95% CI 6.6 to 11, Cohen’s d = 0.53), equating to a clinically important within-group change. One-third of the original cohort was lost to follow-up at 1 year, differing from those retained only on having greater socio-economic deprivation. The study did not detect differences in outcomes at 1 year according to the type of SARC service model (there were four types) they accessed or the location of the ISVA (some ISVAs are part of the SARC team and others are located in the community). There was strong evidence of a positive association between service use and symptom level at baseline, with a one-unit increase in the log of service use count being associated with a 4.5-point higher symptom score at baseline (95% CI 2.6 to 6.4; p < 0.001). For participant-level factors, each additional ACE was associated with a 1.4-point greater score of PTSD symptoms (95% CI 0.8 to 1.9; p < 0.001) and pre-existing mental health problems, with a 7.6-point difference (95% CI 4.0 to 11.1; p < 0.001). Participants with greater financial resources had fewer symptoms than for those with smaller financial resources (p = 0.009). Additionally, there was strong evidence that being unable to work was associated with a 10-point higher baseline score (p < 0.001). For offence-related factors, there was weak evidence that a delay to SARC of more than 10 days was associated with an approximately 4.5-point greater symptom score (p = 0.087), and a similar level of evidence was observed for an association for perpetrator type, where it appears that when the perpetrator was the survivor’s partner/family member, the baseline symptom score was greater. The main predictor of PTSD at 12 months was the baseline score. A high ACE profile doubled the odds of meeting the PTSD diagnostic threshold at baseline, but it reduced to 1.5 at 6 months and was absent at 1 year. SARCs and third-sector agencies achieved consistently high standards of care for survivors across sub-studies, with 50% of participants submitting ratings for these sectors as ≥ 90 on a harm-benefit scale [−100 to 100]. However, harmful responses were much more common in statutory health and justice settings, affecting 15% and 25% of participants, respectively (compared with 1% for SARCs and 4% for the third sector). The children and young people study observed that recovery and healing was influenced by how quickly the CYP accessed support, its content and duration, the location and context of care, how well the services worked together and CYP’s interactions with professionals at SARCs and across sectors. The embedded narrative study identified vital issues around access, as well as risk and recovery, in particular, inequalities arising from chronic mental health, economic disadvantage and family/community-based abuse highly mirroring the risk triad identified in the cohort study. Consistent support for survivors from all professionals and organisations a survivor engages with, ability to move away from the location where abuse has occurred and the opportunity to keep trying different therapies or activities supporting recovery were identified as helpful approaches to the recovery journey. Conclusions Sexual assault referral centres must recognise the high burden of lifetime trauma and chronic mental problems that affect most service users accessing this service. There is evidence that these factors, together with socio-economic status, affect people’s PTSD presentation to a greater degree than aspects of the offence (perpetrator and time since trauma), although these were still important. Different types of SARC and ISVA models did not appear to impinge on trauma symptoms at 1 year, or the way in which survivors experienced care within the SARC and onwards support agencies. Survivor service use was positively related to baseline trauma, which decreased over time, and costs did not differ according to the type of SARC or ISVA service accessed. This emphasises the importance of raising the visibility of SARCs as a care route overall, rather than recommending a specific model of delivery. The SARC pathway may deliver benefits to survivors who report clinically important reductions over time, especially among those with the greatest burden. However, half of the study sample participants remained positive for PTSD at 1 year. Every recovery journey following a sexual assault or abuse is different, and both formal and informal sources of support are important. A consistent trauma-informed societal response to sexual violence is needed. For CYP, early support from SARCs and accessible trauma-informed support throughout adolescence and into adulthood was critical in young people’s recovery. Implications for health care Sexual assault referral centre services deliver a high-quality frontline service for survivors and an effective gateway to health, ISVAs and voluntary sector services. A triad of lifetime traumas, chronic mental health problems and economic deprivation is apparent, which highlights the potential for holistic approaches at SARCs. Enquiring about a wide range of background factors may enhance timely access to appropriate therapies (see our Cochrane Reviews) as well as to social care and advocacy for housing, finances and domestic abuse, as part of the multipronged approach to support recovery and healing among survivors of sexual violence and abuse. Mental health difficulties represented the main barrier to accessing services beyond SARCs, and people affected struggled to consistently access the primary and therapeutic care they needed in the NHS as well as engagement with justice, calling for dedicated ISVA resources with mental health specialism. Inequalities are exacerbated in situations where survivors with relevant resources have the ability to pay for the therapeutic care they need and those without resources do not have the ability to pay and are left waiting. The findings on risk facing racially and other minoritised groups call for concerted efforts to support people to reach care through outreach programmes and campaigns and implement trauma-informed universal health services. Narratives of racial and cultural discrimination by services were not dominant in our qualitative enquiry, but a profound damage was reported when discrimination had occurred. There are vital interconnections between experiences of justice and health outcomes in this context. Harm in police and justice settings was marked, and calls for ongoing efforts to improve communication and other practices by the police in this context are warranted. Our data identified the good practice witnessed, and narratives containing practical measures agencies can take to minimise harms and enhance experiences of justice. We found support for cohesive commissioning strategies that promote a collaborative whole-systems approach to meeting the wide-ranging needs of people after exposure to sexual violence and abuse. The research evidences important improvements in trauma symptoms, but symptoms persisted for many participants at 1 year, supporting calls for tackling wait-lists, enhancing the therapy offering and a commitment to lifelong care for survivors of sexual violence and abuse. Working with survivor stakeholders at all research levels has been demonstrated to enhance feasibility of research and was experienced as empowering by survivor participants; this ethos should be translated into practice settings to diagnose barriers to meeting survivors’ needs and promote services improvement. Future research must focus on expanding evidence for interventions and developing professional interventions for enhancing trauma-informed practice. The MESARCH project identified strengths and urgent gaps in health and justice provision for survivors, and the findings provide a foundation for advancing trauma-informed practices when providing care to and supporting people exposed to the damaging effects of sexual violence and abuse. Study registration This study is registered as ISRCTN30846825 https://doi.org/10.1186/ISRCTN30846825 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: 16/117/04) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 35. See the NIHR Funding and Awards website for further award information.

Background: White spot lesion is a demineralization process indicated by the increased of enamel microporosity. A tegillarca granosa shell contains 98.7% calcium and Vitis vinifera contains phytochemical compounds with fluoride, which has a potential to stimulate remineralization. Purpose: To analyze the Tegillarca granosa shell combination with Vitis vinifera and fluoride in decreasing enamel microporosity. Methods: The cream was prepared by combining 10% and 20% Tegillarca granosa shell with 10 grams of Vitis vinifera extract and 100 mg of fluoride. The cream was tested beforehand for viscocity and pH. Furthermore, 16 premolars were etched and divided into four groups. Group 1 was smeared with placebo (negative control) and Group 2 was smeared with casein phosphopeptide-amorphous calcium phosphate (positive control). The other groups were smeared with cream 10% (Group 3) and 20% (Group 4) Tegillarca granosa shell combination with Vitis vinifera and fluoride. Teeth were treated three times a day for 30 minutes and soaked in artificial saliva. After 14 days, the enamel microporosity was carried out using a scanning electron microscope. The data was analyzed with one-way analysis of variance (ANOVA) test followed by post-hoc least significant difference (LSD). Results: The enamel microporosity showed significant difference between Group 1 and the other groups. There was no significant difference between Groups 2, 3, and 4 (p0.05). Conclusion: The cream, prepared by combining Tegillarca granosa shell with Vitis vinifera and fluoride, is effective in decreasing the enamel microporosity.

BackgroundLimited guidance exists for analyzing participant engagement in provider-guided digital health interventions (DHIs). System usage is commonly assessed, with acknowledged limitations in measuring socio-affective and cognitive aspects of engagement. Nurse WRITE, an 8-week web-based nurse-guided DHI for managing symptoms among women with recurrent ovarian cancer, offers an opportunity to develop a framework for assessing multidimensional engagement. ObjectiveThis study aims to develop a conceptual and analytic framework to measure socio-affective, cognitive, and behavioral engagement with provider-guided DHIs. We then illustrate the framework’s ability to describe and categorize engagement using Nurse WRITE as an example. MethodsA sample of 68 participants from Nurse WRITE who posted on the message boards were included. We adapted a prior framework for conceptualizing and operationalizing engagement across 3 dimensions and finalized a set of 6 distinct measures. Using patients' posts, we created 2 socio-affective engagement measures—total count of socio-affective engagement classes (eg, sharing personal experience) and total word count—and 2 cognitive engagement measures—total count of cognitive engagement classes (eg, asking information-seeking questions) and average question completion percentage. Additionally, we devised behavioral engagement measures using website data—the total count of symptom care plans and plan reviews. k-Means clustering categorized the participants into distinct groups based on levels of engagement across 3 dimensions. Descriptive statistics and narratives were used to describe engagement in 3 dimensions. ResultsOn average, participants displayed socio-affective engagement 34.7 times, writing 14,851 words. They showed cognitive engagement 19.4 times, with an average of 78.3% completion of nurses' inquiries. Participants also submitted an average of 1.6 symptom care plans and 0.7 plan reviews. Participants were clustered into high (n=13), moderate (n=17), and low engagers (n=38) based on the 6 measures. High engagers wrote a median of 36,956 (IQR 26,199-46,265) words. They demonstrated socio-affective engagement approximately 81 times and cognitive engagement around 46 times, approximately 6 times that of the low engagers and twice that of the moderate engagers. High engagers had a median of 91.7% (IQR 82.2%-93.7%) completion of the nurses’ queries, whereas moderate engagers had 86.4% (IQR 80%-96.4%), and low engagers had 68.3% (IQR 60.1%-79.6%). High engagers completed a median of 3 symptom care plans and 2 reviews, while moderate engagers completed 2 plans and 1 review. Low engagers completed a median of 1 plan with no reviews. ConclusionsThis study developed and reported an engagement framework to guide behavioral intervention scientists in understanding and analyzing participants’ engagement with provider-guided DHIs. Significant variations in engagement levels across 3 dimensions highlight the importance of measuring engagement with provider-guided DHIs in socio-affective, cognitive, and behavioral dimensions. Future studies should validate the framework with other DHIs, explore the influence of patient and provider factors on engagement, and investigate how engagement influences intervention efficacy.

Abstract Astronauts experience significant and rapid bone loss as a result of an extended stay in space, making the International Space Station (ISS) the perfect laboratory for studying osteoporosis due to the accelerated nature of bone loss on the ISS. This prompts the question, how does the lack of load due to zero-gravity propagate to bone-forming cells, human fetal osteoblasts (hFOBs), altering their maturation to mineralization? Here, we aim to study the mechanotransduction mechanisms by which bone loss occurs in microgravity. Two automated experiments, microfluidic chips capable of measuring single-cell mechanics via aspiration and cell spheroids incubated in pressure-controlled chambers, were each integrated into a CubeLab deployed to the ISS National Laboratory. For the first experiment, we report protrusion measurements of aspirated cells after exposure to microgravity at the ISS and compare these results to ground control conducted inside the CubeLab. We found slightly elongated protrusions for space samples compared to ground samples indicating softening of hFOB cells in microgravity. In the second experiment, we encapsulated osteoblast spheroids in collagen gel and incubated the samples in pressure-controlled chambers. We found that microgravity significantly reduced filamentous actin levels in the hFOB spheroids. When subjected to pressure, the spheroids exhibited increased pSMAD1/5/9 expression, regardless of the microgravity condition. Moreover, microgravity reduced YAP expression, while pressure increased YAP levels, thus restoring YAP expression for spheroids in microgravity. Our study provides insights into the influence of microgravity on the mechanical properties of bone cells and the impact of compressive pressure on cell signaling in space.

La reflexión sobre interculturalidad en la Educación Superior en los últimos años se ha convertido en un espacio de encuentro para el debate teórico-conceptual acerca de sus comprensiones en los contextos universitarios. En este escenario, el presente artículo identifica los discursos de interculturalidad en Educación Superior a partir de una revisión sistemática del conocimiento en el contexto latinoamericano. Para ello, se seleccionaron 22 artículos de bases de datos de acceso abierto Scielo y Jstor publicados entre el 2018 y 2022 mediante el método Preferred Reporting Items for Systematic reviews and Meta-Analyses. Los términos de búsqueda utilizados fueron: interculturalidad, educación superior, educación intercultural bilingüe, educación intercultural. El análisis se realizó mediante el uso de matrices de contenido desde la hermenéutica. Entre los principales hallazgos, se deduce que la interculturalidad se comprende en términos étnicos y culturalistas. Además, se infiere que los programas y planes de estudios atienden mayoritariamente a las poblaciones originarias de los países latinoamericanos mediante políticas integracionistas. Finalmente, los autores de los estudios sugieren un cambio de paradigma en la comprensión de la interculturalidad, mediante la valoración de los saberes diversos, y como designio de toda la sociedad y no solo de los grupos denominados minoritarios. Se concluye que los discursos giran en torno a tres posicionamientos: lo epistémico, lo político y lo cultural. Palabras clave: Educación intercultural bilingüe, educación superior, interculturalidad, pueblos originarios. ABSTRACT Reflection on interculturality in Higher Education has become a meeting space for theoretical-conceptual debate about its understanding in university contexts in recent years. In this scenario, this article identifies the discourses of interculturality in Higher Education based on a systematic review of knowledge in the Latin American context. To achieve this, 22 articles from Scielo and Jstor open-access databases published between 2018 and 2022 were selected using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. The search terms used were interculturality, higher education, bilingual intercultural education, and intercultural education. The analysis was carried out through the use of content matrices from hermeneutics. Among the main findings, it is deduced that interculturality is understood in ethnic and culturalist terms. Furthermore, it is inferred that the programs and curricula mainly serve the populations originating from Latin American countries through integrationist policies. Finally, the authors of the studies suggest a paradigm shift in the understanding of interculturality through the valuation of diverse knowledge, and as a design of the entire society and not only of the so-called minority groups. In conclusion, the discourses revolve around three positions: the epistemic, the political, and the cultural. Keywords: Bilingual Intercultural Education, Higher education, interculturality, indigenous peoples

Abstract Background Pathological complete response (pCR) is associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, only 30–40% of TNBC patients treated with neoadjuvant chemotherapy (NAC) show pCR, while the remaining 60–70% show residual disease (RD). The role of the tumor microenvironment in NAC response in patients with TNBC remains unclear. In this study, we developed a machine learning-based two-step pipeline to distinguish between various histological components in hematoxylin and eosin (H&E)-stained whole slide images (WSIs) of TNBC tissue biopsies and to identify histological features that can predict NAC response. Methods H&E-stained WSIs of treatment-naïve biopsies from 85 patients (51 with pCR and 34 with RD) of the model development cohort and 79 patients (41 with pCR and 38 with RD) of the validation cohort were separated through a stratified eightfold cross-validation strategy for the first step and leave-one-out cross-validation strategy for the second step. A tile-level histology label prediction pipeline and four machine-learning classifiers were used to analyze 468,043 tiles of WSIs. The best-trained classifier used 55 texture features from each tile to produce a probability profile during testing. The predicted histology classes were used to generate a histology classification map of the spatial distributions of different tissue regions. A patient-level NAC response prediction pipeline was trained with features derived from paired histology classification maps. The top graph-based features capturing the relevant spatial information across the different histological classes were provided to the radial basis function kernel support vector machine (rbfSVM) classifier for NAC treatment response prediction. Results The tile-level prediction pipeline achieved 86.72% accuracy for histology class classification, while the patient-level pipeline achieved 83.53% NAC response (pCR vs. RD) prediction accuracy of the model development cohort. The model was validated with an independent cohort with tile histology validation accuracy of 83.59% and NAC prediction accuracy of 81.01%. The histological class pairs with the strongest NAC response predictive ability were tumor and tumor tumor-infiltrating lymphocytes for pCR and microvessel density and polyploid giant cancer cells for RD. Conclusion Our machine learning pipeline can robustly identify clinically relevant histological classes that predict NAC response in TNBC patients and may help guide patient selection for NAC treatment.

Capture of carbon dioxide from the atmosphere is challenging and thermodynamically expensive because of its dilute concentration (421 ppm, December 2023). Utilizing the concentrating effect of dissolving atmospheric CO2 in alkaline solution to form dissolved inorganic carbon (DIC), we explored the potential of an alkalotolerant hydrogenotrophic methanogen, Methanococcus vannielii, to capture and convert CO2 at low partial pressures to methane. Kinetic constants for CO2 reduction to CH4 were determined from experiments in serum bottles at low pCO2 at 30˚C. At pH 7, 8, and 9, the apparent KM is 0.4, 1.2, and 1.2 mM DIC and the apparent vmax is 5.6, 7.8, and 2.9 mmol CH4 L−1 OD−1 hr−1, respectively. Using atmosphere-equilibrated DIC concentrations at pH 7, 8, and 9, methane formation rates were 1.1, 2.3, and 2.1 mmol CH4 L−1 OD−1 hr−1, respectively. Our data show that alkaline hydrogenotrophic methanogenesis is an alternative to photosynthetic CO2 fixation for biological capture and conversion of CO2 at atmospheric concentrations at reasonable rates.

Background: Recent clinical evidence showed that breast cancer with low HER2 expression levels responded to trastuzumab deruxtecan therapy. The HER2-low cancers comprise immunohistochemistry (IHC) score 1+ and 2+ ISH non-amplified tumours, currently classified as HER2 negative. Little data exists on the reproducibility of pathologists reporting of HER2-low cancer. Patient and methods: Sixteen expert pathologists of the UK National Coordinating Committee for Breast Pathology scored 50 digitally scanned HER2 IHC slides. The overall level of agreement, Fleiss multiple-rater kappa statistics and Cohen's Kappa were calculated. Cases with low concordance were re-scored by the same pathologists after a washout period. Results: Absolute agreement was achieved in 6% of cases, all of which scored 3+. Poor agreement was found in 5/50 (10%) of cases. This was due to heterogeneous HER2 expression, cytoplasmic staining and low expression spanning the 10% cut-off value. Highest concordance (86%) was achieved when scores were clustered as 0 versus others. Improvement in kappa of overall agreement was achieved when scores 1+ and 2+ were combined. Inter-observer agreement was moderate to substantial in the whole cohort but fair to moderate in the HER2-low group. Similarly, consensus-observer agreement was substantial to almost perfect in the whole cohort and moderate to substantial in the HER2-low group. Conclusion: HER2-low breast cancer suffers from lower concordance among expert pathologists. While most cases can reproducibly be classified, a small proportion (10%) remained challenging. Refining the criteria for reporting and consensus scoring will help select appropriate patients for targeted therapy.

The management of the COVID-19 pandemic not only depends on the stringency measures established by governments but also and more importantly on the underlying capacity of territories in economic and health and sanitary infrastructure. This study aims to identify how the underlying conditions of countries influence on their level of COVID-19 lethality rate. To do so, a classification of countries is first conducted by the means of the k-means partitioning method, using COVID-19-related variables such as the lethality rate, the contagion growth rate and the number of days with respect to China. Based on the resulting groups of countries of the first stage, Tobit and Ordinary Least Squares regressions are estimated to determine the effect of the underlying characteristics of countries on their COVID-19 lethality rate. Risks factors which increase the lethality rate in countries are the contagion growth rate, the trade flow with China, the age composition of the population and, to a lesser extent, the population density. Factors that help to reduce the lethality rate are the government effectiveness, the health infrastructure (hospital beds) and, to a lesser extent, the economic growth rate.

Abstract Microplastics (MPs) have become an environmental concern in recent years, with most research focused on the physiological effects of exposure. Comparatively little consideration has been given to the potential behavioral impacts of exposure, which may also have fitness consequences for individuals. Moreover, MPs can serve as vectors for endocrine‐disrupting chemicals and other locally co‐occurring contaminants known to impair behavioral responses. This project aimed to determine whether MPs alone or in association with a common environmental EDC (17‐alpha ethinyl estradiol; EE2) alter reproductive behavior and decision‐making in fish. Male and female fathead minnows (Pimephales promelas) were exposed to MPs associated with either a low (10 ng/L; MPEE2 10) or high (50 ng/L, MPEE2 50) concentration of EE2, or MPs without EE2 (MPvirgin) for 30 days via a dietary feeding protocol. Behavioral trials were conducted on Day 31 to determine the effects of exposure on male–female social interactions. The expression of male sexually selected traits, including courtship, was unaffected by exposure. However, non‐exposed females in all treatment groups trended toward discrimination against exposed males, which reached statistical significance for the MPEE2 50 group. Female fish exposed to MPs, alone or in association with EE2, were equally likely to approach and associate with non‐exposed and exposed males. The results from this study suggest that MPs may alter social behavior in fishes and that the behavioral impacts of exposure may be more strongly pronounced in females than males. Such individual‐level changes in fitness have the potential to impact population size, with downstream effects on the broader aquatic community.

This essay explores the potential of the voice which makes a place of and for itself, as present in Holly Pester’s Eclogues for Idle Workers and in its reception of Virgil’s Eclogues. The relation between Pester’s work and Virgil’s is analysed in terms of Pester ‘speaking with’ Virgil’s text: both ventriloquising it and working ‘in conversation’ with it. It follows Pester’s critical work, as well as readings from Mladen Dolar, Denise Riley and the artist Lypsinka, in order to argue for the presence in both works under discussion of a voice which is made by and makes place. It next argues that the poetry composer-reader must work, as a lip-syncer does, to claim this voice, to intensify its presence. The work done to claim voice is also the work necessary for returning the self to a future otherwise foreclosed by the constraining linguistic context of the waged work relation.

Abstract The Brazilian Society of Angiology and Vascular Surgery, through the Guidelines Project, presents new Abdominal Aortic Aneurysm Guidelines, on the subject of care for abdominal aortic aneurysm patients. Its development prioritized descriptive guidelines, using the EMBASE, LILACS, and PubMed databases. References include randomized controlled trials, systematic reviews, meta-analyses, and cohort studies. Quality of evidence was evaluated by a pair of coordinators, aided by the RoB 2 Cochrane tool and the Newcastle Ottawa Scale forms. The subjects include juxtarenal aneurysms, infected aneurysms, and new therapeutic techniques, especially endovascular procedures. The current version of the guidelines include important recommendations for the primary topics involving diagnosis, treatment, and follow-up for abdominal aortic aneurysm patients, providing an objective guide for medical practice, based on scientific evidence and widely available throughout Brazil.

A community engaged research (CER) approach was used to provide an exposure assessment of poly- and perfluorinated (PFAS) compounds in North Carolina residential drinking water. Working in concert with community partners, who acted as liaisons to local residents, samples were collected by North Carolina residents from three different locations along the Cape Fear River basin: upper, middle, and lower areas of the river. Residents collected either drinking water samples from their homes or recreational water samples from near their residence that were then submitted by the community partners for PFAS analysis. All samples were processed using weak anion exchange (WAX) solid phase extraction and analyzed using a non-targeted suspect screening approach as well as a quantitative approach that included a panel of 45 PFAS analytes, several of which are specific to chemical industries near the collection site locations. The non-targeted approach, which utilized a suspect screening list (obtained from EPA CompTox database) identified several PFAS compounds at a level two confidence rating (Schymanski scale); compounds identified included a fluorinated insecticide, a fluorinated herbicide, a PFAS used in polymer chemistry, and another that is used in battery production. Notably, at several locations, PFOA (39.8 ng/L) and PFOS (205.3 ng/L) were at levels that exceeded the mandatory EPA maximum contaminant level (MCL) of 4 ng/L. Additionally, several sites had detectable levels of PFAS that are unique to a local chemical manufacturer. These findings were communicated back to the community partners who then disseminated this information to the local residents to help empower and aid in making decisions for reducing their PFAS exposure.

Introducción: Los niños con enfermedades respiratorias crónicas se caracterizan por presentar síntomas respiratorios permanentes que ocasionan compromiso pulmonar, debilidad de los músculos respiratorios y periféricos, para lo cual reciben un tratamiento integral que incluye el entrenamiento muscular respiratorio. Objetivo: Analizar los efectos del entrenamiento muscular respiratorio en el paciente pediátrico con enfermedad respiratoria crónica por medio de una revisión de la literatura publicada entre 2010 y 2021. Materiales y métodos: Revisión integrativa de la literatura, en la que se analizó literatura sobre efectos fisiológicos del entrenamiento muscular respiratorio, herramientas de evaluación de la fuerza respiratoria, métodos de entrenamiento y parámetros para prescribir las cargas de trabajo. Los estudios se identificaron y seleccionaron mediante las recomendaciones de la Declaración de PRISMA, además, se valoró el nivel de evidencia y el grado de recomendación de los estudios incluidos a través de la Escala Scottish Intercollegiate Guidelines Network (SIGN). Resultados: El entrenamiento muscular respiratorio ha mostrado ser beneficioso sobre la fuerza muscular respiratoria en pacientes pediátricos con asma, bronquiectasias y enfermedad neuromuscular, sin embargo, en paciente con fibrosis quística la literatura analizada no es concluyente para apoyar o rechazar los efectos de esta estrategia terapéutica. Conclusión: El entrenamiento muscular respiratorio debe ser individualizado en pacientes pediátricos con enfermedad respiratoria crónica de tipo intra o extrapulmonar, por lo que se requiere una evaluación integral que incluya la valoración de la fuerza y la resistencia muscular ventilatoria para prescribir el entrenamiento

We demonstrated an endovascular technique excluding an ascending aorta pseudoaneurysm using an aortic extension. A 32-year-old woman, 3 years after lung transplantation with extracorporeal membrane oxygenation presented with an ascending aortic pseudoaneurysm. Vascular surgery was consulted after open repair was deemed high risk. An aortic extension stent graft was placed in a hybrid operating room with the aid of intraoperative transesophageal echocardiography. Ascending aorta pseudoaneurysms are complex and life-threatening complications. Traditional repair involves high surgical and anesthetic risks whereas endovascular treatment is technically feasible.

Introduction: Most people in the United States live busy stressful lives which can lead to significant health challenges, especially to one’s mental health. After years of being ignored and stigmatized, mental illness has been given the recognition it deserves. It is now associated with the overall health of a person and treated seriously. The same could be said about substance abuse disorder though on a lesser scale. This paper attempts to understand the relationship between drug use and mental health illness differentiated across age groups. The understanding of these causations and relationships could help us better understand the rate and triggers of mental illness in the United States. Methods: We used data from a 2023 survey, which contains a total of 69,850 completed interviews. The data collected were taken from each state individually with each of them implementing the same survey to collect responses. Instead of looking at all fifty states, we decided to analyze only the highest twenty- one most populated states. Various non-parametric tests were used to analyze age groups and their rate of mental health illnesses and drug use within the country. Results: We found that tobacco use is associated with mental illness, while alcohol use is associated with attempted suicide. It appears that indicators of drug use are not homogeneous across states for either age group. We also found that the alcohol consumption is related to a declining proportion of attempted suicides. Conclusion: In this research we found a significant association between drug use and inidcators of mental illness. The association differed across different age groups and also across states. Since we found that the alcohol consumption is related to a declining proportion of attempted suicides, it will be interesting to explore why this is the case and what could be observed to decrease suicidal rates.

ABSTRACT Enteroviruses are one of the most abundant viruses causing mild to serious acute infections in humans and also contributing to chronic diseases like type 1 diabetes. Presently, there are no approved antiviral drugs against enteroviruses. Here, we studied the potency of vemurafenib, an FDA-approved RAF kinase inhibitor for treating BRAFV600E mutant-related melanoma, as an antiviral against enteroviruses. We showed that vemurafenib prevented enterovirus translation and replication at low micromolar dosage in an RAF/MEK/ERK-independent manner. Vemurafenib was effective against group A, B, and C enteroviruses, as well as rhinovirus, but not parechovirus or more remote viruses such as Semliki Forest virus, adenovirus, and respiratory syncytial virus. The inhibitory effect was related to a cellular phosphatidylinositol 4-kinase type IIIβ (PI4KB), which has been shown to be important in the formation of enteroviral replication organelles. Vemurafenib prevented infection efficiently in acute cell models, eradicated infection in a chronic cell model, and lowered virus amounts in pancreas and heart in an acute mouse model. Altogether, instead of acting through the RAF/MEK/ERK pathway, vemurafenib affects the cellular PI4KB and, hence, enterovirus replication, opening new possibilities to evaluate further the potential of vemurafenib as a repurposed drug in clinical care. IMPORTANCE Despite the prevalence and medical threat of enteroviruses, presently, there are no antivirals against them. Here, we show that vemurafenib, an FDA-approved RAF kinase inhibitor for treating BRAFV600E mutant-related melanoma, prevents enterovirus translation and replication. Vemurafenib shows efficacy against group A, B, and C enteroviruses, as well as rhinovirus, but not parechovirus or more remote viruses such as Semliki Forest virus, adenovirus, and respiratory syncytial virus. The inhibitory effect acts through cellular phosphatidylinositol 4-kinase type IIIβ (PI4KB), which has been shown to be important in the formation of enteroviral replication organelles. Vemurafenib prevents infection efficiently in acute cell models, eradicates infection in a chronic cell model, and lowers virus amounts in pancreas and heart in an acute mouse model. Our findings open new possibilities to develop drugs against enteroviruses and give hope for repurposing vemurafenib as an antiviral drug against enteroviruses.

Abstract Background We report an exceedingly rare case of bilateral external iliac artery pseudoaneurysms causing urinary obstruction and acute renal failure. Case presentation A young man presented with acute severe bilateral testicular pain radiating to the back. Clinical and radiological workup showed bilateral external iliac artery pseudoaneurysms, which caused bilateral ureterohydronephrosis due to urinary obstruction with subsequent renal failure. Management included immediate bilateral external iliac artery endovascular repair and bilateral ureterolysis using a retroperitoneal approach, with resolution of the obstruction and successful endovascular treatment of both pseudoaneurysms. The only identifiable risk factor for cardiovascular disease was cocaine addiction. Conclusions This case highlights an unusual and severe clinical presentation of bilateral EIA pseudoaneurysms causing bilateral ureterohydronephrosis and subsequent renal failure. Awareness of this condition may help avoid misdiagnosis and delayed management, which is of utmost importance for a favorable outcome.

Purpose: Electrocardiography (ECG)-derived machine learning models can predict echocardiography (echo)-derived indices of systolic or diastolic function. However, systolic and diastolic dysfunction frequently coexists, which necessitates an integrated assessment for optimal risk-stratification. We explored an ECG-derived model that emulates an echo-derived model that combines multiple parameters for identifying patient phenogroups at risk for major adverse cardiac events (MACE). Methods: In this substudy of a prospective, multicenter study, patients from 3 institutions (n = 727) formed an internal cohort, and the fourth institution was reserved as an external test set (n = 518). A previously validated patient similarity analysis model was used for labeling the patients as low-/high-risk phenogroups. These labels were utilized for training an ECG-derived deep neural network model to predict MACE risk per phenogroup. After 5-fold cross-validation training, the model was tested on the reserved external dataset. Results: Our ECG-derived model showed robust classification of patients, with area under the receiver operating characteristic curve of 0.86 (95% CI: 0.79–0.91) and 0.84 (95% CI: 0.80–0.87), sensitivity of 80% and 76%, and specificity of 88% and 75% for the internal and external test sets, respectively. The ECG-derived model demonstrated an increased probability for MACE in high-risk vs low-risk patients (21% vs 3%; P < 0.001), which was similar to the echo-trained model (21% vs 5%; P < 0.001), suggesting comparable utility. Conclusions: This novel ECG-derived machine learning model provides a cost-effective strategy for predicting patient subgroups in whom an integrated milieu of systolic and diastolic dysfunction is associated with a high risk of MACE.

Surgical revascularization with distal bypass surgery is associated with good outcomes for chronic limb-threatening ischemia. The peroneal artery, the most-often preserved outflow vessel, is commonly reached through a lateral approach involving resection of the fibula. We present two different techniques for a lateral approach to the peroneal artery: the first by proximal exposure and the second by exposing the distal segment of the peroneal artery. Both techniques are performed without bone resection.

BackgroundYouth with anxiety and obsessive–compulsive disorder (OCD) rarely access exposure therapy, an evidence-based treatment. Known barriers include transportation, waitlists, and provider availability. Efforts to improve access to exposure require an understanding of the process that families take to find therapists, yet no prior studies have examined parents’ perspectives of the steps involved.MethodsParents of children who have received exposure therapy for anxiety and/or OCD (N = 23) were recruited from a hospital-based specialty anxiety clinic where the majority of their children previously received exposure. Recruitment was ongoing until thematic saturation was reached. Parents completed questionnaires and attended an online focus group during which they were asked to describe each step they took—from recognizing their child needed treatment to beginning exposure. A process map was created and shown in real-time, edited for clarity, and emailed to parents for member checking. Authors analyzed process maps to identify common themes.ResultsSeveral themes emerged, as visually represented in a final process map. Participants identified a “search-outreach” loop, in which they repeated the cycle of looking for therapists, contacting them, and being unable to schedule an appointment due to factors such as cost, waitlists, and travel time. Parents often did not know about exposure and reported feeling guilty about their lack of knowledge and inability to find a suitable provider. Parents reported frustration that medical providers did not often know about exposure and sometimes dismissed parents’ concerns. Participants emphasized the difficulty of navigating the mental health system; many reported that it took years to find an exposure therapist, and that the search was sometimes stalled due to fluctuating symptoms.ConclusionA common thread among identified barriers was the amount of burden placed on parents to find treatment with limited support, and the resultant feelings of isolation and guilt. Findings point to several directions for future research, such as the development of parent support groups for navigating the mental health system; enhancing coordination of care between medical and mental health providers; and streamlining referral processes.

Background Protecting all human rights of people with mental health conditions is globally important. However, to facilitate practical implementation of rights, it is often necessary to decide which of these rights should be given priority, especially when they conflict with each other. Aims The aim of the Priorities of Human Rights and Mental Health (PHRAME) project is to develop a replicable approach to establish a proposed set of high-priority human rights of people with mental health conditions, to facilitate practical decision-making and implementation of such rights. Method A two-stage Delphi-style study with stakeholders was conducted to generate a list of key rights of people with mental health conditions, and rank priorities among these rights in terms of feasibility, urgency and overall importance. Results The stakeholders in this study consistently ranked three rights as top priorities: (a) the right to freedom from torture, cruel inhuman treatment and punishment; (b) the right to health and access to services/treatment; and (c) the right to protection and safety in emergency situations. Conclusions Insights from PHRAME can support decision-making about the priority to be given to human rights, to guide practical action. This approach can also be used to assess how human rights are prioritised in different settings and by different stakeholders. This study identifies the clear need for a central voice for people with lived experience in research and implementation of decisions about the priority of human rights, ensuring that action respects the opinion of people whose rights are directly affected.

Abstract Groundwater withdrawal can cause localized and rapid poroelastic subsidence, spatially broad elastic uplift of low amplitude, and changes in the gravity field. Constraining groundwater loss in Mexico City, we analyze data from the Gravity Recovery and Climate Experiment and its follow‐on mission (GRACE/FO) and Synthetic Aperture Radar (SAR) Sentinel‐1A/B images between 2014 and 2021. GRACE/FO observations yield a groundwater loss of 0.85–3.87 km3/yr for a region of ∼300 × 600 km surrounding Mexico City. Using the high‐resolution interferometric SAR data set, we measure >35 cm/yr subsidence within the city and up to 2 cm/yr of uplift in nearby areas. Attributing the long‐term subsidence to poroelastic aquifer compaction and the long‐term uplift to elastic unloading, we apply respective models informed by local geology, yielding groundwater loss of 0.86–12.57 km3/yr. Our results suggest Mexico City aquifers have been depleting at faster rates since 2015, exacerbating the socioeconomic and health impacts of long‐term groundwater overdrafts.

Domestic wells provide drinking water to 44 million people nationwide. Many of these wells, which remain federally unregulated and rarely tested for pollutants, serve rural populations clustered near surface-contaminated sites (e.g., hazardous waste sites, animal agriculture operations, coal ash ponds, etc.). The potential for natural disasters to deteriorate drinking water quality is well documented. Less understood is whether opportunistic post-disaster sampling might underrepresent vulnerable populations. When disaster strikes, well water sampling campaigns offer a glimpse into the quality of water for exposed residents. We examined over 8,000 well water samples from 2016 and 2017 to measure Hurricane Matthew’s impact on the presence of indicator bacteria. Bacteria presence was predicted at the household level following Hurricane Matthew’s landfall. The residential addresses associated with birth records as well as clinically estimated dates of conception and birth dates were used to predict the likelihood of indicator bacteria in drinking water sources that were unsampled but likely to have served pregnant women. We estimate that opportunistic well water sampling captures the average predicted contamination rates among households with pregnant women. Our approach documents a distribution of contamination risk where 2.7% of the vulnerable sample (670 unsampled households) have a 75% likelihood of total coliform presence. The predicted likelihood of indicator bacteria is elevated for a small share of households nearby swine lagoons that experienced the most torrential rainfall. However, the gap between sampled and unsampled households cannot otherwise be explained by the storm event or proximity to surface-contaminated sites. Findings suggest that sophisticated and holistic water quality prediction models may support post-disaster sampling campaigns by targeting individual households within vulnerable groups that are likely to experience higher risks from groundwater contamination.

Cellular unjamming is the collective fluidization of cell motion and has been linked to many biological processes, including development, wound repair, and tumor growth. In tumor growth, the uncontrolled proliferation of cancer cells in a confined space generates mechanical compressive stress. However, because multiple cellular and molecular mechanisms may be operating simultaneously, the role of compressive stress in unjamming transitions during cancer progression remains unknown. Here, we investigate which mechanism dominates in a dense, mechanically stressed monolayer. We find that long-term mechanical compression triggers cell arrest in benign epithelial cells and enhances cancer cell migration in transitions correlated with cell shape, leading us to examine the contributions of cell–cell adhesion and substrate traction in unjamming transitions. We show that cadherin-mediated cell–cell adhesion regulates differential cellular responses to compressive stress and is an important driver of unjamming in stressed monolayers. Importantly, compressive stress does not induce the epithelial–mesenchymal transition in unjammed cells. Furthermore, traction force microscopy reveals the attenuation of traction stresses in compressed cells within the bulk monolayer regardless of cell type and motility. As traction within the bulk monolayer decreases with compressive pressure, cancer cells at the leading edge of the cell layer exhibit sustained traction under compression. Together, strengthened intercellular adhesion and attenuation of traction forces within the bulk cell sheet under compression lead to fluidization of the cell layer and may impact collective cell motion in tumor development and breast cancer progression.

Quantifying the extent and evolution of cerebral edema developing after stroke is an important but challenging goal. Lesional net water uptake (NWU) is a promising CT-based biomarker of edema, but its measurement requires manually delineating infarcted tissue and mirrored regions in the contralateral hemisphere. We implement an imaging pipeline capable of automatically segmenting the infarct region and calculating NWU from both baseline and follow-up CTs of large-vessel occlusion (LVO) patients. Infarct core is extracted from CT perfusion images using a deconvolution algorithm while infarcts on follow-up CTs were segmented from non-contrast CT (NCCT) using a deep-learning algorithm. These infarct masks were flipped along the brain midline to generate mirrored regions in the contralateral hemisphere of NCCT; NWU was calculated as one minus the ratio of densities between regions, removing voxels segmented as CSF and with HU outside thresholds of 20–80 (normal hemisphere and baseline CT) and 0–40 (infarct region on follow-up). Automated results were compared with those obtained using manually-drawn infarcts and an ASPECTS region-of-interest based method that samples densities within the infarct and normal hemisphere, using intraclass correlation coefficient (ρ). This was tested on serial CTs from 55 patients with anterior circulation LVO (including 66 follow-up CTs). Baseline NWU using automated core was 4.3% (IQR 2.6–7.3) and correlated with manual measurement (ρ = 0.80, p < 0.0001) and ASPECTS (r = −0.60, p = 0.0001). Automatically segmented infarct volumes (median 110-ml) correlated to manually-drawn volumes (ρ = 0.96, p < 0.0001) with median Dice similarity coefficient of 0.83 (IQR 0.72–0.90). Automated NWU was 24.6% (IQR 20–27) and highly correlated to NWU from manually-drawn infarcts (ρ = 0.98) and the sampling-based method (ρ = 0.68, both p < 0.0001). We conclude that this automated imaging pipeline is able to accurately quantify region of infarction and NWU from serial CTs and could be leveraged to study the evolution and impact of edema in large cohorts of stroke patients.

Cordomas são neoplasias raras originadas da notocorda primitiva, que se localizam predominantemente em região sacroccígena e menos freqüentemente intracranianas, correspondendo de 3 a 5% dos tumores primários cerebrais. Os cordomas intracranianos são de manejo difícil, a ressecção cirúrgica geralmente é incompleta e os pacientes podem evoluir para óbito em decorrência do crescimento incontrolável do tumor e/ou compressão de estruturas nobres adjacentes. Neste trabalho os autores relatam dois pacientes com cordoma intracraniano cuja evolução clínica foi absolutamente distinta, dissertando sobre os diversos aspectos relacionados ao diagnóstico, tratamento e evolução dos dois casos.

Introduction Sexual violence is commonplace and has serious adverse consequences for physical and mental health. Sexual Assault Referral Centres (SARCs) are viewed as a best practice response. Little is known about their effectiveness and cost-effectiveness. Long-term data on the health and well-being of those who have experienced rape and sexual assault are also lacking.Methods and analysis This is a mixed-methods protocol for a 1-year cohort study aiming to examine the health and well-being in survivors of sexual violence after attending a SARC in England. Quantitative measures are being taken at baseline, 6 and 12 months. Post-traumatic stress (PTS) is the primary outcome (target N=270 at 12-month follow-up). Secondary measures include anxiety, depression, substance use and sexual health and well-being. Using mixed-effects regression, our main analysis will examine whether variation in SARC service delivery and subsequent mental healthcare is associated with improvement in trauma symptoms after 12 months. An economic analysis will compare costs and outcomes associated with different organisational aspects of SARC service delivery and levels of satisfaction with care. A nested qualitative study will employ narrative analysis of transcribed interviews with 30 cohort participants and 20 survivors who have not experienced SARC services.Ethics and dissemination The research is supported by an independent study steering committee, data monitoring and ethics committee and patient and public involvement (PPI) group. A central guiding principle of the research is that being involved should feel diametrically opposed to being a victim of sexual violence, and be experienced as empowering and supportive. Our PPI representatives are instrumental in this, and our wider stakeholders encourage us to consider the health and well-being of all involved. We will disseminate widely through peer-reviewed articles and non-academic channels to maximise the impact of findings on commissioning of services and support for survivors.Trial registration number ISRCTN30846825.

Science teacher knowledge for effective teaching consists of multiple knowledge bases, one of which includes science content knowledge and pedagogical knowledge. With the inclusion of science and engineering practices into the national science education standards in the US, teachers’ content knowledge goes beyond subject matter knowledge and into the realm of how scientists use practices for scientific inquiry. This study compares two approaches to constructing and validating two different versions of a survey that aims to measure the construct of teachers’ knowledge of models and modeling in science teaching. In the first version, a 24-item Likert scale survey containing content and pedagogical knowledge items was found to lack the ability to distinguish different knowledge levels for respondents, and validation through factor analysis indicated content and pedagogical knowledge items could not be separated. Findings from the validation results of the first survey influenced revisions to the second version of the survey, a 25-item multiple-choice instrument. The second survey employed a competence model framework for models and modeling for item specifications, and results from exploratory factor analysis revealed this approach to assessing the construct to be more appropriate. Recommendations for teacher assessment of science practices using competence models and points to consider in survey design, including norm-referenced or criterion-referenced tests, are discussed.

Mosses play important roles in the regulation of environmental or metabolic conditions in boreal forest ecosystems. Sphagnum and feathermoss are the two main bryophytes found in boreal forest understory. Clearcut harvesting (common method of boreal forest regeneration) can expose understory vegetation to water and light stress. Water and light stress can significantly impact moss growth during boreal forest regeneration. Analysis of the membrane lipidome, photosynthetic parameters and pigments can be very effective in assessing moss response to abiotic stress following clearcut harvesting. Although lipidomics is commonly used in environmental stress assessment of plants, application to assess moss lipidome and stress response is very limited. Bryophytes may alter or remodel their membrane lipid composition to acclimate or adapt to environmental stressors. Thus, this perspective provides insights into how moss lipids may serve as useful biomarkers of moss stress response or adaptation to environmental stress during boreal forest regeneration following clearcut harvesting.

Background: Borderline Personality Disorder (BPD) is a psychiatric condition characterized by impulsivity, affect instability, dysregulation, low self-image, and interpersonal difficulties. There are many instruments to measure traits of BPD, however, few can be administered quickly. The Screening Instrument for Borderline Personality Disorder (SI-Bord) is an instrument offering a brief administration time with comparable psychometric properties to more comprehensive measures. The present study aimed to evaluate the psychometric properties of the SI-Bord in a healthy community-based sample and its relatedness to measures of social cognition. Methods: A community-based sample of participants completed an online survey consisting of measures of BPD traits and social cognition including: the Screening Instrument for Borderline Personality Disorder (SI-Bord), the Personality Assessment Inventory (PAI), the Florida Affect Battery (FAB), the Interpersonal Reactivity Index (IRI), and the Narcissistic Personality Inventory (NPI). Reliability was assessed using Cronbach’s alpha and inter-item correlations. Validity was assessed using factor analysis, examining associations with other measures of BPD traits, and examining associations with measures not measuring BPD traits. Results: 151 participants were included in the study. Participants’ age ranged from 20–76 (mean age of 38.79 ± 12.37) and comprised 76 females (50.33%) and 75 males (49.67%). Good internal consistency was found with a Cronbach’s alpha of 0.71. Good inter-item reliability was found with a mean inter-item cross correlation of 0.25, with each item of the SI-Bord showing an inter-item correlation coefficient of >0.5. Factor analysis identified good construct validity with a strong singular dimension explaining a large proportion of variance (Question 1). The SI-Bord showed good concurrent validity with significantly strong positive correlations with the subscales of the PAI borderline scale measuring affect instability (r = 0.60; p < 0.001), identity problems (r = 0.67; p < 0.001), negative relationships (r = 0.61; p < 0.001), total score (r = 0.76; p < 0.001), and to a moderately strong positive correlation with self-harm (r = 0.39; p < 0.001). The SI-Bord was not correlated with the NPI-16 (r = 0.131; p = 0.11), showing good divergent validity. Conclusions: These findings support the SI-Bord as a quick and useful screening tool for traits associated with BPD. Further clinical validation is warranted.

The preparation of new, enantiomerically pure, α-amino acids from easily available starting materials is an ongoing challenge in synthetic organic chemistry. Here, we describe the syntheses and crystal structures of three chiral oxazolidinone derivatives prepared from L-alanine and pivalaldehyde to form a Schiff base intermediate and then reaction with the appropriate acid chloride to form the heterocycle. In each compound, the methyl and tert-butyl substituents lie to the same side of the molecule: these homochiral ‘cis’ structures were separated from their trans diastereomers by fractional crystallisation. The five-membered rings in these structures adopt various conformations including envelopes with either a C or O atom as the flap and twisted about a C–O bond. The extended structures of two of these compounds feature C(6) chains of molecules linked by C–H···O hydrogen bonds: one of these has a notably short H···O separation of 2.24 (3) Å.

Breast cancer is the one of the most common cancers and causes a significant disease burden. Currently, postmastectomy radiotherapy (PMRT) is indicated for breast cancer patients with higher risk of recurrence, such as those with positive surgical margins or high-risk breast cancer (T3 with positive lymph nodes, ≥4 positive lymph nodes or T4 disease). Whether PMRT should be used in intermediate-risk breast cancer (T3 with no positive lymph nodes or T1-2 with 1-3 positive lymph nodes) is contentious. Rates of breast reconstruction postmastectomy are increasing in countries like Australia, and PMRT usage in such settings is another area of active research. Ongoing trials are also assessing the safety and efficacy of hypofractionated PMRT, a clinical scenario now widely accepted for early-stage breast cancer. This brief review is unique in that it aims to examine three current and controversial aspects of the PMRT field (PMRT in intermediate-risk breast cancer, PMRT in conjunction with breast reconstruction and its hypofractionation). To achieve this aim, we discuss available and emerging literature and guidelines to offer insights important to the PMRT field. Current literature suggests that PMRT could play a role in improving the overall survival rate and in reducing locoregional recurrence in intermediate-risk breast cancer. In terms of recommending a timing or type of breast reconstruction best suited to the setting of PMRT, we found that individual patient preferences and circumstances need to be considered alongside a multidisciplinary approach. Research into PMRT hypofractionation safety and efficacy is ongoing and its place remains to be elucidated.

In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generate Leishmania genomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes., Competing Interests: The authors declare no competing interests., (Copyright: © 2023 Pilling 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.)

Visceral leishmaniasis (VL) is a potentially fatal disease caused mainly by Leishmania infantum in South America and Leishmania donovani in Asia and Africa. Disease outcomes have been associated with patient genotype, nutrition, age, sex, comorbidities, and coinfections. In this study, we examine the effects of parasite genetic variation on VL disease severity in Brazil. We collected and sequenced the genomes of 109 L. infantum isolates from patients in northeastern Brazil and retrieved matching patient clinical data from medical records, including mortality, sex, HIV coinfection, and laboratory data (creatinine, hemoglobin, and leukocyte and platelet counts). We identified genetic differences between parasite isolates, including single nucleotide polymorphisms (SNPs), small insertions/deletions (indels), and variations in genic, intergenic, and chromosome copy numbers (copy number variants [CNVs]). To describe associations between the parasite genotypes and clinical outcomes, we applied quantitative genetics methods of heritability and genome-wide association studies (GWAS), treating clinical outcomes as traits that may be influenced by parasite genotype. Multiple aspects of the genetic analysis indicate that parasite genotype affects clinical outcomes. We estimate that parasite genotype explains 83% chance of mortality (narrow-sense heritability [ h 2 ] = 0.83 ± 0.17) and has a significant relationship with patient sex ( h 2 = 0.60 ± 0.27). Impacts of parasite genotype on other clinical traits are lower ( h 2 ≤ 0.34). GWAS analysis identified multiple parasite genetic loci that were significantly associated with clinical outcomes; 17 CNVs were significantly associated with mortality, two with creatinine, and one with bacterial coinfection, jaundice, and HIV coinfection, and two SNPs/indels and six CNVs were associated with age, jaundice, HIV and bacterial coinfections, creatinine, and/or bleeding sites. Parasite genotype is an important factor in VL disease severity in Brazil. Our analysis indicates that specific genetic differences between parasites act as virulence factors, enhancing risks of severe disease and mortality. More detailed understanding of these virulence factors could be exploited for novel therapies. IMPORTANCE Multiple factors contribute to the risk of mortality from visceral leishmaniasis (VL), including, patient genotype, comorbidities, and nutrition. Many of these factors are influenced by socioeconomic biases. Our work suggests that the virulence of the infecting parasite is an important risk factor for mortality. We pinpoint some specific genomic markers that are associated with mortality, which can lead to a greater understanding of the molecular mechanisms that cause severe VL disease, to the identification of genetic markers for virulent parasites, and to the development of drug and vaccine therapies.