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Purpose: The Every Student Succeeds Act (ESSA) reduced the role of the federal government in K-12 education, giving states more flexibility while maintaining protections for marginalized groups. Despite the potential to leverage flexibility, little is known about how states are addressing equity. Research Methods: Using a critical policy analysis (CPA) approach, this qualitative case study uses semi-structured interviews and document analysis to examine the design and implementation of equity efforts by the state education agency (SEA) in North Carolina. Findings: SEA officials describe writing the state ESSA plan as an exercise in compliance and believe the plan could have gone further in pushing equitable solutions. Competing priorities within the SEA, including the struggle to fulfill its dual roles as service provider and regulatory agency, complicated ESSA implementation, as did state-level political maneuvers. A significant, unexpected finding is that participants were much more comfortable discussing the needs of economically disadvantaged students than students of color, and often avoided mentioning race specifically. Additionally, although the pandemic caused major disruptions to schooling, SEA officials identified "keeps" that were begun as a pandemic response and may continue as the SEA pushes equitable solutions for traditionally underserved students. Implications for Research and Practice: This study suggests that competing initiatives, staff turnover, and political ideology may limit the SEA's capacity to address power and resource imbalances and hinder efforts to promote greater equity in the educational system. Moreover, the SEA's focus shifted to ESSER funding during the COVID-19 pandemic.

We consider two local reparations cases--the Evanston Restorative Housing Program and Chicago reparations for police torture survivors. We argue that the programs are shaped by the differing political opportunities, the local context, and the social location of their advocates given that one was constructed within government systems in Evanston and the other largely by grassroots organizers in Chicago. Furthermore, both programs are criticized to varying degrees as being exclusive in their design and implementation. We term this exclusion a process of deliberative marginalization, whereby some of the most vulnerable and most directly affected beneficiaries of a redress initiative are left out of deliberations and implementation decisions about the initiative's design. Subsequently, this study shows both the promise and constraints of reparations policy at the level of local government.

The value of high-impact practices in undergraduate higher education is well documented. However, very little is known about high-impact practices in Human Development and Family Science (HDFS) programs. The goal of this study was to explore one specific high-impact practice: undergraduate research. Specifically, our study explored the benefits and barriers of undergraduate research for HDFS students as well as the pathways HDFS students use to become involved in undergraduate research. College student identity theory served as a guide for our inquiry. Semi-structured interviews were conducted with 22 undergraduate HDFS students, 13 of whom had participated in undergraduate research and nine who had not. Results revealed three pathways students took to participate in undergraduate research: interest in a specific research topic, connection with the researcher, and preparation for graduate school. Enhanced learning, professional skills, personal growth, and relationships with others were identified as benefits of participation in undergraduate research. Barriers to participation in research included time, lack of awareness, and feelings of fear or intimidation. Specific processes for students and faculty to overcome these barriers are suggested. It is recommended that HDFS faculty and administrators provide multiple pathways and supports for undergraduate students to become involved in research.

This article looks past the gifted classics of children's literature to explore the incredible opportunity that is missed all too often: an opportunity to intentionally choose books in which diversity is not the point but showcase much-needed representation. Drawing on the concepts of mirrors, windows, and sliding glass doors this article explores how shifting titles for better representation is a seemingly small choice but one that classroom teachers can make to better engage the identities and possibilities for early childhood engagement.

Abstract Background Malaria-endemic countries are increasingly adopting data-driven risk stratification, often at district or higher regional levels, to guide their intervention strategies. The data typically comes from population-level surveys collected by rapid diagnostic tests (RDTs), which unfortunately perform poorly in low transmission settings. Here, a high-resolution survey of Plasmodium falciparum prevalence rate (PfPR) was conducted in two Tanzanian districts using rapid diagnostic tests (RDTs), microscopy, and quantitative polymerase chain reaction (qPCR) assays, enabling the comparison of fine-scale strata derived from these different diagnostic methods. Methods A cross-sectional survey was conducted in 35 villages in Ulanga and Kilombero districts, south-eastern Tanzania between 2022 and 2023. A total of 7,628 individuals were screened using RDTs (SD-BIOLINE) and microscopy, with two thirds of the samples further analysed by qPCR. The data was used to categorize each district and village as having very low (PfPR 50%. Prevalence varied by testing method: Kilombero was low risk by RDTs (PfPR = 3%) and microscopy (PfPR = 2%) but moderate by qPCR (PfPR = 9%); Ulanga was high risk by RDTs (PfPR = 39%) and qPCR (PfPR = 54%) but moderate by microscopy (PfPR = 26%). RDTs and microscopy classified majority of the 35 villages as very low to low risk (18–21 villages). In contrast, qPCR classified most villages as moderate to high risk (29 villages). Using qPCR as the reference, PPV for RDTs and microscopy ranged from as low as 80% in moderate and high transmission villages. Sensitivity was 62% for RDTs and 41% for microscopy; specificity was 93% and 96%, respectively. Kappa values were 0.7 for RDTs and 0.5 for microscopy. School-age children (5–15 years) had higher malaria prevalence and parasite densities than adults (P

Abstract Studies across various pathogens highlight the importance of pathogen genetic differences in disease manifestation. In the human fungal pathogen Cryptococcus neoformans, sequence type (ST) associates with patient outcome. We performed a meta-analysis of four genomic studies and identified overlapping gene regions associated with virulence, suggesting the importance of these gene regions in cryptococcal disease in diverse clinical isolates. We explored the relationship between virulence and strain genetic differences using the cryptococcosis mouse model and a closely related library of ST93 clinical isolates. We identified four in vivo virulence phenotypes: hypervirulence, typical virulence with CNS disease, typical virulence with non-CNS disease, and latent disease. Hypervirulent isolates were clade specific and associated with an interferon gamma (IFNγ) dominated immune response. Using a genome wide association study (GWAS), we identified nine genes with polymorphisms associated with IFNγ production, including the inositol sensor ITR4. The itr4Δ mutant recapitulated the hypervirulence phenotype and ITR4 affects expression of two IFNγ associated genes. Finally, we showed that IFNγ production is associated with SNPs that downregulate ITR4 and with SNP accumulation in other IFNγ associated genes. These data highlight the complex role of pathogen genetics in virulence and identify genes associated with hypervirulence and IFNγ in Cryptococcus neoformans.

High Mountain Asia (HMA) is undergoing unprecedented warming, affecting the cryosphere – including permafrost (frozen ground) – and leading to various hazards. However, understanding the prevalence, distribution, and dynamics of these hazards and how they respond to a changing climate is challenging. Permafrost is extensive in HMA, and China makes up a significant portion of this. The permafrost area in China is about 1.6×106 km2, 66 % of which is on the Qinghai–Tibet Plateau. However, most of the scientific literature concerning permafrost in China is published in Chinese and, hence, remains largely unnoticed by the non-Chinese-speaking scientific communities. In this article, we used a systematic review to evaluate the Chinese scientific literature on permafrost-related hazards and found that the studied areas are concentrated in certain areas, especially on the Qinghai–Tibet Engineering Corridor (QTEC). The increasing amount of literature on permafrost hazards reflects the increased impact of climate warming on infrastructure built on permafrost. Not only is permafrost affecting infrastructure; these anthropogenic disturbances themselves also have amplified the occurrence of hazards around settlements and infrastructure. The literature shows the strong relationship between latitude and elevation with permafrost thickness. The permafrost classification system and nomenclature used by Chinese scientists is different to that used elsewhere, which is a potential source of confusion and deserves attention.

Abstract Background Between 2006 and 2016 the prevalence of overweight and obesity among children and adolescents aged 5–19 years in Peru increased from 22.7 to 27.0%. This investment case quantifies the economic impacts of childhood and adolescent overweight and obesity in Peru. It identifies and quantifies the potential impact of a set of new or expanded interventions that can strengthen current national efforts to prevent and reduce child and adolescent overweight and obesity. Methods A deterministic Markov cohort model with a societal cost perspective estimated reductions in mortality and morbidity from implementing interventions to prevent and reduce child and adolescent overweight and obesity and the impact in savings in healthcare costs and gains in wages and productivity. Interventions identified through a review of published literature includes a school-based social marketing campaign, exclusive breastfeeding promotion and support, a healthy food and drink policy for school premises, and a 20% subsidy on fruits and vegetables for people living below the national poverty line. The return on investment (ROI) was calculated along with the estimated cost savings associated with the interventions. Analysis was conducted to test ROI sensitivity to changes in the key parameters and assumptions. Results Between 2025 and 2092, the expected combined direct and indirect healthcare costs attributable to child and adolescent overweight and obesity in Peru are 210.6 billion USD. The direct healthcare costs are 1.8 billion USD, and the indirect costs are 208.8 billion USD. Expected savings for all interventions combined is 13.9 billion USD with a per-person savings of 12,089.8 USD. The expected ROI of the four interventions combined is 39.3 USD (30-years), 64.6 USD (50-years), and 164.1 USD (66-years) per one USD invested. Conclusions The overweight and obesity epidemic among children and adolescents in Peru requires wide-ranging and expanded implementation of policies to achieve long-term reductions in prevalence. This study’s findings show that the four priority interventions have high ROIs and can be used to guide policy to address the complex interplay of factors that contribute to the obesogenic environment.

Abstract Uniaxial materials have achieved new prominence in photonics because they can have hyperbolic spectral regions with metallic (ε0) permittivities along different crystal axes. In the lossless case, this results in an open hyperboloid dispersion relation, allowing materials to support highly confined modes with extremely large wavevectors. However, even small losses change the character of the hyperbolic dispersion from open hyperboloids to closed surfaces with finite maximum k, significantly limiting the extent to which highly-confined modes can be achieved. Here, we derive a simple analytic formula for the dispersion relation in the presence of loss and show that for some typical materials the maximum wavevector in hyperbolic materials is roughly ten times the free-space. The scaling of the maximum wavevector is derived, and it is shown that there is a universal scaling relation between the propagation length and the wavelength, which implies that the shortest wavelengths in any hyperbolic material are strongly attenuated.

Abstract Background The acquisition of knowledge and use of skills from digital mental health interventions (DMHIs) are considered important for effectiveness. However, our understanding of user experiences implementing skills learned from these interventions is limited, particularly outside of research trials. This qualitative study aimed to investigate how community users learn and apply knowledge and skills from DMHIs based on cognitive behavioural therapy (CBT) in daily life. The study also examined factors influencing the selection and use of skills and explored perceived changes in mental health resulting from the intervention. Methods Thirteen adults aged 26 to 66 years (10 females) were recruited using social media advertising and participated in semi-structured interviews by telephone or videoconference. All participants were living in Australia and had used a digital CBT program within the past 3 months. Interviews lasted on average 45 min. Transcripts were analysed using theoretical thematic analysis. Results Participants demonstrated high levels of program engagement. Findings were organised into three topics with six major themes. Participants reported that their chosen intervention reinforced existing knowledge and fostered new skills and insights (Topic 1, Theme 1: knowledge consolidation). Most described actively applying skills (Topic 1, Theme 2: active approach to skill enactment), although the extent of learning and range of skills enacted varied across participants. Influences on skill selection included the perceived relevance of intervention strategies to the user’s needs and personal characteristics (Topic 2, Theme 1: relevance of intervention strategies), as well as the perceived or experienced effectiveness of those strategies (Topic 2, Theme 2: perceived and experienced benefit). Challenges to ongoing skill enactment included time scarcity, prioritisation difficulties, and lack of motivation (Topic 2, Theme 3: navigating time constraints and low motivation). Improvements in mental health were generally modest and attributed mainly to participants’ proactive efforts (Topic 3, Theme 1: perceived changes). Conclusions DMHIs may reinforce existing understanding of psychotherapeutic strategies, offer new knowledge, and encourage the application of skills in everyday life among community users who actively engage with these interventions. Future research should prioritise personalising DMHIs and investigating methods to optimise the acquisition, retention, and sustained application of knowledge and skills.

Abstract Therapeutic hypothermia is the standard treatment for hypoxic-ischemic encephalopathy (HIE), but despite its widespread use, the rates of mortality and neurodevelopmental impairment for moderate to severe HIE remain around 30%. Methylxanthines, such as caffeine and aminophylline, have potential neuroprotective effects in the setting of hypoxic-ischemic injury. However, data on the safety and efficacy of methylxanthines in the setting of therapeutic hypothermia for HIE are limited. This retrospective multicenter study examined in-hospital outcomes in 52 infants with HIE receiving methylxanthines and therapeutic hypothermia. The frequency of mortality and in-hospital morbidities were similar to those of infants enrolled in clinical trials undergoing therapeutic hypothermia without adjunctive therapies. Clinical trials of methylxanthines for neuroprotection in HIE are needed to determine safety and efficacy and should explore optimal dosing and timing of methylxanthine administration.

Emotion-focused teaching in early childhood promotes children's early academic and social-emotional development and can occur through planned or informal classroom interactions. We observed video recordings of preschool teachers engaging in typical teaching practices and carrying out researcher-assigned book reading and social-emotional learning (SEL) lessons. Video cycles were coded using a measure of emotion-focused teaching, which captures teachers' modeling of, responding to, and instructing about emotions. This study examines (1) whether emotion-focused teaching will be greater during guided SEL activities (SEL lessons and book readings) compared to teaching as usual; and (2) which types of SEL activities are associated with higher levels of EFT-scripted lessons or book readings. Analyses indicate that emotion-focused teaching is greater during SEL activities but only planned SEL lessons had significantly higher scores than the non-intervention occasions. Findings are discussed with exemplar practices drawn from activity transcripts to highlight malleable practices suitable for coaching and professional development.

ABSTRACT Cryptococcus neoformans is a pathogenic yeast that is the causative agent of cryptococcal meningitis. While it is well known that the genotype of C. neoformans impacts patient outcomes, the reason for this association has not been well elucidated. In this study, we examined the relationship between two subpopulations in the sequence type 93 clade of C. neoformans: ST93A and ST93B. We found extensive linkage disequilibrium (LD) among the single nucleotide polymorphisms (SNPs) that differentiate ST93A from ST93B. We also found differences in the extent of linkage among SNPs within each subpopulation; LD was more extensive within ST93B than ST93A. SNPs associated with virulence were in long-range linkage disequilibrium with less frequency than recurrent SNPs not associated with virulence. We investigated the karyotype of ST93A and ST93B using contour-clamped gel electrophoresis and long-read sequencing and found that the extensive long-range linkage was not due to chromosomal rearrangements. Overall, we found that the two subpopulations in ST93 are driven by SNPs in LD. We additionally found that recurrent SNPs associated with virulence were less frequently evolutionarily linked and were two times more likely to be independent, congruent mutations rather than tied to phylogeny.IMPORTANCECryptococcus neoformans is an important pathogen that is widely distributed and ubiquitous in the environment. The majority of the human population has a latent, controlled infection suggesting that C. neoformans is uniquely adapted to cause infection. In spite of this, the reason C. neoformans is a pathogen remains unknown; interestingly, most environmental isolates are avirulent but are genetically very similar to disease-causing virulent isolates. Recent evidence from genome-wide association studies shows that small mutations in key virulence-associated genes are associated with the virulence of specific isolates. The data presented here provide an evolutionary framework for those small mutations. The mutations that impact disease are not being collected over long-term evolution. The mutations may instead occur independently during infection. Identifying these genes that are more likely to be mutated during infection will be fundamental for understanding C. neoformans virulence.

Rapid environmental change is altering coastal phytoplankton dynamics and, thereby the productivity of coastal marine food webs. Unfortunately, a paucity of phytoplankton community data hinders the prediction of future conditions in ecologically productive regions such as the coastal northeast Pacific. To help fill this gap, this study characterized phytoplankton communities from 2018 to 2020 across a fjord, channel and shelf station transect on the central coast of British Columbia, Canada. Monthly samples were collected for microscopy-based taxonomy and pigment-based phytoplankton composition (i.e. CHEMTAX and size-fractionated chlorophyll). Correlation analysis was used to investigate drivers of phytoplankton biomass and hierarchical clustering and redundancy analysis highlighted drivers of compositional trends. Spring blooms formed the peak of annual biomass at each station and earlier blooms at the fjord station suggested a sheltering effect from winter wind conditions. Later spring blooms at the channel station coincided with seasonal wind reductions and increased sunlight. Of the six derived compositional clusters, three represented flagellate dominated conditions at all stations: two represented low biomass winter conditions and the third, moderate biomass spring and autumn blooms occurring under nutrient replete conditions. The remaining three clusters were diatom-dominated and spanned much of the growing season. The first diatom cluster represented Skeletonema marinoi dominated samples, many from 2020, observed under moderate nutrient and high stratification and freshwater discharge conditions. The second represented high diatom richness spring bloom conditions at all stations that were associated with nutrient depletion. Finally, the third included 2018 and 2019 summer shelf samples showing harmful Rhizosolenia setigera and Pseudo-nitzschia seriata blooms under high surface water salinity and temperature. These results highlight high spatial-temporal variability and sensitivity of coastal northeast Pacific phytoplankton communities to altered freshwater, temperature and wind dynamics with potential for profound ecosystem level implications.

Teaching and learning of clinical reasoning are core principles of medical education. However, little guidance exists for faculty leaders to navigate curricular transitions between pre-clerkship and clerkship curricular phases. This study compares how educational leaders in these two phases understand clinical reasoning instruction. Previously reported cross-sectional surveys of pre-clerkship clinical skills course directors, and clerkship leaders were compared. Comparisons focused on perceived importance of a number of core clinical reasoning concepts, barriers to clinical reasoning instruction, level of familiarity across the undergraduate medical curriculum, and inclusion of clinical reasoning instruction in each area of the curriculum. Analyses were performed using the Mann Whitney U test. Both sets of leaders rated lack of curricular time as the largest barrier to teaching clinical reasoning. Clerkship leaders also noted a lack of faculty with skills to teach clinical reasoning concepts as a significant barrier (p

Purpose: The global cancer burden and mortality rates are increasing, with significant disparities in access to care in low- and middle-income countries (LMICs). This study aimed to identify radiology and radiation therapy needs in LMICs from the perspective of departmental and institutional leaders. Methods and Materials: A survey was developed and conducted by the American Association of Physicists in Medicine Global Needs Assessment Committee and the American Association of Physicists in Medicine International Council. The survey, organized into 5 sections (Introduction, Infrastructure Needs, Education Needs, Research Needs, and General Information), was open to respondents from March 1, to August 16, 2022. Results: A total of 175 responses were received from 6 global regions: Africa (31.4%), the Americas (17.7%), the Eastern Mediterranean (14.3%), Europe (9.1%), Southeast Asia (23.4%), and the Western Pacific (4.0%). The greatest reported need was for new or updated equipment, particularly positron emission tomography/computed tomography imaging technology. There was also a high demand for clinical and equipment training. Approximately 25% of institutions reported a lack of radiology-based cancer screening programs because of high health care costs and a shortage of specialized equipment. Many institutions that expressed interest in research face funding and grant challenges. Conclusions: The findings highlight critical areas where organizations can support LMICs in enhancing radiology and radiation therapy services to mitigate the growing cancer burden.

Abstract Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity. We show that inhibiting NETosis protects mice from immunopathology in a model of virus-exacerbated COPD. NETs drive inflammation during exacerbations through release of double stranded DNA (dsDNA) and administration of DNAse in mice has similar protective effects. Thus, NETosis, through release of dsDNA, has a functional role in the pathogenesis of COPD exacerbations. These studies open up the potential for therapeutic targeting of NETs or dsDNA as a strategy for treating virus-exacerbated COPD.

Abstract Background Effective testing for malaria, including the detection of infections at very low densities, is vital for the successful elimination of the disease. Unfortunately, existing methods are either inexpensive but poorly sensitive or sensitive but costly. Recent studies have shown that mid-infrared spectroscopy coupled with machine learning (MIRs-ML) has potential for rapidly detecting malaria infections but requires further evaluation on diverse samples representative of natural infections in endemic areas. The aim of this study was, therefore, to demonstrate a simple AI-powered, reagent-free, and user-friendly approach that uses mid-infrared spectra from dried blood spots to accurately detect malaria infections across varying parasite densities and anaemic conditions. Methods Plasmodium falciparum strains NF54 and FCR3 were cultured and mixed with blood from 70 malaria-free individuals to create various malaria parasitaemia and anaemic conditions. Blood dilutions produced three haematocrit ratios (50%, 25%, 12.5%) and five parasitaemia levels (6%, 0.1%, 0.002%, 0.00003%, 0%). Dried blood spots were prepared on Whatman™ filter papers and scanned using attenuated total reflection-Fourier Transform Infrared (ATR-FTIR) for machine-learning analysis. Three classifiers were trained on an 80%/20% split of 4655 spectra: (I) high contrast (6% parasitaemia vs. negative), (II) low contrast (0.00003% vs. negative) and (III) all concentrations (all positive levels vs. negative). The classifiers were validated with unseen datasets to detect malaria at various parasitaemia levels and anaemic conditions. Additionally, these classifiers were tested on samples from a population survey in malaria-endemic villages of southeastern Tanzania. Results The AI classifiers attained over 90% accuracy in detecting malaria infections as low as one parasite per microlitre of blood, a sensitivity unattainable by conventional RDTs and microscopy. These laboratory-developed classifiers seamlessly transitioned to field applicability, achieving over 80% accuracy in predicting natural P. falciparum infections in blood samples collected during the field survey. Crucially, the performance remained unaffected by various levels of anaemia, a common complication in malaria patients. Conclusion These findings suggest that the AI-driven mid-infrared spectroscopy approach holds promise as a simplified, sensitive and cost-effective method for malaria screening, consistently performing well despite variations in parasite densities and anaemic conditions. The technique simply involves scanning dried blood spots with a desktop mid-infrared scanner and analysing the spectra using pre-trained AI classifiers, making it readily adaptable to field conditions in low-resource settings. In this study, the approach was successfully adapted to field use, effectively predicting natural malaria infections in blood samples from a population-level survey in Tanzania. With additional field trials and validation, this technique could significantly enhance malaria surveillance and contribute to accelerating malaria elimination efforts.

The management of state forests is increasingly adopting participatory forest management (PFM), a collaborative approach involving various stakeholders. PFM aims to enhance transparency in forest governance by involving local communities in decision-making and processes. The Forest Act of 2005 formalized PFM in Kenya, granting community forest associations (CFAs) the right to collaborate with the Kenya Forest Service (KFS). This framework empowers CFAs with both responsibilities and rights related to forest management and benefit sharing. This study evaluated the effectiveness of PFM in Kenya by analyzing the forest policy, legislative framework, and institutional mechanisms that support the transition to sustainable forest management (SFM). It also aimed to identify and address key challenges in forest law enforcement and governance. The study focused on three key questions: (i) How has Forest Act of 2005 and subsequent policies influenced PFM? (ii) How effective are CFAs in managing forests? (iii) What challenges in Forest Law Enforcement and Governance (FLEG) hinder PFM, and what strategies can address these issues? A mixed-methods approach was used, combining qualitative and quantitative data for cross-validation. The methodology included a comprehensive literature review, alongside data from key informant interviews (KIIs), household surveys, and participant observation. The analysis revealed gaps in forest governance, including conflicting legislation, weak enforcement, insufficient KFS funding, limited CFA involvement in decision-making, and ambiguous CFA roles. Other challenges included illegal logging, inadequate judicial understanding of forestry law, insufficient PFM benefits for the local communities, and the need for more inclusive practices to improve forest conservation and management.

Background: Immune thrombocytopenia (ITP) is an acquired thrombocytopenia caused by auto-antibodies against platelet antigens. Over the last 20 years numerous reports of venous thromboembolic complications with ITP patients have been published, including several large-scale population-based studies. However, data in children is scarce. Herein we report four cases of pediatric patients who were found to have cerebral venous sinus thrombosis (CSVT) after ITP. These cases and prior literature raise the possibility of ITP, and or its treatment being a thrombotic risk factor. Aims: The present study sought to report 4 cases of CSVT in the setting of ITP. Methods: Chart review of 4 patients who presented with CSVT following a diagnosis of ITP were conducted. Parental consent was obtained. Results: Four male patients with mean age of CSVT presentation being 6 years (3-10 years of age), who developed CSVT post ITP, received therapeutic anticoagulation. They did not develop bleeding complications while on anticoagulation therapy. All had good clinical outcomes, with partial or complete radiological resolution of thrombosis. Recurrence or extension of CSVT occurred in 3 of 4 patients. Despite having intracranial hemorrhage at the time of the ITP presentation in 2 patients, anticoagulation was still initiated, and did not result in further bleeding. Conclusion: The etiology of the increased risk of venous thrombosis in patients with ITP is unclear, and it appears to be multifactorial as to why some patients may be prone to thrombosis and others not, and how important the role of treatment is in this complication. However, ITP and or the treatment of ITP may be contributing risk factors for thrombosis. Bleeding remains the most feared complication for patients with ITP. Nevertheless, anticoagulation can be administered, without further bleeding complications. An association between ITP and thrombosis, specifically CSVT in children is possible, but data is lacking in the literature. Further studies are needed to better describe associations between ITP, and thrombotic events in children.

BackgroundThere is significant conflicting evidence as to how using cannabis while drinking alcohol (ie, simultaneous alcohol and cannabis use) impacts alcohol volume consumed, patterns of drinking, and alcohol-related consequences. The impact of simultaneous use on drinking outcomes may be influenced by several within-person (eg, contextual) and between-person (individual) factors. ObjectiveThis study was designed to examine naturalistic patterns of alcohol and cannabis use to understand how simultaneous use may impact drinking outcomes. The primary aims were to understand the following: (1) if simultaneous use is associated with increased alcohol consumption and riskier patterns of drinking, (2) if simultaneous use leads to increased alcohol consequences, and (3) how contextual circumstances moderate the impact of simultaneous use on consumption and consequences. MethodsData collection involves a 28-day ambulatory assessment protocol in which a sample of non–treatment-seeking young adults who report simultaneous use of alcohol and cannabis complete ecological momentary assessments (random, event-contingent, and time-contingent surveys) of alcohol and cannabis use, contexts, motives, and consequences on their personal smartphones while continuously wearing an alcohol biosensor bracelet. Participants also complete a baseline assessment, brief internet-based check-in on day 14, and a final session on day 28. Community-based recruitment strategies (eg, social media and flyers) were used to enroll 95 participants to obtain a target sample of 80, accounting for attrition. ResultsRecruitment and data collection began in May 2021 and continued through June 2024. Initial results for primary aims are expected in October 2024. As of March 2024, the project had recruited 118 eligible participants, of whom 94 (79.7%) completed the study, exceeding initial projections for the study time frame. Remaining recruitment will provide the capacity to probe cross-level interactions that were not initially statistically powered. Strengths of the project include rigorous data collection, good retention and compliance rates, faster-than-expected enrollment procedures, use of a novel alcohol biosensor, and successful adaptation of recruitment and data collection procedures during the COVID-19 pandemic. ConclusionsThis is the first investigation to assess the key momentary predictors and outcomes of simultaneous use as well as self-reported and objective (via alcohol biosensor) measures of alcohol consumption and patterns. The results of this study will inform prevention efforts and studies of individuals who use cannabis who are engaged in alcohol treatment. International Registered Report Identifier (IRRID)DERR1-10.2196/58685

Pancreatic resection not infrequently requires portal vein (PV) repair or replacement. PV reconstruction often requires bypass grafting or patch venoplasty, and these grafts and patches require time to thaw or harvest. Mesenteric ischemia and congestion with associated bowel edema may result from prolonged venous occlusion during thawing, harvesting, and reconstructing. Temporary shunting of the mesenteric venous circulation may mitigate these adverse effects. Twenty-one patients were shunted using Argyle shunts during PV reconstruction from 2010 to 2020. Reconstructions in this series consisted of aortic homograft interposition grafts (52%), bovine pericardial patches (38%), internal jugular vein interposition grafts (5%), and internal jugular patches (5%). No intraoperative complications resulted from shunt placement; technical success of PV reconstruction was 100%. Temporary venous shunting during PV reconstruction is safe, technically straightforward, and may serve to decrease the duration of venous mesenteric occlusion.

Background: Cytomegalovirus (CMV) is the most common viral infection among lung transplant recipients and is associated with chronic lung allograft dysfunction. There is a need for better therapeutics as well as biomarkers to enable effective stratification of CMV seropositive patient risk for developing CMV DNAemia to inform prophylaxis duration. Methods: CMV-specific immunoglobulin G (IgG) binding and functional responses were evaluated in a discovery cohort of longitudinal plasma samples from 51 CMV seropositive human lung transplant recipients, collected as part of the clinical trials in organ transplantation (CTOT)-20 and CTOT-22 consortium studies. Pre-transplant plasma from an additional 43 CMV seropositive lung transplant recipients was evaluated as a validation cohort. Results: In the discovery cohort with longitudinal samples, pre-transplant plasma IgG binding to CMV surface glycoproteins glycoprotein H (gH)/glycoprotein L (gL), gH/gL/glycoprotein O (gO), and pentameric complex, as well as neutralization of CMV in epithelial cells, is associated with increased risk of CMV DNAemia post-prophylaxis. However, these results were not confirmed by the validation cohort. Conclusions: While quantification of pre-transplant CMV-specific antibody responses showed association with DNAemia in the discovery cohort, additional clinical variables and/or known risk factors for CMV, such as patient CMV-specific T-cell responses, may need to be considered in combination with humoral immunity to effectively stratify risk of CMV DNAemia.

BackgroundNumerous studies have demonstrated the effectiveness of digital interventions for improving the mental health of university students. However, low rates of engagement with these interventions are an ongoing challenge and can compromise effectiveness. Brief, transdiagnostic, web-based video interventions are capable of targeting key mental health and related issues affecting university students and may be more engaging and accessible for this population. ObjectiveThis study used a 2-arm randomized controlled trial to evaluate the effectiveness of Uni Virtual Clinic-Lite (UVC-Lite), a fully automated, transdiagnostic, web-based video intervention, relative to an attention-control condition. The primary outcomes were symptoms of depression and generalized anxiety disorder. The secondary outcomes included psychological distress, social anxiety symptoms, body appreciation, quality of life, well-being, functioning, general self-efficacy, academic self-efficacy, and help seeking. Program use (intervention uptake and engagement) and satisfaction were also assessed. MethodsUniversity students (n=487) with mild to moderate symptoms of distress were recruited from universities across Australia and randomly allocated to receive access to the UVC-Lite intervention or an attention-control condition targeting general health for a period of 6 weeks. UVC-Lite includes 12 modules, each comprising a brief animated video and an accompanying exercise. Of the 12 modules, 7 also included a brief symptom screening quiz. Outcomes were assessed at baseline, postintervention, and 3- and 6-months postintervention. ResultsThe primary and secondary outcomes were analyzed on an intention-to-treat basis using mixed models repeated measures ANOVA. The intervention was not found to be effective relative to the control condition on any of the primary or secondary outcomes. While 67.9% (114/168) of participants accessed at least 1 module of the intervention, module completion was extremely low. Subgroup analyses among those who engaged with the program (completed at least 1 video) and those with higher baseline distress (Distress Questionnaire-5 score ≥15) did not reveal any differences between the conditions over time. However, uptake (accessing at least 1 video) and engagement (completing at least 1 video) were higher among those with higher baseline symptoms. Satisfaction with the intervention was high. ConclusionsThe UVC-Lite intervention was not effective relative to a control program, although it was associated with high satisfaction among students and was not associated with symptom deterioration. Given the challenges faced by universities in meeting demand for mental health services, flexible and accessible interventions such as UVC-Lite have the potential to assist students to manage symptoms of mental health problems. However, low uptake and engagement (particularly among students with lower levels of symptomatology) are significant challenges that require further attention. Future studies should examine the effectiveness of the intervention in a more highly symptomatic sample, as well as implementation pathways to optimize effective engagement with the intervention. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12621000375853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380146

BackgroundMental health problems are common among university students, yet many students do not seek professional help. Digital mental health interventions can increase students’ access to support and have been shown to be effective in preventing and treating mental health problems. However, little is known about the extent to which students implement therapeutic skills from these programs in everyday life (ie, skill enactment) or about the impact of skill enactment on outcomes. ObjectiveThis study aims to assess the effects of a low-intensity video-based intervention, Uni Virtual Clinic Lite (UVC-Lite), in improving skill enactment relative to an attention-control program (primary aim) and examine whether skill enactment influences symptoms of depression and anxiety (secondary aim). The study also qualitatively explored participants’ experiences of, and motivations for, engaging with the therapeutic techniques. MethodsWe analyzed data from a randomized controlled trial testing the effectiveness of UVC-Lite for symptoms of depression and anxiety among university students with mild to moderate levels of psychological distress. Participants were recruited from universities across Australia and randomly assigned to 6 weeks of self-guided use of UVC-Lite (243/487, 49.9%) or an attention-control program (244/487, 50.1%). Quantitative data on skill enactment, depression, and anxiety were collected through baseline, postintervention, and 3- and 6-month follow-up surveys. Qualitative data were obtained from 29 intervention-group participants through open-ended questions during postintervention surveys (n=17, 59%) and semistructured interviews (n=12, 41%) after the intervention period concluded. ResultsMixed model repeated measures ANOVA demonstrated that the intervention did not significantly improve skill enactment (F3,215.36=0.50; P=.68). Skill enactment was also not found to influence change in symptoms of depression (F3,241.10=1.69; P=.17) or anxiety (F3,233.71=1.11; P=.35). However, higher levels of skill enactment were associated with lower symptom levels among both intervention and control group participants across time points (depression: F1,541.87=134.61; P

Objective Digital interventions can be effective in preventing and treating common mental health conditions among university students. Incorporating student experiences and perspectives in the design and implementation of these programmes may improve uptake and engagement. This qualitative study explored university students’ perspectives of a low-intensity video-based mental health intervention, their recommendations for implementing the programme in university settings, and their views and recommendations to address barriers to engagement. Methods Participants (N = 115) were students (mean = 20.63 years, SD = 2.10) with elevated distress from 31 Australian universities drawn from a randomised controlled trial of the Uni Virtual Clinic-Lite (UVC-Lite). Data from students randomised to the intervention condition were collected via semi-structured interviews (n = 12) and open-ended questions during post-intervention surveys (n = 103). Data were analysed using content analysis. Results Participants generally reported positive views of the intervention, and most felt it should be offered to students as a universal intervention. Multiple methods of disseminating the intervention were suggested, including through university counselling, official platforms (e.g. student support services) and informal channels (e.g. word-of-mouth promotion). Difficulty integrating the programme into everyday life, pre-existing beliefs about mental health and technology-related factors were highlighted as barriers to engagement. Conclusion A low-intensity video-based mental health intervention was generally considered to be acceptable and appropriate for students with mild to moderate distress. Participants provided several suggestions to encourage uptake of the intervention and possible pathways to disseminate the intervention to students. The effectiveness of these should be examined in future trials.

Abstract Seismic and mineralogical studies have suggested regions at Earth’s core-mantle boundary may be highly enriched in FeO, reported to exhibit metallic behavior at extreme pressure-temperature (P–T) conditions. However, underlying electronic processes in FeO remain poorly understood. Here we explore the electronic structure of B1-FeO at extreme conditions with large-scale theoretical modeling using state-of-the-art embedded dynamical mean field theory (eDMFT). Fine sampling of the phase diagram reveals that, instead of sharp metallization, compression of FeO at high temperatures induces a gradual orbitally selective insulator-metal transition. Specifically, at P–T conditions of the lower mantle, FeO exists in an intermediate quantum critical state, characteristic of strongly correlated electronic matter. Transport in this regime, distinct from insulating or metallic behavior, is marked by incoherent diffusion of electrons in the conducting t 2g orbital and a band gap in the e g orbital, resulting in moderate electrical conductivity (~105 S/m) with modest P–T dependence as observed in experiments. Enrichment of solid FeO can thus provide a unifying explanation for independent observations of low seismic velocities and elevated electrical conductivities in heterogeneities at Earth’s mantle base.

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a poor prognosis. Doxorubicin is part of standard curative therapy for TNBC, but chemotherapy resistance remains an important clinical challenge. Bocodepsin (OKI-179) is a small molecule class I histone deacetylase (HDAC) inhibitor that promotes apoptosis in TNBC preclinical models. The purpose of this study was to investigate the combination of bocodepsin and doxorubicin in preclinical TNBC models and evaluate the impact on terminal cell fate, including apoptosis and senescence. Methods TNBC cell lines were treated with doxorubicin and CellTiter-Glo was used to assess proliferation and determine doxorubicin sensitivity. Select cell lines were treated with OKI-005 (in vitro version of bocodepsin) and doxorubicin and assessed for proliferation, apoptosis as measured by Annexin V/PI, and cell cycle by flow cytometry. Immunoblotting was used to assess changes in mediators of apoptosis, cell cycle arrest, and senescence. Senescence was measured by the senescence-associated β-galactosidase assay. An MDA-MB-231 xenograft in vivo model was treated with bocodepsin, doxorubicin, or the combination and assessed for inhibition of tumor growth. shRNA knockdown of p53 was performed in the CAL-51 cell line and proliferation, apoptosis and senescence were assessed in response to combination treatment. Results OKI-005 and doxorubicin resulted in synergistic antiproliferative activity in TNBC cells lines regardless of p53 mutation status. The combination led to increased apoptosis and decreased senescence. In vivo, the combination resulted in increased tumor growth inhibition compared to either single agent. shRNA knock-down of p53 led to increased doxorubicin-induced senescence that was decreased with the addition of OKI-005 in vitro. Conclusion The addition of bocodepsin to doxorubicin resulted in synergistic antiproliferative activity in vitro, improved tumor growth inhibition in vivo, and promotion of apoptosis which makes this a promising combination to overcome doxorubicin resistance in TNBC. Bocodepsin is currently in clinical development and has a favorable toxicity profile compared to other HDAC inhibitors supporting the feasibility of evaluating this combination in patients with TNBC.

Fjords are deep nearshore zones that connect watersheds and oceans, typically behaving as an estuary. In some fjords, strong katabatic winds in winter (also known as Arctic outflow wind events) can lead to cooling and reoxygenation of subsurface waters, with effects lasting until the following autumn, as observed in 2019 in Bute Inlet, British Columbia, Canada. We used high-resolution, three-dimensional ocean model summer simulations to investigate the mechanisms allowing for the persistence of these cool, oxygen-rich subsurface conditions in Bute Inlet. The slow residual circulation underneath the brackish outflow (and consequent slow advection) in this long, deep fjord is a main reason why the cold subsurface water mass stays in place until conditions change in autumn (i.e., start of stronger wind mixing and reduced freshwater forcing). Another mechanism is a positive feedback provided by the presence of this subsurface water mass, since it further reduces the already weak residual circulation. These findings are applicable to any similar long, deep fjord that experiences katabatic winds in winter, and they could have implications not only for the preservation of water masses but other possible subsurface features (e.g., pollutant spills, planktonic larvae). Furthermore, the identification of mechanisms that permit persistent cold and oxygenated conditions is key to understanding potential areas of ecological refugia in a warming and deoxygenating ocean.

Abstract Background Food insecurity is an important social determinant of health that was exacerbated by the COVID-19 pandemic. Both food insecurity and COVID-19 infection disproportionately affect racial and ethnic minority groups, particularly American Indian and Alaska Native communities; however, there is little evidence as to whether food insecurity is associated with COVID-19 infection or COVID-19 preventive behaviors such as vaccination uptake. The purpose of this study was to evaluate associations between food insecurity, COVID-19 infection, and vaccination status among urban American Indian and Alaska Native adults seen at 5 clinics serving urban Native people. Methods In partnership with health organizations in Alaska, Colorado, Kansas, Minnesota, and New Mexico, the study team conducted a cross-sectional survey in 2021 to assess food security status and attitudes, barriers, and facilitators for COVID-19 testing and vaccination. Logistic regression was used to examine the association of food security status with sociodemographic factors and COVID-19 infection and vaccination status. Marginal standardization was applied to present results as prevalence differences. Results Among 730 American Indian and Alaska Native adults, the prevalence of food insecurity measured during the pandemic was 38%. For participants who reported persistent food security status before and during the pandemic (n = 588), the prevalence of food insecurity was 25%. Prevalence of COVID-19 infection and vaccination did not vary by food security status after adjustment for confounders. Conclusions High rates of food insecurity among American Indian and Alaska Native communities likely increased during the COVID-19 pandemic. However, despite the high prevalence of food insecurity, community-led efforts to reduce COVID-19 infection and increase vaccination uptake across Indian Health Service and Tribal healthcare facilities may have mitigated the negative impacts of the pandemic for families experiencing food insecurity. These successful approaches serve as an important reference for future public health efforts that require innovative strategies to improve overall health in American Indian and Alaska Native communities.