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IntroductionFederal policies and guidelines have expanded the return of individual results to participants and expectations for data sharing between investigators and through repositories. Here, we report investigators' and study participants' views and experiences with data stewardship practices within frontotemporal lobal degeneration (FTLD) research, which reveal unique ethical challenges.MethodsSemi-structured interviews with (1) investigators conducting FTLD research that includes genetic data collection and/or analysis and (2) participants enrolled in a single site longitudinal FTLD study.ResultsAnalysis of the interviews identified three meta themes: perspectives on data sharing, experiences with enrollment and participation, and data management and security as mechanisms for participant protections.DiscussionThis study identified a set of preliminary gaps and needs regarding data stewardship within FTLD research. The results offer initial insights on ethical challenges to data stewardship aimed at informing future guidelines and policies.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study, TM9 was effective against three murine coronavirus strains, demonstrating that the therapeutic window is large enough to allow the use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber, and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from the liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

IntroductionAltered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early-onset Alzheimer's disease (EOAD).MethodsWe examined single-cell RNA-sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital polymerase chain reaction (ddPCR) data from CD4 T cells from participants with EOAD and clinically normal controls.ResultsWe analyzed PBMCs from 16 individuals by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAGhi T cells in EOAD. Isolating CD4 T cells from 19 individuals, including four cases analyzed by scRNA-seq, we confirmed increased expression of ISAGhi marker genes. Publicly available cerebrospinal fluid leukocyte scRNA-seq data from late-onset mild cognitive impairment and AD also revealed increased expression of interferon-response genes.DiscussionAntiviral-like ISAGhi T cells are expanded in EOAD. Additional research into these cells and the role of heightened peripheral IFN signaling in neurodegeneration is warranted.HighlightsInterferon-responsive T cells expanded in early-onset Alzheimer's disease (AD). Increased interferon-associated gene expression present in early- and late-onset AD. Peripheral immune changes in T and NK cells driven by females with early-onset AD.

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.

Postgraduate study can be mentally, physically and emotionally challenging. The levels of anxiety and depression in postgraduate students are much higher than those in the general population, and isolation can also be a problem, especially for students who are marginalised due to gender, race, sexuality, disability or being a first-generation and/or international student. These challenges are not new, but awareness of them has increased over the past decade, as have efforts by institutions to make students feel supported. Under the umbrella of a Doctoral Training Partnership, we developed a programme in which reflective practice is employed to help postgraduate students navigate work environments, deal with difficult supervisory or professional relationships, and improve their work-life balance. Additionally, this reflective practice is allowing the training partnership to tailor support to its students, enabling them to effectively nurture our next generation of bioscientists.

Prologue All authors are disabled scholars with varying experiences of learning disability, long term illness, chronic health conditions. All authors are neurodivergent. Three are currently unemployed, underemployed, and/or precariously employed. Two are from a marginalised ethnic/racial group. Two are the first in their generation to access higher education. Three have known severe poverty. Not all involved could be named on this publication. The lived experience of the authors is woven into a singular cautionary tale to provide an every-person understanding of career-block within academia for disabled scholars. This artistic endeavour, inherently analytic in its documentation of the ‘identity work’ of our authors, draws on past experience (memory) weaved through imagination. The writing and publishing of this piece required a brutal honesty that lays us open, vulnerable, and at risk. However, as you will read, the risk of silence could be greater still. Human experience can be understood through stories. Our work is concerned with performing the narrative of our daily lives (Langellier and Peterson, 2004); making the mundane magical and instilling belief in the unbelievable. Our lived experiences are stranger than fiction, and combined they enchant a fictional narrative that describes the necropolitics of career-blocking (Mbembe 2003) through a new methodology we call PanEthnography. As authors of different disciplines/fields and universities, we were united in our experiences of disability in the academe. We conceived and constructed PanEthnography through a lens of Embodied Inquiry (Bochner & Ellis 2016; Leigh and Brown 2021; Apostolidou and Daskalaki, 2021). During the month of October 2022 we formed a research collective (or writing coven), to explore our collective experiences of career blocking related to disability. The data gathering process was undertaken by digital means by using online video-conferencing and countless WhatsApp (Halliwell and Wilkinson 2

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p -FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Most Filipinos are fond of home-cooked meals, but due to their hectic schedules, they tend to eat at fast food restaurants. As a result, several successful restaurants have increased their branches locally and internationally due to the overwhelming demand of millions of Filipino customers. However, health experts warn that fast food has more negative and serious effects on Filipino communities than positive outcomes. Fast food can cause vitamin deficiencies that may, in turn, lead to diseases.   This study utilized the descriptive method for collecting information about the cause and effect of eating at Jollibee Corporation on the health of BSHM students. The researcher gathered data using survey questionnaires administered via Google Forms to fifty (50) respondents at Bestlink College of the Philippines.   The survey results show that most of the respondents are female, and most are between the ages of 21 and 22 years old. All of them are single, and according to the survey, most students who eat at fast food restaurants have a monthly income of less than 1000 or more than 1000.   Based on the survey, the respondents have reasons for eating at fast food restaurants and consuming fast food one to five times a month. The highest reason for consuming fast food is the craving that they can control. Respondents know that obesity is a possible effect of eating fast food and that cravings can be substituted with healthier food to avoid the possible negative effects of eating fast food. Healthy food can be made easily and inexpensively.   Based on the gathered data and conclusions drawn, the researcher formulated a cause and effect of Jollibee Corporation on health to determine the effects of fast food on health and what the respondents need to do to control their fast food consumption. The faculty should utilize modern ways of teaching in this new normal and assist the students in basic learning in their chosen field of expertise in the hospitality in

Objective We sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60-64 years from the Medical Research Council National Survey of Health and Development, a nationally representative British birth cohort. Methods Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at age 20 years. 10 modes of variation in hip shape (HM1-10), described by statistical shape models, were previously ascertained from DXA images taken at ages 60-64 years. Associations between (1) height at each age; (2) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity; and (3) height gain during specific periods of childhood and adolescence, and HM1-10 were tested. Results Faster growth velocity was associated with a wider, flatter femoral head and neck, as described by positive scores for HM6 (regression coefficient 0.014; 95% CI 0.08 to 0.019; p<0.001) and HM7 (regression coefficient 0.07; 95% CI 0.002 to 0.013; p=0.009), and negative scores for HM10 (regression coefficient -0.006; 95% CI -0.011 to 0.00, p=0.04) and HM2 (males only, regression coefficient -0.017; 95% CI -0.026 to -0.09; p<0.001). Similar associations were observed with greater height size and later height tempo. Examination of height gains during specific periods of childhood and adolescence identified those during the adolescence period as being most consistently associated. Conclusion Our analyses suggest that individual growth patterns, particularly in the adolescent period, are associated with modest variations in hip shape at 60-64 years, which are consistent with features seen in osteoarthritis.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation., Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

This report describes the procedures and results of the full-scale implementation of the B&B:93/03 study. Students who earned a bachelor's degree in 1992-93 were first interviewed in 1993 and then subsequently in 1994 and 1997. This is the final follow-up interview of the B&B:93 cohort, 10 years following completion of the bachelor's degree. The results of this study offer an opportunity to assess the value of a baccalaureate degree at a time when sample members are becoming established in their careers. Specific topics of interest include length of time to complete a baccalaureate degree, the pursuit of additional postsecondary education beyond a bachelor's degree, and employment outcomes. The following are appended: (1) Data Collection Mailout Materials; (2) Technical Review Panel Members; (3) Final Set of Data Elements Used in B&B:93/03 Survey; (4) Facsimiles of B&B:93/03 Interview and Previous Interviews; (5) Self-Administered, Telephone, and Field Interviewer Training Manuals; (6) Listing of Analysis Variables Derived for B&B:93/03; (7) Design Effect Tables; and (8) Item Nonresponse Bias Tables. (Contains 43 tables and 9 figures.)

This curriculum was developed to support American Indian high school students in their transition from high school to postsecondary life. It provides a structured process and culturally relevant activities that can be led by either teachers, tribal elders, community members, or paraprofessionals. The curriculum is based on principles such as a belief in the resilience of American Indian youth and their communities and the awareness of sensitive topic areas. It is organized into four themes and within each theme into topical units and lesson plans (each approximately 30-60 minutes). The four themes are: (1) discovery; (2) framework; (3) choice; and (4) reflection. Units address the following topics: the first day, social supports, my family, my community, about me, responding to change, goal-setting, self-advocacy, problem-solving, organizational skills, communication skills, diversity awareness, vision, postsecondary education, career development, military training, and bringing it all together. Each lesson plan includes activity name, student outcome/s, portfolio placement, time frame, size of group, preparation, directions, discussion, closure, and additional suggestions, resources. Additional information includes a brief history of American Indian education and a chart showing Minnesota graduation standards. (DB)

This report describes the methods and procedures used for the Beginning Postsecondary Students Longitudinal Study: 1996-2001 (BPS:1996/2001). These students, who started their postsecondary education during the 1995-96 academic year, were first interviewed in 1996 as part of the National Postsecondary Student Aid Study (NPSAS:96). A follow-up interview was conducted in 1998, during the third academic year since entry. This second and final follow-up used telephone and field interviewing to collect data from first-time beginning students in 4-year, 2-year, and less-than-2-year public, private, nonprofit, and private, for-profit institutions. Interviews focused on degree attainment, undergraduate experiences, additional education and training, transition into employment, current job, demographics, family formation, civic participation, and disability status. [The attached document presents the complete version of ED469501.]

This report describes the methods and procedures used for the full-scale data collection effort of the Beginning Postsecondary Students Longitudinal Study First Follow-Up 1996-98 (BPS:96/98). These students, who started their postsecondary education during the 1995-96 academic year, were first interviewed during 1996 as part of the National Postsecondary Student Aid Study, 1996. This study is the first follow-up of this cohort. Data collected includes postsecondary enrollment, employment, and demographics; a field locating/interviewing component allows comparative analyses with the first (1990) BPS cohort. Chapter 1 provides an introduction, some background, and the purpose of the study; chapter 2 covers the design and methodology of the full-scale study; chapter 3 covers data collection outcomes; chapter 4 covers evaluation of data quality; chapter 5 covers data file construction; and chapter 6 covers weighting and variance estimation. Appendixes include a list of technical review panel members; final data elements; facsimile questionnaire; table of contents of interviewer training manual; and sample mailout materials. (CH)

This report describes the methods and procedures used for the field test of the Beginning Postsecondary Students Longitudinal Study First Followup 1996-98 (BPS:96/98). Students in this survey were first interviewed during 1995 as part of the National Postsecondary Student Aid Study 1996 field test. The BPS:96/98 full-scale student sample includes students who started their postsecondary education during the 1995-96 academic year. Evaluation of procedures used in the field test has led to refinements that benefit the full-scale study. The introductory chapter describes the study and the unique purposes of the field test. Chapter 2 reviews the study design and methodology for the field test. Chapter 3 presents overall outcomes of data collection and the special procedures implemented during the field test. Chapter 4 examines issues related to the quality of the data collected. The major recommendations for changes in the design of the full-scale study are included by topic in chapters 3 and 4, and summarized at the end of chapter 4. Materials used in the field test, including 5 facsimile interviews are provided as five appendixes to the report. (Contains 2 figures and 17 tables.) (SLD)

The visual system offers unparalleled precision in the assessment of neuroaxonal damage. With the majority of patients with multiple sclerosis (MS) experiencing afferent and efferent visual dysfunction, outcome measures capturing these deficits provide insight into neuroaxonal injury, even in those with minimal disability. Ideal for use in clinical trials, visual measures are generally inexpensive, accessible, and reproducible. Quantification of visual acuity, visual fields, visual quality of life, and electrophysiologic parameters allows assessment of function, whereas optical coherence tomography (OCT) provides reliable measures of the structural integrity of the anterior afferent visual pathway. The technology of oculomotor biometrics continues to advance, and discrete measures of fixation, smooth pursuit, and saccadic eye movement abnormalities are ready for inclusion in future trials of MS progression. Visual outcomes allow tracking of neuroaxonal injury and aid in distinguishing MS from diseases such as neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). OCT has also provided unique insights into pathophysiology, including the identification of foveal pitting in NMOSD, possibly from damage to Müller cells, which carry an abundance of aquaporin-4 channels. For some study designs, the cost-benefit ratio favors visual outcomes over more expensive MRI outcomes. With the next frontier of therapeutics focused on remyelination and neuroprotection, visual outcomes are likely to take center stage. As an international community of collaborative, committed, vision scientists, this review by the International MS Visual System Consortium (IMSVISUAL) outlines the quality standards, informatics, and framework needed to routinely incorporate vision outcomes into MS and NMOSD trials.

Introduction: To address persistent gender inequities in academic medicine, women professional development groups (PDG) have been developed to support the advancement of women in medicine. While these programs have shown promising outcomes, long-term evaluative metrics do not currently exist. The objective of this study was to establish metrics to assess women’s PDGs.  Methods: This was a modified Delphi study that included an expert panel of current and past emergency department (ED) chairs and Academy for Women in Academic Emergency Medicine (AWAEM) presidents. The panel completed three iterative surveys to develop and rank metrics to assess women PDGs. Metrics established by the expert panel were also distributed for member-checking to women EM faculty.  Results: The expert panel ranked 11 metrics with high to moderate consensus ranking with three metrics receiving greater than 90% consensus: gender equity strategy and plan; recruitment; and compensation. Members ranked 12 metrics with high consensus with three metrics receiving greater than 90% consensus: gender equity strategy and plan; compensation; and gender equity in promotion rates among faculty. Participants emphasized that departments should be responsible for leading gender equity efforts with PDGs providing a supportive role.  Conclusion: In this study, we identified metrics that can be used to assess academic EDs’ gender equity initiatives and the advisory efforts of a departmental women’s PDG. These metrics can be tailored to individual departmental/institutional needs, as well as to a PDG’s mission. Importantly, PDGs can use metrics to develop and assess programming, acknowledging that many metrics are the responsibility of the department rather than the PDG.

From the Soil, to the People shows how representations of rural society and the rural environment in Chinese literature from the 1940s to the present illuminate changing attitudes towards community, land, and modern life. It spans the explicitly political and state-regulated literature of the 1950s-1970s, literature produced under the relaxed guidelines of the 1980s, and literature written amid the increased commercialization of the 1990s and early 2000s. Conventional scholarship often separates these periods to examine them in isolation or focuses on pre- and post-socialist literature while ignoring the socialist period in between. In contrast, From the Soil, to the People uses “the rural question” to bring these disparate periods together, examining a persistent sociopolitical challenge through vastly different literary contexts.From the Soil, To the People examines the relationship between formal shifts in the literary portrayal of rural society with changes in the social, economic, and political conditions for both rural society and literary production. Close readings of 2-3 canonical novels from each era serve as vantage points, revealing signs of shifting ideologies of the rural that allow a longer timeline to emerge. Examining traditional literary categories including characterization and description across an 80-year period of monumental change, From the Soil, To the People argues that the relationship between literary production and historical change was not simply a matter of the representation of reality or a blueprint for an ideal society. From the Soil, To the People breaks down monolithic, timeless approaches to thinking about rural life through its historicization of particular moments in literary production across place and time in an environment of constant, yet not linear, change. Tracing the fluctuations of rural ideologies across these changes shows moments of both forward movement and circular return. Questioning linear narratives of rural moder

Although persister cells are the root cause of resistance development and relapse of chronic infections, more attention has been focused on developing antimicrobial agents against resistant bacterial strains than on developing anti-persister agents. Frustratingly, the global preclinical antibacterial pipeline does not include any anti-persister drug. Therefore, the central point of this work is to explore antimicrobial peptidomimetics called peptoids (sequence-specific oligo-N-substituted glycines) as a new class of anti-persister drugs. In this study, we demonstrate that one particular antimicrobial peptoid, the sequence-specific pentamer TM5, is active against planktonic persister cells and sterilizes biofilms formed by both Gram-negative and Gram-positive bacteria. Moreover, we demonstrate the potential of TM5 to inhibit cytokine production induced by lipopolysaccharides from Gram-negative bacteria. We anticipate that this work can pave the way to the development of new anti-persister agents based on antimicrobial peptoids of this class to simultaneously help address the crisis of bacterial resistance and reduce the occurrence of the relapse of chronic infections.

The Toxicology Investigators Consortium (ToxIC) Core Registry was established by the American College of Medical Toxicology in 2010. The Core Registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultations will be entered. This twelfth annual report summarizes the registry's 2021 data and activity with its additional 8552 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2021. Detailed data was collected from these cases and aggregated to provide information, which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.4% of cases in females, 48.2% of cases in males, and 1.4% of cases in transgender or gender non-conforming individuals. Non-opioid analgesics were the most commonly reported agent class (14.9%), followed by opioids (13.1%). Acetaminophen was the most common agent reported. Fentanyl was the most common opioid reported and was responsible for the greatest number of fatalities. There were 120 fatalities, comprising 1.4% of all cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe new demographic characteristics, including marital status, housing status and military service, the continued COVID-19 pandemic and related toxicologic exposures, and novel substances of exposure.

BackgroundYoung adult testicular cancer survivors experience adverse impacts after treatment. We developed Goal-focused Emotion-regulation Therapy (GET) to improve distress symptoms, emotion regulation, and goal navigation skills.PurposeThis pilot study examined GET versus an active control intervention in young adult survivors of testicular cancer.MethodsSeventy-five eligible survivors treated with chemotherapy were randomized to receive GET or Individual Supportive Listening (ISL). Study acceptability, engagement, and tolerability were examined, and intervention fidelity and therapeutic alliance were compared between arms. Preliminary efficacy was evaluated by effect sizes for between-group changes in primary (anxiety and depressive symptoms) and secondary (career confusion, goal navigation, and emotion regulation) outcomes from baseline to immediately and 3-month post-intervention.ResultsAmong the 38 men randomized to GET, 81.1% completed all study sessions compared with 82.4% of the 37 men assigned to ISL. Fidelity to the intervention was 87% in GET. Therapeutic alliance wassignificantly higher among those receiving GET versus ISL. Participants exhibited a medium group-by-time effect size with greater reductions in depressive (d = 0.45) and anxiety (d = 0.29) symptoms for those in GET versus ISL, with a similar pattern at 3 months for depressive (d = 0.46) and anxiety (d = 0.46) symptoms.ConclusionsGET is a feasible and acceptable intervention for reducing adverse outcomes after testicular cancer for young adults. Observed effect sizes preliminarily suggest meaningful change, though should be interpreted with caution in small samples. GET may be a developmentally-matched behavioral approach to improve psychosocial function in this cancer group.Clinical trial informationClinicaltrials.gov, NCT04150848. Registered on October 28, 2019.

In addition to endangering sea traffic, cable routes, and wind farms, sunken warship wrecks with dangerous cargo, fuel, or munitions on board may emerge as point sources for environmental damage. Energetic compounds such as TNT (which could leak from these munitions) are known for their toxicity, mutagenicity, and carcinogenicity. These compounds may cause potential adverse effects on marine life via contamination of the marine ecosystem, and their entry into the marine and human food chain could directly affect human health. To ascertain the impending danger of an environmental catastrophe posed by sunken warships, the North Sea Wrecks (NSW) project (funded by the Interreg North Sea Region Program) was launched in 2018. Based on historical data (derived from military archives) including the calculated amount of munitions still on board, its known location and accessibility, the German World War II ship “Vorpostenboot 1302” (former civilian name - “JOHN MAHN”) was selected as a case study to investigate the leakage and distribution of toxic explosives in the marine environment. The wreck site and surrounding areas were mapped in great detail by scientific divers and a multibeam echosounder. Water and sediment samples were taken in a cross-shaped pattern around the wreck. To assess a possible entry into the marine food chain, aged mussels were exposed at the wreck, and wild fish (pouting), a sedentary species that stays locally at the wreck, were caught. All samples were analyzed for the presence of TNT and derivatives thereof by GC–MS/MS analysis. As a result, we could provide evidence that sunken warship wrecks emerge as a point source of contamination with nitroaromatic energetic compounds leaking from corroding munitions cargo still on board. Not only did we find these explosive substances in bottom water and sediment samples around the wreck, but also in the caged mussels as well as in wild fish living at the wreck. Fortunately so far, the concentrations found i

Leader–follower interactions during times of complexity are critical in managing rapid change demands and ensuring organizational sustainability. Between early 2020 and 2023, many organizations worldwide witnessed an unprecedented need for organizational change that rapidly transformed the work environment. This study focused on understanding the contexts of leader and follower interactions during times of change using the shifting organizational landscapes of the COVID-19 pandemic. Applying a qualitative methodology, we collected data from 12 leaders across multiple business sectors in Africa, Asia, and the United States using semi-structured interviews. We then transcribed the interviews and applied an iterative phronetic approach to analyze the data by engaging complexity leadership, emotion in organizations, leading with empathy, belonging, and power and control as theoretical lenses for data analysis. We analyzed how individual leadership experiences during a time of complexity fostered a shift in leadership paradigms and leadership styles within organizations. The findings indicated that due to the unprecedented situations faced during COVID-19, leaders shifted from leadership styles that applied a lens of power and control to an adaptable model that follows the framework of complexity leadership and applies a lens of leading with emotional intelligence. The findings provided a nuanced understanding of the leader–follower relationship by allowing for a complex and varied description of how individuals discursively situate their experiences around issues of power and control. The findings also showed that leaders became more intentional about leading, purposely changing their leadership style to create an environment that supported open communication, belonging, empathy, and awareness. The findings also suggested that when leaders adapt elements of emotional intelligence in leading during times of organizational complexity, they do so with the goal of motivatin

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Harvey, T., Hamlington, B. D., Frederikse, T., Nerem, R. S., Piecuch, C. G., Hammond, W. C., Blewitt, G., Thompson, P. R., Bekaert, D. P. S., Landerer, F. W., Reager, J. T., Kopp, R. E., Chandanpurkar, H., Fenty, I., Trossman, D. S., Walker, J. S., & Boening, C. W. Ocean mass, sterodynamic effects, and vertical land motion largely explain US coast relative sea level rise. Communications Earth & Environment, 2(1), (2021): 233, https://doi.org/10.1038/s43247-021-00300-w., Regional sea-level changes are caused by several physical processes that vary both in space and time. As a result of these processes, large regional departures from the long-term rate of global mean sea-level rise can occur. Identifying and understanding these processes at particular locations is the first step toward generating reliable projections and assisting in improved decision making. Here we quantify to what degree contemporary ocean mass change, sterodynamic effects, and vertical land motion influence sea-level rise observed by tide-gauge locations around the contiguous U.S. from 1993 to 2018. We are able to explain tide gauge-observed relative sea-level trends at 47 of 55 sampled locations. Locations where we cannot explain observed trends are potentially indicative of shortcomings in our coastal sea-level observational network or estimates of uncertainty., The research was carried out in part at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. C.G.P. was supported by NASA grant 80NSSC20K1241. B.D.H., T.C.H., and T.F. were supported by NASA JPL Task 105393.281945.02.25.04.59. R.E.K. and J.S.W. were supported by U.S. National Aeronautics and Space Administration (grants 80NSSC17K0698, 80NSSC20K1724 and JPL task 105393.509496.02.08.13.31) and U.S. National Science Foundation (grant ICER-1663807). P.R.T. acknowledges financial support from the NOAA Global Ocean Monitoring and Observing program in support of the University of Hawaii Sea Level Center (NA11NMF4320128). The ECCO project is funded by the NASA Physical Oceanography; Modeling, Analysis, and Prediction; and Cryosphere Programs.

Visceral leishmaniasis (VL) is among the most neglected tropical diseases in the world. Drug cell permeability is essential for killing the intracellular residing parasites responsible for VL, making cell-permeating peptides a logical choice to address VL. Unfortunately, the limited biological stability of peptides restricts their usage. Sequence-specific oligo-N-substituted glycines ('peptoids') are a class of peptide mimics that offers an excellent alternative to peptides in terms of ease of synthesis and good biostability. We tested peptoids against the parasite Leishmania donovani in both forms, that is, intracellular amastigotes and promastigotes. N-alkyl hydrophobic chain addition (lipidation) and bromination of oligopeptoids yielded compounds with good antileishmanial activity against both forms, showing the promise of these antiparasitic peptoids as potential drug candidates to treat VL.

Traits underlie organismal responses to their environment and are essential to predict community responses to environmental conditions under global change. Species differ in life-history traits, morphometrics, diet type, reproductive characteristics and habitat utilization. Trait associations are widely analysed using phylogenetic comparative methods (PCM) to account for correlations among related species. Similarly, traits are measured for some but not all species, and missing continuous traits (e.g. growth rate) can be imputed using ‘phylogenetic trait imputation’ (PTI), based on evolutionary relatedness and trait covariance. However, PTI has not been available for categorical traits, and estimating covariance among traits without ecological constraints risks inferring implausible evolutionary mechanisms. Here, we extend previous PCM and PTI methods by (1) specifying covariance among traits as a structural equation model (SEM), and (2) incorporating associations among both continuous and categorical traits. Fitting a SEM replaces the covariance among traits with a set of linear path coefficients specifying potential evolutionary mechanisms. Estimated parameters then represent regression slopes (i.e. the average change in trait Y given an exogenous change in trait X) that can be used to calculate both direct effects (X impacts Y) and indirect effects (X impacts Z and Z impacts Y). We demonstrate phylogenetic structural-equation mixed-trait imputation using 33 variables representing life history, reproductive, morphological, and behavioural traits for all >32,000 described fishes worldwide. SEM coefficients suggest that one degree Celsius increase in habitat is associated with an average 3.5% increase in natural mortality (including a 1.4% indirect impact that acts via temperature effects on the growth coefficient), and an average 3.0% decrease in fecundity (via indirect impacts on maximum age and length). Cross-validation indicates that the model explains 54%–89% o

BackgroundHip minimum joint space width (mJSW) provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify new genetic determinants of mJSW and (ii) identify which mJSW loci convey hip osteoarthritis (HOA) risk and would therefore be of therapeutic interest.MethodsGWAS meta-analysis of hip mJSW derived from plain X-rays and DXA was performed, stratified by sex and adjusted for age and ancestry principal components. Mendelian randomisation (MR) and cluster analyses were used to examine causal effect of mJSW on HOA.Findings50,745 individuals were included in the meta-analysis. 42 SNPs, which mapped to 39 loci, were identified. Mendelian randomisation (MR) revealed little evidence of a causal effect of mJSW on HOA (ORIVW 0.98 [95% CI 0.82-1.18]). However, MR-Clust analysis suggested the null MR estimates reflected the net effect of two distinct causal mechanisms cancelling each other out, one of which was protective, whereas the other increased HOA susceptibility. For the latter mechanism, all loci were positively associated with height, suggesting mechanisms leading to greater height and mJSW increase the risk of HOA in later life.InterpretationsOne group of mJSW loci reduce HOA risk via increased mJSW, suggesting possible utility as targets for chondroprotective therapies. The second group of mJSW loci increased HOA risk, despite increasing mJSW, but were also positively related to height, suggesting they contribute to HOA risk via a growth-related mechanism.FundingPrimarily funded by the Medical Research Council and Wellcome Trust.

ObjectiveMicrotubule-associated protein tau (MAPT) mutations cause frontotemporal lobar degeneration, and novel biomarkers are urgently needed for early disease detection. We used task-free functional magnetic resonance imaging (fMRI) mapping, a promising biomarker, to analyze network connectivity in symptomatic and presymptomatic MAPT mutation carriers.MethodsWe compared cross-sectional fMRI data between 17 symptomatic and 39 presymptomatic carriers and 81 controls with (1) seed-based analyses to examine connectivity within networks associated with the 4 most common MAPT-associated clinical syndromes (ie, salience, corticobasal syndrome, progressive supranuclear palsy syndrome, and default mode networks) and (2) whole-brain connectivity analyses. We applied K-means clustering to explore connectivity heterogeneity in presymptomatic carriers at baseline. Neuropsychological measures, plasma neurofilament light chain, and gray matter volume were compared at baseline and longitudinally between the presymptomatic subgroups defined by their baseline whole-brain connectivity profiles.ResultsSymptomatic and presymptomatic carriers had connectivity disruptions within MAPT-syndromic networks. Compared to controls, presymptomatic carriers showed regions of connectivity alterations with age. Two presymptomatic subgroups were identified by clustering analysis, exhibiting predominantly either whole-brain hypoconnectivity or hyperconnectivity at baseline. At baseline, these two presymptomatic subgroups did not differ in neuropsychological measures, although the hypoconnectivity subgroup had greater plasma neurofilament light chain levels than controls. Longitudinally, both subgroups showed visual memory decline (vs controls), yet the subgroup with baseline hypoconnectivity also had worsening verbal memory and neuropsychiatric symptoms, and extensive bilateral mesial temporal gray matter decline.InterpretationNetwork connectivity alterations arise as early as the presymptomatic pha

BackgroundA study was undertaken to evaluate remote monitoring via smartphone sensor-based tests in people with multiple sclerosis (PwMS). This analysis aimed to explore regional neural correlates of digital measures derived from these tests.MethodsIn a 24-week, non-randomized, interventional, feasibility study (NCT02952911), sensor-based tests on the Floodlight Proof-of-Concept app were used to assess cognition (smartphone-based electronic Symbol Digit Modalities Test), upper extremity function (Draw a Shape Test, Pinching Test), and gait and balance (Static Balance Test, Two-Minute Walk Test, U-Turn Test). In this post-hoc analysis, digital measures and standard clinical measures (e.g., Nine-Hole Peg Test [9HPT]) were correlated against regional structural magnetic resonance imaging outcomes. Seventy-six PwMS aged 18-55 years with an Expanded Disability Status Scale score of 0.0-5.5 were enrolled from two different sites (USA and Spain). Sixty-two PwMS were included in this analysis.ResultsWorse performance on digital and clinical measures was associated with smaller regional brain volumes and larger ventricular volumes. Whereas digital and clinical measures had many neural correlates in common (e.g., putamen, globus pallidus, caudate nucleus, lateral occipital cortex), some were observed only for digital measures. For example, Draw a Shape Test and Pinching Test measures, but not 9HPT score, correlated with volume of the hippocampus (r = 0.37 [drawing accuracy over time on the Draw a Shape Test]/ - 0.45 [touching asynchrony on the Pinching Test]), thalamus (r = 0.38/ - 0.41), and pons (r = 0.35/ - 0.35).ConclusionsMultiple neural correlates were identified for the digital measures in a cohort of people with early MS. Digital measures showed associations with brain regions that clinical measures were unable to demonstrate, thus providing potential novel information on functional ability compared with standard clinical assessments.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described CNS inflammatory disorder that may manifest with optic neuritis, myelitis, seizures, and/or acute disseminated encephalomyelitis. While MOG-specific antibodies in patients with MOGAD are IgG1, a T-cell-dependent antibody isotype, immunologic mechanisms of this disease are not fully understood. Thymic hyperplasia can be associated with certain autoimmune diseases. In this report we describe a case of MOGAD associated with thymic hyperplasia in a young adult.

BackgroundIrritable bowel syndrome (IBS) is a common gastrointestinal disorder that is thought to involve alterations in the gut microbiome, but robust microbial signatures have been challenging to identify. As prior studies have primarily focused on composition, we hypothesized that multi-omics assessment of microbial function incorporating both metatranscriptomics and metabolomics would further delineate microbial profiles of IBS and its subtypes.MethodsFecal samples were collected from a racially/ethnically diverse cohort of 495 subjects, including 318 IBS patients and 177 healthy controls, for analysis by 16S rRNA gene sequencing (n = 486), metatranscriptomics (n = 327), and untargeted metabolomics (n = 368). Differentially abundant microbes, predicted genes, transcripts, and metabolites in IBS were identified by multivariate models incorporating age, sex, race/ethnicity, BMI, diet, and HAD-Anxiety. Inter-omic functional relationships were assessed by transcript/gene ratios and microbial metabolic modeling. Differential features were used to construct random forests classifiers.ResultsIBS was associated with global alterations in microbiome composition by 16S rRNA sequencing and metatranscriptomics, and in microbiome function by predicted metagenomics, metatranscriptomics, and metabolomics. After adjusting for age, sex, race/ethnicity, BMI, diet, and anxiety, IBS was associated with differential abundance of bacterial taxa such as Bacteroides dorei; metabolites including increased tyramine and decreased gentisate and hydrocinnamate; and transcripts related to fructooligosaccharide and polyol utilization. IBS further showed transcriptional upregulation of enzymes involved in fructose and glucan metabolism as well as the succinate pathway of carbohydrate fermentation. A multi-omics classifier for IBS had significantly higher accuracy (AUC 0.82) than classifiers using individual datasets. Diarrhea-predominant IBS (IBS-D) demonstrated shifts in the metatranscriptome