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LEGEND-200's Sensitivity to Fractionally Charged Particles
No full textLEGEND-200 is an ultra-low-background experiment designed to search for neutrinoless double-beta decay using high-purity germanium detectors enriched in Ge^76. Its low background rates and high sensitivity also make it a powerful tool for probing Beyond-the-Standard-Model physics. This work presents simulation studies of fractionally charged particles (FCPs) passing through LEGEND-200 to assess the sensitivity of the experiment to such particles. FCPs are hypothetical particles that carry an electric charge smaller than the elementary charge . The primary goal of this study is to determine whether existing LEGEND-200 data can be used to set a world-leading limit on the flux of FCPs. In addition, we explore how a new data-taking strategy could improve sensitivity. Based on these simulations, LEGEND-200 can set a world leading limit on the flux of FCPs in the charge range e/82 to e/18 with one year of data collection and a new data taking strategy, and range e/18 to e/48 with the current data taking strategy
HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers
Get PDFBACKGROUND: The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC). PATIENTS AND METHODS: HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay's predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts. Comparative analyses included HER2DX scores, gene signatures, and expression of individual genes between patients with IBC and non-IBC. RESULTS: Notable differences in clinicopathological characteristics included higher pertuzumab and chemotherapy usage and lower axillary burden in patients with IBC compared with non-IBC. In the combined cohort (n = 179), HER2DX pCR score and pertuzumab use were significant predictors of pCR, but not IBC status. The pCR rates in patients treated with trastuzumab-based chemotherapy (including IBC and non-IBC) were 68.9%, 58.5%, and 16.3% in the HER2DX pCR-high, -medium, and -low groups, respectively. Comparative gene expression analysis indicated minor differences between IBC and non-IBC affecting individual HER2, immune, and proliferation genes. CONCLUSIONS: The HER2DX pCR score could predict pCR in stage III HER2-positive IBC following treatment with de-escalated neoadjuvant systemic therapy and in stage III HER2-positive non-IBC. Elevated pCR rates in HER2-positive IBC with high HER2DX pCR scores suggest there may be a role for treatment de-escalation in these patients and confirmatory studies are justified
PUBH 992 973C Proposal Packet
Get PDFThis proposal packet examines lifelong learning as a vital condition that shapes individual and community well-being, with a focus on early childhood education in Granville and Vance counties, North Carolina. Through analysis of county assets, challenges, and cross-sector influences, the work highlights how educational opportunity, particularly in Kindergarten through 3rd grade, supports long-term health outcomes. Parental education emerges as a key determinant of intergenerational health, contributing to improved behaviors, resource access, and knowledge transmission. The assignment emphasizes the importance of integrating health and education systems to address children’s developmental, physical, and emotional needs early in life. Recommendations for the Granville Vance Public Health Department (GVPH) center on strengthening partnerships, promoting equitable policies, and enhancing data systems to advance community well-being and support sustainable improvement across the vital condition of lifelong learning.Master of Public Healt
ASSESSING ACCESS TO KINDERGARTEN THROUGH THIRD GRADE EDUCATION AND LIFELONG LEARNING IN GRANVILLE AND VANCE COUNTIES
Get PDFLifelong learning is increasingly recognized as a vital condition, as it influences both individual and community well-being by ensuring that all people have opportunities to acquire knowledge and skills. This analysis focuses on the importance of education for Kindergarten through 3rd grade in Granville County and Vance County, North Carolina. Parental education improves intergenerational health, resulting in healthier lives for both parents and children by promoting healthy behaviors, improving access to resources, and knowledge sharing across generations. A unifying theme is the integration of health and education systems to ensure that children’s developmental, physical, and emotional needs are recognized and addressed early, setting a foundation for long-term well-being. Recommendations for the Granville Vance Public Health Department (GVPH) focus on strengthening partnerships, advancing equitable education policies, and improving systems for data collection and reporting.
Keywords: Community engagement, leadership, kindergarten, 3rd grade, Granville and Vance Counties Master of Public Healt
Artificial Intelligence-Guided Molecular Determinants of PI3K Pathway Alterations in Early-Onset Colorectal Cancer Among High-Risk Groups Receiving FOLFOX
Get PDFBackground: Early-onset colorectal cancer (EOCRC), defined as diagnosis before the age of 50, is rising rapidly and disproportionately affects high-risk populations, particularly Hispanic/Latino (H/L) individuals, who experience the steepest increases in incidence and mortality. While prevention and screening strategies have curbed late-onset CRC rates, EOCRC remains outside standard screening guidelines and is projected to become the leading cause of cancer-related death in individuals aged 20–49 by 2030. FOLFOX (folinic acid, fluorouracil, and oxaliplatin) is a standard first-line therapy for microsatellite stable (MSS) CRC lacking actionable driver mutations; however, its efficacy and genomic impact in EOCRC, particularly in underrepresented groups, remain poorly understood. The phosphatidylinositol 3-kinase (PI3K) pathway regulates cell growth, survival, and metabolism, and its alterations have been implicated in therapeutic resistance and adverse outcomes. Yet, the prevalence, clinical relevance, and treatment-specific associations of PI3K pathway alterations in EOCRC remain underexplored. Methods: We analyzed somatic mutation and clinical data from 2515 CRC patients (266 H/L and 2249 Non-Hispanic White [NHW]) across publicly available genomic datasets. Patients were stratified by age at diagnosis (EOCRC < 50 vs. LOCRC ≥ 50), ancestry (H/L vs. NHW), and FOLFOX treatment status. PI3K pathway alterations—including mutations in PIK3CA, PTEN, AKT isoforms, and regulatory genes—were identified using curated pathway definitions. Mutation prevalence was compared across groups using Fisher’s exact or chi-squared tests. AI-HOPE-PI3K, a conversational AI platform, was deployed to automate cohort construction, stratify subgroups, and perform post hoc survival analysis. Results: PI3K pathway alterations were observed across all demographic groups. In EO NHW patients treated with FOLFOX, Kaplan–Meier analysis revealed significantly reduced overall survival among those with PI3K pathway alterations (n = 124) compared with their unaltered counterparts (n = 251; p = 0.0008), identifying alterations as a candidate prognostic biomarker in this subgroup. AI-guided subgroup interrogation further highlighted mutation-specific signals: INPP4B and RPTOR emerged as exploratory candidates in EO H/L patients but did not show significant treatment- or ancestry-specific enrichment upon confirmatory testing. Similarly, ancestry-stratified analysis of PIK3R2 mutations revealed comparable rates in EO H/L (1.37%) and EO NHW (1.6%) FOLFOX-treated patients (p = 1.0). Across ancestry and age groups, mutational landscape analysis revealed diverse molecular events—including missense, nonsense, splice-site, frameshift, and in-frame deletions—underscoring the heterogeneity of PI3K pathway dysregulation. Conclusions: This study identifies PI3K pathway alterations as a potential prognostic marker of poor survival in EO NHW patients receiving FOLFOX and uncovers ancestry- and treatment-specific mutational differences in high-risk CRC populations. By integrating clinical, molecular, and treatment variables, the AI-HOPE and AI-HOPE-PI3K platforms enabled rapid, reproducible, and fine-grained analysis of complex datasets. These findings underscore the need for ancestry-informed molecular profiling to optimize therapeutic strategies and highlight AI-guided interrogation as a powerful tool for advancing precision oncology in underrepresented and disproportionately affected CRC populations
Ultrarunning as a Model for Neuroplasticity: A Review of Structural, Functional, and Neurobiological Adaptations
Get PDFUltra-endurance running serves as a powerful, non-linear model for studying the adaptive limits of human neuroplasticity, moving beyond the established paradigm that exercise is simply neuroprotective. This narrative review synthesizes the complex relationship between chronic ultrarunning training and the acute physiological insult of an ultramarathon event, focusing on structural, functional, and neurobiological adaptations.
The review establishes a clear dichotomy: Chronic Adaptation aligns with positive exercise neuroscience, characterized by hippocampal neurogenesis, sustained upregulation of Brain-Derived Neurotrophic Factor (BDNF), enhanced cognitive function, and the development of psychological resilience, acting as a form of “stress inoculation.” In stark contrast, the Acute Adaptation to the event is paradoxical. It is characterized by acute cognitive impairment (e.g., decreased psychomotor speed and central fatigue) and contradictory structural changes. Magnetic Resonance Imaging (MRI) studies report both a transient gray matter (GM) volume increase following single-stage ultras (likely fluid shifts) and a profound, yet reversible, 6% global GM volume decrease during extreme, multi-day events (attributed to systemic catabolism).
The synthesis of this data culminates in a non-linear dose-response model, suggesting the acute insults of the race are the catalyst for the brain’s chronic, resilient adaptations. This process forces the central nervous system to develop a more regulated HPA-axis response and plastic resource-allocation protocols, such as the potential shunting of BDNF to peripheral muscles for repair (the "BDNF Sink" hypothesis). In conclusion, ultrarunning uniquely demonstrates the brain's remarkable and dynamic capacity for structural plasticity, regulation, and recovery from extreme physiological stress
Perceived risks, reasons for use, and barriers to cessation among youth who use multiple tobacco products
Get PDFBackground Many interventions aim to reduce youth tobacco use, but few have focused on youth who use multiple tobacco products (MTPs). This qualitative study sought to understand how youth who use MTPs view tobacco product risks, describe reasons for MTP use, and perceive barriers and facilitators to cessation. Methods We conducted seven virtual focus groups with 30 US youth ages 14–20 years who reported using e-cigarettes and smoking a combustible tobacco product in the past 30 days. We used a semi-structured focus group guide to ask youth about perceived health risks of tobacco products, reasons for MTP use, and thoughts about quitting. We conducted a thematic analysis of transcripts. Results The mean age of participants was 18.7 years; 47% identified as white. Most participants were female (63%) and lesbian, gay, or bisexual (63%). Three central themes emerged: 1) uncertainty or misperceptions about e-cigarettes were common, including what ingredients they contain, whether they are tobacco products, and their harm relative to cigarettes; 2) convenience and social factors were mentioned as reasons for using MTPs, rather than using e-cigarettes to quit cigarettes; 3) barriers to cessation included nicotine dependence (especially to e-cigarettes) and environmental factors, while cessation resources were rarely mentioned. Conclusions These findings suggest that educational interventions to reduce youth MTP use could focus on correcting misperceptions about e-cigarettes and communicating the harms of combustible tobacco use. Furthermore, behavioral interventions could capitalize on peer and social support while acknowledging unique barriers resulting from MTP use, such as high nicotine dependence
Mycobacterium chelonae outbreak investigation at a quaternary pediatric hospital following the opening of a LEED-certified critical care tower: where does water sustainability intersect with infection control?
Get PDFOBJECTIVE: Investigate the increased incidence of Mycobacterium chelonae positive respiratory cultures in hospitalized patients. DESIGN: Apply the Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria (HALT NTM) toolkit to an outbreak investigation of M. chelonae. SETTING: Quaternary-care pediatric hospital and medical center in the United States with a recently opened LEED-certified critical care tower. PATIENTS: Adult and pediatric patients with M. chelonae positive respiratory cultures between June 2022 and January 2024. METHODS: An epidemiological investigation involving clinical and laboratory practices, water management, building construction and renovation projects. Environmental sampling of air vents, water sources and endoscope reprocessing equipment was performed. M. chelonae isolates recovered from patients and the environment were analyzed using whole genome sequencing and compared for relatedness. RESULTS: Three clusters of matching environmental and patient isolates were identified. The most common environmental source of M. chelonae was ice/water dispensers with 40% positivity of sampled units. The critical care tower's water system performance and metrics were suboptimal, leading to four physical remediation activities along with a hyperchlorination treatment. CONCLUSIONS: Recent and ongoing construction along with the implementation of a LEED-certified, low-flow water system in a new critical care tower provided enhanced opportunities for M. chelonae exposure at point of use locations such as ice/water dispensers. More national infection prevention and control guidance is needed to address the infection risks from water sustainability efforts and construction activities in healthcare facilities
Comparative effectiveness of immunotherapy alone or with chemotherapy as first-line treatment for marginal zone lymphoma.
Get PDFMarginal zone lymphoma (MZL) is a heterogeneous indolent B-cell malignancy comprising splenic (SMZL), nodal (NMZL), and extranodal (EMZL) subtypes. Owing to its low incidence and variable presentation, prospective randomized data are limited. Most NMZL regimens mirror those for follicular lymphoma, while localized EMZL is frequently treated with local therapies or antibiotics for Helicobacter pylori-associated gastric disease. The IELSG-19 trial remains the only histology-specific phase 3 study of systemic first-line therapy in MZL, demonstrating longer progression-free survival (PFS) with rituximab plus chlorambucil versus either agent alone, but no overall survival (OS) benefit
Data analysis strategies for the Accelerating Medicines Partnership® Schizophrenia Program
Get PDFThe Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) project assesses a large sample of individuals at clinical high-risk for developing psychosis (CHR) and community controls. Subjects are enrolled in 43 sites across 5 continents. The assessments include domains similar to those acquired in previous CHR studies along with novel domains that are collected longitudinally across a period of 2 years. In parallel with the data acquisition, multidisciplinary teams of experts have been working to formulate the data analysis strategy for the AMP SCZ project. Here, we describe the key principles for the data analysis. The primary AMP SCZ analysis aim is to use baseline clinical assessments and multimodal biomarkers to predict clinical endpoints of CHR individuals. These endpoints are defined for the AMP SCZ study as transition to psychosis (i.e., conversion), remission from CHR syndrome, and persistent CHR syndrome (non-conversion/non-remission) obtained at one year and two years after baseline assessment. The secondary aim is to use longitudinal clinical assessments and multimodal biomarkers from all time points to identify clinical trajectories that differentiate subgroups of CHR individuals. The design of the analysis plan is informed by reviewing legacy data and the analytic approaches from similar international CHR studies. In addition, we consider properties of the newly acquired data that are distinct from the available legacy data. Legacy data are used to assist analysis pipeline building, perform benchmark experiments, quantify clinical concepts and to make design decisions meant to overcome the challenges encountered in previous studies. We present the analytic design of the AMP SCZ project, mitigation strategies to address challenges related to the analysis plan, provide rationales for key decisions, and present examples of how the legacy data have been used to support design decisions for the analysis of the multimodal and longitudinal data. Watch Prof. Ofer Pasternak discuss his work and this article: https://vimeo.com/1023394132?share=copy#t=0