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Sexual identity, sexual behavior, and drug use behaviors among people who use drugs in the rural U.S.
Get PDFIntroduction People who use drugs (PWUD) are at risk of HIV infection, but the frequency and distribution of transmission-associated behaviors within rural communities is not well understood. Further, while interventions designed to more explicitly affirm individuals' sexual orientation and behaviors may be more effective, descriptions of behavior variability by orientation are lacking. We sought to describe how disease transmission behaviors and overdose risk vary by sexual orientation and activity among rural PWUD. Methods From 01/2018–03/2020, rural PWUD participating in the Rural Opioid Initiative were surveyed across 8 sites. Collected data included: demographics; experiences with drug use, overdose, and healthcare; stigma; gender identity; and sexual orientation and partners. Participants were categorized as: monosexual by orientation and behavior (Mono-only), monosexual by orientation but behaviorally bisexual (Mono/Bi), and bisexual by orientation (Bi+). Analyses included descriptive summaries, bivariate examination (chi-square), and logistic regression (relative risk [RR] and 95 % confidence interval [CI]). Results The 1455 participants were 84.8 % Mono-only, 3.2 % Mono/Bi, and 12.0 % Bi+. Compared to Mono-only men, Mono/Bi and Bi+ men had greater risk of transactional sex (RR = 9.71, CI = 6.66–14.2 and RR = 5.09, CI = 2.79–9.27, respectively) and sharing syringes for injection (RR = 1.58, CI = 1.06–2.35 and RR = 1.85, CI = 1.38–2.47). Compared to Mono-only women, Mono-Bi and Bi+ women had greater risk of transactional sex (RR = 4.47, CI = 2.68–7.47 and RR = 2.63, CI = 1.81–3.81); and Bi+ women had greater risk of sharing syringes for injection (RR = 1.49, CI = 1.23–1.81), sharing syringes to mix drugs (RR = 1.44, CI = 1.23–1.69), and experiencing an overdose (RR = 1.32, CI = 1.12–1.56). Bi+ men and women both more frequently reported selling sex as a source of income (versus Mono-only, both p < 0.050) and measures of perceived stigma (all p < 0.050). Conclusions Rural PWUD who are bisexual by orientation or behavior are significantly more likely to engage in behaviors associated with infectious disease transmission and to experience stigma and drug overdose. Given the growing recognition of bisexuality as a distinct orientation that warrants individualized consideration, interventions that are specifically acknowledging and affirming to the circumstances of this group are needed
Correction to: Psychometric evaluation of the Yale-Brown obsessive-compulsive scale in pregnant women
Get PDFCorrection to: Psychometric evaluation of the Yale-Brown obsessive-compulsive scale in pregnant wome
Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer.
Get PDFPURPOSE: In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy. METHODS: In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS). SET2,3 was tested on the 682 banked RNA samples from ER+ cancers. RESULTS: Dose-dense chemotherapy improved DFS in the overall study population by 23% (HR, 0.77 [95% CI, 0.66 to 0.90]) and OS by 20% (HR, 0.80 [95% CI, 0.67 to 0.95]); the benefits of dose-dense therapy were seen for ER+ and ER-negative subsets, without significant interaction between treatment arm and ER status. Low SET2,3 status was highly prognostic, but also predicted improved outcomes from dose-dense chemotherapy (interaction P = .0998 for DFS; 0.027 for OS), independent of menopausal status. Specifically, low endocrine transcriptional activity predicted benefit from dose-dense chemotherapy, whereas tumor burden and proliferation-driven signatures for molecular subtype classification did not. CONCLUSION: At 12-year follow-up, C9741 confirmed the sustained long-term benefit of adjuvant dose-dense chemotherapy for node-positive breast cancer. SET2,3 identified patients with ER+ breast cancer who benefited from dose-dense chemotherapy, and specifically, this benefit was predicted by low endocrine activity in the cancer, rather than tumor burden, molecular subtype, or menopausal status
Rural Disinvestment and the Fragility of North Carolina’s Expansion: Responding to the One Big Beautiful Bill Act
Get PDFThe federal House Resolution 1 (HR1), also known as the “One Big Beautiful Bill Act,” introduces new Medicaid work requirements, financing restrictions, and limits on future SNAP benefit growth. These provisions could weaken the foundations of North Carolina’s Medicaid expansion and reduce the federal dollars that sustain rural hospitals, food access, and local economies
Causal Discovery from Time-Series Data with Short-Term Invariance-Based Convolutional Neural Networks
Get PDFCausal discovery from time-series data seeks to capture both intra-slice (contemporaneous) and inter-slice (time-lagged) causal relationships among variables, which are essential for many scientific domains. Unlike causal discovery from static data, the time-series setting requires longer sequences with a larger number of observed time steps. To address this challenge, we propose STIC, a novel gradient-based framework that leverages Short-Term Invariance with Convolutional Neural Networks (CNNs) to uncover causal structures. Specifically, STIC exploits both temporal and mechanistic invariance within short observation windows, treating them as independent units to improve sample efficiency. We further design two causal convolution kernels corresponding to these two types of invariance, enabling the estimation of window-level causal graphs. To justify the use of CNNs for causal discovery, we theoretically establish the equivalence between convolution and the generative process of time-series data under the assumption of identifiability in additive noise models. Extensive experiments on synthetic data, as well as an fMRI benchmark, demonstrate that STIC consistently outperforms existing baselines and achieves state-of-the-art performance, particularly when the number of available time steps is limited
‘You feel like it’s better to just die’: Death-centric stereotypes and stigma contribute to suicide risk for adolescents living with HIV in Malawi
Get PDFSuicide is the second leading cause of death for adolescents worldwide. Adolescents living with HIV (ALWH) in Malawi are particularly at risk, due to stigmatization and a high comorbid prevalence of depression. Internalized stigma is an indicator of depression and suicidality, yet we have a limited understanding of the drivers and impacts of internalized stigma. In this analysis, we assessed how death-centric stereotypes and experienced stigma contribute to the development of internalized stigma and elevate suicide risk for ALWH in Malawi. This qualitative study recruited 68 total participants from three government healthcare facilities in Lilongwe, Malawi. We conducted 13 in-depth interviews and 10 focus group discussions with ALWH, caregivers of ALWH, adolescent peers without HIV, schoolteachers, HIV care providers, and mental health providers. We sought to understand how stigma manifests in key parts of an ALWH’s life and contributes to internalized stigma and suicidal ideation. Guided by thematic analysis, we organized the relevant data into four themes: death-centric stereotypes, experienced stigma, internalized stigma, and suicidality. Death-centric stereotypes were identified as HIV’s association with being a death sentence, obstructing one’s future, and weak physical and mental capacity. From these stereotypes originate specific manifestations of experienced stigma, including insults and mockery, reduced social and economic prospects for adulthood, caregiver lack of investment in vital resources, and exclusion from community activities. Stereotypes and experienced stigma contribute to internalized stigma which manifests as low self-esteem, loss of future-oriented mindset, and self-isolation. This stigmatization process, particularly when perpetuated by family, increased suicide risk for ALWH. This study describes how death-centric stereotypes dominate the public discourse around ALWH, influence stigmatizing behaviors towards ALWH that disenfranchise them in their daily lives, and contribute to the development of internalized stigma and suicidality. Suicide screening and prevention programming, with attention to culturally sensitive stigma reduction, is urgently needed for ALWH
CARDIAC SURGERY ERACS PATHWAY: A PROGRAM EVALUATION
Get PDFEnhanced Recovery After Surgery (ERAS) pathways have demonstrated improvementsin surgical outcomes across specialties, yet limited evidence exists on their sustainedimplementation in cardiac surgery (Engelman et al., 2019). ERAS in cardiac surgery firstemerged in 2017 with the establishment of the ERAS Cardiac Society, a nonprofit organizationdedicated to developing evidence-based pathways to optimize patient care in cardiac surgery.This society—composed of cardiac surgeons, anesthesiologists, and intensivists—created aseries of interventions aimed at improving outcomes across the continuum of care. Theseinterventions are organized into preoperative, intraoperative, and postoperative phases ofrecovery (Engelman et al., 2019).This project aimed to evaluate the ERACS program at a large academic center in NorthCarolina and was implemented in 2023. The evaluation assessed adherence to ERACS protocolelements, evaluated patient and staff experiences, and identified barriers and facilitators topathway sustainability. This project used the Centers for Disease Control and Prevention’sProgram Evaluation Framework (Centers for Disease Control and Prevention, 2024; Kidder etal., 2024).This program evaluation demonstrated that ERACS contributes to improvedpostoperative outcomes but requires targeted strategies for consistent adoption. Strengtheningstaff education, redesigning workflows, and utilizing real-time dashboards may improve adherence and sustainability. These findings contribute to the growing evidence that ERASpathways in cardiac surgery enhance recovery and reduce complications.Doctor of Nursing Practic
Role of Metal Availability in Modulating Antibiotic Efficacy
Get PDFUnderstanding how host factors influence antibiotic efficacy is critical to preserving or enhancing treatment efficacy. The limitation of trace metals is a key aspect of the immune response, with the infection microenvironment depleted of essential metals through the action of host immune proteins. Here, we demonstrate that the limitation of zinc and manganese has opposing effects on β-lactam antibiotic efficacy against Staphylococcus aureus. Our results show that zinc chelation by the host immune protein calprotectin directly inactivates bacterial autolysins, zinc-dependent enzymes required for cell wall degradation and bacterial lysis following β-lactam treatment. Comparison of antibiotic efficacy in the presence and absence of calprotectin, both in vitro and in vivo, shows significantly decreased antibiotic killing under conditions of zinc limitation. On the other hand, in zinc-replete environments, manganese limitation was found to potentiate β-lactam antibiotic killing. Our data suggests that bacterial adaptation to intracellular oxidative stress under Mn-limiting conditions results in the increased expression and activity of bacterial autolysins, ultimately sensitizing S. aureus to antibiotic treatment. These findings demonstrate how zinc and manganese availability can dramatically influence the outcome of antibiotic treatment against S. aureus, highlighting a previously unrecognized determinant of antibiotic susceptibility for β-lactam antibiotics within the host.Doctor of Philosoph
HUMAN INFLUENCE ON BARRIER ISLAND AND OYSTER REEF EVOLUTION
Get PDFBarrier islands and oyster reefs are critical components of dynamic coastal systems, providing natural resiliency and coastal protection, yet both are increasingly altered by human activity. The aims of this dissertation are to: (1) quantify the long-term geomorphic impacts of barrier island management on washover flux and island persistence, (2) assess how human-driven land-use change alters oyster reef sedimentology and persistence, and (3) identify universal patterns of natural oyster reef growth and geometry to guide the design of resilient living shorelines.Objective 1 was addressed by analyzing decadal-scale remote sensing data along a 30-km stretch of northern Hatteras Island, North Carolina. Results show that dune and road maintenance reduce washover flux and extent by ~50%, constraining natural barrier rollover and accelerating island vulnerability. Objective 2 was addressed by comparing core sediment records, geochronology, and satellite imagery from natural intertidal oyster reefs in two estuaries with contrasting LUC histories and environmental settings. In the Newport River, major LUC led to mud-dominated reefs, marsh encroachment, and reef decline. In contrast, reefs in the more tidally flushed White Oak River maintained sandy substrates and active oyster populations, highlighting the role of hydrodynamic setting in mediating human impacts.Objective 3 was addressed using multi-core transects and geochronology to document reef growth over centuries. Results reveal consistent patterns of lateral and vertical reef accretion, with reefs evolving into shore-perpendicular geometries near mean high water. Trajectories diverged under different environmental regimes in the three NC estuaries, with low-flow, fine-sediment systems prone to marsh takeover and tidally flushed, sandy systems supporting reef resilience. These findings can inform living shoreline and restoration reef design and site selection to align with natural growth patterns and environmental conditions that promote long-term success.Overall, this research shows that human management decisions, whether through shoreline stabilization, watershed land use, or reef restoration design, can influence the long-term resilience of coastal systems from barrier beaches to estuaries. By incorporating lessons from natural barrier islands and oyster reefs, managers can better balance protection of people and infrastructure with the long-term sustainability of these critical coastal environments.Doctor of Philosoph
A LATENT CHANGE SCORE FRAMEWORK FOR OPERATIONALLY DEFINING AND ESTIMATING MEANINGFUL SCORE DIFFERENCES
Get PDFResearchers have long grappled with how to evaluate the meaningfulness of a treatment effect. Recently, understanding what constitutes a meaningful change has become a key research area in the clinical outcomes assessment (COA) field, where the patient perspective is strongly considered. A latent change score (LCS) modeling framework for operationally defining and estimating meaningful score differences (MSDs) in COA scores is detailed. It is shown that the most commonly used method for estimating meaningful change in COA scores—the transition rating average change (TRAC) method—can be recast as an LCS model and several alternative LCS models for estimating meaningful change are described. The MSD parameter recovery performance of two newly developed methods for operationally defining and estimating MSDs was evaluated in two simulation studies. Results indicate that MSD_(TRAC_θ ) and MSD_LRV consistently exhibit lower relative bias under the studied conditions than does the commonly used MSD_TRAC. When estimated with maximum likelihood in particular, MSD_(TRAC_θ ) exhibited trivial bias in the majority of conditions studied. Additionally, MSD_LRV exhibited trivial bias when transition rating item thresholds were truly invariant or when there was only one non-invariant threshold. The precision of MSD_(TRAC_θ ) and MSD_LRV was also more stable across the studied conditions than that of MSD_TRAC.Doctor of Philosoph