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The association between social drivers of health, HIV status and physical activity with perceived stress in U.S. women with or without HIV
Get PDFBackground The physiological adaptation to chronic stress can have deleterious health effects. Although higher physical activity (PA) has been linked to lower stress, it is unknown whether social driver of health (SDOH) burden and HIV status impact the stress reduction effects of PA due to their unique contributions to stress. Methods Using a cross-sectional sample (n = 444) from the Women’s Interagency HIV Study during 2014–2019, multivariate linear regression modeling was used to estimate the effect of SDOH burden and PA on stress. SDOH burden was defined as the sum of individual-level indicators: inadequate housing, income, and education as well as unemployment, and food insecurity. Results Unadjusted, there was a significant relationship between SDOH burden, Heavy PA and Moderate PA with stress (rs = 0.22 [p < .001], -0.10 [p < .05], and − 0.11 [p < .05] respectively) After adjusting for age, HIV status and race, and including both SDOH and PA, only SDOH predicted stress (β = 0.20, 95% CI [0.6, 1.87]; p < .001). Among this sample, food insecurity was the strongest predictor of stress, reducing the effects of PA when included in the model (β = 0.24, 95% CI [2.38, 5.99]; p < .001). Conclusions Findings indicated that, after adjusting for age, HIV status and race, SDOH burden reduced the association between PA and stress, and was a stronger predictor of stress in women living with HIV than those living without HIV. The impact of food insecurity appears to be a powerful driver of stress in both women living with and without HIV
The electroencephalography protocol for the Accelerating Medicines Partnership® Schizophrenia Program: Reliability and stability of measures
Get PDFIndividuals at clinical high risk for psychosis (CHR) have variable clinical outcomes and low conversion rates, limiting development of novel and personalized treatments. Moreover, given risks of antipsychotic drugs, safer effective medications for CHR individuals are needed. The Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) Program was launched to address this need. Based on past CHR and schizophrenia studies, AMP SCZ assessed electroencephalography (EEG)-based event-related potential (ERP), event-related oscillation (ERO), and resting EEG power spectral density (PSD) measures, including mismatch negativity (MMN), auditory and visual P300 to target (P3b) and novel (P3a) stimuli, 40-Hz auditory steady state response, and resting EEG PSD for traditional frequency bands (eyes open/closed). Here, in an interim analysis of AMP SCZ EEG measures, we assess test-retest reliability and stability over sessions (baseline, month-2 follow-up) in CHR (n = 654) and community control (CON; n = 87) participants. Reliability was calculated as Generalizability (G)-coefficients, and changes over session were assessed with paired t-tests. G-coefficients were generally good to excellent in both groups (CHR: mean = 0.72, range = 0.49–0.85; CON: mean = 0.71, range = 0.44–0.89). Measure magnitudes significantly (p < 0.001) decreased over session (MMN, auditory and visual target P3b, visual novel P3a, 40-Hz ASSR) and/or over runs within sessions (MMN, auditory/visual novel P3a and target P3b), consistent with habituation effects. Despite these small systematic habituation effects, test-retest reliabilities of the AMP SCZ EEG-based measures are sufficiently strong to support their use in CHR studies as potential predictors of clinical outcomes, markers of illness progression, and/or target engagement or secondary outcome measures in controlled clinical trials
Sample Ascertainment and Recruitment Sources in the Accelerating Medicines Partnership Schizophrenia Program
Get PDFThis paper presents the recruitment sources of clinical high-risk (CHR) and community controls (CC) from the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program, which aims to study various clinical variables and biomarkers in 2040 CHR and 652 CC participants. A total of 1640 CHR and 514 CC had recruitment source data. The Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the SIPS was utilized to assess CHR criteria and severity of attenuated psychotic symptoms (APSs), and the Global Functioning: Social Scale was used for social functioning. Participants were recruited through various methods, including referrals from healthcare providers, schools, and community agencies, and self-referrals via outreach efforts and advertising. Participants were recruited from 13 different sources, with self-referral being the most common for both CHR and CC. Other notable sources included child and youth services and psychiatric hospitals and departments. Regional differences in recruitment patterns were observed across continents. Differences in age, APS, and social functioning for CHR participants were examined in the top 5 recruitment sources. Overall, self-referred individuals were typically older, with less severe APS and higher levels of functioning, whereas those from adult community mental health services had poorer functioning and more severe APS. The remaining recruitment groups fell between these 2 extremes. This paper highlights the diverse recruitment sources for the AMP SCZ program. Self-referral was a significant source, particularly in North America, reflecting changing help-seeking behaviors influenced by the internet and social media. The findings underscore the importance of understanding recruitment sources to optimize future CHR research
Proteogenomic analysis of the CALGB 40601 (Alliance) HER2+ breast cancer neoadjuvant trial reveals resistance biomarkers
Get PDFProteogenomic analysis is applied to samples from the CALGB 40601 (Alliance) randomized neoadjuvant trial of trastuzumab, lapatinib, or the combination to identify biomarkers associated with pathological response status. Absence of ERBB2 gene amplification and human epidermal growth factor receptor 2 (HER2) protein overexpression by proteogenomics is associated with non-pathological compete response (pCR) (p < 0.05), highlighting potential false positives from standard diagnostics. Pathway analysis in proteogenomics-confirmed HER2+ samples identifies elevated epithelial-mesenchymal transition (EMT) and WNT-β-catenin signaling in non-pCR cases before treatment. Twenty-four pCR-associated proteins reproduce in a second proteomic dataset, and four (GPRC5A, TPBG, SP140L, and NEU1) are significant in a third. A meta-analysis of ten diverse neoadjuvant anti-HER2 treatment regimens from four independent studies confirms that non-pCR cases express higher levels of mRNA for G protein-coupled receptor class C group 5 member A (GPRC5A, p = 0.0002) and trophoblast glycoprotein (TPBG, p = 0.00008). Thus, proteogenomic analysis identifies negative biomarkers for pCR and alternative plasma membrane targets for treatment-resistant HER2+ breast cancer. This trial is registered at clinicaltrials.gov (NCT00770809)
The Comuna Question: Jurisdiction, the State, and Legitimacy in Rural Ecuador
Get PDFIn 2019 and 2022, Indigenous leaders mobilized rural comunas in general strikes that forced the national government of Ecuador to negotiate the terms of newly introduced fiscal and policy measures. These mobilizations came despite long-term demographic decline in these same rural comunas . Further, the ministries charged with granting this authority to comunas today exercise little oversight. Why, then, has the comuna persisted as the preferred form of local organization amid widespread shifts to postagrarian ways of life? We have approached this problem through field research in over a dozen rural comunas , a review of comuna registrations, interviews with comuna leadership, and intergenerational dialogues among comuna members. In practical terms, we find comuna leadership consolidating an agenda focused on infrastructure development in the place of activism for land or the pursuit of agricultural investments. At the same time, it is through rituals of registration and management that local authorities not only find legitimacy but also secure a measure of “cultural autonomy” insofar as comuna members associate the disciplined fulfillment of procedures with the historical expansion of social rights. As the younger generation pursues nonagrarian careers, older comuna members underscore the mutuality of comuna life and lay out a moral purpose and a pathway that in effect centers state procedure as essential for indigenous autonomy. En 2019 y 2022, líderes indígenas movilizaron a las comunas rurales en paros nacionales que obligaron al gobierno nacional de Ecuador a negociar los términos de las nuevas medidas fiscales y políticas implementadas. Estas movilizaciones se produjeron a pesar del descenso demográfico a largo plazo en estas mismas comunas rurales. Además, los ministerios encargados de otorgar esta autoridad a las comunas ejercen actualmente poca supervisión. ¿Por qué, entonces, la comuna ha persistido como la forma preferida de organización local en medio de cambios generalizados hacia formas de vida post-agrarias? Hemos abordado este problema mediante investigación de campo en más de una docena de comunas rurales, una revisión de los registros comunales, entrevistas con líderes comunales y diálogos intergeneracionales entre sus miembros. En la práctica, observamos que los líderes comunales están consolidando una agenda centrada en el desarrollo de infraestructura en lugar del activismo por la tierra o la búsqueda de inversiones agrícolas. Al mismo tiempo, es a través de los rituales de registro y gestión que las autoridades locales no solo encuentran legitimidad, sino que también aseguran cierta “autonomía cultural”, en la medida en que los comuneros asocian el cumplimiento disciplinado de los procedimientos con la expansión histórica de los derechos sociales. A medida que las generaciones más jóvenes se dedican a carreras no agrarias, los comuneros mayores subrayan la mutualidad de la vida comunal y establecen un propósito moral y una vía que, en efecto, centra el procedimiento estatal como esencial para la autonomía indígena
Who Participates in Research and Why: Reducing Barriers to Diversifying Samples in Developmental Psychobiology
Get PDFRecent calls emphasize the need to diversify samples in developmental psychobiology regarding race and ethnicity. However, there is limited guidance on effective methods to involve individuals from marginalized communities in research, or which issues these participants prioritize when considering involvement in studies with neurobiological data collection. Here, we explore these motivations for caregivers with children of color who participated in developmental psychobiology research and how their racial/ethnic identities influenced their experience. Semistructured interviews were conducted with 13 caregivers whose children participated in a study exploring adversity and brain development (61.5% self-identify as Black; 100% self-identifying as a woman). Using thematic analysis, we observed that caregivers participated to spend quality time with their child, gain insights to inform their parenting, diversify research, and satisfy their own scientific curiosity. While caregivers generally reported enjoying their participation, they additionally reported remaining mindful of how they present themselves among research staff to mitigate negative stereotypes and keep their families safe, consistent with known historical harm from the scientific community. Lastly, caregiver's feedback on how to increase representation and better disseminate study findings are reported. These results emphasize the importance of centering participants of color to improve representation and minimize harm in psychobiological study procedures
A Vision Toward Risk-Stratified Postoperative Surveillance for Lung Cancer: Harnessing CT and AI
Get PDFSurvivors of lung cancer are an understudied but growing population with unmet needs. As of January 1, 2025, there were 680,450 lung cancer survivors in the United States, representing 3.6% of all cancer survivors. This count is projected to increase considerably to 870,980 over the next decade, due to the growth and aging of the US population. Combined with the rising incidence of pulmonary nodules, either detected by low-dose CT for lung cancer screening or incidentally from imaging for other reasons, the number of lung cancer survivors will only increase. Continued uptake of lung cancer screening will further lead to a proportional shift toward survivors of early-stage non–small-cell lung cancer (NSCLC) treated with curative-intent surgery. After definitive treatment, survivors of early-stage NSCLC carry an elevated risk for developing disease recurrence or second primary lung cancer (SPLC), and presently, only about 65% live beyond 5 years. These statistics collectively underscore a pressing need to optimize postoperative surveillance for lung cancer, as the growing number of survivors will inevitably drive greater demand for health care services
A Guide for Initiating and Managing Chimeric Antigen Receptor T Cell Therapy Clinical Trials in Autoimmune Rheumatic Diseases
Get PDFChimeric antigen receptor (CAR) T-cell therapy, long transformative in oncology, is now rapidly emerging as a frontier in autoimmune rheumatic diseases, particularly systemic lupus erythematosus (SLE), driven by accumulating evidence of deep B-cell depletion, immune "resetting," and durable drug-free remission in early studies, yet its translation into rheumatology demands mastery of formidable logistical, regulatory, clinical, and ethical complexities that span institutional readiness, multidisciplinary team formation, stringent regulatory compliance, sophisticated operational workflows, comprehensive patient selection and education, meticulous clinical management of both classical toxicities (CRS, ICANS, ICAHT) and autoimmune-specific reactions such as LICATS, robust financial and resource planning, and long-term follow-up extending 15 years or more; successful implementation requires coordinated expertise among rheumatologists, hematologist-oncologists, cellular therapy units, pharmacists, research coordinators, and ICU-capable teams, all embedded within disciplined communication structures, harmonized SOPs, validated PROs, biorepository governance frameworks, and adherence to national and international cellular therapy standards; in parallel, investigators must anticipate bottlenecks such as apheresis access, manufacturing slot scarcity, competing trial enrollment, fluctuating SLE phenotypes, and heterogeneity-driven signal variability, while sustaining patient engagement over years through education, navigation support, and transparent risk/benefit communication; finally, collaboration with industry partners, clinical trial networks, and patient-advocacy organizations is essential for overcoming operational barriers, securing financial sustainability, and ensuring ethical stewardship, so that CAR T-cell clinical trials in autoimmunity can be executed safely, rigorously, and with maximal therapeutic promise for patients
Consensus Recommendations for Anti-Racist Child Health Research: A Modified Delphi Study
Get PDFOBJECTIVES This study aimed to develop consensus on a comprehensive and abridged list of recommendations for conducting anti-racist research across all stages of a pediatric research project. Anti-racist research aims to ensure that the construct of race is correctly interpreted, and that racially and ethnically minoritized communities are fairly engaged throughout a research project. METHODS Using a modified Delphi approach, experts in equitable pediatric research methods completed three rounds of surveys and virtual focus groups between April and December 2023. Round 1 asked experts to add to or revise themes and subthemes gathered from a systematic review of published anti-racist practices. Round 2 included ranking items’ importance; items voted in the top 50% by 60% of experts were included in an abridged list of essential practices. In Round 3, experts reviewed the final guidance and had the option to rescue items for inclusion in the abridged guidance. RESULTS Fourteen experts with diverse personal and professional backgrounds participated. Experts added new themes and edited existing ones, creating a comprehensive list of 68 recommendations by consensus and identifying 36 to include in the abridged list of essential practices. They also discussed complex topics such as who these recommendations apply to, the nuances of equitable community engagement, and the dangers of health equity tourism. CONCLUSIONS An expert panel achieved consensus on a comprehensive and abridged list of recommendations for how to conduct research in an anti-racist, equitable way. These can inform research teams, regulatory agencies, and funders to improve pediatric research
Challenges and Opportunities in Characterizing the Genetics of Stuttering: From Sample Acquisition to Functional Interpretation of the Genome.
Get PDFPURPOSE: Converging etiological evidence supports a genetic risk for developmental stuttering; however, major gaps detailing the genetic architecture remain. Technological advances in genetics have allowed us to explore novel approaches to analyzing this complex trait, but conducting robust and replicable genetic studies requires large, well-phenotyped cohorts of subjects. This article reviews previous research strategies employed to overcome these challenges in identifying genetic variants associated with stuttering and translating stuttering-associated variants into molecular and cellular mechanisms. METHOD: We present an overview of data sources and strategies research teams have utilized for the genetic study of stuttering, highlighting the advantages and limitations of each approach. Primary data sources include (a) the International Stuttering Project, (b) the National Longitudinal Study of Adolescent to Adult Health, (c) BioVU, and (d) 23andMe, Inc. In addition to genome-wide association studies (GWASs), we review multiple post-GWAS follow-up analyses to probe the functional impact of stuttering-associated genetic variants and offer new transcriptome-wide analyses. RESULTS: To date, a diverse array of approaches has resulted in the identification of over 50 stuttering-associated genes. Many genetic associations were near or within genes previously linked to known neurological traits, highlighting a neurological role in stuttering. Additionally, validation studies using polygenic risk scores suggested a high level of genetic concordance between our samples. Functional follow-up studies suggest stuttering-associated variants may affect gene expression in tissues relevant to speech-related structures and neural correlates. CONCLUSIONS: While understanding how specific regions of the genome contribute to stuttering risk remains complex, research from our team and others has utilized a variety of data sources in an attempt to overcome previous limitations in the identification of genetic variation associated with stuttering. As the field of genetics evolves toward large-scale biobanks for research and discovery, prioritizing inclusion of traits such as stuttering will be key. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.30299764