27941 research outputs found
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Using immunization registry data to explore initiation of HPV vaccination at ages 9 and 10
Full text linkDespite evidence highlighting benefits of age 9/10 initiation of human papillomavirus (HPV) vaccination, little is known about who is initiating the series earlier. We describe the population of children who initiate earlier and assess the relationship of earlier initiation with series completion. We used individual-level immunization registry data from Iowa which contained data on male (49.9%) and female (50.1%) children born between 2004-2013 ages 9 and 17. We compared sociodemographic characteristics using chi-square statistics and used logistic regression to assess odds of initiation. Of children with a record of HPV vaccination, only 3.2% initiated early. In comparison to children who initiated at later, the early initiator group had a higher percentage of females ( < .0001), greater representation of nonwhite children ( < .0001), higher percentage living in urban areas ( < .0001) and higher private insurance ( < .0001). In logistic regression models, earlier initiation was significantly associated with higher rates of on-time completion (OR: 10.8 (8.6, 13.5)). These results can support prioritization of efforts to promote earlier initiation. For example, rural areas may need targeted outreach. Future work could integrate geospatial analyses so that local organizations could be able to target specific counties or even zip codes with the lowest rates of initiation.No embarg
Implementation and evaluation of a group peer mentoring and leadership development program for research faculty in academic medicine
Full text linkIntroduction: Research faculty often experience poor mentoring, low vitality, and burnout. We report on our logic model inputs, activities, measurable outcomes, and impact of a novel mentoring intervention for biomedical research faculty: the C-Change Mentoring & Leadership Institute. We present a) a detailed description of the curriculum and process, b) evaluation of the program's mentoring effectiveness from the perspective of participants, and c) documentation of mentoring correlated with key positive outcomes.
Methods: A yearlong facilitated group peer mentoring program that convened quarterly in person was conducted twice (2020-2022) as part of an NIH-funded randomized controlled study. The culture change intervention aimed to increase faculty vitality, career advancement, and cross-cultural competence through structured career planning and learning of skills essential for advancement and leadership in academic medicine. Participants were 40 midcareer MD and PhD research faculty, half women, and half underrepresented by race or ethnicity from 27 US medical schools.
Results: Participants highly rated their mentoring received at the Institute. Extent of effective mentoring experienced correlated strongly with the measurable outcomes of enhanced vitality, self-efficacy in career advancement, research and work-life integration, feelings of inclusion in the program, valuing diversity, and skills for addressing inequity.
Conclusions: The mentoring model fully included men and women and historically underrepresented persons in medicine and minimized problems of power, gender, race, and ethnicity discordance. The intervention successfully addressed the urgencies of sustaining faculty vitality, developing faculty careers, facilitating cross-cultural engagement and inclusion, and contributing to cultivating cultures of inclusive excellence in academic medicine.No embarg
Physiological and brain mechanisms contributing to postural tremor in aging with and without alcohol use disorder
Full text linkPostural instability, a concomitant of falls, can persist in people with alcohol use disorder (AUD) even with sustained sobriety. Balance testing using a force plate, which detects micromovements while standing still, can be quantified with spectral analysis and expressed as temporal frequency, an index of truncal (i.e., postural) tremor. Here, we investigated physiological and brain structural factors that may contribute to a mechanistic understanding of postural instability during quiet standing in AUD. This mixed cross-sectional/longitudinal design included 462 observations in 292 participants (age 25-75 years): 120 men and 44 women with DSM-5-determined AUD and 75 control men and 53 control women. All participants completed balance testing on a force plate under two conditions: eyes open and eyes closed, both with feet together. Most participants also underwent two-point discrimination testing on the soles of the feet and structural MRI, typically within the week of balance testing. Linear mixed-effects models revealed greater tremor in all conditions in the AUD than control group with the diagnostic differences attributed to AUD men. Age effects did not differ significantly between AUD and control groups. By contrast, stronger correlations were detected between greater tremor, measured as a 2-5 Hz/0-2 Hz frequency quotient, and smaller regional brain volumes selective to motor centers (frontal supplemental motor cortex, thalamus, pallidum, cerebellar white matter) of the AUD men. The salient signs of postural instability were attributable to AUD men who consumed alcohol exceeding NIAAA guideline limits in the year prior to testing.No embarg
UMCCTS Newsletter, September 2025
Full text linkThis is the September 2025 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.Supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grants UL1 TR001453, TL1 TR001454 and KL2 TR001455.No embarg
MYC and p53 Alterations Cooperate through VEGF Signaling to Repress Cytotoxic T-cell and Immunotherapy Responses in Prostate Cancer
No full textPatients with castration-resistant prostate cancer (CRPC) are generally unresponsive to tumor-targeted treatments and immunotherapies. Genetic alterations acquired during the evolution of CRPC may affect antitumor immunity and immunotherapy responses, which could inform personalized therapeutic strategies. Using our innovative electroporation-based mouse models, we generated distinct genetic subtypes of CRPC found in patients and uncovered unique immune microenvironments. Specifically, mouse and human prostate tumors with MYC amplification and p53 disruption had weak cytotoxic lymphocyte infiltration and an overall dismal prognosis. MYC and p53 cooperated to induce tumor-intrinsic secretion of VEGF, which signaled through VEGFR2 expressed on CD8+ T cells to directly inhibit T-cell migration and effector functions. Targeting VEGF-VEGFR2 signaling in vivo remodeled the immunosuppressive prostate tumor microenvironment, leading to CD8+ T-cell-mediated primary tumor and metastasis growth suppression and significantly increased overall survival in MYC- and p53-altered CRPC. VEGFR2 blockade also led to the induction of PD-L1 in tumors and produced antitumor efficacy in combination with PD-L1 immune checkpoint blockade in multiple preclinical CRPC mouse models. Thus, these results identify a genetic mechanism of immunosuppression through VEGF signaling in prostate cancer that can be targeted to reactivate immune and immunotherapy responses in an aggressive subtype of CRPC.
Significance: VEGFR2 blockade inhibits VEGF-mediated T-cell suppression and potentiates the effects of PD-L1 immune checkpoint blockade to treat castration-resistant prostate cancer driven by MYC and p53 alterations.No embarg
The Somatic Mosaicism across Human Tissues Network
No full textFrom fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues Network, which aims to create a reference catalogue of somatic mutations and their clonal patterns across 19 different tissue sites from 150 non-diseased donors and develop new technologies and computational tools to detect somatic mutations and assess their phenotypic consequences, including clonal expansions. This strategy enables a comprehensive examination of the mutational landscape across the human body, and provides a comparison baseline for somatic mutation in diseases. This will lead to a deep understanding of somatic mutations and clonal expansions across the lifespan, as well as their roles in health, in ageing and, by comparison, in diseases.No embarg
Revealing associations between exposure to cyanobacteria toxins and COVID-19 outcomes in Colorado [preprint]
Full text linkThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.While environmental exposures are known to play a significant role in human disease, these effects are understudied compared to genomic and molecular components of disease. One example is the effect of chronic, low-level exposures to cyanobacteria toxins on health outcomes. Here we perform a retrospective analysis on real-world data in the National Clinical Cohort Collaborative (N3C) COVID Enclave, examining the possible impact of chronic exposure to cyanobacteria toxin on the severity of COVID-19 outcomes in patients from Colorado. We combined data from N3C, satellite data from the USEPA CyAN project, and field observations from the Colorado Department of Public Health & Environment (CDPHE). Our results show that COVID-19 patients living near recurring cyanobacteria blooms had 2.75 times higher odds of experiencing severe outcomes (hospitalization or death) than individuals who do not. In addition, living in a county with low to middle levels of poverty had protective effects. Further work is needed to understand the precise mechanism of action and fully understand the long-term risk of chronic exposures to low-level cyanobacteria toxins on health outcomes. International Committee of Medical Journal Editors (ICMJE) Statement: Authorship was determined using ICMJE recommendations. IRB: 24-2680 DUR ID: DUR-15EB88A.The UMass Center for Clinical and Translational Science (UMCCTS), UL1TR001453, helped fund this study.No embarg
Comparative Safety of Short-Acting Opioid Dose Escalation and Long-Acting Opioid Initiation in Nursing Home Residents
No full textBackground: For patients with continued pain while receiving an initial course of a short-acting opioid (SAO), clinicians may intensify the opioid regimen by escalating the SAO dose or initiating a long-acting opioid (LAO). The objective of this study was to assess the comparative safety of opioid intensification regimens in nursing home residents with nonmalignant pain.
Methods: We conducted a retrospective cohort analysis of US long-stay nursing home residents identified from the national Minimum Data Set (MDS) 3.0 and linked Medicare data, 2011-2016. Opioid regimen changes were assessed using Part D claims to identify dose escalation of SAO, adding LAO to SAO, or a switch from SAO to LAO. The outcomes of interest were hospitalized falls/fractures and delirium identified in the MDS or hospitalization. Resident attributes were described by opioid regimen. Hazard ratios of study outcomes were quantified using as-treated (primary analysis) and intent-to-treat (secondary analysis) doubly robust inverse probability of treatment (IPT) weighted Fine & Gray regression models with a competing risk of death.
Results: In the as-treated analysis, relative to residents in the SAO escalation cohort, the hazard of delirium was elevated in the LAO cohorts (aHR [LAO switch]: 2.05, 95% CI: 1.57-2.67; aHR [LAO add-on]: 1.55, 95% CI: 1.23-1.96). Results for falls and fractures were inconclusive. We did not observe evidence of an association with falls and fractures in the primary as-treated analysis; however, the intent-to-treat analysis observed increased hazards in the LAO switch cohort relative to the SAO escalation cohort (aHR 2.86, 95% CI:1.64-4.99).
Conclusions: There is limited evidence to inform the clinical judgment between escalating the SAO dose or incorporating a LAO. Our study suggests increased risks of delirium in nursing home residents with nonmalignant pain when switching or adding an LAO to the opioid regimen relative to increasing the dose of SAOs.No embarg
Patient perspectives of jail based MOUD treatment: views of individuals who have returned to the community following incarceration
Full text linkBackground: Massachusetts passed legislation in 2018 to mandate provision of medications for opioid use disorder (MOUD) in select jails to address the high risk of opioid overdose after release. Since 2019, we have conducted a Type-1 hybrid effectiveness-implementation study of this program. We present findings on the perspectives and experiences of persons treated in these jails.
Methods: We conducted qualitative analyses of semi-structured interviews that were conducted in 2022 with 38 adults released to the community who had been treated with MOUD while living in one of eight Massachusetts jails. The Exploration, Preparation, Implementation, and Sustainment (EPIS) framework informed development of the interview guide and analysis of qualitative data. Deductive and inductive strategies were used for coding and analyses.
Results: Participants were 41.5 years old; predominantly male; 84.2% white, 23.7% Hispanic/Latino and 7.9% Black; and most continued taking MOUD. Thematic analysis focused on four code reports: Perception of Addiction/MOUD, Barriers/Facilitators, Impact of MOUD in Jails, and Stigma. Participants perceived that MOUD helped to prevent relapse. Prompt and consistent access to medication, and respectful treatment by healthcare and carceral staff were highlighted as facilitators. In contrast, some participants perceived that policy-centered rather than patient-centered treatment drove timing of medication initiation or response to medication changes. Insufficient staffing and the COVID-19 pandemic contributed to treatment delays. Overall, individuals incarcerated in jails that have expanded treatment eligibility to include earlier induction with MOUD generally felt more positive about their experience than individuals reporting delayed induction.
Conclusions: Participants valued the ability of jail based MOUD programs to help clients achieve recovery from OUD. Their perceptions highlight the intrinsic value of MOUD programs that promote and support wellbeing through a person-centered approach to treatment. Participants stressed that MOUD programs should be patient-centered and guided by patients' symptoms and needs.No embarg
UMCCTS Newsletter, December 2024
Full text linkThis is the December 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.Supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grants UL1 TR001453, TL1 TR001454 and KL2 TR001455.No embarg