Long-term exercise therapy resolves ethnic differences in baseline health status in older adults with knee osteoarthritis

OBJECTIVES: To determine whether ethnicity was associated with baseline and 18-month health status within a merged sample of older adults with knee osteoarthritis (OA) from the Fitness Arthritis in Seniors Trial and the Arthritis, Diet, and Activity Promotion Trial. DESIGN: Cross-sectional and prospective study. SETTING: Center-based exercise therapy at two universities. PARTICIPANTS: A total of 584 African-American (n = 143) and Caucasian-American (n = 441) adults aged 60 and older with knee OA were examined for baseline and 18-month health status. MEASUREMENTS: Six-minute-walk distance, 36-item Short Form General Health Scale (SF-36 GHS), and Physical Functioning Questionnaire index score. Ethnicity was obtained via self-report. RESULTS: Analyses of covariance testing the effect of ethnicity, adjusted for demographic and health status covariates, revealed significant effects for ethnicity upon baseline 6-minute-walk distance and SF-36 GHS, with Caucasian Americans reporting better scores (P = .001), although these differences were not significant after 18 months of exercise therapy. CONCLUSION: Ethnicity and baseline function are important factors that should not be overlooked in knee OA research involving exercise interventions. Moreover, not only should physical activity be recommended to improve functional outcomes, it may also be a useful strategy in reducing health disparities. © 2005 by the American Geriatrics Society

Analysing spatially referenced public health data: a comparison of three methodological approaches

In the analysis of spatially referenced public health data, members of different disciplinary groups (geographers, epidemiologists and statisticians) tend to select different methodological approaches, usually those with which they are already familiar. This paper compares three such approaches in terms of their relative value and results. A single public health dataset, derived from a community survey, is analysed by using ‘traditional’ epidemiological methods, GIS and point pattern analysis. Since they adopt different ‘models’ for addressing the same research question, the three approaches produce some variation in the results for specific health-related variables. Taken overall, however, the results complement, rather than contradict or duplicate each other

Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells <sup>1-14</sup> . The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies <sup>15-17</sup> to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8 <sup>+</sup> T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time