PubMed · 13985773
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
E POULI-PATERAKI, I CARNI-CATSADIMA, Z MELAS-IOANNIDIS. 1962. [Trace elements influencing BCG development].. https://pubmed.ncbi.nlm.nih.gov/13985773/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Meta-regression has become a commonly used tool for investigating whether study characteristics may explain heterogeneity of results among studies in a systematic review. However, such explorations of heterogeneity are prone to misleading false-positive results. It is unclear how many covariates can reliably be investigated, and how this might depend on the number of studies, the extent of the heterogeneity and the relative weights awarded to the different studies. Our objectives in this paper are two-fold. First, we use simulation to investigate the type I error rate of meta-regression in various situations. Second, we propose a permutation test approach for assessing the true statistical significance of an observed meta-regression finding. Standard meta-regression methods suffer from substantially inflated false-positive rates when heterogeneity is present, when there are few studies and when there are many covariates. These are typical of situations in which meta-regressions are routinely employed. We demonstrate in particular that fixed effect meta-regression is likely to produce seriously misleading results in the presence of heterogeneity. The permutation test appropriately tempers the statistical significance of meta-regression findings. We recommend its use before a statistically significant relationship is claimed from a standard meta-regression analysis.
The extent of human memory T cell proliferation, differentiation, and telomere erosion that occurs after a single episode of immune challenge in vivo is unclear. To investigate this, we injected tuberculin purified protein derivative (PPD) into the skin of immune individuals and isolated responsive T cells from the site of antigenic challenge at different times. PPD-specific CD4+ T cells proliferated and differentiated extensively in the skin during this secondary response. Furthermore, significant telomere erosion occurred in specific T cells that respond in the skin, but not in those that are found in the blood from the same individuals. Tissue fluid obtained from the site of PPD challenge in the skin inhibited the induction of the enzyme telomerase in T cells in vitro. Antibody inhibition studies indicated that type I interferon (IFN), which was identified at high levels in the tissue fluid and by immunohistology, was responsible in part for the telomerase inhibition. Furthermore, the addition of IFN-alpha to PPD-stimulated CD4+ T cells directly inhibited telomerase activity in vitro. Therefore, these results suggest that the rate of telomere erosion in proliferating, antigen-specific CD4+ T cells may be accelerated by type I IFN during a secondary response in vivo.
CONTEXT: The duration of protection from tuberculosis of BCG vaccines is not known. OBJECTIVE: To determine the long-term duration of protection of a BCG vaccine that was previously found to be efficacious. DESIGN: Retrospective record review using Indian Health Service records, tuberculosis registries, death certificates, and supplemental interviews with trial participants. SETTING AND PARTICIPANTS: Follow-up for the period 1948-1998 among American Indians and Alaska Natives who participated in a placebo-controlled BCG vaccine trial during 1935-1938 and who were still at risk of developing tuberculosis. Data from 1483 participants in the BCG vaccine group and 1309 in the placebo group were analyzed. MAIN OUTCOME MEASURES: Efficacy of BCG vaccine, calculated for each 10-year interval using a Cox regression model with time-dependent variables based on tuberculosis events occurring after December 31, 1947 (end of prospective case finding). RESULTS: The overall incidence of tuberculosis was 66 and 138 cases per 100 000 person-years in the BCG vaccine and placebo groups, respectively, for an estimate of vaccine efficacy of 52% (95% confidence interval, 27%-69%). Adjustments for age at vaccination, tribe, subsequent BCG vaccination, chronic medical illness, isoniazid use, and bacille Calmette-Guérin strain did not substantially affect vaccine efficacy. There was slight but not statistically significant waning of the efficacy of BCG vaccination over time, greater among men than women. CONCLUSION: In this trial, BCG vaccine efficacy persisted for 50 to 60 years, suggesting that a single dose of an effective BCG vaccine can have a long duration of protection.