T Cells Enhance Stem-Like Properties and Conditional Malignancy in Gliomas

Small populations of highly tumorigenic stem-like cells (cancer stem cells; CSCs) can exist within, and uniquely regenerate cancers including malignant brain tumors (gliomas). Many aspects of glioma CSCs (GSCs), however, have been characterized in non-physiological settings.We found gene expression similarity superiorly defined glioma "stemness", and revealed that GSC similarity increased with lower tumor grade. Using this method, we examined stemness in human grade IV gliomas (GBM) before and after dendritic cell (DC) vaccine therapy. This was followed by gene expression, phenotypic and functional analysis of murine GL26 tumors recovered from nude, wild-type, or DC-vaccinated host brains.GSC similarity was specifically increased in post-vaccine GBMs, and correlated best to vaccine-altered gene expression and endogenous anti-tumor T cell activity. GL26 analysis confirmed immune alterations, specific acquisition of stem cell markers, specifically enhanced sensitivity to anti-stem drug (cyclopamine), and enhanced tumorigenicity in wild-type hosts, in tumors in proportion to anti-tumor T cell activity. Nevertheless, vaccine-exposed GL26 cells were no more tumorigenic than parental GL26 in T cell-deficient hosts, though they otherwise appeared similar to GSCs enriched by chemotherapy. Finally, vaccine-exposed GBM and GL26 exhibited relatively homogeneous expression of genes expressed in progenitor cells and/or differentiation.T cell activity represents an inducible physiological process capable of proportionally enriching GSCs in human and mouse gliomas. Stem-like gliomas enriched by strong T cell activity, however, may differ from other GSCs in that their stem-like properties may be disassociated from increased tumor malignancy and heterogeneity under specific host immune conditions

Evaluation of service quality in family planning clinics in Lusaka, Zambia

OBJECTIVE: To determine the quality of contraceptive services in family planning clinics in Lusaka, Zambia using a standardized approach. STUDY DESIGN: We utilized the Quick Investigation of Quality, a cross-sectional survey tool consisting of a facility assessment, client-provider observation, and client exit interview, in public-sector family planning clinics. Data were collected on availability of seven contraceptive methods, information given to clients, interpersonal relations between providers and clients, providers’ technical competence, and mechanisms for continuity and follow-up. RESULTS: Data were collected from five client-provider observations and client exit interviews in each of six public-sector family planning clinics. All clinics had at least two contraceptive methods continuously available for the preceding six months. Most providers asked clients about concerns with their contraceptive method (80%) and told clients when to return to the clinic (87%). Most clients reported that the provider advised what to do if a problem develops (93%); described possible side effects (89%); explained how to use the method effectively (85%); and told them when to come for follow-up (83%). Clients were satisfied with services received (93%). CONCLUSION(S): This application of the Quick Investigation of Quality showed that the participating family planning clinics in Lusaka, Zambia were prepared to offer high quality services with the available commodities, and clients were satisfied with the received services. Despite the subjective client satisfaction, quality improvement efforts are needed to increase contraceptive availability. IMPLICATIONS: Although clients perceived the quality of care received to be high, family planning service quality could be improved to continuously offer the full spectrum of contraceptive options. The Quick Investigation of Quality was easily implemented in Lusaka, Zambia, and this simple approach could be utilized in a variety of settings as a modality for quality improvement

Harmonizing Genetic Ancestry and Self-identified Race/Ethnicity in Genome-wide Association Studies

Large-scale multi-ethnic cohorts offer unprecedented opportunities to elucidate the genetic factors influencing complex traits related to health and disease among minority populations. At the same time, the genetic diversity in these cohorts presents new challenges for analysis and interpretation. We consider the utility of race and/or ethnicity categories in genome-wide association studies (GWASs) of multi-ethnic cohorts. We demonstrate that race/ethnicity information enhances the ability to understand population-specific genetic architecture. To address the practical issue that self-identified racial/ethnic information may be incomplete, we propose a machine learning algorithm that produces a surrogate variable, termed HARE. We use height as a model trait to demonstrate the utility of HARE and ethnicity-specific GWASs