Comprehensive characterization of the genomic alterations in human gastric cancer.

Gastric cancer is one of the most prevalent and aggressive cancers worldwide, and its molecular mechanism remains largely elusive. Here we report the genomic landscape in primary gastric adenocarcinoma of human, based on the complete genome sequences of five pairs of cancer and matching normal samples. In total, 103,464 somatic point mutations, including 407 nonsynonymous ones, were identified and the most recurrent mutations were harbored by Mucins (MUC3A and MUC12) and transcription factors (ZNF717, ZNF595 and TP53). 679 genomic rearrangements were detected, which affect 355 protein-coding genes; and 76 genes show copy number changes. Through mapping the boundaries of the rearranged regions to the folded three-dimensional structure of human chromosomes, we determined that 79.6% of the chromosomal rearrangements happen among DNA fragments in close spatial proximity, especially when two endpoints stay in a similar replication phase. We demonstrated evidences that microhomology-mediated break-induced replication was utilized as a mechanism in inducing ∼40.9% of the identified genomic changes in gastric tumor. Our data analyses revealed potential integrations of Helicobacter pylori DNA into the gastric cancer genomes. Overall a large set of novel genomic variations were detected in these gastric cancer genomes, which may be essential to the study of the genetic basis and molecular mechanism of the gastric tumorigenesis.

Effects of the Community Score Card approach on reproductive health service-related outcomes in Malawi.

BACKGROUND: Social accountability approaches are increasingly being employed in low-resource settings to improve government services. In line with the continuous quality improvement (CQI) philosophy that quality is the product of a linked chain, collaborative social accountability approaches like the Community Score Card (CSC) aim to empower clients and frontline service providers to transform their own lives and hold public officials to account for state obligations. Despite being a critical focus of collaborative social accountability approaches, to our knowledge, a quantitative survey of health workers to understand the impact of these approaches on their self-reported responsibilities and service provision has not been conducted. To fill this gap, we carried out a quantitative survey with health workers to assess the CSC's impact on health worker-reported service responsibilities and provision and complement women's self-reports. METHODS: We evaluated the effect of the CSC on reproductive health-related outcomes using a cluster-randomized design in Ntcheu district, Malawi. We matched 10 pairs of health facilities and surrounding catchment communities; one from each pair was randomly assigned to the intervention and control arms. The intervention communities and health workers each completed 3-4 cycles of the CSC process by endline. We then surveyed all health workers in the 20 intervention and comparison sites at endline (n = 412) to estimate the intervention's impact. RESULTS: Significantly (p < .05) more health workers in the CSC intervention areas compared to control areas reported responsibility for antenatal care, comprehensive antenatal care counseling, recording of the number of pregnant and postpartum women seen each month, and the average age of their last family planning client was younger. In addition, marginally significantly (p < .10) more health workers in treatment versus control areas report visiting women at their home at least once during their pregnancy. However, health worker-reported responsibility for HIV testing was significantly lower in intervention areas than in control. CONCLUSIONS: The CSC aims to empower health workers to collaborate with the community and rest of the health system to identify and overcome the diverse and context-specific range of performance barriers they face. In doing so, it aims to support them to demand and ensure quality care for themselves from the health system so they can, in turn, deliver quality services to clients. Our results contribute to the evidence that the CSC may hold promise at improving service provision. While there is increasing evidence that collaborative social accountability approaches like the CSC are effective means to improving reproductive health-related service provision and outcomes in low-resource settings, additional research is needed.

Effects of a social accountability approach, CARE's Community Score Card, on reproductive health-related outcomes in Malawi: A cluster-randomized controlled evaluation.

BACKGROUND: Social accountability approaches, which emphasize mutual responsibility and accountability by community members, health care workers, and local health officials for improving health outcomes in the community, are increasingly being employed in low-resource settings. We evaluated the effects of a social accountability approach, CARE's Community Score Card (CSC), on reproductive health outcomes in Ntcheu district, Malawi using a cluster-randomized control design. METHODS: We matched 10 pairs of communities, randomly assigning one from each pair to intervention and control arms. We conducted two independent cross-sectional surveys of women who had given birth in the last 12 months, at baseline and at two years post-baseline. Using difference-in-difference (DiD) and local average treatment effect (LATE) estimates, we evaluated the effects on outcomes including modern contraceptive use, antenatal and postnatal care service utilization, and service satisfaction. We also evaluated changes in indicators developed by community members and service providers in the intervention areas. RESULTS: DiD analyses showed significantly greater improvements in the proportion of women receiving a home visit during pregnancy (B = 0.20, P < .01), receiving a postnatal visit (B = 0.06, P = .01), and overall service satisfaction (B = 0.16, P < .001) in intervention compared to control areas. LATE analyses estimated significant effects of the CSC intervention on home visits by health workers (114% higher in intervention compared to control) (B = 1.14, P < .001) and current use of modern contraceptives (57% higher) (B = 0.57, P < .01). All 13 community- and provider-developed indicators improved, with 6 of them showing significant improvements. CONCLUSIONS: By facilitating the relationship between community members, health service providers, and local government officials, the CSC contributed to important improvements in reproductive health-related outcomes. Further, the CSC builds mutual accountability, and ensures that solutions to problems are locally-relevant, locally-supported and feasible to implement.

Entertainment-education radio serial drama and outcomes related to HIV testing in Botswana.

Makgabaneng is an entertainment-education radio serial drama written and produced in Botswana to promote prevention of HIV. This effort is part of the national response to HIV/AIDS. Broadcast of the serial drama began in August 2001, and two new 15-minute episodes air each week. We examined associations between exposure to Makgabaneng and outcomes related to HIV testing, including stigmatizing attitudes, intention to be tested, talking with a partner about testing, and testing for HIV, among 555 sexually active respondents. The four measures of exposure to Makgabaneng were frequency of listening, duration of listening, talking about the program, and attentiveness to and identification with relevant characters. Data were collected approximately 18 months after the drama began airing. We found positive associations between exposure to the program and intermediate outcomes, including lower level of stigmatizing attitudes, stronger intention to have HIV testing, and talking to a partner about testing. Although associations were identified with all four measures of exposure, increased duration of listening was associated with more positive outcomes than the other measures. This finding suggests that longer term exposure to entertainment-education programming may be important for behavior change.