Treatment options for pediatric patent ductus arteriosus: Systematic review and meta-analysis

BACKGROUND: Patent ductus arteriosus (PDA) in the nonpremature pediatric patient is currently treated by surgical ligation or catheter occlusion. There is no clear superiority of one technique over the other. This meta-analysis compares the clinical outcomes of the two treatment options for PDA. METHODS: We performed a literature search of MEDLINE, Embase, PubMed, and the Cochrane database of randomized controlled trials (RCTs) that took place between 1950 and February 2014 and hand-searched references from included studies. We excluded studies of adult or premature patients and those without a direct comparison between surgical and catheter-based treatments of PDAs. Outcomes of interest were reintervention, total complications, length of stay, and cost. RESULTS: One thousand three hundred thirty-three manuscripts were screened. Eight studies fulfilled the inclusion criteria (one RCT and seven observational studies [N = 1,107]). In pooled observational studies, there were significantly decreased odds (OR, 0.12; 95% CI, 0.03-0.42) for reintervention in the surgical ligation group but insignificantly higher odds for overall complications (OR, 2.01; 95% CI, 0.68-5.91). There were no complications reported in the RCT, but surgical ligation was associated with decreased odds for reintervention and a longer length of stay. Funnel plots revealed a possible publication bias and a quality review identified comparability bias. CONCLUSIONS: Both therapies have comparable outcomes. Reintervention is more common with catheter-based treatment, but overall complication rates are not higher and hospital stay is shorter. Our data span \u3e 2 decades and may not reflect current surgical and catheterization outcomes. Large, randomized, prospective studies may help determine the optimal treatment strategy

Bringing scientific rigor to community-developed programs in Hong Kong

BACKGROUND: This paper describes efforts to generate evidence for community-developed programs to enhance family relationships in the Chinese culture of Hong Kong, within the framework of community-based participatory research (CBPR). METHODS: The CBPR framework was applied to help maximize the development of the intervention and the public health impact of the studies, while enhancing the capabilities of the social service sector partners. RESULTS: Four academic-community research teams explored the process of designing and implementing randomized controlled trials in the community. In addition to the expected cultural barriers between teams of academics and community practitioners, with their different outlooks, concerns and languages, the team navigated issues in utilizing the principles of CBPR unique to this Chinese culture. Eventually the team developed tools for adaptation, such as an emphasis on building the relationship while respecting role delineation and an iterative process of defining the non-negotiable parameters of research design while maintaining scientific rigor. Lessons learned include the risk of underemphasizing the size of the operational and skills shift between usual agency practices and research studies, the importance of minimizing non-negotiable parameters in implementing rigorous research designs in the community, and the need to view community capacity enhancement as a long term process. CONCLUSIONS: The four pilot studies under the FAMILY Project demonstrated that nuanced design adaptations, such as wait list controls and shorter assessments, better served the needs of the community and led to the successful development and vigorous evaluation of a series of preventive, family-oriented interventions in the Chinese culture of Hong Kong

Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort

BACKGROUND: Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line. METHODS: Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event. RESULTS: In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor-based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively. CONCLUSIONS: High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years

Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development

The mammalian telencephalon contains distinct GABAergic projection neuron and interneuron types, originating in the germinal zone of the embryonic basal ganglia. How genetic information in the germinal zone determines cell types is unclear. Here we use a combination of in vivo CRISPR perturbation, lineage tracing and ChIP-sequencing analyses and show that the transcription factor MEIS2 favors the development of projection neurons by binding enhancer regions in projection-neuron-specific genes during mouse embryonic development. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity toward the appropriate binding sites. In interneuron precursors, the transcription factor LHX6 represses the MEIS2-DLX5-dependent activation of projection-neuron-specific enhancers. Mutations of Meis2 result in decreased activation of regulatory enhancers, affecting GABAergic differentiation. We propose a differential binding model where the binding of transcription factors at cis-regulatory elements determines differential gene expression programs regulating cell fate specification in the mouse ganglionic eminence. How genetic information in the germinal zone determines neuronal cell types is unclear. Here the authors show that MEIS2 plays an important role in determining GABAergic neuron diversity during development

CEO duality, board size and firm performance : Evidence in Vietnam

From the perspective of the agency and stewardship theories for explaining the relationship between corporate governance and firm performance, this study examines the impacts of CEO duality and board size on the firm performance. We assess the association between CEO duality, board size and firm performance of top 200 companies listed on the Vietnam Stock Exchange (VSE) over 2014–2015. Our findings show that: 1) CEO duality limits the monitoring function of the board, and a large board size promotes dominance and power of leaders that create more conflicts; 2) the number of executive directors in the top management positively influences firm performance. Findings of our study certainly help policymakers and other stakeholders understand the relationship between CEO duality, board size and firm performance. Overall, this study highlights the CEO duality and the relationship of board size and firm performance in a nation with less protection of minority shareholders

RELICS: Strong Lens Models for Five Galaxy Clusters From the Reionization Lensing Cluster Survey

Strong gravitational lensing by galaxy clusters magnifies background galaxies, enhancing our ability to discover statistically significant samples of galaxies at z>6, in order to constrain the high-redshift galaxy luminosity functions. Here, we present the first five lens models out of the Reionization Lensing Cluster Survey (RELICS) Hubble Treasury Program, based on new HST WFC3/IR and ACS imaging of the clusters RXC J0142.9+4438, Abell 2537, Abell 2163, RXC J2211.7-0349, and ACT-CLJ0102-49151. The derived lensing magnification is essential for estimating the intrinsic properties of high-redshift galaxy candidates, and properly accounting for the survey volume. We report on new spectroscopic redshifts of multiply imaged lensed galaxies behind these clusters, which are used as constraints, and detail our strategy to reduce systematic uncertainties due to lack of spectroscopic information. In addition, we quantify the uncertainty on the lensing magnification due to statistical and systematic errors related to the lens modeling process, and find that in all but one cluster, the magnification is constrained to better than 20% in at least 80% of the field of view, including statistical and systematic uncertainties. The five clusters presented in this paper span the range of masses and redshifts of the clusters in the RELICS program. We find that they exhibit similar strong lensing efficiencies to the clusters targeted by the Hubble Frontier Fields within the WFC3/IR field of view. Outputs of the lens models are made available to the community through the Mikulski Archive for Space TelescopesComment: Accepted to Ap