Coalicion de Salud Comunitaria (COSACO): using a Healthy Community Partnership framework to integrate short-term global health experiences into broader community development

BACKGROUND: There is growing concern that short-term experiences in global health experiences (STEGH), undertaken by healthcare providers, trainees, and volunteers from high income countries in lower and middle income countries, risk harming the community by creating a parallel system of care separate from established community development efforts. At the same time, the inclusion of non-traditional actors in health planning has been the basis of the development of many Healthy Community Partnerships (HCP) being rolled out in Canada and the United States. These partnerships aim to bring all stakeholders with a role to play in health to the table to align efforts, goals and programs towards broad community health goals. RESULTS: This methodology paper reports on the process used in La Romana, Dominican Republic, in applying a modified HCP framework. This project succeeded at bringing visiting STEGH organizations into a coalition with key community partners and supported attempts to embed the work of STEGH within longer-term, established development plans. CONCLUSIONS: In presenting the work and process and lessons learned, the hope is that other communities that encounter significant investment from STEGH groups, and will gain the same benefits that were seen in La Romana with regards to improved information exchange, increased cross-communication between silos, and the integration of STEGH into the work of community partners

A Protocol to Develop Practice Guidelines for Primary Care Medical Service Trips

BackgroundNorth American clinicians are increasingly participating in medical service trips (MSTs) that provide primary healthcare in Latin America and the Caribbean. Literature reviews have shown that the existence and use of evidence-based guidelines by these groups are limited, which presents potential for harm.ObjectiveThis paper proposes a 5-step methodology to develop protocols for diagnosis and treatment of conditions encountered by MST clinicians.MethodsWe reviewed the 2010 American College of Physicians guidance statement on guidelines development and developed our own adaptation. Ancestry search of the American College of Physicians statement identified specific publications that provided additional detail on key steps in the guideline development process, with additional focus given to evidence, equity, and local adaptation considerations.FindingsOur adaptation produced a 5-step process for developing locally optimized protocols for diagnosis and treatment of common conditions seen in MSTs. For specified conditions, this process includes: 1) a focused environmental scan of current practices based on grey literature protocols from MST sending organizations; 2) a review of relevant practice guidelines; 3) a literature review assessing the epidemiology, diagnosis, and treatment of the specified condition; 4) an eDelphi process with experts representing MST and Latin American and the Caribbean partner organizations assessing identified guidelines; and 5) external peer review and summary.ConclusionsThis protocol will enable the creation of practice guidelines that are based on best available evidence, local knowledge, and equitable considerations. The development of guidelines using this process could optimize the conduct of MSTs, while prioritizing input from local community partners

Health and Social Needs in Three Migrant Worker Communities around La Romana, Dominican Republic, and the Role of Volunteers: A Thematic Analysis and Evaluation

Objective. For decades, Haitian migrant workers living in bateyes around La Romana, Dominican Republic, have been the focus of short-term volunteer medical groups from North America. To assist these efforts, this study aimed to characterize various health and social needs that could be addressed by volunteer groups. Design. Needs were assessed using semistructured interviews of community and professional informants, using a questionnaire based on a social determinants of health framework, and responses were qualitatively analysed for common themes. Results. Key themes in community responses included significant access limitations to basic necessities and healthcare, including limited access to regular electricity and potable water, lack of health insurance, high out-of-pocket costs, and discrimination. Healthcare providers identified the expansion of a community health promoter program and mobile medical teams as potential solutions. English and French language training, health promotion, and medical skills development were identified as additional strategies by which teams could support community development. Conclusion. Visiting volunteer groups could work in partnership with community organizations to address these barriers by providing short-term access to services, while developing local capacity in education, healthcare, and health promotion in the long-term. Future work should also carefully evaluate the impacts and contributions of such volunteer efforts

The Extremely High Energy Cosmic Rays

Experimental results from Haverah Park, Yakutsk, AGASA and Fly's Eye are reviewed. All these experiments work in the energy range above 0.1 EeV. The 'dip' structure around 3 EeV in the energy spectrum is well established by all the experiments, though the exact position differs slightly. Fly's Eye and Yakutsk results on the chemical composition indicate that the cosmic rays are getting lighter over the energy range from 0.1 EeV to 10 EeV, but the exact fraction is hadronic interaction model dependent, as indicated by the AGASA analysis. The arrival directions of cosmic rays are largely isotropic, but interesting features may be starting to emerge. Most of the experimental results can best be explained with the scenario that an extragalactic component gradually takes over a galactic population as energy increases and cosmic rays at the highest energies are dominated by particles coming from extragalactic space. However, identification of the extragalactic sources has not yet been successful because of limited statistics and the resolution of the data.Comment: The review paper including 21 figures. 39 pages: To be published in Journal of Physics

Extension of the Cosmic-Ray Energy Spectrum Beyond the Predicted Greisen-Zatsepin-Kuz'min Cutoff

The cosmic-ray energy spectrum above 10^{18.5} eV is reported using the updated data set of the Akeno Giant Air Shower Array (AGASA) from February 1990 to October 1997. The energy spectrum extends beyond 10^{20} eV and the energy gap between the highest energy event and the others is being filled up with recently observed events. The spectral shape suggests the absence of the 2.7 K cutoff in the energy spectrum or a possible presence of a new component beyond the 2.7 K cutoff.Comment: to be published in PRL, 3 figures, REVTEX forma

Mutator Suppression and Escape from Replication Error–Induced Extinction in Yeast

Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ) proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10−3 inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex) rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust

Shedding Light on the Galaxy Luminosity Function

From as early as the 1930s, astronomers have tried to quantify the statistical nature of the evolution and large-scale structure of galaxies by studying their luminosity distribution as a function of redshift - known as the galaxy luminosity function (LF). Accurately constructing the LF remains a popular and yet tricky pursuit in modern observational cosmology where the presence of observational selection effects due to e.g. detection thresholds in apparent magnitude, colour, surface brightness or some combination thereof can render any given galaxy survey incomplete and thus introduce bias into the LF. Over the last seventy years there have been numerous sophisticated statistical approaches devised to tackle these issues; all have advantages -- but not one is perfect. This review takes a broad historical look at the key statistical tools that have been developed over this period, discussing their relative merits and highlighting any significant extensions and modifications. In addition, the more generalised methods that have emerged within the last few years are examined. These methods propose a more rigorous statistical framework within which to determine the LF compared to some of the more traditional methods. I also look at how photometric redshift estimations are being incorporated into the LF methodology as well as considering the construction of bivariate LFs. Finally, I review the ongoing development of completeness estimators which test some of the fundamental assumptions going into LF estimators and can be powerful probes of any residual systematic effects inherent magnitude-redshift data.Comment: 95 pages, 23 figures, 3 tables. Now published in The Astronomy & Astrophysics Review. This version: bring in line with A&AR format requirements, also minor typo corrections made, additional citations and higher rez images adde