Decentralization and Health: Case Studies of Kenya, Pakistan, and the Philippines

Decentralization, defined by the World Bank (2001) as, “the transfer of authority and responsibility for public functions from the central government to intermediate and local governments or quasi-­‐independent government organizations and/or the private sector,” is a movement that has gained much traction in recent history. For many countries undergoing decentralization, a major driver has been a desire to increase the role and participation of local governments in the decision-­‐making space. In doing this, it is hoped to create governance structures that are more accountable and responsive to the people. For health, decentralization has been touted as a potential way to improve responsiveness to local needs, improve service delivery, and improve equitability. In light of these goals, many countries as part of their political decentralization have also opted to decentralize healthcare.https://jdc.jefferson.edu/cwicposters/1020/thumbnail.jp

Stroke Ready Intervention: Community Engagement to Decrease Prehospital Delay

Background: Time-limited acute stroke treatments are underused, primarily due to prehospital delay. One approach to decreasing prehospital delay is to increase stroke preparedness, the ability to recognize stroke, and the intention to immediately call emergency medical services, through community engagement with high-risk communities. Methods and Results: Our community-academic partnership developed and tested "Stroke Ready," a peer-led, workshop-based, health behavior intervention to increase stroke preparedness among African American youth and adults in Flint, Michigan. Outcomes were measured with a series of 9 stroke and nonstroke 1-minute video vignettes; after each video, participants selected their intended response (primary outcome) and symptom recognition (secondary outcome), receiving 1 point for each appropriate stroke response and recognition. We assessed differences between baseline and posttest appropriate stroke response, which was defined as intent to call 911 for stroke vignettes and not calling 911 for nonstroke, nonemergent vignettes and recognition of stroke. Outcomes assessments were performed before workshop 1 (baseline), at the conclusion of workshop 2 (immediate post-test), and 1 month later (delayed post-test). A total of 101 participants completed the baseline assessment (73 adults and 28 youths), 64 completed the immediate post-test, and 68 the delayed post-test. All participants were African American. The median age of adults was 56 (interquartile range 35-65) and of youth was 14 (interquartile range 11-16), 65% of adults were women, and 50% of youths were women. Compared to baseline, appropriate stroke response was improved in the immediate post-test (4.4 versus 5.2, P < 0.01) and was sustained in the delayed post-test (4.4 versus 5.2, P < 0.01). Stroke recognition did not change in the immediate post-test (5.9 versus 6.0, P=0.34), but increased in the delayed post-test (5.9 versus 6.2, P=0.04). Conclusions: Stroke Ready increased stroke preparedness, a necessary step toward increasing acute stroke treatment rates

Coupling snowpack and groundwater dynamics to interpret historical streamflow trends in the western United States

A key challenge for resource and land managers is predicting the consequences of climate warming on streamflow and water resources. During the last century in the western United States, significant reductions in snowpack and earlier snowmelt have led to an increase in the fraction of annual streamflow during winter and a decline in the summer. Previous work has identified elevation as it relates to snowpack dynamics as the primary control on streamflow sensitivity to warming. But along with changes in the timing of snowpack accumulation and melt, summer streamflows are also sensitive to intrinsic, geologically mediated differences in the efficiency of landscapes in transforming recharge (either as rain or snow) into discharge; we term this latter factor drainage efficiency. Here we explore the conjunction of drainage efficiency and snowpack dynamics in interpreting retrospective trends in summer streamflow during 1950–2010 using daily streamflow from 81 watersheds across the western United States. The recession constant (k) and fraction of precipitation falling as snow (S[subscript f]) were used as metrics of deep groundwater and overall precipitation regime (rain and/or snow), respectively. This conjunctive analysis indicates that summer streamflows in watersheds that drain slowly from deep groundwater and receive precipitation as snow are most sensitive to climate warming. During the spring, however, watersheds that drain rapidly and receive precipitation as snow are most sensitive to climate warming. Our results indicate that not all trends in western United States are associated with changes in snowpack dynamics; we observe declining streamflow in late fall and winter in rain-dominated watersheds as well. These empirical findings support both theory and hydrologic modelling and have implications for how streamflow sensitivity to warming is interpreted across broad regions. Copyright © 2012 John Wiley & Sons, Ltd.Keywords: Groundwater processes, Climate, Warming, Hydrologic processes, Streamflow tren

Initiation of Psychotropic Medication after Partner Bereavement: A Matched Cohort Study

Background Recent changes to diagnostic criteria for depression in DSM-5 remove the bereavement exclusion, allowing earlier diagnosis following bereavement. Evaluation of the potential effect of this change requires an understanding of existing psychotropic medication prescribing by non-specialists after bereavement. Aims To describe initiation of psychotropic medication in the first year after partner bereavement. Methods In a UK primary care database, we identified 21,122 individuals aged 60 and over with partner bereavement and no psychotropic drug use in the previous year. Prescribing (anxiolytic/hypnotic, antidepressant, antipsychotic) after bereavement was compared to age, sex and practice matched controls. Results The risks of receiving a new psychotropic prescription within two and twelve months of bereavement were 9.5% (95% CI 9.1 to 9.9%) and 17.9% (17.3 to 18.4%) respectively; an excess risk of initiation in the first year of 12.4% compared to non-bereaved controls. Anxiolytic/hypnotic and antidepressant initiation rates were highest in the first two months. In this period, the hazard ratio for initiation of anxiolytics/hypnotics was 16.7 (95% CI 14.7 to 18.9) and for antidepressants was 5.6 (4.7 to 6.7) compared to non-bereaved controls. 13.3% of those started on anxiolytics/hypnotics within two months continued to receive this drug class at one year. The marked variation in background family practice prescribing of anxiolytics/hypnotics was the strongest determinant of their initiation in the first two months after bereavement. Conclusion Almost one in five older people received a new psychotropic drug prescription in the year after bereavement. The early increase and trend in antidepressant use after bereavement suggests some clinicians did not adhere to the bereavement exclusion, with implications for its recent removal in DSM-5. Family practice variation in use of anxiolytics/hypnotics suggests uncertainty over their role in bereavement with the potential for inappropriate long term use

Urinary Iodine, Perchlorate, and Thiocyanate Concentrations in U.S. Lactating Women

Background: Iodine is an essential micronutrient for thyroid hormone production. Adequate iodine intake and normal thyroid function are important during early development, and breastfed infants rely on maternal iodine excreted in breast milk for their iodine nutrition. The proportion of women in the United States of childbearing age with urinary iodine concentration (UIC) <50 μg/L has been increasing, and a subset of lactating women may have inadequate iodine intake. UIC may also be influenced by environmental exposure to perchlorate and thiocyanate, competitive inhibitors of iodine transport into thyroid, and lactating mammary glands. Data regarding UIC in U.S. lactating women are limited. To adequately assess the iodine sufficiency of lactating women and potential associations with environmental perchlorate and thiocyanate exposure, we conducted a multicenter, cross-sectional study of urinary iodine, perchlorate, and thiocyanate concentrations in healthy U.S. lactating women. Methods: Lactating women ≥18 years of age were recruited from three U.S. geographic regions: California, Massachusetts, and Ohio/Illinois from November 2008 to June 2016. Demographic information and multivitamin supplements use were obtained. Iodine, perchlorate, and thiocyanate levels were measured from spot urine samples. Correlations between urinary iodine, perchlorate, and thiocyanate levels were determined using Spearman's rank correlation. Multivariable regression models were used to assess predictors of urinary iodine, perchlorate, and thiocyanate levels, and UIC <100 μg/L. Results: A total of 376 subjects (≥125 from each geographic region) were included in the final analyses [mean (SD) age 31.1 (5.6) years, 37% white, 31% black, and 11% Hispanic]. Seventy-seven percent used multivitamin supplements, 5% reported active cigarette smoking, and 45% were exclusively breastfeeding. Median urinary iodine, perchlorate, and thiocyanate concentrations were 143 μg/L, 3.1 μg/L, and 514 μg/L, respectively. One-third of women had UIC <100 μg/L. Spot urinary iodine, perchlorate, and thiocyanate levels all significantly positively correlated to each other. No significant predictors of UIC, UIC <100 μg/L, or urinary perchlorate levels were identified. Smoking, race/ethnicity, and marital status were significant predictors of urinary thiocyanate levels. Conclusion: Lactating women in three U.S. geographic regions are iodine sufficient with an overall median UIC of 143 μg/L. Given ubiquitous exposure to perchlorate and thiocyanate, adequate iodine nutrition should be emphasized, along with consideration to decrease these exposures in lactating women to protect developing infants

Twenty year fitness trends in young adults and incidence of prediabetes and diabetes: the CARDIA study

The prospective association between cardiorespiratory fitness (CRF) measured in young adulthood and middle age on development of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance, or diabetes by middle age remains unknown. We hypothesised that higher fitness levels would be associated with reduced risk for developing incident prediabetes/diabetes by middle age

A Highly-Conserved Residue of the HIV-1-gp120 Inner Domain is Important for ADCC Responses Mediated by Anti-Cluster A Antibodies

Previous studies have shown that sera from HIV-1-infected individuals contain antibodies able to mediate antibody-dependent cellular cytotoxicity (ADCC). These antibodies preferentially recognize envelope glycoprotein (Env) epitopes induced upon CD4 binding. Here, we show that a highly conserved tryptophan at position 69 of the gp120 inner domain is important for ADCC mediated by anti-cluster A antibodies and sera from HIV-1-infected individuals

Poziotinib Inhibits HER2-Mutant-Driven Therapeutic Resistance and Multiorgan Metastasis in Breast Cancer

UNLABELLED: The pan-HER tyrosine kinase inhibitor (TKI) neratinib is therapeutically active against metastatic breast cancers harboring activating HER2 mutations, but responses are variable and often not durable. Here we demonstrate that recurrent HER2 mutations have differential effects on endocrine therapy responsiveness, metastasis, and pan-HER TKI therapeutic sensitivity. The prevalence and prognostic significance may also depend on whether the HER2 mutant has arisen in the context of lobular versus ductal histology. The most highly recurrent HER2 mutant, L755S, was particularly resistant to neratinib but sensitive to the pan-HER TKI poziotinib, alone or in combination with fulvestrant. Poziotinib reduced tumor growth, diminished multiorgan metastasis, and inhibited mTOR activation more effectively than neratinib. Similar therapeutic effects of poziotinib were observed in both an engineered HER2L755S MCF7 model and a patient-derived xenograft harboring a HER2G778_P780dup mutation. Overall, these findings support the need for clinical evaluation of poziotinib for the treatment of HER2-mutant metastatic breast cancer. SIGNIFICANCE: Evaluation of the functional impact of HER2 mutations on therapy-induced resistance and metastasis identifies robust antitumor activity of poziotinib and supports the clinical evaluation of poziotinib in ER+ HER2 mutant breast cancer

The efficacy of whole human genome capture on ancient dental calculus and dentin

Objectives: Dental calculus is among the richest known sources of ancient DNA in the archaeological record. Although most DNA within calculus is microbial, it has been shown to contain sufficient human DNA for the targeted retrieval of whole mitochondrial genomes. Here, we explore whether calculus is also a viable substrate for whole human genome recovery using targeted enrichment techniques. Materials and methods: Total DNA extracted from 24 paired archaeological human dentin and calculus samples was subjected to whole human genome enrichment using in-solution hybridization capture and high-throughput sequencing. Results: Total DNA from calculus exceeded that of dentin in all cases, and although the proportion of human DNA was generally lower in calculus, the absolute human DNA content of calculus and dentin was not significantly different. Whole genome enrichment resulted in up to fourfold enrichment of the human endogenous DNA content for both dentin and dental calculus libraries, albeit with some loss in complexity. Recovering more on-target reads for the same sequencing effort generally improved the quality of downstream analyses, such as sex and ancestry estimation. For nonhuman DNA, comparison of phylum-level microbial community structure revealed few differences between precapture and postcapture libraries, indicating that off-target sequences in human genome-enriched calculus libraries may still be useful for oral microbiome reconstruction. Discussion: While ancient human dental calculus does contain endogenous human DNA sequences, their relative proportion is low when compared with other skeletal tissues. Whole genome enrichment can help increase the proportion of recovered human reads, but in this instance enrichment efficiency was relatively low when compared with other forms of capture. We conclude that further optimization is necessary before the method can be routinely applied to archaeological samples

The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans

<p>Abstract</p> <p>Background</p> <p>Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (<it>FADS</it>) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date.</p> <p>Results</p> <p>In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10^-48) and lower DGLA levels (p = 9.80 × 10^-11) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (<it>FADS</it>) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10^-16in African Americans, 2.68 × 10^-23in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with <it>enhanced </it>conversion of DGLA to AA, on enzymatic efficiency was similar in both groups.</p> <p>Conclusions</p> <p>We conclude that the impact of <it>FADS </it>genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.</p