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996 result(s) for "Shearer, C."
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Chlorine Isotope Composition of the Moon and Implications for an Anhydrous Mantle
Arguably, the most striking geochemical distinction between Earth and the Moon has been the virtual lack of water (hydrogen) in the latter. This conclusion was recently challenged on the basis of geochemical data from lunar materials that suggest that the Moon's water content might be far higher than previously believed. We measured the chlorine isotope composition of Apollo basalts and glasses and found that the range of isotopic values [from -1 to +24 per mil ([per thousand]) versus standard mean ocean chloride] is 25 times the range for Earth. The huge isotopic spread is explained by volatilization of metal halides during basalt eruption--a process that could only occur if the Moon had hydrogen concentrations lower than those of Earth by a factor of approximately 10⁴ to 10⁵, implying that the lunar interior is essentially anhydrous.
Effects of niacin and omega-3 fatty acids on HDL-apolipoprotein A-I exchange in subjects with metabolic syndrome
HDL-apolipoprotein A-I exchange (HAE) measures a functional property associated with HDL’s ability to mediate reverse cholesterol transport. HAE has been used to examine HDL function in case-control studies but not in studies of therapeutics that alter HDL particle composition. This study investigates whether niacin and omega-3 fatty acids induce measurable changes in HAE using a cohort of fifty-six subjects with metabolic syndrome (MetS) who were previously recruited to a double-blind trial where they were randomized to 16 weeks of treatment with dual placebo, extended-release niacin (ERN, 2g/day), prescription omega-3 ethyl esters (P-OM3, 4g/day), or the combination. HAE was assessed at the beginning and end of the study. Compared to placebo, ERN and P-OM3 alone significantly increased HAE by 15.1% [8.2, 22.0] ( P <0.0001) and 11.1% [4.5, 17.7] ( P <0.0005), respectively, while in combination they increased HAE by 10.0% [2.5, 15.8] ( P = 0.005). When HAE was evaluated per unit mass of apoA-I ERN increased apoA-I specific exchange activity by 20% (2, 41 CI, P = 0.02) and P-OM3 by 28% (9.6, 48 CI, P< 0.0006). However the combination had no statistically significant effect, 10% (-9, 31 CI, P = 0.39). With regard to P-OM3 therapy in particular, the HAE assay detected an increase in this property in the absence of a concomitant rise in HDL-C and apoA-I levels, suggesting that the assay can detect functional changes in HDL that occur in the absence of traditional biomarkers.
A realist systematic review of evidence from low- and middle-income countries of interventions to improve immunization data use
Background The use of routine immunization data by health care professionals in low- and middle-income countries remains an underutilized resource in decision-making. Despite the significant resources invested in developing national health information systems, systematic reviews of the effectiveness of data use interventions are lacking. Applying a realist review methodology, this study synthesized evidence of effective interventions for improving data use in decision-making. Methods We searched PubMed, POPLINE, Centre for Agriculture and Biosciences International Global Health, and African Journals Online for published literature. Grey literature was obtained from conference, implementer, and technical agency websites and requested from implementing organizations. Articles were included if they reported on an intervention designed to improve routine data use or reported outcomes related to data use, and targeted health care professionals as the principal data users. We developed a theory of change a priori for how we expect data use interventions to influence data use. Evidence was then synthesized according to data use intervention type and level of the health system targeted by the intervention. Results The searches yielded 549 articles, of which 102 met our inclusion criteria, including 49 from peer-reviewed journals and 53 from grey literature. A total of 66 articles reported on immunization data use interventions and 36 articles reported on data use interventions for other health sectors. We categorized 68 articles as research evidence and 34 articles as promising strategies . We identified ten primary intervention categories, including electronic immunization registries, which were the most reported intervention type ( n  = 14). Among the research evidence from the immunization sector, 32 articles reported intermediate outcomes related to data quality and availability, data analysis, synthesis, interpretation, and review. Seventeen articles reported data-informed decision-making as an intervention outcome, which could be explained by the lack of consensus around how to define and measure data use. Conclusions Few immunization data use interventions have been rigorously studied or evaluated. The review highlights gaps in the evidence base, which future research and better measures for assessing data use should attempt to address.
A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort
Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis.
Apolipoprotein A-I exchange is impaired in metabolic syndrome patients asymptomatic for diabetes and cardiovascular disease
We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a measure of high-density lipoprotein (HDL) function and a key step in reverse cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients who are asymptomatic for diabetes and cardiovascular disease. We also compared HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports that CEC is enhanced in MetSyn populations. HAE and ABCA1-specific CEC were measured as tests of HDL function in 60 MetSyn patients and 14 normolipidemic control subjects. Predictors of HAE and CEC were evaluated with multiple linear regression modeling using clinical markers of MetSyn and CVD risk. HAE was significantly reduced in MetSyn patients (49.0 ± 10.9% vs. 61.2 ± 6.1%, P < 0.0001), as was ABCA1-specific CEC (10.1 ± 1.6% vs. 12.3 ± 2.0%, P < 0.002). Multiple linear regression analysis identified apoA-I concentration as a significant positive predictor of HAE, and MetSyn patients had significantly lower HAE per mg/dL of apoA-I (P = 0.004). MetSyn status was a negative predictor of CEC, but triglyceride (TG) was a positive predictor of CEC, with MetSyn patients having higher CEC per mg/dL of TG, but lower overall CEC compared to controls. MetSyn patients have impaired HAE that contributes to reduced capacity for ABCA1-mediated CEC. MetSyn status is inversely correlated with CEC but positively correlated with TG, which explains the contradictory results from earlier MetSyn studies focused on CEC. HAE and CEC are inhibited in MetSyn patients over a broad range of absolute apoA-I and HDL particle levels, supporting the observation that this patient population bears significant residual cardiovascular disease risk.
Policy entrepreneurs and structural influence in integrated community case management policymaking in Burkina Faso
Policy entrepreneurs are individuals who attempt to influence the policy process and its outcomes through their opportunistic or incremental actions. Their success in the policy-making process has been associated with the convergence of four factors: behavioural traits; institutional factors; network position and political capital. Policy entrepreneurs have received little study in low-and middleincome country policy research despite observations of individualized decision-making, informal institutions and the unequal distribution and exercise of power in policymaking. This article aims to identify whether policy entrepreneurs were present in the policy process around integrated community case management (iCCM) in Burkina Faso, whether they were successful in achieving policy change, and whether success or failure can be explained using existing policy entrepreneur frameworks from high-income polities. This mixed methods policy study collected data from in-depth qualitative interviews and social network surveys of actors involved in iCCM policymaking [known locally as C-integrated management of childhood illness (IMCI)]; data were analysed based on the framework categories. Interview data pointed to one key individual who played a significant role in the inclusion of pneumonia treatment into the country’s iCCM policy, an issue that had been a point of contention between government policy elites and development partners. Social network data confirmed that this actor was strategically located in the policy network to be able to reach the most other actors and to be able to control the flow of information. Although some development partner actors were as strategically located, none had the same level of authority or trust as was imbued by being a member of the government civil service. The entrepreneur’s mid-level rank in the health ministry may have encouraged him/her to invest political capital and take risks that would not have been feasible or attractive to a more senior actor. This study highlights the convergence of factors needed to be an entrepreneur, as well as the role of development partner actors in creating a facilitating environment.
In Situ Infrared Spectroscopic and Gravimetric Characterisation of the Solvent Removal and Dehydroxylation of the Metal Organic Frameworks UiO-66 and UiO-67
Herein, the desolvation, dehydroxylation and rehydroxylation of the metal organic frameworks UiO-66 and -67 are followed by in situ DRIFTS and TG–DSC. The spectra recorded on UiO-66 feature multiple bands corresponding to chemically inequivalent isolated hydroxyl groups, whereas UiO-67 has the expected single μ3-OH band from the Zr6O4(OH)4 cornerstone. Complete rehydration is demonstrated on both materials. Based on further experimental insights, hypotheses are given to explain the observed differences between UiO-66 and -67. Quantum chemical calculations are employed in order to deduce the feasibility of one possible explanation for the observed behaviour on UiO-66.
Reduced Apolipoprotein Glycosylation in Patients with the Metabolic Syndrome
The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls. Very low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D) gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays. Metabolic syndrome patients differed from healthy controls in the following ways: (1) total plasma--apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL--apoB, apoC3, and apoE were increased; (3) LDL--apoC3 was increased, (4) HDL--associated constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for all). In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001). Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.
Childhood vaccines in Uganda and Zambia: Determinants and barriers to vaccine coverage
Improving childhood vaccine coverage is a priority for global health, but challenging in low and middle-income countries. Although previous research has sought to measure determinants of vaccination, most has limitations. We measure determinants using a clearly-defined hypothetical model, multi-faceted data, and modeling strategy that makes full use of the hypothesis and data. We use linked, cross-sectional survey data from households, health facilities, patients and health offices in Uganda and Zambia, and Bayesian Structural Equation Modeling to quantify the proportion of variance in childhood vaccination that is explained by key determinants, controlling for known confounding. We find evidence that the leading determinant of vaccination is different for different outcomes. For three doses of pentavalent vaccine, intent to vaccinate (on the part of the mother) is the leading driver, but for one dose of the vaccine, community access is a larger factor. For pneumococcal conjugate vaccine, health facility readiness is the leading driver. Considering specifically-modifiable determinants, improvements in cost, facility catchment populations and staffing would be expected to lead to the largest increase in coverage according to the model. This analysis measures vaccination determinants using improved methods over most existing research. It provides evidence that determinants should be approached in the context of relevant outcomes, and evidence of specific determinants that could have the greatest impact in these two countries, if targeted. Future studies should seek to improve our analytic framework, apply it in different settings, and utilize stronger study designs. Programs that focus on a particular determinant should use these results to select an outcome that is appropriate to measure their effectiveness. Vaccination programs in these countries should use our findings to better target interventions and continue progress against vaccine preventable diseases.
Esterified Oxylipins: Do They Matter?
Oxylipins are oxygenated metabolites of fatty acids that share several similar biochemical characteristics and functions to fatty acids including transport and trafficking. Oxylipins are most commonly measured in the non-esterified form which can be found in plasma, free or bound to albumin. The non-esterified form, however, reflects only one of the possible pools of oxylipins and is by far the least abundant circulating form of oxylipins. Further, this fraction cannot reliably be extrapolated to the other, more abundant, esterified pool. In cells too, esterified oxylipins are the most abundant form, but are seldom measured and their potential roles in signaling are not well established. In this review, we examine the current literature on experimental oxylipin measurements to describe the lack in reporting the esterified oxylipin pool. We outline the metabolic and experimental importance of esterified oxylipins using well established roles of fatty acid trafficking in non-esterified fatty acids and in esterified form as components of circulating lipoproteins. Finally, we use mathematical modeling to simulate how exchange between cellular esterified and unesterified pools would affect intracellular signaling.. The explicit inclusion of esterified oxylipins along with the non-esterified pool has the potential to convey a more complete assessment of the metabolic consequences of oxylipin trafficking.