224 research outputs found

    The health disparities cancer collaborative: a case study of practice registry measurement in a quality improvement collaborative

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    <p>Abstract</p> <p>Background</p> <p>Practice registry measurement provides a foundation for quality improvement, but experiences in practice are not widely reported. One setting where practice registry measurement has been implemented is the Health Resources and Services Administration's Health Disparities Cancer Collaborative (HDCC).</p> <p>Methods</p> <p>Using practice registry data from 16 community health centers participating in the HDCC, we determined the completeness of data for screening, follow-up, and treatment measures. We determined the size of the change in cancer care processes that an aggregation of practices has adequate power to detect. We modeled different ways of presenting before/after changes in cancer screening, including count and proportion data at both the individual health center and aggregate collaborative level.</p> <p>Results</p> <p>All participating health centers reported data for cancer screening, but less than a third reported data regarding timely follow-up. For individual cancers, the aggregate HDCC had adequate power to detect a 2 to 3% change in cancer screening, but only had the power to detect a change of 40% or more in the initiation of treatment. Almost every health center (98%) improved cancer screening based upon count data, while fewer (77%) improved cancer screening based upon proportion data. The aggregate collaborative appeared to increase breast, cervical, and colorectal cancer screening rates by 12%, 15%, and 4%, respectively (p < 0.001 for all before/after comparisons). In subgroup analyses, significant changes were detectable among individual health centers less than one-half of the time because of small numbers of events.</p> <p>Conclusions</p> <p>The aggregate HDCC registries had both adequate reporting rates and power to detect significant changes in cancer screening, but not follow-up care. Different measures provided different answers about improvements in cancer screening; more definitive evaluation would require validation of the registries. Limits to the implementation and interpretation of practice registry measurement in the HDCC highlight challenges and opportunities for local and aggregate quality improvement activities.</p

    Climatic regions as an indicator of forest coarse and fine woody debris carbon stocks in the United States

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    <p>Abstract</p> <p>Background</p> <p>Coarse and fine woody debris are substantial forest ecosystem carbon stocks; however, there is a lack of understanding how these detrital carbon stocks vary across forested landscapes. Because forest woody detritus production and decay rates may partially depend on climatic conditions, the accumulation of coarse and fine woody debris carbon stocks in forests may be correlated with climate. This study used a nationwide inventory of coarse and fine woody debris in the United States to examine how these carbon stocks vary by climatic regions and variables.</p> <p>Results</p> <p>Mean coarse and fine woody debris forest carbon stocks vary by KΓΆppen's climatic regions across the United States. The highest carbon stocks were found in regions with cool summers while the lowest carbon stocks were found in arid desert/steppes or temperate humid regions. Coarse and fine woody debris carbon stocks were found to be positively correlated with available moisture and negatively correlated with maximum temperature.</p> <p>Conclusion</p> <p>It was concluded with only medium confidence that coarse and fine woody debris carbon stocks may be at risk of becoming net emitter of carbon under a global climate warming scenario as increases in coarse or fine woody debris production (sinks) may be more than offset by increases in forest woody detritus decay rates (emission). Given the preliminary results of this study and the rather tenuous status of coarse and fine woody debris carbon stocks as either a source or sink of CO<sub>2</sub>, further research is suggested in the areas of forest detritus decay and production.</p

    For which side the bell tolls: The laterality of approach-avoidance associative networks

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    The two hemispheres of the brain appear to play different roles in emotion and/or motivation. A great deal of previous research has examined the valence hypothesis (left hemisphere = positive; right = negative), but an increasing body of work has supported the motivational hypothesis (left hemisphere = approach; right = avoidance) as an alternative. The present investigation (N = 117) sought to provide novel support for the latter perspective. Left versus right hemispheres were briefly activated by neutral lateralized auditory primes. Subsequently, participants categorized approach versus avoidance words as quickly and accurately as possible. Performance in the task revealed that approach-related thoughts were more accessible following left-hemispheric activation, whereas avoidance-related thoughts were more accessible following right-hemispheric activation. The present results are the first to examine such lateralized differences in accessible motivational thoughts, which may underlie more β€œdownstream” manifestations of approach and avoidance motivation such as judgments, decision making, and behavior

    The Main Belt Comets and ice in the Solar System

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    We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

    Operationalizing Appropriate Sepsis Definitions in Children Worldwide: Considerations for the Pediatric Sepsis Definition Taskforce

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    Sepsis is a leading cause of global mortality in children, yet definitions for pediatric sepsis are outdated and lack global applicability and validity. In adults, the Sepsis-3 Definition Taskforce queried databases from high-income countries to develop and validate the criteria. The merit of this definition has been widely acknowledged; however, important considerations about less-resourced and more diverse settings pose challenges to its use globally. To improve applicability and relevance globally, the Pediatric Sepsis Definition Taskforce sought to develop a conceptual framework and rationale of the critical aspects and context-specific factors that must be considered for the optimal operationalization of future pediatric sepsis definitions. It is important to address challenges in developing a set of pediatric sepsis criteria which capture manifestations of illnesses with vastly different etiologies and underlying mechanisms. Ideal criteria need to be unambiguous, and capable of adapting to the different contexts in which children with suspected infections are present around the globe. Additionally, criteria need to facilitate early recognition and timely escalation of treatment to prevent progression and limit life-threatening organ dysfunction. To address these challenges, locally adaptable solutions are required, which permit individualized care based on available resources and the pretest probability of sepsis. This should facilitate affordable diagnostics which support risk stratification and prediction of likely treatment responses, and solutions for locally relevant outcome measures. For this purpose, global collaborative databases need to be established, using minimum variable datasets from routinely collected data. In summary, a "Think globally, act locally" approach is required

    Diversity dynamics in New Caledonia: towards the end of the museum model?

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    <p>Abstract</p> <p>Background</p> <p>The high diversity of New Caledonia has traditionally been seen as a result of its Gondwanan origin, old age and long isolation under stable climatic conditions (the museum model). Under this scenario, we would expect species diversification to follow a constant rate model. Alternatively, if New Caledonia was completely submerged after its breakup from Gondwana, as geological evidence indicates, we would expect species diversification to show a characteristic slowdown over time according to a diversity-dependent model where species accumulation decreases as space is filled.</p> <p>Results</p> <p>We reanalyze available datasets for New Caledonia and reconstruct the phylogenies using standardized methodologies; we use two ultrametrization alternatives; and we take into account phylogenetic uncertainty as well as incomplete taxon sampling when conducting diversification rate constancy tests. Our results indicate that for 8 of the 9 available phylogenies, there is significant evidence for a diversification slowdown. For the youngest group under investigation, the apparent lack of evidence of a significant slowdown could be because we are still observing the early phase of a logistic growth (i.e. the clade may be too young to exhibit a change in diversification rates).</p> <p>Conclusions</p> <p>Our results are consistent with a diversity-dependent model of diversification in New Caledonia. In opposition to the museum model, our results provide additional evidence that original New Caledonian biodiversity was wiped out during the episode of submersion, providing an open and empty space facilitating evolutionary radiations.</p

    The Cryptosporidium parvum Kinome

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    <p>Abstract</p> <p>Background</p> <p>Hundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets and compounds, our study spans the classification of the <it>Cryptosporidium parvum </it>kinome and the structural and biochemical characterization of representatives from the CDPK family and a MAP kinase.</p> <p>Results</p> <p>The <it>C</it>. <it>parvum </it>kinome comprises over 70 members, some of which may be promising drug targets. These <it>C. parvum </it>protein kinases include members in the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35% could only be classified as OPK (other protein kinases). In addition, about 25% of the kinases identified did not have any known orthologues outside of <it>Cryptosporidium spp</it>. Comparison of specific kinases with their <it>Plasmodium falciparum </it>and <it>Toxoplasma gondii </it>orthologues revealed some distinct characteristics within the <it>C. parvum </it>kinome, including potential targets and opportunities for drug design. Structural and biochemical analysis of 4 representatives of the CaMK group and a MAP kinase confirms features that may be exploited in inhibitor design. Indeed, screening <it>Cp</it>CDPK1 against a library of kinase inhibitors yielded a set of the pyrazolopyrimidine derivatives (PP1-derivatives) with IC<sub>50 </sub>values of < 10 nM. The binding of a PP1-derivative is further described by an inhibitor-bound crystal structure of <it>Cp</it>CDPK1. In addition, structural analysis of <it>Cp</it>CDPK4 identified an unprecedented Zn-finger within the CDPK kinase domain that may have implications for its regulation.</p> <p>Conclusions</p> <p>Identification and comparison of the <it>C. parvum </it>protein kinases against other parasitic kinases shows how orthologue- and family-based research can be used to facilitate characterization of promising drug targets and the search for new drugs.</p

    Vascular Dysfunction Induced in Offspring by Maternal Dietary Fat Involves Altered Arterial Polyunsaturated Fatty Acid Biosynthesis

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    Nutrition during development affects risk of future cardiovascular disease. Relatively little is known about whether the amount and type of fat in the maternal diet affect vascular function in the offspring. To investigate this, pregnant and lactating rats were fed either 7%(w/w) or 21%(w/w) fat enriched in either18:2n-6, trans fatty acids, saturated fatty acids, or fish oil. Their offspring were fed 4%(w/w) soybean oil from weaning until day 77. Type and amount of maternal dietary fat altered acetylcholine (ACh)-mediated vaso-relaxation in offspring aortae and mesenteric arteries, contingent on sex. Amount, but not type, of maternal dietary fat altered phenylephrine (Pe)-induced vasoconstriction in these arteries. Maternal 21% fat diet decreased 20:4n-6 concentration in offspring aortae. We investigated the role of Ξ”6 and Ξ”5 desaturases, showing that their inhibition in aortae and mesenteric arteries reduced vasoconstriction, but not vaso-relaxation, and the synthesis of specific pro-constriction eicosanoids. Removal of the aortic endothelium did not alter the effect of inhibition of Ξ”6 and Ξ”5 desaturases on Pe-mediated vasoconstriction. Thus arterial smooth muscle 20:4n-6 biosynthesis de novo appears to be important for Pe-mediated vasoconstriction. Next we studied genes encoding these desaturases, finding that maternal 21% fat reduced Fads2 mRNA expression and increased Fads1 in offspring aortae, indicating dysregulation of 20:4n-6 biosynthesis. Methylation at CpG βˆ’394 bp 5β€² to the Fads2 transcription start site predicted its expression. This locus was hypermethylated in offspring of dams fed 21% fat. Pe treatment of aortae for 10 minutes increased Fads2, but not Fads1, mRNA expression (76%; P<0.05). This suggests that Fads2 may be an immediate early gene in the response of aortae to Pe. Thus both amount and type of maternal dietary fat induce altered regulation of vascular tone in offspring though differential effects on vaso-relaxation, and persistent changes in vasoconstriction via epigenetic processes controlling arterial polyunsaturated fatty acid biosynthesis
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