Mapping spaces in Quasi-categories

We apply the Dwyer-Kan theory of homotopy function complexes in model categories to the study of mapping spaces in quasi-categories. Using this, together with our work on rigidification from [DS1], we give a streamlined proof of the Quillen equivalence between quasi-categories and simplicial categories. Some useful material about relative mapping spaces in quasi-categories is developed along the way

Rigidification of quasi-categories

We give a new construction for rigidifying a quasi-category into a simplicial category, and prove that it is weakly equivalent to the rigidification given by Lurie. Our construction comes from the use of necklaces, which are simplicial sets obtained by stringing simplices together. As an application of these methods, we use our model to reprove some basic facts from Lurie's "Higher Topos Theory" regarding the rigidification process.Comment: 26 page

Developing predictive models of health literacy.

IntroductionLow health literacy (LHL) remains a formidable barrier to improving health care quality and outcomes. Given the lack of precision of single demographic characteristics to predict health literacy, and the administrative burden and inability of existing health literacy measures to estimate health literacy at a population level, LHL is largely unaddressed in public health and clinical practice. To help overcome these limitations, we developed two models to estimate health literacy.MethodsWe analyzed data from the 2003 National Assessment of Adult Literacy (NAAL), using linear regression to predict mean health literacy scores and probit regression to predict the probability of an individual having 'above basic' proficiency. Predictors included gender, age, race/ethnicity, educational attainment, poverty status, marital status, language spoken in the home, metropolitan statistical area (MSA) and length of time in U.S.ResultsAll variables except MSA were statistically significant, with lower educational attainment being the strongest predictor. Our linear regression model and the probit model accounted for about 30% and 21% of the variance in health literacy scores, respectively, nearly twice as much as the variance accounted for by either education or poverty alone.ConclusionsMultivariable models permit a more accurate estimation of health literacy than single predictors. Further, such models can be applied to readily available administrative or census data to produce estimates of average health literacy and identify communities that would benefit most from appropriate, targeted interventions in the clinical setting to address poor quality care and outcomes related to LHL

Advancing functional connectivity research from association to causation

Cognition and behavior emerge from brain network interactions, such that investigating causal interactions should be central to the study of brain function. Approaches that characterize statistical associations among neural time series-functional connectivity (FC) methods-are likely a good starting point for estimating brain network interactions. Yet only a subset of FC methods ('effective connectivity') is explicitly designed to infer causal interactions from statistical associations. Here we incorporate best practices from diverse areas of FC research to illustrate how FC methods can be refined to improve inferences about neural mechanisms, with properties of causal neural interactions as a common ontology to facilitate cumulative progress across FC approaches. We further demonstrate how the most common FC measures (correlation and coherence) reduce the set of likely causal models, facilitating causal inferences despite major limitations. Alternative FC measures are suggested to immediately start improving causal inferences beyond these common FC measures

Functional characterization of a melon alcohol acyl-transferase gene family involved in the biosynthesis of ester volatiles. Identification of the crucial role of a threonine residue for enzyme activity

Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT). We demonstrate here that, in Charentais melon (Cucumis melo var. cantalupensis), AAT are encoded by a gene family of at least four members with amino acid identity ranging from 84% (Cm-AAT1/Cm-AAT2) and 58% (Cm-AAT1/Cm-AAT3) to only 22% (Cm-AAT1/Cm-AAT4). All encoded proteins, except Cm-AAT2, were enzymatically active upon expression in yeast and show differential substrate preferences. Cm-AAT1 protein produces a wide range of short and long-chain acyl esters but has strong preference for the formation of E-2-hexenyl acetate and hexyl hexanoate. Cm-AAT3 also accepts a wide range of substrates but with very strong preference for producing benzyl acetate. Cm-AAT4 is almost exclusively devoted to the formation of acetates, with strong preference for cinnamoyl acetate. Site directed mutagenesis demonstrated that the failure of Cm-AAT2 to produce volatile esters is related to the presence of a 268-alanine residue instead of threonine as in all active AAT proteins. Mutating 268-A into 268-T of Cm-AAT2 restored enzyme activity, while mutating 268-T into 268-A abolished activity of Cm-AAT1. Activities of all three proteins measured with the prefered substrates sharply increase during fruit ripening. The expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. The data presented in this work suggest that the multiplicity of AAT genes accounts for the great diversity of esters formed in melon

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

<b>Objective</b> <i>ABCB1</i> encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).<p></p> <b>Methods</b> The best candidates from fine-mapping analysis of 21 <i>ABCB1</i> SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.<p></p> <b>Result</b> Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, <i>ABCB1</i> expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.<p></p> <b>Conclusion</b> Our study represents the largest analysis of <i>ABCB1</i> SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.<p></p&gt

Pooled analysis of the association of PTGS2 rs5275 polymorphism and NSAID use with invasive ovarian carcinoma risk

Inflammation is postulated to play an important role in ovarian carcinogenesis. Prostaglandin endoperoxide synthase 2 (PTGS2) is responsible for the conversion of arachidonic acid to prostaglandins in response to inflammation. We examined the association of the PTGS2 rs5275 polymorphism with the risk of invasive ovarian carcinoma and the joint effect of rs5275 and use of nonsteroidal antiinflammatory drugs (NSAIDs) on risk in a pooled analysis of two population-based studies, the Hawaii Ovarian Cancer Case-Control Study and the New England Case-Control Study, including 1025 women with invasive ovarian carcinoma and 1687 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. In the pooled analysis, the CC genotype was associated with a reduced risk of nonserous ovarian carcinoma (OR=0.66; CI: 0.44-0.98). In addition, the lowest risk was observed among carriers of the CC genotype who were users of nonaspirin NSAIDs (OR=0.43; CI:0.20-0.93) in all women combined. The association of PTGS2 rs5275 with nonserous ovarian carcinoma and possible effect modification by NSAID use needs further validation, preferably in the prospective studies