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aggregate consumption growth.

Objective Patients with rheumatoid arthritis (RA) develop autoantibodies against a spectrum of antigens, but the clinical significance of these autoantibodies is unclear. Using a phenome‐wide association study (PheWAS) approach, we examined the association between autoantibodies and clinical subphenotypes of RA. Methods This study was conducted in a cohort of RA patients identified from the electronic medical records (EMRs) of 2 tertiary care centers. Using a published multiplex bead assay, we measured 36 autoantibodies targeting epitopes implicated in RA. We extracted all International Classification of Diseases, Ninth Revision (ICD‐9) codes for each subject and grouped them into disease categories (PheWAS codes), using a published method. We tested for the association of each autoantibody (grouped by the targeted protein) with PheWAS codes. To determine significant associations (at a false discovery rate [FDR] of ≤0.1), we reviewed the medical records of 50 patients with each PheWAS code to determine positive predictive values (PPVs). Results We studied 1,006 RA patients; the mean ± SD age of the patients was 61.0 ± 12.9 years, and 79.0% were female. A total of 3,568 unique ICD‐9 codes were grouped into 625 PheWAS codes; the 206 PheWAS codes with a prevalence of ≥3% were studied. Using the PheWAS method, we identified 24 significant associations of autoantibodies to epitopes at an FDR of ≤0.1. The associations that were strongest and had the highest PPV for the PheWAS code were autoantibodies against fibronectin and obesity (P = 6.1 × 10−4, PPV 100%), and that between fibrinogen and pneumonopathy (P = 2.7 × 10−4, PPV 96%). Pneumonopathy codes included diagnoses for cryptogenic organizing pneumonia and obliterative bronchiolitis. Conclusion We demonstrated application of a bioinformatics method, the PheWAS, to screen for the clinical significance of RA‐related autoantibodies. Using the PheWAS approach, we identified potentially significant links between variations in the levels of autoantibodies and comorbidities of interest in RA.

Electronic medical records data are valuable resources for discovery research. They contain detailed phenotypic information on individual patients, opening opportunities for simultaneously studying multiple phenotypes. A useful tool for such simultaneous assessment is the phenome-wide association study, which relates a genomic or biological marker of interest to a wide spectrum of disease phenotypes, typically defined by the diagnostic billing codes. One challenge arises when the biomarker of interest is expensive to measure on the entire electronic medical record cohort. Performing phenome-wide association study based on supervised estimation using only subjects who have marker measurements may yield limited power. In this paper, we focus on the setting where the marker is measured on a small fraction of the patients while a few surrogate markers such as historical measurements of the biomarker are available on a large number of patients. We propose an efficient semi-supervised estimation procedure to estimate the covariance between the biomarker and the billing code, leveraging the surrogate marker information. We employ surrogate marker values to impute the missing outcome via a two-step semi-non-parametric approach and demonstrate that our proposed estimator is always more efficient than the supervised counterpart without requiring the imputation model to be correct. We illustrate the proposed procedure by assessing the association between the C-reactive protein and some inflammatory diseases with an electronic medical record study of inflammatory bowel disease performed with the Partners HealthCare electronic medical record database where C-reactive protein was only measured for a small fraction of the patients due to budget constraints.

associé; International audience; Evolutionary economics sees the economy as always in motion with change being driven largely by continuing innovation. This approach to economics, heavily influenced by the work of Joseph Schumpeter, saw a revival as an alternative way of thinking about economic advancement as a result of Richard Nelson and Sidney Winter's seminal book, An Evolutionary Theory of Economic Change, first published in 1982. In this long-awaited follow-up, Nelson is joined by leading figures in the field of evolutionary economics, reviewing in detail how this perspective has been manifest in various areas of economic inquiry where evolutionary economists have been active. Providing the perfect overview for interested economists and social scientists, readers will learn how in each of the diverse fields featured, evolutionary economics has enabled an improved understanding of how and why economic progress occurs. [Résumé de l'éditeur]

Primary care is often thought of as the gateway to improved health outcomes and can lead to more efficient use of health care resources. Because of primary care's cardinal importance, adequate access is an important health policy priority. In densely populated urban areas, spatial access to primary care providers across neighborhoods is poorly understood. We examined spatial variation in primary care access in Philadelphia, Pennsylvania. We calculated ratios of adults per primary care provider for each census tract and included buffer zones based on prespecified drive times around each tract. We found that the average ratio was 1,073; the supply of primary care providers varied widely across census tracts, ranging from 105 to 10,321. We identified six areas of Philadelphia that have much lower spatial accessibility to primary care relative to the rest of the city. After adjustment for sociodemographic and insurance characteristics, the odds of being in a low-access area were twenty-eight times greater for census tracts with a high proportion of African Americans than in tracts with a low proportion of African Americans.

This paper provides supportive evidence to the notion that the division of labour is limited by the extent of the (local) market. We first propose a theoretical model. Its main prediction is that scarce specialists occupations are over-represented in large cities. Using census data for French cities, we find strong empirical support for this prediction.

We develop a Bayesian model for globular clusters composed of multiple stellar populations, extending earlier statistical models for open clusters composed of simple (single) stellar populations (vanDyk et al. 2009, Stein et al. 2013). Specifically, we model globular clusters with two populations that differ in helium abundance. Our model assumes a hierarchical structuring of the parameters in which physical properties---age, metallicity, helium abundance, distance, absorption, and initial mass---are common to (i) the cluster as a whole or to (ii) individual populations within a cluster, or are unique to (iii) individual stars. An adaptive Markov chain Monte Carlo (MCMC) algorithm is devised for model fitting that greatly improves convergence relative to its precursor non-adaptive MCMC algorithm. Our model and computational tools are incorporated into an open-source software suite known as BASE-9. We use numerical studies to demonstrate that our method can recover parameters of two-population clusters, and also show model misspecification can potentially be identified. As a proof of concept, we analyze the two stellar populations of globular cluster NGC 5272 using our model and methods. (BASE-9 is available from GitHub: https://github.com/argiopetech/base/releases)., Comment: 18 pages, 9 figures, 2 tables. To be published in The Astrophysical Journal

Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population and functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. Together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.

Yoshito Okada rozpoczyna od przedstawienia aktualnego stanu gospodarek Japonii i Polski i ich pozycji konkurencyjnej na światowych rynkach. Zwraca między innymi uwagę na wyraźne osłabienie konkurencyjności i innowacyjności japońskiej branży elektroniki użytkowej. Z kolei, w opisie gospodarki polskiej na czoło wysuwają się spostrzeżenia, że znajduje się ona obecnie w fazie przejściowej − od gospodarki o średnim poziomie dochodów do gospodarki kraju wysoko rozwiniętego. Aby to przejście faktycznie nastąpiło, dalszy rozwój nie może obejmować jedynie przemysłu przetwórczego, ale przede wszystkim opierać się na implementacji nowoczesnych technologii. Jest to wyzwanie szczególnie istotne w warunkach zmniejszającej się liczby ludności (spadek liczby urodzeń, emigracja zarobkowa) i „starzenia się” społeczeństwa. Jeśli Polska nie sprosta tym oczekiwaniom, może wpaść w pułapkę pozostania w grupie państw o średnich dochodach, jak stało się to w przypadku niektórych krajów Azji Południowo-Wschodniej. W drugiej części artykułu autor analizuje ewolucję japońskiej strategii inwestowania w naszym kraju. Wspomina, że jeszcze przed przystąpieniem Polski do UE wiele japońskich firm zdecydowało się wybudować tu swoje fabryki (inwestycje typu „green field”), a powstała w ten sposób baza produkcyjna miała stać się przyczółkiem eksportowym do krajów Europy Zachodniej lub Rosji/WNP. Taka polityka znalazła uzasadnienie w niskich kosztach siły roboczej i ogromnych zachętach inwestycyjnych ze strony polskiego państwa. Jakkolwiek rozwój w oparciu o znaczące środki publiczne i niskie koszty pracy jest właściwy dla krajów rozwijających się, stopniowo przestał być adekwatny wraz ze wzrostem jakości życia i towarzyszącym mu wzrostem gospodarczym. Bezpośrednia zmiana strategii inwestycji japońskich w Polsce wiązała się z trzema zjawiskami: (1) wejściem Polski do UE; (2) upadkiem Banku Lehman Brothers i pęknięciem spekulacyjnej bańki wzrostu; (3) upowszechnieniem telewizorów z płaskim ekranem i pojawieniem się koreańskich konkurentów. W czasie globalnego kryzysu ekonomicznego w 2009 r. Polska okazała się jedynym europejskim krajem, który odnotował dodatni wzrost gospodarczy. Ten ostatni fakt dopełnił zmiany w postrzeganiu naszego kraju z tranzytowego na docelowy, jeśli chodzi o japońskie strategie inwestycyjne. Zdaniem Y. Okady, w obecnej sytuacji korzyści ekonomiczne mogą odnieść obie strony, a podwyższenie poziomu technologicznego polskiej gospodarki może z powodzeniem dokonać się z udziałem strony japońskiej. Jest to wniosek z rozważań zawartych w artykule. Oryginalność podejścia polega na wskazaniu, iż współpraca między naszymi krajami to nie tylko duże japońskie BIZ (bezpośrednie inwestycje zagraniczne) w Specjalnych Strefach Ekonomicznych, lecz przede wszystkim kontakty biznesowe i przepływ innowacyjnych technologii między małymi i średnimi przedsiębiorstwami z obu stron. A japońscy partnerzy mają w tej dziedzinie z pewnością bardzo wiele do zaoferowania. The organizers of the conference wish to acknowledge the National Bank of Poland’s generous funding of this publication.

International audience; Cette recherche aide les créateurs de sites web/internet à appliquer la connaissance sur les coûts de recherche de l'information à l'élaboration de sites web/internet qui vendent des produits ou des services au consommateur. Le but de cette recherche est de prédire comment des changements subtils dans la structure de l'interface avec l'utilisateur influencent les coûts de recherche de l'information. Dans une étude empirique, les auteurs comparent 1411 choix faits par des sujets pour accorder leur clientèle à un fournisseur en utilisant des annuaires papier et des annuaires électroniques. Les choix dépendaient des coûts de recherche de l'information imposés par les différents médias. En élaborant une base théorique pour prédire les différences de coûts de recherche de l'information, les auteurs aident les créateurs à rendre leurs sites web/internet plus efficaces pour atteindre leurs objectifs marketing.

We develop a new methodology to estimate the elasticity of urban costs with respect to city population using French house and land price data. After handling a number of estimation concerns, we find that the elasticity of urban costs increases with city population with an estimate of about 0.03 for an urban area with 100,000 inhabitants to 0.08 for an urban area of the size of Paris. Our approach also yields a number of intermediate outputs of independent interest such as the share of housing in expenditure, the elasticity of unit house and land prices with respect to city population, and within-city distance gradients for house and land prices.

International audience; Firms are more productive, on average, in larger cities. Two main explanations have been offered: firm selection (larger cities toughen competition, allowing only the most productive to survive) and agglomeration economies (larger cities promote interactions that increase productivity), possibly reinforced by localized natural advantage. To distinguish between them, we nest a generalized version of a tractable firm selection model and a standard model of agglomeration. Stronger selection in larger cities left-truncates the productivity distribution, whereas stronger agglomeration right-shifts and dilates the distribution. Using this prediction, French establishment-level data, and a new quantile approach, we show that firm selection cannot explain spatial productivity differences. This result holds across sectors, city size thresholds, establishment samples, and area definitions.

D78 ; D81 ; G22 ; G38; In the U.S., flood insurance is provided essentially through the National Flood Insurance Program (NFIP), a public-private program established in 1968. In the past 10 years, the program has radically expanded to cover $1.1 trillion in assets today. This paper provides a detailed analysis of the largest flood insurance sample ever studied by focusing on the state of Florida, which accounts for 40 percent of the entire NFIP portfolio. We study the demand for flood insurance with a database of more than 7.5 million flood policies-in-force for the years 2000-2005, and all the claims filed in Florida during that period. We answer four questions: What are the characteristics of the buyers of flood insurance? What types of contracts (deductibles and coverage levels) are purchased? Where and when are claims paid and to what extent does mitigation work? How are prices determined and how much does NFIP insurance cost? Given the recent significant increase in the cost of catastrophes worldwide and the debate about the role that insurance can play to enhance adaptation to climate change, the responses to these questions shall be of interest to other countries too.