University of Siena

About: University of Siena is a education organization based out in Siena, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 12179 authors who have published 33334 publications receiving 1008287 citations. The organization is also known as: Università degli studi di Siena & Universita degli studi di Siena.

Testing the Robustness of the Likelihood-Ratio Test in a Variance-Component Quantitative-Trait Loci–Mapping Procedure

Abstract: Detection of linkage to genes for quantitative traits remains a challenging task. Recently, variance components (VC) techniques have emerged as among the more powerful of available methods. As often implemented, such techniques require assumptions about the phenotypic distribution. Usually, multivariate normality is assumed. However, several factors may lead to markedly nonnormal phenotypic data, including (a) the presence of a major gene (not necessarily linked to the markers under study), (b) some types of gene x environment interaction, (c) use of a dichotomous phenotype (i.e., affected vs. unaffected), (d) nonnormality of the population within-genotype (residual) distribution, and (e) selective (extreme) sampling. Using simulation, we have investigated, for sib-pair studies, the robustness of the likelihood-ratio test for a VC quantitative-trait locus-detection procedure to violations of normality that are due to these factors. Results showed (a) that some types of nonnormality, such as leptokurtosis, produced type I error rates in excess of the nominal, or alpha, levels whereas others did not; and (b) that the degree of type I error-rate inflation appears to be directly related to the residual sibling correlation. Potential solutions to this problem are discussed. Investigators contemplating use of this VC procedure are encouraged to provide evidence that their trait data are normally distributed, to employ a procedure that allows for nonnormal data, or to consider implementation of permutation tests.

Emulation, Inequality, and Work Hours: Was Thorsten Veblen Right?

Abstract: We investigate the manner in which a desire to emulate the rich influences individuals allocation of time between labour and leisure, greater inequality inducing longer work hours as a result. Data on work hours in ten countries over the period 1963‐98 show that greater inequality is indeed associated longer work hours. These Veblen effects are large and the estimates are robust using country fixed effects and other specifications. Because consumption inequality is a public bad, a social welfare optimum cannot be implemented by a flat tax on consumption but may be accomplished by more complicated (progressive) consumption taxes. At the close of the nineteenth century, Thorsten Veblen proposed what he termed pecuniary emulation as the foundation of a theory of consumption. Spending, he maintained, is driven by relative status considerations, that is by the desire to be a particular type of person as much as bythedesire to enjoytheconsumer goodsper se. The Joneses, with whom one had to keep up, were not the neighbours but the rich; theirleveloflivingbecamethenever-attainableobjectiveinaconsumptionarmsrace among the less well-to-do. In The Theory of the Leisure Class, he wrote: The motive is emulation ‐ the stimulus of an invidious comparison ... especially in any community in which class distinctions are quite vague, all canons and reputability and decency and all standards of consumption are traced back by insensible gradations to the usages and thoughts of the highest social and pecuniary class, the wealthy leisure class. (1934, p. 81). While valued by some economists as capturing common-sense aspects of consumption as a form of status seeking, Veblen’s view of social preferences was soon eclipsed by the simpler and more tractable neoclassical theory of the consumer. Relegated to the underworld of economics, Veblen’s ideas have nonetheless resonated over the ensuing years in the writing of Duesenberry (1949), Leibenstein (1950) and Galbraith (1958) at the middle of the past century and Schor (1998)

International consensus statement on allergy and rhinology: rhinosinusitis 2021

Abstract: I. Executive summary BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. Methods ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. Conclusion This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.

In Vivo Emergence of Colistin Resistance in Klebsiella pneumoniae Producing KPC-Type Carbapenemases Mediated by Insertional Inactivation of the PhoQ/PhoP mgrB Regulator

Abstract: Colistin is one of the few agents that retain activity against extensively drug-resistant strains of Klebsiella pneumoniae producing KPC-type carbapenemases (KPC-KP). However, resistance to colistin is increasingly reported among KPC-KP. Comparative genomic analysis of a pair of sequential KPC-KP isolates from the same patient including a colistin-susceptible isolate (KKBO-1) and a colistin-resistant isolate (KKBO-4) selected after colistin exposure revealed that insertional inactivation of the mgrB gene, encoding a negative regulator of the PhoQ/PhoP signaling system, is a genetic mechanism for acquired colistin resistance. The role of mgrB inactivation in acquired colistin resistance was confirmed by complementation experiments with wild-type mgrB, which restored colistin susceptibility in KKBO-4, and by construction of an mgrB deletion mutant from KKBO-1, which exhibited a colistin-resistant phenotype. Insertional mgrB inactivation was also detected in 60% of colistin-resistant mutants selected from KKBO-1 in vitro, following plating on colistin-containing medium, confirming the role (although not unique) of this mechanism in the emergence of acquired colistin resistance. In colistin-resistant mutants carrying insertional inactivation or deletion of the mgrB gene, upregulated transcription of phoP, phoQ, and pmrK (which is part of the pmrHFIJKLM operon) was detected. These findings confirmed the MgrB regulatory role in K. pneumoniae and were in agreement with the known association between upregulation of the PhoQ/PhoP system and activation of the pmrHFIJKLM operon, which eventually leads to resistance to polymyxins by modification of the lipopolysaccharide target.