Multi-ancestry genome-wide association study of asthma exacerbations

Altres ajuts: European Regional Development Fund "ERDF A way of making Europe"; Allergopharma-EAACI award 2021; SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020; Sandler Family Foundation; American Asthma Foundation; RWJF Amos Medical Faculty Development Program; National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117004, R01HL128439, R01HL135156, X01HL134589, R01HL141992, R01HL141845); National Institute of Health and Environmental Health Sciences (R01ES015794, R21ES24844); National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443, R56MD013312); National Institute of General Medical Sciences (NIGMS) (RL5GM118984); Tobacco-Related Disease Research Program (24RT-0025, 27IR-0030); National Human Genome Research Institute (NHGRI) (U01HG009080); GlaxoSmithKline and Utrecht Institute for Pharmaceutical Sciences; Slovenian Research Agency (P3-0067); SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (C3330-16-500106); NHS Research Scotland; Wellcome Trust Biomedical Resource (099177/Z/12/Z); Genotyping National Centre (CeGEN) CeGen-PRB3-ISCIII (AC15/00015); UK Medical Research Council and Wellcome (102215/2/13/2); University of Bristol; Swedish Heart-Lung Foundation, Swedish Research Council; Region Stockholm (ALF project and database maintenance); NHS Chair of Pharmacogenetics via the UK Department of Health; Innovative Medicines Initiative (IMI) (115010); European Federation of Pharmaceutical Industries and Associations (EFPIA); Spanish National Cancer Research Centre; Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC19/17); Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF); U.S. National Institutes of Health (HL07966); European Social Fund "ESF Investing in your future"; Ministerio de Ciencia, Innovación y Universidades; Universidad de La Laguna (ULL); European Academy of Allergy and Clinical Immunology (EAACI); European Respiratory Society (ERS) (LTRF202101-00861); Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012); Singapore Ministry of Education Academic Research Fund; Singapore Immunology Network (SIgN); National Medical Research Council (NMRC Singapore); Biomedical Research Council (BMRC Singapore); Agency for Science Technology and Research (A*STAR Singapore, N-154-000-038-001, R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R-154-000-B99-114, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, SIgN-06-006, SIgN-08-020, NMRC/1150/2008, H17/01/a0/008); Sime Darby Technology Centre; First Resources Ltd; Genting Plantation; Olam International; U.S. National Institutes of Health (HL138098).Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR) = 0.82, p = 9.05 × 10 and replication: OR = 0.89, p = 5.35 × 10) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR = 0.85, p = 3.10 × 10 and replication: OR = 0.89, p = 1.30 × 10). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense

Adherence issues related to sublingual immunotherapy as perceived by allergists

Objectives: Sublingual immunotherapy (SLIT) is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern. The objective of this study was to evaluate the perception by allergists of issues related to SLIT adherence. Methods: We performed a questionnaire-based survey of 296 Italian allergists, based on the adherence issues known from previous studies. The perception of importance of each item was assessed by a VAS scale ranging from 0 to 10. Results: Patient perception of clinical efficacy was considered the most important factor (ranked 1 by 54% of allergists), followed by the possibility of reimbursement (ranked 1 by 34%), and by the absence of side effects (ranked 1 by 21%). Patient education, regular follow-up, and ease of use of SLIT were ranked first by less than 20% of allergists. Conclusion: These findings indicate that clinical efficacy, cost, and side effects are perceived as the major issues influencing patient adherence to SLIT, and that further improvement of adherence is likely to be achieved by improving the patient information provided by prescribers. © 2010 Scurati et al, publisher and licensee Dove Medical Press Ltd

Multiple Traits for People Identification: Face, Ear and Fingerprints

Present biometric systems mostly rely on a single physical or behavioral feature for either identification or verification. However, day to day use of single biometries in massive or uncontrolled scenarios still has several shortcomings. These can be due to complex or unstable hardware settings, to changing environmental conditions or even to immature software procedures: some classification problems are intrinsically hard to solve. Possible spoofing of single biometric features is an additional issue. Last but not least, some features may occasionally lack the requisite of universality. As a consequence, biometric systems based on a single feature often have poor reliability, especially in applications where high security is needed. Multimodal systems, i.e., systems that concurrently exploit multiple features, are a possible way to achieve improved effectiveness and reliability. There are several issues that must be addressed when designing such a system, including the choice of the set of biometric features, the normalization method, the integration schema and the fusion process, and the use of a measure of reliability for each subsystem on a single response basis. This chapter describes the state of the art regarding such issues and sketches some suggestions for future work

On the Usability Evaluation of E-Learning Applications

Despite the advances of the electronic technologies in e-learning, a consolidated evaluation methodology for e-learning applications does not yet exist. The goal of e-learning is to offer the users the possibility to become skillful and acquire knowledge on a new domain. The evaluation of educational software must consider its pedagogic effectiveness as well as its usability. The design of its interface should take into account the way students learn and also provide good usability so that student's interactions with the software are as natural and intuitive as possible. In this paper, we present the results obtained from a first phase of observation and analysis of the interactions of people with e-learning applications. The aim is to provide a methodology for evaluating such applications

Usability of e-learning tools

The new challenge for designers and HCI researchers is to develop software tools for effective e-learning. Learner-Centered Design (LCD) provides guidelines to make new learning domains accessible in an educationally productive manner. A number of new issues have been raised because of the new “vehicle” for education. Effective e-learning systems should include sophisticated and advanced functions, yet their interface should hide their complexity, providing an easy and flexible interaction suited to catch students’ interest. In particular, personalization and integration of learning paths and communication media should be provided. It is first necessary to dwell upon the difference between attributes for platforms (containers) and for educational modules provided by a platform (contents). In both cases, it is hard to go deeply into pedagogical issues of the provided knowledge content. This work is a first step towards identifying specific usability attributes for e-learning systems, capturing the peculiar features of this kind of applications. We report about a preliminary users study involving a group of e-students, observed during their interaction with an e-learning system in a real situation. We then propose to adapt to the e-learning domain the so called SUE (Systematic Usability Evaluation) inspection, providing evaluation patterns able to drive inspectors’ activities in the evaluation of an e-learning tool

An approach to usability evaluation of e-learning applications

Despite recent advances of electronic technologies in e-learning, a consolidated evaluation methodology for e-learning applications is not available. The evaluation of educational software must consider its usability and more in general its accessibility, as well as its didactic effectiveness. This work is a first step towards the definition of a methodology for evaluating e-learning applications. Specific usability attributes capturing the peculiar features of these applications are identified. A preliminary user study involving a group of e-students, observed during their interaction with an e-learning application in a real situation, is reported. Then, the proposal is put forward to adapt to the e-learning domain a methodology for systematic usability evaluation, called SUE. Specifically, evaluation patterns are proposed that are able to drive the evaluators in the analysis of an e-learning application. © Springer-Verlag 2005

Una Proposta di Criteri di Valutazione per l’E-Learning

Nella valutazione dell'usabilità di sistemi per la didattica a distanza, occorre considerare la distinzione tra la piattaforma (il contenitore) e i contenuti. Questi due elementi presentano caratteristiche diverse, anche se qualche volta collegate, che vanno valutate separatamente