El angioedema hereditario: estudio genético de la población española y análisis funcionales en pacientes homocigotos para la deficiencia de C1 inhibidor

Tesis doctoral inédita realizada en la Universidad Autónoma de Madrid. Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 29 de Noviembre de 2010

A firm-level analysis of differences between adopters and non-adopters of ICT

Information and Communication Technologies investments have drastically modified the competitive markets due to the impact on firm performance and productivity. This paper aims to analyse the differences between ICT adopter firms and non-adopter firms. OLS regressions and ordered logit models provide the methodological approach. From data based on a questionnaire survey to 327 Spanish firms in 2002, the empirical results indicate the essential role played by some variables in the ICT adoption. The results confirm, for example, the influence of variables such as firm size. The role of human capital and competitive strategies based on product and service quality are relevant in ICT adoption. The paper is organised as follows. First, the section 1 introduces the paper. The section 2 provides the establishment and explanation of the theoretical hypotheses. This section is followed in the section 3 by the methodology adopted in this study, including both the model and the data sources employed in the estimations. Some basic statistics and the results of the model estimations are presented and interpreted in the penultimate section, before concluding the paper with some remarks on the findings and important implications in the ICT adoption

Autoantibodies against perilipin 1 as a cause of acquired generalized lipodystrophy

Acquired generalized lipodystrophy (AGL) is a rare condition characterized by an altered distribution of adipose tissue and predisposition to develop hepatic steatosis and fibrosis, diabetes, and hypertriglyceridemia. Diagnosis of AGL is based on the observation of generalized fat loss, autoimmunity and lack of family history of lipodystrophy. The pathogenic mechanism of fat destruction remains unknown but evidences suggest an autoimmune origin. Anti-adipocyte antibodies have been previously reported in patients with AGL, although their involvement in the pathogenesis has been poorly studied and the autoantibody target/s remain/s to be identified. Using a combination of immunochemical and cellular studies, we investigated the presence of anti-adipocyte autoantibodies in patients with AGL, acquired partial lipodystrophy, localized lipoatrophy due to intradermic insulin injections or systemic lupus erythematosus. Moreover, the impact of anti-adipocyte autoantibodies from AGL patients was assessed in cultured mouse preadipocytes. Following this approach, we identified anti-perilipin 1 IgG autoantibodies in the serum of patients with autoimmune variety-AGL, but in no other lipodystrophies tested. These autoantibodies altered the ability of perilipin 1 to regulate lipolysis in cultured preadipocytes causing abnormal, significantly elevated basal lipolysis. Our data provide strong support for the conclusion that perilipin 1 autoantibodies are a cause of generalized lipodystrophy in these patientsFC, ML-T, AL-L, and SG were supported by grants PI15- 00255 from Instituto de Salud Carlos III (ISCIII, Ministerio de Economía y Competitividad) and Fondos FEDER, Complemento II-CM network (B2017/BMD3673), Acciones Cooperativas y Complementarias Intramurales (ACCI) from CIBERER (ISCIII), and Fundación SENEFRO. MdMwas supported by Roche Farma SA and Foundation Domingo Martínez. VA was financed by Consejería de Educación, Juventud y Deporte of Comunidad de Madrid and by Fondo Social Europeo (Programa Operativo de Empleo Juvenil, and Iniciativa de Empleo Juvenil (YEI), (PEJ15/BIO/AI/0045). DA-V was supported by the intramural research program of the Xunta de Galicia (Programa de Consolidación e Estructuración de Unidades de Investigación Competitivas, grant ED341b 2017/19), by the Instituto de Salud Carlos III (grant number: PI08-1449) and the European Regional Development Fund, FEDER and by the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP

Perceived performance effects of ICT in manufacturing SMEs

Purpose. We aim to investigate whether ICT resources, including investment and use of specific types of ICT as well as innovative work practices, have a positive impact on several dimensions of firm performance, taking into account both direct and indirect effects and both short and long-term effects. Design/methodology/approach. An empirical study using data from a sample of 267 Spanish manufacturing SMEs was conducted. We have used path analysis to study direct and indirect ICT impacts. OLS regression is the estimation method employed. Findings. Our findings show a positive relationship between ICT adoption and all the measures of perceived performance analyzed, although the impact is not always immediate since the lag effects and length differ according to the type of ICT. Managers’ perceptions of ICT impact are related to the adoption of new work practices but the effects also depend positively on the number of years since new work practices were implemented. ICT impact on final performance (market share and profits and margin) takes place mainly indirectly through the improvement of internal and external communication as well as through operational performance. Originality/value. This research extends the scope of the analysis of ICT payoff literature by analyzing direct and indirect effects and by focusing on a broad range of technologies, a variety of performance measures and several time lags to study ICT adoption impacts in SMEs. Research limitations/implications. The main limitations of the research stem from the specific geographical context under consideration and restrictions relating to the cross-sectional nature of the data. Practical implications. Our results reveal the wide scope of the benefits of ICT adoption in SMEs and point to the need for persistence in use so as to obtain good results in some areas. They also stress the positive effects of adopting ICTs together with organizational innovation

Immunological features of patients affected by Barraquer-Simons syndrome

Background: C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells. Results: C3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti- FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% allelic frequency in the general population). Conclusions: Our results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.This work was supported by Instituto de Salud Carlos III (Ministerio de Ciencia, Innovación y Universidades, Gobierno de España) and Fondos FEDER (PI15–00255 to M.L-T. and PI08–1449 to D.A-V.), Complemento II-CM network (B2017/BMD3673 to M.L-T), the intramural research program of the Xunta de Galicia (Programa de Consolidación e Estructuración de Unidades de Investigación Competitivas, grant ED341b 2017/19 to D.A-V.), the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP) (to D.A-V., to F.C. and to P.N.

Effectiveness of a transdiagnostic internet-based protocol for the treatment of emotional disorders versus treatment as usual in specialized care: study protocol for a randomized controlled trial

Background Emotional disorders (depression and anxiety disorders) are highly prevalent mental health problems. Although evidence showing the effectiveness of disorder-specific treatments exists, high comorbidity rates among emotional disorders limit the utility of these protocols. This has led some researchers to focus their interest on transdiagnostic interventions, a treatment perspective that might be more widely effective across these disorders. Also, the current way of delivering treatments makes it difficult provide assistance to all of the population in need. The use of the Internet in the delivery of evidence-based treatments may help to disseminate treatments among the population. In this study, we aim to test the effectiveness of EmotionRegulation, a new transdiagnostic Internet-based protocol for unipolar mood disorders, five anxiety disorders (panic disorder, agoraphobia, social anxiety disorder, generalized anxiety disorder and anxiety disorder not otherwise specified), and obsessive-compulsive disorder in comparison to treatment as usual as provided in Spanish public specialized mental health care. We will also study its potential impact on basic temperament dimensions (neuroticism/behavioral inhibition and extraversion/behavioral activation). Expectations and opinions of patients about this protocol will also be studied. Methods/Design The study is a randomized controlled trial. 200 participants recruited in specialized care will be allocated to one of two treatment conditions: a) EmotionRegulation or b) treatment as usual. Primary outcome measures will be the BAI and the BDI-II. Secondary outcomes will include a specific measure of the principal disorder, and measures of neuroticism/behavioral inhibition and extraversion/behavioral activation. Patients will be assessed at baseline, post-treatment, and 3- and 12-month follow-ups. Intention to treat and per protocol analyses will be performed. Discussion Although the effectiveness of face-to-face transdiagnostic protocols has been investigated in previous studies, the number of published transdiagnostic Internet-based programs is still quite low. To our knowledge, this is the first randomized controlled trial studying the effectiveness of a transdiagnostic Internet-based treatment for several emotional disorders in public specialized care. Combining both a transdiagnostic approach with an Internet-based therapy format may help to decrease the burden of mental disorders, reducing the difficulties associated with disorder-specific treatments and facilitating access to people in need of treatment. Strengths and limitations are discussed

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research