University of Pavia

About: University of Pavia is a education organization based out in Pavia, Italy. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 21173 authors who have published 52524 publications receiving 1610492 citations. The organization is also known as: Università degli Studi di Pavia & Università di Pavia.

The Wiskott-Aldrich syndrome.

Abstract: In 1936-1937, Alfred A. Wiskott (1898-1978) envisioned as a \"famili~irer, angeborener Morbus Werlhofii?\" [familial congenital form of Werlhof's disease], the autonomy of the clinical triad constituted by (1) hemorrhages caused by thrombocytopenia or thrombocytopathia, (2) susceptibility to infections attributable to apparently primary (or congenital) anergy (or resistance deficit), and (3) eczema [3]. Wiskott's report referred to three brothers (who had four healthy sisters) and was the first complete description (ahead of its time) of the Wiskott-Aldrich syndrome. The incidence of the syndrome among male patients had not gone unnoticed, although sex-linked recessive heredity had not been pointed out; Wiskott had in fact surmised that one paternal cousin was also slightly affected by the same condition. Actually, in 1937, some of the groundwork for recognition of the sex-linked recessive heredity of certain diseases (especially hemophilia and color blindness) was already long established, but this was not demonstrated for the triad described by Wiskott until 1954, when Robert A. Aldrich (born in 1917), unaware of Wiskott's observations 18 years earlier, published a \"Pedigree demonstrating a sex linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea\" [1]. Several studies on the \"Aldrich syndrome\" began at that time in Europe and in the US. The condition came to be known as \"WiskottAldrich syndrome\" on the suggestion of Lenz and as a consequence of a A. A. Wiskott R.A. Aldrich

Multinational evidence-based recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative

Abstract: We aimed to develop evidence-based multinational recommendations for the diagnosis and management of gout. Using a formal voting process, a panel of 78 international rheumatologists developed 10 key clinical questions pertinent to the diagnosis and management of gout. Each question was investigated with a systematic literature review. Medline, Embase, Cochrane CENTRAL and abstracts from 2010–2011 European League Against Rheumatism and American College of Rheumatology meetings were searched in each review. Relevant studies were independently reviewed by two individuals for data extraction and synthesis and risk of bias assessment. Using this evidence, rheumatologists from 14 countries (Europe, South America and Australasia) developed national recommendations. After rounds of discussion and voting, multinational recommendations were formulated. Each recommendation was graded according to the level of evidence. Agreement and potential impact on clinical practice were assessed. Combining evidence and clinical expertise, 10 recommendations were produced. One recommendation referred to the diagnosis of gout, two referred to cardiovascular and renal comorbidities, six focused on different aspects of the management of gout (including drug treatment and monitoring), and the last recommendation referred to the management of asymptomatic hyperuricaemia. The level of agreement with the recommendations ranged from 8.1 to 9.2 (mean 8.7) on a 1–10 scale, with 10 representing full agreement. Ten recommendations on the diagnosis and management of gout were established. They are evidence-based and supported by a large panel of rheumatologists from 14 countries, enhancing their utility in clinical practice.

Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species

Abstract: TAR DNA-binding protein (TDP-43, also known as TARDBP) is the major pathological protein in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Large TDP-43 aggregates that are decorated with degradation adaptor proteins are seen in the cytoplasm of remaining neurons in ALS and FTD patients post mortem. TDP-43 accumulation and ALS-linked mutations within degradation pathways implicate failed TDP-43 clearance as a primary disease mechanism. Here, we report the differing roles of the ubiquitin proteasome system (UPS) and autophagy in the clearance of TDP-43. We have investigated the effects of inhibitors of the UPS and autophagy on the degradation, localisation and mobility of soluble and insoluble TDP-43. We find that soluble TDP-43 is degraded primarily by the UPS, whereas the clearance of aggregated TDP-43 requires autophagy. Cellular macroaggregates, which recapitulate many of the pathological features of the aggregates in patients, are reversible when both the UPS and autophagy are functional. Their clearance involves the autophagic removal of oligomeric TDP-43. We speculate that, in addition to an age-related decline in pathway activity, a second hit in either the UPS or the autophagy pathway drives the accumulation of TDP-43 in ALS and FTD. Therapies for clearing excess TDP-43 should therefore target a combination of these pathways.

Models beyond the Dirichlet process

Abstract: Bayesian nonparametric inference is a relatively young area of research and it has recently undergone a strong development. Most of its success can be explained by the considerable degree of exibility it ensures in statistical modelling, if compared to parametric alternatives, and by the emergence of new and ecient simulation techniques that make nonparametric models amenable to concrete use in a number of applied statistical problems. Since its introduction in 1973 by T.S. Ferguson, the Dirichlet process has emerged as a cornerstone in Bayesian nonparametrics. Nonetheless, in some cases of interest for statistical applications the Dirichlet process is not an adequate prior choice and alternative nonparametric models need to be devised. In this paper we provide a review of Bayesian nonparametric models that go beyond the Dirichlet process.