Open Government Data: A Focus on Key Economic and Organizational Drivers

Grounding the analysis on multidisciplinary literature on the topic, the existing EU legislation and relevant examples, this working paper aims at highlighting some key economic and organizational aspects of the "Open Government Data" paradigm and its drivers and implications within and outside Public Administrations. The discussion intends to adopt an "Internet Science" perspective, taking into account as enabling factors the digital environment itself, as well as specific models and tools. More "traditional" and mature markets grounded on Public Sector Information are also considered, in order to indirectly detect the main differences with respect to the aforementioned paradig

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Inactivation of class II PI3K-C2 alpha induces leptin resistance, age-dependent insulin resistance and obesity in male mice

AIMS/HYPOTHESIS: While the class I phosphoinositide 3-kinases (PI3Ks) are well-documented positive regulators of metabolism, the involvement of class II PI3K isoforms (PI3K-C2α, -C2β and -C2γ) in metabolic regulation is just emerging. Organismal inactivation of PI3K-C2β increases insulin signalling and sensitivity, whereas PI3K-C2γ inactivation has a negative metabolic impact. In contrast, the role of PI3K-C2α in organismal metabolism remains unexplored. In this study, we investigated whether kinase inactivation of PI3K-C2α affects glucose metabolism in mice. METHODS: We have generated and characterised a mouse line with a constitutive inactivating knock-in (KI) mutation in the kinase domain of the gene encoding PI3K-C2α (Pik3c2a). RESULTS: While homozygosity for kinase-dead PI3K-C2α was embryonic lethal, heterozygous PI3K-C2α KI mice were viable and fertile, with no significant histopathological findings. However, male heterozygous mice showed early onset leptin resistance, with a defect in leptin signalling in the hypothalamus, correlating with a mild, age-dependent obesity, insulin resistance and glucose intolerance. Insulin signalling was unaffected in insulin target tissues of PI3K-C2α KI mice, in contrast to previous reports in which downregulation of PI3K-C2α in cell lines was shown to dampen insulin signalling. Interestingly, no metabolic phenotypes were detected in female PI3K-C2α KI mice at any age. CONCLUSIONS/INTERPRETATION: Our data uncover a sex-dependent role for PI3K-C2α in the modulation of hypothalamic leptin action and systemic glucose homeostasis. ACCESS TO RESEARCH MATERIALS: All reagents are available upon request

Ageing and changes in phosphate transport: clinical implications

Hyperphosphatemia is pivotal in some complications secondary to kidney dysfunction. Current guidelines suggest that hyperphosphatemia secondary to kidney dysfunction develops only when glomerular filtration rate is reduced well below the threshold of 60 ml/min. This paper deals with the relationship of age with serum phosphorus and with the possible influences of this relationship on hyperphosphatemia secondary to kidney dysfunction. A recent epidemiologic study shows that serum phosphorus decreases over time not only in pediatric age but also during adulthood. This decrease differs between men and women: continuous in men, but not in women, because of a transitory serum phosphorus increase during climacterics. Data show also that age-associated differences in serum phosphorus among adults are explained by differences in the maximal phosphorus reabsorption in the renal proximal tubule (TmP/GFR). Other studies suggest that the opposite influences on TmP/GFR of growth hormone (stimulation) and estrogen (inhibition) are the determinants of the age-associated changes in TmP/GFR and serum phosphorus. The decline of serum phosphorus with age leads to the hypothesis that, in the presence of a disorder inducing phosphorus retention, the prevalence of hyperphosphatemia should be higher in young adults than in the elderly because the healthy elderly have lower serum phosphorus. A large clinical study supports this hypothesis showing that hyperphosphatemia secondary to kidney dysfunction is approximately 4 times higher at age 65. Data suggest that the relation between kidney function and serum phosphorus should be reevaluated considering the possible confounding effect of age

Phosphatemia and age: a neglected relation in medical practice

Hyperphosphatemia is pivotal in some complications secondary to kidney dysfunction. Current guidelines suggest that hyperphosphatemia due to kidney dysfunction develops only when kidney function is reduced to 65 years. Data suggest that the relation between kidney function and phosphatemia should be re-evaluated considering possible confounding due to age

Dietary protein, kidney function and mortality: Review of the evidence from epidemiological studies

The World Health Organization recommends a minimum requirement of 0.8 g/day protein/kg ideal weight. Low protein diets are used against kidney failure progression. Efficacy and safety of these diets are uncertain. This paper reviews epidemiological studies about associations of protein intake with kidney function decline and mortality. Three studies investigated these associations; two reported data on mortality. Protein intake averaged >60 g/day and 1.2 g/day/kg ideal weight. An association of baseline protein intake with long-term kidney function decline was absent in the general population and/or persons with normal kidney function but was significantly positive in persons with below-normal kidney function. Independent of kidney function and other confounders, a J-curve relationship was found between baseline protein intake and mortality due to ≈35% mortality excess for non-cardiovascular disease in the lowest quintile of protein intake, a quintile where protein intake averaged <0.8 g/day/kg ideal weight. Altogether, epidemiological evidence suggests that, in patients with reduced kidney function, protein intakes of ≈0.8 g/d/kg ideal weight could limit kidney function decline without adding non-renal risks. Long-term lower protein intake could increase mortality. In most patients, an intake of ≈0.8 g/day/kg would represent a substantial reduction of habitual intake considering that average intake is largely higher

IL CONTROLLO DEL RISCHIO ONCOGENO NEGLI AMBIENTI DI LAVORO. PROPOSTA DI UN PIANO DI SOLUZIONE

FOLIA MEDIC