Search

Background Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. Methods After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alte plase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P = 0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P

Bipolar disorder (BD) is a leading cause of worldwide disability among mood disorders. Pathological mechanisms are still vastly unclear, and current treatments with conventional medications are often unsatisfactory in maintaining symptoms control and an adequate quality of life. Consequently, current research is focusing on shedding new light on disease pathogenesis, to improve therapeutic effectiveness. Recent evidence has suggested a prominent role of inflammation in mood disorders. Elevated levels of peripheral proinflammatory mediators have been reported in BD, as well as in other mood disorders, and people with systemic autoimmune diseases have an increased risk of developing BD. These immunological alterations are stable, and current medications are unable to alter peripheral concentrations even when clinical improvement is evident. These findings have also been replicated in the central nervous system (CNS) milieu, whereas genetic studies have shown that these immune alterations are not due to the disorder itself, being detectable before the illness onset. Moreover, these inflammatory modifications seem to be affected by and linked to other biomarkers of the disorder, such as alterations of white matter (WM) microstructure, metabolism, kynurenine pathway, and circadian rhythmicity. Finally, these immune variations seem to be useful as predictors of therapeutic responsiveness to medications, and in discriminating between clinically different outcomes. The objective of this review is to summarize available evidence on the connection between inflammation and BD, focusing on peripheral inflammatory markers and recent findings on their connection with other typical features of BD, to outline a general overview of the disorder. Moreover, it is meant to analyze the issues with data gathering and interpretation, given the partially contradictory and inconsistent nature of results.

Sampling a rare and clustered trait in a finite population is challenging: traditional sampling designs usually require a large sample size in order to obtain reasonably accurate estimates, resulting in a considerable investment of resources infront of the detection of a small number of cases. A notable example is the case of WHO’s tubercoulosis (TB) prevalence surveys, crucial for countries that bear a high TB burden, the prevalence of cases being still less than 1%. In the latest WHO guidelines, spatial patterns are not explicitly accounted for, with the risk of missing a large number of cases; moreover, cost and logistic constraints can pose further problems. After reviewing the methodology in use by WHO, the use of adaptive and sequential approaches is discussed as natural alternatives to overcome the limitations of the current practice. A small simulation study is presented to highlight possible advantages and limitations of these alternatives, and an integrated approach, combining both adaptive and sequential features in a single sampling strategy is discussed as a promising methodological perspective.

In this paper we focus on finding clusters of multidimensional curves with spatio-temporal structure, applying a variant of a k-means algorithm based on the principal component rotation of data. The main advantage of this approach is to combine the clustering functional analysis of the multidimensional data, with smoothing methods based on generalized additive models, that cope with both the spatial and the temporal variability, and with functional principal components that takes into account the dependency between the curves.

Changing environmental conditions, the demographic trends and the consequent increase of mobility demand lead us to consider a new integrated mobility model that is able to guarantee efficient management of traffic flows, reduction of accidents and consumption, and improvements in driving and travel comfort. Accurate localization, vehicular connectivity and communication, as well as cybersecurity, will play a key role for development of future Cooperative and Intelligent Transportation Systems (C-ITS). This work presents research activities underway at the University of L' Aquila and the Radiolabs Consortium, concerning the study of techniques and technologies for secure communication and accurate geo-localization, the design and prototype implementation of management architectures and vehicle platforms, the development of dynamic and cooperative navigation services. These activities also aim to support future services in the ITS field, with a particular focus on mobility of commercial vehicles, both in normal and emergency operating conditions. Distinctive elements of this work are the identification and the services implementation of real use cases, supported by the new GALILEO satellite constellation, currently available communication technologies (V2X/4G), and the emerging 5G.