Circuit Based Quantification: Back to State Set Manipulation within Unbounded Model Checking

In this paper a non-canonical circuit-based state set representation is used to efficiently perform quantifier elimination. The novelty of this approach lies in adapting equivalence checking and logic synthesis techniques, to the goal of compacting circuit based state set representations resulting from existential quantification. The method can be efficiently combined with other verification approaches such as inductive and SAT-based pre-image verifications

Multicultural Interdisciplinary Handbook: tools for learning history and geography in a multicultural perspective (MIH)

[ES] MIH project (Multicultural Interdisciplinary Handbook: tools for learning History and Geography in a multicultural perspective) is a Comenius Multilateral Project funded with support from the European Commission that has been developed from 2009 to 2011.Conceived from the idea of educating lower and upper Secondary School pupils in a process of construction of a European identity by involving them in the culture of other countries, MIH project meets this need by providing new methodological and ICT tools that could help teachers and pupils to plunge deeper into both cultures and languages of another nations via their History and Geography, and opens the way to introduce a European perspective in History and Geography school curricula and classroom activities

Intercultural Education through Religious Studies (IERS): COMENIUS Multilateral project

[EN] Religious and cultural diversity are today more than ever a critical and political challenge as the recent emergencies related to geo-political and economical global transformations clearly show. European countries are concerned by a big immigration flow that demands an educational effort in order to foster the mutual understanding and integration. According to Toledo guiding principles, IERS project meets the needs of an innovative approach in teaching about religions and beliefs at school by providing teachers of humanistic disciplines with new tools that help teachers and pupils to plunge deeper into religions and cultures of non-european countries, as well as raising the knowledge of the religious traditions that contributed to the common European cultural Identity, promoting it in the best way suited for encourage intra -and extra- European cultural dialogue attitudes. The Project aims to support the development of social, civic and intercultural transversal key competences by educating towards a positive understanding of cultural and religious differences, a readiness to engage in dialogue and to avoid or manage conflicts. By encouraging teachers and pupils to expose themselves to the differences and commonalities of religious topics, it promotes also the values of democracy, equality and human rights as it deals with social and civic dimensions of both intercultural and interreligious dialogue. The project will involve high school in-service teachers by developing a complete set of didactical tools and training experiences. The results will be: 1. A baseline study which analyzes the actual situation of teaching about religions throughout Europe; 2. New innovative didactic tools such as Multimedia Digital Modules to be used in classroom activities, accompanied by a Handbook with didactical guidelines for teachers. 3. Teacher support activities (virtual community, training activities, developing of didactical projects to apply in classroom)

Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center

<p>Abstract</p> <p>Background</p> <p>To evaluate the therapeutic strategies commonly employed in the clinic for the management of brain metastases (BMs) and to correlate disease outcome with type of treatment and therapeutic resources available at the treating center.</p> <p>Methods</p> <p>Four Cancer centres participated to the survey. Data were collected through a questionnaire filled in by one physician for each centre.</p> <p>Results</p> <p>Clinical data regarding 290 cancer patients with BMs from solid tumors were collected. Median age was 59 and 59% of patients had ≤ 3 brain metastases. A local approach (surgery and stereotactic radiosurgery) was adopted in 31% of patients. The local approach demonstrated to be superior in terms of survival compared to the regional/systemic approach (whole brain radiotherapy and chemotherapy, p = <.0001 for survival at 2 years). In the multivariate analysis local treatment was an independent prognostic factor for survival. When patients were divided into 2 groups whether they were treated in centers where local approaches were available or not (group A vs group B respectively, 58% of patients with ≤ 3 BMs in both cohorts), more patients in group A received local strategies although no difference in time to brain progression at 1 year was observed between the two groups of patients.</p> <p>Conclusions</p> <p>In clinical practice, local strategies should be integrated in the management of brain metastases. Proper selection of patients who are candidate to local treatments is of crucial importance.</p

Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status

INTRODUCTION: To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse. METHODS: The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR. RESULTS: The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007–0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51–101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97–12.84; P = 0.001) were independent predictive factors for CNS relapse. CONCLUSION: CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis

Importance: Meropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, setting, and participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main outcomes and measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial registration: ClinicalTrials.gov Identifier: NCT03452839

Ultraluminous X-ray Sources in the Chandra and XMM-Newton Era

Ultraluminous X-ray sources (ULXs) are accreting black holes that may contain the missing population of intermediate mass black holes or reflect super-Eddington accretion physics. Ten years of Chandra and XMM-Newton observations of ULXs, integrated by multiband studies of their counterparts, have produced a wealth of observational data and phenomenological classifications. We review the properties of their host galaxies, list popular spectral models and implications for standard and supercritical accretion physics, demonstrate how X-ray timing of these objects places constraints on their masses. We also review multiwavelength studies of ULXs, including the optical emission of the binary system and nebulosity around them. We summarize that three classes of black holes could power ULXs: normal stellar mass black holes (~10 solar masses), massive stellar black holes (~< 100 solar masses), and intermediate mass black holes (10^2 - 10^4 solar masses). We collect evidence for the presence of these three types of compact objects, including caveat of each interpretation, and briefly review their formation processes.Comment: Solicited review in New Astronomy Reviews. v2: final version for publication, 21 pages, 5 figures, references added, small revisions made, thanks to many colleagues for useful comment