Statistical analysis of inter-arrival times of rainfall events for Italian Sub-Alpine and Mediterranean areas

Abstract. In this work a set of time-series of inter-arrival times of rainfall events, at daily scale, was analysed, with the aim to verify the issue of increasing duration of dry periods. The set consists of 12 time-series recorded at rain gauges in 1926–2005, six of them belong to an Italian Sub-Alpine area (Piedmont) and six to a Mediterranean one (Sicily). In order to overcome the problem related to limited sample size for high values of inter-arrival times, the discrete probability polylog-series distribution was used to fit the empirical data from partial (20 yr) time-series. Moreover, a simple qualitative trend analysis was applied to some high quantiles of inter-arrival times as well as to the average extent of rain clusters. The preliminary analysis seems to confirm the issue of increasing duration of dry periods for both environments, which is limited to the ''cold'' season

Association Between Plasma Monocyte Chemoattractant Protein-1 Concentration and Cardiovascular Disease Mortality in Middle-Aged Diabetic and Nondiabetic Individuals

OBJECTIVE Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine involved into the pathogenesis of atherosclerosis and has prognostic value in the acute and chronic phases in patients with acute coronary syndromes. RESEARCH DESIGN AND METHODS MCP-1/CCL2 concentration was measured in plasma fractions of 363 middle-aged overweight/obese individuals (aged 61 \ub1 12 years, BMI 30.1 \ub1 6.6 kg/m2, 15% with type 2 diabetes, and 12% with impaired glucose tolerance) of a population survey carried out in 1990\u20131991 in Lombardy, Italy (Cremona Study), and cardiovascular disease (CVD) mortality was assessed in 2006 through Regional Health Registry files. RESULTS At baseline MCP-1/CCL2 was increased in individuals with type 2 diabetes (P < 0.05) and showed significant correlations with biochemical risk markers of atherosclerosis. After 15 years, among the 363 subjects, there were 82 deaths due to CVD. In univariate analysis age, sex, fasting glucose and insulin, fibrinogen, glucose tolerance status, smoking habit, and MCP-1/CCL2 were associated with CVD mortality. Age, sex, fasting serum glucose, MCP-1/CCL2, and smoking habit maintained an independent association with CVD mortality in multiple regression analysis. In a subgroup of 113 subjects in whom data for C-reactive protein (CRP) were available, its level was not predictive of CVD mortality. CONCLUSIONS In middle-aged overweight/obese individuals MCP-1/CCL2 was independently associated with CVD mortality. Further studies will be necessary to establish its role as a surrogate biomarker and as a potential therapeutic target

The Birth of a Hawaiian Fissure Eruption

Most basaltic explosive eruptions intensify abruptly, allowing little time to document processes at the start of eruption. One opportunity came with the initiation of activity from fissure 8 (F8) during the 2018 eruption on the lower East Rift Zone of Klauea, Hawaii. F8 erupted in four episodes. We recorded 28 minutes of high-definition video during a 51-minute period, capturing the onset of the second episode on 5 May. From the videos we were able to analyze the following in-flight parameters: frequency and duration of explosions; ejecta heights; pyroclast exit velocities; in-flight total mass and estimated mass eruption rates; and the in-flight total grain size distributions. Videos record a transition from initial pulsating outgassing, via spaced, but increasingly rapid, discrete explosions, to quasi-sustained, unsteady fountaining. This transition accompanied waxing intensity (mass flux) of the F8 eruption. We infer that all activity was driven by a combination of the ascent of a coupled mixture of small bubbles and melt, and the buoyant rise of decoupled gas slugs and/or pockets. The balance between these two types of concurrent flow determined the exact form of the eruptive activity at any point in time, and changes to their relative contributions drove the transition we observed at early F8. Qualitative observations of other Hawaiian fountains at Klauea suggest that this physical model may apply more generally. This study demonstrates the value of in-flight parameters derived from high resolution videos, which offer a rapid and highly time-sensitive alternative to measurements based on sampling of deposits post-eruption

autologous pancreatic islet transplantation in human bone marrow diabetes 2013 62 3523 3531

In the article listed above, there is an error in Fig. 3. In panel B , the immunohistochemical staining of insulin ( top middle panel

A HIGH RESOLUTION TEMPERATURE CLIMATOLOGY FOR THE GREATER ALPINE REGION (GAR)

The Greater Alpine Region (the GAR) covering the area between 4-19°E and 43-50°N and an altitude range between 0 and more than 4000 m asl. offers a challenging climate worth to be studied in any detail. However, it is surprising that up to now no comprehensive Alpine Temperature Climatology covering the whole region is existing. To overcome this deficiency as a first step we want to produce monthly temperature maps for this region in spatial resolution as high as possible. The period under investigation will be 1961-1990. In this paper we will describe the first steps of our initiative as well as the further plans

Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are stromal cells with the ability to proliferate and differentiate into many tissues. Although they represent powerful tools for several therapeutic settings, mechanisms regulating their migration to peripheral tissues are still unknown. Here, we report chemokine receptor expression on human BM-MSCs and their role in mediating migration to tissues. A minority of BM-MSCs (2% to 25%) expressed a restricted set of chemokine receptors (CXC receptor 4 [CXCR4], CX3C receptor 1 [CX3CR1], CXCR6, CC chemokine receptor 1 [CCR1], CCR7) and, accordingly, showed appreciable chemotactic migration in response to the chemokines CXC ligand 12 (CXCL12), CX3CL1, CXCL16, CC chemokine ligand 3 (CCL3), and CCL19. Using human pancreatic islets as an in vitro model of peripheral tissue, we showed that islet supernatants released factors able to attract BM-MSCs in vitro, and this attraction was principally mediated by CX3CL1 and CXCL12. Moreover, cells with features of BM-MSCs were detected within the pancreatic islets of mice injected with green fluorescent protein (GFP)-positive BM. A population of bona fide MSCs that also expressed CXCR4, CXCR6, CCR1, and CCR7 could be isolated from normal adult human pancreas. This study defines the chemokine receptor repertoire of human BM-MSCs that determines their migratory activity. Modulation of homing capacity may be instrumental for harnessing the therapeutic potential of BM-MSCs

A HIGH RESOLUTION TEMPERATURE CLIMATOLOGY FOR THE GREATER ALPINE REGION (GAR)

The Greater Alpine Region (the GAR) covering the area between 4-19°E and 43-50°N and an altitude range between 0 and more than 4000 m asl. offers a challenging climate worth to be studied in any detail. However, it is surprising that up to now no comprehensive Alpine Temperature Climatology covering the whole region is existing. To overcome this deficiency as a first step we want to produce monthly temperature maps for this region in spatial resolution as high as possible. The period under investigation will be 1961-1990. In this paper we will describe the first steps of our initiative as well as the further plans

GATEKEEPER’s Strategy for the Multinational Large-Scale Piloting of an eHealth Platform: Tutorial on How to Identify Relevant Settings and Use Cases

Background: The World Health Organization’s strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs. Objective: We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform. Methods: The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities. Results: Seven European countries were selected, covering Europe’s geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence–based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors. Conclusions: This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space

Biological activity of the thyroid TRK-T3 oncogene requires signalling through Shc

The thyroid TRK-T3 oncogene, produced by a chromosomal translocation, is a chimeric, constitutively activated version of the NTRK1/NGF receptor and it is able to transform NIH3T3 cells and differentiate PC12 cells. TRK-T3 oncoprotein triggers multiple signal transduction pathways. Among others, TRK-T3 binds and phosphorylates the Shc and SNT1/FRS2 adaptor proteins both involved in coupling the receptor tyrosine kinase to the mitogen-activated protein kinase pathway by recruiting Grb2/SOS. We were interested in defining the role of Shc in the oncogenesis by TRK-T3. The mutation of TRK-T3 tyrosine 291, docking site for both Shc and FRS2, abrogates the oncogene biological activity. To directly explore the role of Shc we used the ShcY317F mutant, which carries the mutation of a tyrosine residue involved in Grb2 recruitment. We demonstrated that the ShcY317F mutant exerts an inhibitory effect on TRK-T3 transforming activity. Such effect can be modulated by the amount of ShcY317F protein and affects the viability of cells expressing TRK-T3 by means of a mechanism involving apoptosis. Our results indicate a definitive role of the adaptor protein Shc in TRK-T3 transforming activity

A preclinical evaluation of pemetrexed and irinotecan combination as second-line chemotherapy in pancreatic cancer

Gemcitabine (GEM)-based chemotherapy is regarded as the standard treatment of pancreatic adenocarcinoma, but yields a very limited disease control. Very few studies have investigated salvage chemotherapy after failure of GEM or GEM-containing chemotherapy and preclinical studies attempting to widen the therapeutic armamentarium, not including GEM, are warranted. MIA PaCa2, CFPAC-1 and Capan-1 pancreatic cancer cell lines were treated with GEM, fluouracil (5-FU), docetaxel (DCT), oxaliplatin (OXP), irinotecan (CPT-11), pemetrexed (PMX) and raltitrexed (RTX) as single agent. Pemetrexed, inducing apoptosis with IC50s under the Cmax in the three lines tested, appeared the most effective drug as single agent. Based on these results, schedule- and concentration-dependent drug interactions (assessed using the combination index) of PMX/GEM, PMX/DCT and PMX–CPT-11 were evaluated. The combinatory study clearly indicated the PMX and CPT-11 combination as the most active against pancreatic cancer. To confirm the efficacy of PMX–CPT-11 combination, we extended the study to a panel of 10 pancreatic cancer cell lines using clinically relevant concentrations (PMX 10 μM; CPT-11 1 μm). In eight of 10 lines, the PMX–CPT-11 treatment significantly reduced cell recovery and increased both the subG1 and caspase 3/7 fraction. After a 5-day wash out period, an increased fraction of subG1 and caspase3/7 persisted in PMX–CPT-11-pretreated cell lines and a significant reduction in the clonogenicity capacity was evident. Finally, in vivo, the PMX/CPT-11 combination showed the ability to inhibit xenograft tumours growth as second-line therapy after GEM treatment. The PMX and CPT-11 combination displays a strong schedule-independent synergistic cytotoxic activity against pancreatic cancer, providing experimental basis for its clinical testing as salvage chemotherapy in pancreatic cancer patients