University of Udine

About: University of Udine is a education organization based out in Udine, Italy. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 6745 authors who have published 20530 publications receiving 669088 citations. The organization is also known as: Università degli Studi di Udine & Universita degli Studi di Udine.

LL-37 Protects Rats against Lethal Sepsis Caused by Gram-Negative Bacteria

Abstract: We investigated the efficacy of LL-37, the C-terminal part of the only cathelicidin in humans identified to date (termed human cationic antimicrobial protein), in three experimental rat models of gram-negative sepsis. Adult male Wistar rats (i) were given an intraperitoneal injection of 1 mg Escherichia coli 0111:B4 LPS, (ii) were given 2 x 10(10) CFU of Escherichia coli ATCC 25922, or (iii) had intra-abdominal sepsis induced via cecal ligation and puncture. For each model, all animals were randomized to receive intravenously isotonic sodium chloride solution, 1-mg/kg LL-37, 1-mg/kg polymyxin B, 20-mg/kg imipenem, or 60-mg/kg piperacillin. Lethality; growth of bacteria in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; and endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma were evaluated. All compounds reduced lethality compared to levels in controls. Endotoxin and TNF-alpha plasma levels were significantly higher in conventional antibiotic-treated rats than in LL-37- and polymyxin B-treated animals. All drugs tested significantly reduced bacterial growth compared to saline treatment. No statistically significant differences between LL-37 and polymyxin B were noted for antimicrobial and antiendotoxin activities. LL-37 and imipenem proved to be the most effective treatments in reducing all variables measured. Due to its multifunctional properties, LL-37 may become an important future consideration for the treatment of sepsis.

CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors.

Abstract: Cyclin-dependent kinases (CDK) 4/6 inhibitors, namely abemaciclib, palbociclib, and ribociclib, interfere with cell cycle progression, induce cell senescence and might promote cancer cell disruption by a cytotoxic T cells-mediated effect. Phase III randomized clinical trials have proven that CDK4/6 inhibitors (CDK4/6i) in combination with several endocrine agents improve treatment efficacy over endocrine agents alone for hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (MBC). Based on such results, these combinations have been approved for clinical use. Preclinical studies in cell cultures and mouse models proved that CDK4/6i are active against a broad spectrum of solid tumors other than breast cancer, including liposarcoma, rhabdomyosarcoma, non-small cell lung cancer, glioblastoma multiforme, esophageal cancer, and melanoma. The role of CDK4/6i in monotherapy in several solid tumors is currently under evaluation in phase I, II, and III trials. Nowadays, abemaciclib is the only of the three inhibitors that has received approval as single agent therapy for pretreated HR+ HER2- MBC. Here we review biological, preclinical and clinical data on the role of CDK4/6 inhibitors as single agents in advanced solid tumors.

Precise measurement of the W-boson mass with the CDF II detector

Abstract: We have measured the W-boson mass M{sub W} using data corresponding to 2.2 fb{sup -1} of integrated luminosity collected in p{bar p} collisions at {radical}s = 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470 126 W {yields} e{nu} candidates and 624 708 W {yields} {mu}{nu} candidates yield the measurement M{sub W} = 80 387 {+-} 12{sub stat} {+-} 15{sub syst} = 80 387 {+-} 19 MeV/c{sup 2}. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined.

Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial.

Abstract: Summary Background Creutzfeldt-Jakob disease (CJD) is a fatal, untreatable prion encephalopathy. Previous studies showed that doxycycline is effective in in-vitro and in-vivo models of disease, and patients with CJD who received compassionate treatment with doxycycline showed increased survival time compared with historical series. We therefore did a randomised, double-blind study of doxycycline versus placebo in CJD. Methods We recruited patients older than 18 years old who had a diagnosis of definite or probable sporadic CJD or genetic forms of the disease via Italian reference centres and the French national referral system. Patients were randomly assigned (ratio 1:1) to receive oral doxycycline (100 mg daily) or placebo under double-blind conditions from the day of randomisation to death. Centralised randomisation was done independently of enrolment or evaluation of patients using a minimisation method in Italy and a simple randomisation in France. Participants, caregivers, and clinicians were masked to group assignment. The primary efficacy variable was the survival time from randomisation. Interim analyses were planned to detect a significant effect of treatment as early as possible. This trial is registered with EudraCT, 2006-001858-27 for the Italian study and 2007-005553-34 for the French study. Findings From April 12, 2007, to Aug 19, 2010, in Italy, and from Jan 30, 2009, to Jan 10, 2012, in France, 121 patients with CJD were enrolled in the study, 62 of whom were randomly assigned to the treatment group and 59 to the placebo group. The first interim analysis showed absence of superiority of doxycycline compared with placebo, and the trial was stopped for futility. Efficacy analyses did not show significant differences between patients treated with doxycycline and placebo with regard to survival times (HR 1·1, 95% CI 0·8–1·7, p=0·50). Serious adverse events were judged not to be related to treatment, whereas a relation was deemed probable or possible for five non-serious adverse events that occurred in each treatment group. Interpretation Doxycycline at a dose of 100 mg per day was well tolerated but did not significantly affect the course of CJD, at variance with the results of previous observational studies. Our experience could be useful in the design of large multinational controlled trials of potential anti-prion molecules in this rare disease. Funding Agenzia Italiana Farmaco, Italian Ministry of Health, AIEnP, and French Ministry of Health.

Definitions and linkages between operational and strategic flexibilities

Abstract: This paper aims at clarifying the concept of strategic flexibility, starting from that much more common of manufacturing flexibility (or operational one). After characterizing the dimensions of the latter, a classification of strategic flexibility is presented which distinguishes four categories. The measures of strategic flexibility are also investigated. Then two analogies are pointed out with the operational flexibility. The first, of the cause-effect type, is on two levels: at the business level, the operational flexibility estimates the variation of practices, while the strategic flexibility measures the effect obtained on performances; at the corporate level, the operational flexibility estimates the variation of competences, while the strategic flexibility evaluates the change in business. The second analogy, related to the classification variables, permits the main types of operational and strategic flexibilities to be placed in a single framework. So this study seeks to provide a framework—which has not been proposed in prior literature—for analyzing and evaluating the correlated concepts of operational and strategic flexibilities, to create a theoretical foundation for future research and empirical testing.