Capabilities of Nanostructured Tungsten for Plasma Facing Material

One of the bottle necks for fusion to become a reality is the lack of materials able to withstand the harsh conditions taken place in a reactor environment. In particular, plasma facing materials (PFM) have to resist large radiation fluxes and thermal loads. Nowadays, tungsten is one of the most attractive materials proposed for PFM. However, it is known that the irradiation of tungsten with H leads to surface blistering and subsequent cracking and exfoliation which is unacceptable. In particular, these effects have been observed to be more severe when W is subjected to pulse irradiation

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Efficient DNA extraction from 25-year-old paraffin-embedded tissues: Study of 365 samples

Aims: Archival fixed paraffin-embedded tissue (PET) is a valuable source for population-based molecular genetic studies but the extraction of high quality DNA is still a problematic issue. The present study tested the grade of DNA fragmentation and the DNA adequacy for genetic investigations in a large series of tissue specimens that were formalin- or Bouin-fixed and paraffin-embedded between 1979 and 1983. Specific aims were to: (1) estimate the amount of archival tissue samples from which DNA is recoverable by conventional methods and the influence of variables (origin, fixative, section size) on DNA recovery; and (2) evaluate the feasibility of genetic investigations in large scale population studies. Methods: DNA was extracted in 2005 from 365 PET samples from Italy and Spain and subjected to PCR analysis targeting fragments of 152, 268 and 676 bp of the ß-globin gene. Results: Amplification of a 152 bp fragment was obtained in 252/365 (69%) PET samples, a 268 bp fragment in 62/365 (17%), a 676 bp fragment in 19/365 (5%) and no amplification for any fragment was obtained in 113/365 (31%). A second processing of newly cut sections performed in a 25% simple random sample gave comparable results, with substantial concordance between the first and second tests (kappa value 0.62 [95% CI 0.59-0.64]). Conclusions: The results of this study show that DNA can be efficiently extracted from PETs archived for more than 20 years, and that large scale population studies based on PCR amplification of short target sequences are feasible. © 2007 Royal College of Pathologists of Australasia

Bleeding complications associated with anticoagulant therapy in patients with cancer

Background: Cancer patients with venous thromboembolism (VTE) have an increased incidence of bleeding complications while on anticoagulant therapy. Methods: RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for major bleeding. Results: Up to May 2009, 4,709 patients with active cancer had been enrolled in RIETE registry. During the first 3 months of anticoagulant therapy, 200 (4.2%) patients developed major bleeding. Then, 38 (0.8%) further patients bled beyond the first 90 days of therapy, 3 bled after withholding anticoagulant therapy. The most common sites of bleeding were the gastrointestinal tract (118 patients, 49%), genitourinary system (43 patients, 18%) and the brain (27 patients, 11%). In all, 160 patients (66%) died within 30 days after bleeding: 88 (55%) died of bleeding, 3 (1.9%) died of recurrent pulmonary embolism. Conclusions: Major bleeding is a frequent and severe complication in cancer patients with VTE, even beyond the third month. One third of the patients who bled died due the bleeding event

Inferior vena cava agenesis in patients with lower limb deep vein thrombosis in the RIETE registry. When and why to suspect

Background: Limited data exist about the clinical presentation and outcomes of patients with inferior vena cava agenesis (IVCA) who develop deep vein thrombosis (DVT). Methods: We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) registry to compare clinical characteristics and outcomes of patients with lower limb DVT, according to the presence or absence of IVCA. Major outcomes included recurrent DVT, major bleeding and post-thrombotic syndrome (PTS). Results: Among 50,744 patients with lower-limb DVT recruited in October 2018, 31 (0.06%) had IVCA. On multivariable analysis, patients aged < 30 years (odds ratio [OR]: 17.9; 95%CI: 7.05–45.3), with unprovoked DVT (OR: 2.49; 95%CI: 1.17–5.29), proximal (OR: 2.81; 95%CI: 1.05–7.53) or bilateral DVT (OR: 11.5; 95%CI: 4.75–27.8) were at increased risk to have IVCA. Patients with DVT and IVCA had lower odds to present with coexisting PE (OR: 0.22; 95%CI: 0.07–0.73). During the first year of follow-up, the rates of DVT recurrences (hazard ratio [HR]: 1.30; 95%CI: 0.07–6.43), pulmonary embolism (HR: 2.30; 95%CI: 0.11–11.4) or major bleeding (HR: 1.32; 95%CI: 0.07–6.50) were not significantly different with those with versus those without IVCA. One year after the index DVT, IVCA patients had a higher rate of skin induration (OR: 3.70; 95%CI: 1.30–9.52), collateral vein circulation (OR: 3.57; 95%CI: 1.42–8.79) or venous ulcer (OR: 5.87; 95%CI: 1.36–1.87) in the lower limb than those without IVCA. Conclusions: Certain clinical features such as unprovoked and bilateral proximal DVT in young patients should raise the suspicion for IVCA. Patients with IVCA had higher odds for symptoms of post-thrombotic syndrome