Mutational analysis of BCORL1 in the leukemic transformation of chronic myeloproliferative neoplasms.

BCORL1 mutations do not seem to be commonly associated with leukemic transformation of MPN, further substantiating the different molecular profile compared with denovo leukemias. Although the small number of cases does not allow us to exclude that BCORL1 mutations can be found also in post-MPN AML, their occurrence is, at least, very infrequent and their detection does not appear to deserve clinical relevance

Value of cytogenetic abnormalities in post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a study of the MYSEC project

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Uracil as an index of lactic acid bacteria contamination of tomato products

Aim of this research was to evaluate the suitability of uracil as an hygienic quality index of tomato products. While uridine was naturally present throughout tomato berries ripening, uracil appeared only after microbial contamination. In tomato pulp inoculated with nine different microbial strains, all the five lactic acid bacteria (LAB) studied released relevant quantities of uracil (150 - 1040 mg/kg dm), with a correlated partial or total decrease of uridine. Uracil production by yeasts and moulds was very low or non existent; the starting uridine concentration (ca. 960 mg/kg dm) remained constant or increased. Uracil thermostability was also verified. Twenty six samples of tomato paste (30 \ub0Brix) were collected from bag-in-drums produced in an industrial processing plant, some with evident swelling symptoms. All the samples with high microbial count presented uracil. Uracil was also detected in samples with microbial contamination under the detection limit and Howard Mould Count (HMC) below legislation limits, implying the reprocessing, at least partial, of altered tomato product. The results indicate that uracil presence in tomato products represents an index of LAB contamination occurred before heat treatment

Approaches to Designing Complex Dependable Systems

The problem of designing complex dependable systems is addressed in this paper. Due to some peculiarities of their application and behavior these are often referred to as reactive systems. Two main paradigms for their design have recently been proposed# we name these paradigms living processes and hidden concurrency, depending on their approach to concurrency handling. The analysis of application requirements and constraints is proposed as a methodology for selecting the most suitable implementation paradigm for a given application. Finally,itisshown that in some cases an intermediate paradigm mayprovide a suitable solution

Accelerated erythroid repopulation with no stem-cell competition effect in children treated with recombinant human erythropoietin after allogeneic bone marrow transplantation.

We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) to accelerate erythropoietic engraftment in paediatric patients undergoing allogeneic BMT. rHuEPO was administered intravenously at a dose of 75 U/kg per day for 30 d after transplant. Erythroid repopulation, evaluated sequentially through the serum transferrin receptor, was faster in 15 patients receiving rHuEPO than in 16 historical controls (P = 0.0003). This faster erythroid engraftment resulted in a reduction in the total number of red blood cell units required to reach transfusion independence (2.7 +/- 1.2 v 4.2 +/- 2.3, P = 0.027). No significant difference in leucocyte or platelet regeneration was observed. These findings indicate that rHuEPO administration can accelerate erythroid recovery after allogeneic BMT and reduce red cell transfusion requirements with no stem-cell competition effect

Calreticulin mutation does not modify the IPSET score for predicting the risk of thrombosis among 1150 patients with essential thrombocythemia

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An Extraterritorial FDA: Could the Food and Drug Administration Apply Its Informed Consent Requirement Abroad Consistent with International Law?

This paper addresses the regulatory challenges wrought by the increasing amount of human subject drug testing conducted in developing countries in support of new drug applications to the Food and Drug Administration. Specifically, it examines the difficulty of enforcing the “informed consent” requirement for ethical scientific research performed in foreign territory. In poorer regions, a lack of government oversight, lower regulatory standards, and barriers to communication have too frequently resulted in allegations of human experimentation performed without its participants’ informed consent. In order to solve this problem, some commentators have suggested that the FDA could apply its human subject protections to foreign clinical research, and enforce them through injunctions or criminal prosecutions. However, the international legal limits on states’ prescriptive jurisdiction may prohibit this exercise of extraterritoriality. After analyzing the proposed extraterritorial regulation of foreign drug testing under the traditional bases and limitations of prescriptive jurisdiction, this paper concludes that such regulation would likely violate international law. However, because nonconsensual clinical research has previously been regarded as a crime against humanity, the FDA might be able to bring criminal prosecutions under the principal of “universal jurisdiction” against investigators or sponsors who conducted studies without their subjects’ informed consent. This analysis offers both positive and normative conclusions regarding the international legal system and the human rights regime

Impact of ruxolitinib on the natural history of primary myelofibrosis: a comparison of the DIPSS and the COMFORT-2 cohorts

The international prognostic scoring system (IPSS) provides reliable risk assessment in patients with primary myelofibrosis (PMF). Recent clinical trials in PMF patients with intermediate-2 or high IPSS risk have shown a survival advantage of ruxolitinib over placebo (COMFORT-1) or best available therapy (COMFORT-2). Because crossover was allowed in these studies, we analyzed the cohort of ruxolitinib-naive patients used for developing the dynamic IPSS (DIPSS). By adopting ad hoc statistical analyses, we compared survival from diagnosis of 100 PMF patients receiving ruxolitinib within COMFORT-2 with that of 350 patients of the DIPSS study. Subjects were properly matched, and both left-truncation and right-censoring were accounted in order to compare higher IPSS risks exclusively. Patients receiving ruxolitinib had longer survival (5 years, 95% confidence interval [CI]: 2.9-7.8 vs 3.5 years, 95% CI: 3.0-3.9) with a hazard ratio of 0.61 (95% CI: 0.41-0.91; P = .0148). This observation suggests that ruxolitinib may modify the natural history of PMF

Pregnancy complications predict thrombotic events in young women with essential thrombocythemia

Although Philadelphia-negative myeloproliferative neoplasms (MPNs) occur typically in middle to advanced age, any age group may be affected, posing a challenge for their management during pregnancy when they occur in young females. There is a high incidence of thromboembolic events and pregnancy complications in patients with myeloproliferative neoplasms, and a possible relationship between these complications is a matter of concern. The aim of this article was to correlate thrombosis and pregnancy outcome in 158 females with ET experiencing 237 pregnancies. Seven patients had a thrombotic event before their first pregnancy, one of them ended (14.3%) in a miscarriage. Among the 151 patients with no history of thrombosis before they became pregnant, 40 (26.5%) had a miscarriage (P=NS). Eighteen patients (11.4%) developed major thrombotic complications (12 splanchnic vein, 1 cerebral vein, 2 coronary syndromes, and 3 strokes) after at least one pregnancy (4 uneventful and 14 complicated). The occurrence of thrombosis was significantly more frequent (P<0.001) in patients with a history of pregnancy complications (28%) than in those experiencing a normal pregnancy and delivery (3.7%). Pregnancy complications in women with ET are associated with a higher risk of subsequent thromboses, so pregnant women with this neoplasm who miscarry need to be carefully monitored