1,083 research outputs found

    Haydeeite: a spin-1/2 kagome ferromagnet

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    The mineral haydeeite, alpha-MgCu3(OD)6Cl2, is a S=1/2 kagome ferromagnet that displays long-range magnetic order below TC=4.2 K with a strongly reduced moment. Our inelastic neutron scattering data show clear spin-wave excitations that are well described by a Heisenberg Hamiltonian with ferromagnetic nearest-neighbor exchange J1=-38 K and antiferromagnetic exchange Jd=+11 K across the hexagons of the kagome lattice. These values place haydeeite very close to the quantum phase transition between ferromagnetic order and non-coplanar twelve-sublattice cuboc2 antiferromagnetic order. Diffuse dynamic short-range ferromagnetic correlations observed above TC persist well into the ferromagnetically ordered phase with a behavior distinct from critical scattering

    Genetic Features of Metachronous Esophageal Cancer Developed in Hodgkin's Lymphoma or Breast Cancer Long-Term Survivors: An Exploratory Study.

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    Background Development of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin's Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms. Methods Using microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC). Results We found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes. Conclusions Altogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis

    Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

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    Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

    Integration studies of RF solid-state generators in the electrical system of NBTF experiments and ITER HNB

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    SPIDER operation, started in 2018, pointed out performance-limiting issues caused by the technology employed in RF generators, based on tetrode free-running oscillators. One of these limits, namely the onset of frequency instabilities, prevented operation at the full rated power of 200 kW. In addition, tetrodes require high voltage to operate, which translates to risk of flashovers and the necessity to perform conditioning procedures, limiting the overall reliability. These disadvantages, combined with the positive experience gained in the meanwhile on smaller facilities with solid state amplifiers, led to the proposal of a complete re-design of the radiofrequency power supplies. This paper describes the modelling activities used to define specifications and design criteria of the solid-state amplifiers for SPIDER and MITICA, which can be directly transposed to the ITER HNB units when their functionality is proven. We detail the topology of the generators, consisting of class D amplifier modules combined to achieve the required 200 kW, which design is mainly driven by the necessity to deliver nominal power to the ion source, mitigate the risk of obsolescence, and improve the reliability through modularity. Due to the non-standard application, we gave particular focus to the integration of generators in the RF systems of SPIDER and MITICA. Numerical analyses were performed to verify the impact of harmonic distortion on transmission line and RF load components, to address the effect of mutual coupling between RF circuits on the generator output modulation, and to assess the magnitude of common mode currents in the electric system. These studies, as well as the experience gained from SPIDER operation, helped to define dedicated circuit design provisions and control strategies, which are currently being implemented in the detailed design and construction phase of the new RF amplifiers

    Efficacy and Safety of Taspoglutide Versus Sitagliptin for Type 2 Diabetes Mellitus (T-Emerge 4 Trial)

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    INTRODUCTION: The efficacy and safety of taspoglutide, a long-acting human glucagon-like peptide-1 analog, were compared with sitagliptin or placebo, as adjunct to metformin, in patients with inadequately controlled type 2 diabetes. METHODS: In this randomized, double-blind, double-dummy, parallel-group trial, patients were randomized to taspoglutide 10 mg once weekly (QW), 20 mg QW, 100 mg sitagliptin once daily (QD), or placebo for 24 weeks, followed by 28-week short-term and 104-week long-term extension periods. The primary endpoint was change in glycosylated hemoglobin (HbA(1c)) after 24 weeks. RESULTS: In this study, 666 patients (baseline HbA(1c), 7.96% [SD, 0.87]; fasting plasma glucose, 9.61 mmol/L [2.56]; body weight, 92.4 kg [19.3]) were randomized to taspoglutide 10 mg QW (n = 190), 20 mg QW (n = 198), 100 mg sitagliptin QD (n = 185), or placebo (n = 93) for 24 weeks. After 24 weeks, least squares mean (SE) HbA(1c) reductions were greater with taspoglutide 10 mg (−1.23% [0.06]) and 20 mg (−1.30% [0.06]) versus sitagliptin (−0.89% [0.06]) or placebo (−0.10% [0.08]). Mean treatment differences with taspoglutide 10 mg and 20 mg were −0.34 (95% confidence intervals [CI]: −0.49, −0.19) and −0.41 (−0.56, −0.26) versus sitagliptin; and −1.13 (−1.31, −0.95) and −1.20 (−1.38, −1.02) versus placebo. Weight loss was greater with taspoglutide 10 mg (−1.8 kg [0.3]) and 20 mg (−2.6 kg [0.3]) than sitagliptin (−0.9 kg [0.3]) or placebo (−0.5 kg [0.4]). Effects on HbA(1c) and weight loss continued through 52 weeks of treatment. No cases of severe hypoglycemia occurred with any active treatment. Gastrointestinal adverse events, and allergic and injection-site reactions were higher in the taspoglutide groups, causing higher discontinuation rates. Anti-taspoglutide antibodies were confirmed in 46% of patients. CONCLUSION: Taspoglutide demonstrated better efficacy on glycemic control and weight loss than sitagliptin, but a high incidence of adverse events led to high discontinuation rates. The safety profile of taspoglutide in this trial was similar to other trials in the clinical program, and led to the discontinuation of dosing
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