402 research outputs found

    Size-Dependent Grain Boundary Scattering in Topological Semimetals

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    We assess the viability of topological semimetals for application in advanced interconnect technology, where conductor size is on the order of a few nanometers and grain boundaries are expected to be prevalent. We investigate the electron transport properties and grain boundary scattering in thin films of the topological semimetals CoSi and CoGe using first-principles calculations combined with the Non-Equilibrium Green's Function (NEGF) technique. Unlike conventional interconnect metals like Cu and Al, we find that CoSi and CoGe conduct primarily through topologically-protected surface states in thin film structures even in the presence of grain boundaries. The area-normalized resistance decreases with decreasing film thickness for CoSi and CoGe thin films both with and without grain boundaries; a trend opposite to that of the conventional metals Cu and Al. The surface-dominated transport mechanisms in thin films of topological semimetals with grain boundaries demonstrates a fundamentally new paradigm of the classical resistivity size-effect, and suggests that these materials may be promising candidates for applications as nano-interconnects where high electrical resistivity acts as a major bottleneck limiting semiconductor device performance.Comment: 18 pages, 9 figures. To be published in Physical Review Applie

    Healthcare costs for treating relapsing multiple sclerosis and the risk of progression: a retrospective Italian cohort study from 2001 to 2015

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    Background Disease modifying treatments (DMTs) are the main responsible for direct medical costs in multiple sclerosis (MS). The current investigation aims at evaluating possible associations between healthcare costs for treating relapsing remitting MS (RRMS) and disease evolution. Methods The present cohort study retrospectively included 544 newly diagnosed RRMS patients, prospectively followed up for 10.1±3.3 years. Costs for DMT administration and management were calculated for each year of observation. Following clinical endpoints were recorded: time to first relapse, 1-point EDSS progression, reaching of EDSS 4.0, reaching of EDSS 6.0, and conversion to secondary progressive MS (SP). Covariates for statistical analyses were age, gender, disease duration and EDSS at diagnosis. Results At time varying Cox regression models, 10% increase in annual healthcare costs was associated with 1.1% reduction in 1-point EDSS progression (HR = 0.897; p = 0.018), with 0.7% reduction in reaching EDSS 6.0 (HR = 0.925; p = 0.030), and with 1.0% reduction in SP conversion (HR = 0.902; p = 0.006). Conclusion Higher healthcare costs for treating MS have been associated with a milder disease evolution after 10 years, with possible reduction of long-term non-medical direct and indirect costs

    Ontogeny of ependymoglial cells lining the third ventricle in mice.

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    During hypothalamic development, the germinative neuroepithelium gives birth to diverse neural cells that regulate numerous physiological functions in adulthood. Here, we studied the ontogeny of ependymal cells in the mouse mediobasal hypothalamus using the BrdU approach and publicly available single-cell RNAseq datasets. We observed that while typical ependymal cells are mainly produced at E13, tanycyte birth depends on time and subtypes and lasts up to P8. Typical ependymocytes and ÎČ tanycytes are the first to arise at the top and bottom of the dorsoventral axis around E13, whereas α tanycytes emerge later in development, generating an outside-in dorsoventral gradient along the third ventricle. Additionally, α tanycyte generation displayed a rostral-to-caudal pattern. Finally, tanycytes mature progressively until they reach transcriptional maturity between P4 and P14. Altogether, this data shows that ependyma generation differs in time and distribution, highlighting the heterogeneity of the third ventricle

    Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy.

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    A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing–remitting multiple sclerosis patients, aged 18–50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 mg (three times weekly) for 12 months, were randomized to combination therapy (interferon+atorvastatin 20mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A (n 1⁄4 21) or B (n 1⁄4 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline (p 1⁄4 0.007) and significantly fewer relapses versus the two pre-randomization years (p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p 1⁄4 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone

    Single-Center 8-Years Clinical Follow-Up of Cladribine-Treated Patients From Phase 2 and 3 Trials

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    Background: Cladribine is approved for the treatment of highly-active relapsing multiple sclerosis (MS), where it is also effective on disability progression. In the present single-center study, we aim to report on the 8-years clinical follow-up of 27 patients included in phase 2 and 3 clinical trials for cladribine. Methods: We included patients exposed to cladribine (n = 13) or placebo (n = 14) in ONWARD, CLARITY, and ORACLE-MS trials, and followed-up at the same center after trial termination. Outcomes of long-term disease progression were recorded. Results: During 8-year follow-up, patients treated with cladribine presented with reduced risk of EDSS progression (HR = 0.148; 95%CI = 0.031, 0.709; p = 0.017), of reaching EDSS 6.0 (HR = 0.115; 95%CI = 0.015, 0.872; p = 0.036), and of SP conversion (HR = 0.010; 95%CI = 0.001, 0.329; p = 0.010), when compared with placebo. Conclusions: Our exploratory study provides additional evidence that cladribine may be useful to prevent or, at least, mitigate the risk of disability progression after 8 years

    Ionome variations in tomato Introgressed Lines (Solanum Pennellii x S. Lycopersicum cv. M82) following metal treatements shed new light on food health.

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    A tomato introgression line population that combines single chromosomal segments introgressed from the wild, green fruited species Solanum pennelli in the background of the domesticated tomato, S. lycopersicum cv. M82, was used in this study. Results shed light both on the metal accumulation of ILs tomato plants and on theirs ionome modifications