Effects of Rivaroxaban on Biomarkers of Coagulation and Inflammation: A Post Hoc Analysis of the X-VeRT Trial.

Introduction  This X-VeRT (eXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in patients with nonvalvular aTrial fibrillation scheduled for cardioversion) substudy evaluated the effects of treatment with rivaroxaban or a vitamin-K antagonist (VKA) on levels of biomarkers of coagulation (D-dimer, thrombin-antithrombin III complex [TAT] and prothrombin fragment [F1.2]) and inflammation (high sensitivity C-reactive protein [hs-CRP] and high-sensitivity interleukin-6 [hs-IL-6]) in patients with atrial fibrillation (AF) who were scheduled for cardioversion and had not received adequate anticoagulation at baseline (defined as, in the 21 days before randomization: no oral anticoagulant; international normalized ratio <2.0 with VKA treatment; or <80% compliance with non-VKA oral anticoagulant treatment). Methods  Samples for biomarker analysis were taken at baseline ( n  = 958) and treatment completion (42 days after cardioversion; n  = 918). The influence of clinical characteristics on baseline biomarker levels and the effect of treatment on changes in biomarker levels were evaluated using linear and logistic models. Results  Baseline levels of some biomarkers were significantly associated with type of AF (D-dimer and hs-IL-6) and with history of congestive heart failure (hs-CRP, D-dimer, and hs-IL-6). Rivaroxaban and VKA treatments were associated with reductions from baseline in levels of D-dimer (-32.3 and -37.6%, respectively), TAT (-28.0 and -23.1%, respectively), hs-CRP (-12.5 and -17.9%, respectively), and hs-IL-6 (-9.2 and -9.8%, respectively). F1.2 levels were reduced from baseline in patients receiving a VKA (-53.0%) but not in those receiving rivaroxaban (2.7%). Conclusion  Anticoagulation with rivaroxaban reduced levels of key inflammation and coagulation biomarkers to a similar extent as VKAs, with the exception of F1.2. Further investigation to confirm the value of these biomarkers in patients with AF is merited

Spin transport and accumulation in the persistent photoconductor Al0.3_{0.3}Ga0.7_{0.7}As

Electrical spin transport and accumulation have been measured in highly Si doped Al0.3Ga0.7As utilizing a lateral spin transport device. Persistent photoconductivity allows for the tuning of the effective carrier density of the channel material in situ via photodoping. Hanle effect measurements are completed at various carrier densities and the measurements yield spin lifetimes on the order of nanoseconds, an order of magnitude smaller than in bulk GaAs. These measurements illustrate that this methodology can be used to obtain a detailed description of how spin lifetimes depend on carrier density in semiconductors across the metal-insulator transition

OR13-2 Burosumab Resulted in Greater Improvement in Rickets Than Conventional Therapy in Children with X-Linked Hypophosphatemia (XLH)

XLH is characterized by excess FGF23, hypophosphatemia, skeletal deformities, and growth impairment. For the last 40 years, XLH has been treated with multiple daily doses of oral phosphate and active vitamin D (Pi/D). Burosumab, a fully human monoclonal antibody to FGF23, has been approved by the FDA for the treatment of XLH in patients ≥1 year-old. In this Phase 3 trial (NCT02915705), 61 children with XLH (1-12 years old) were randomized (1:1) to receive subcutaneous burosumab starting at 0.8 mg/kg every 2 weeks or continue Pi/D titrated and individualized for each subject by investigators. Eligibility criteria included a Total Rickets Severity Score (RSS) ≥2.0 despite prior treatment with Pi/D (>7-day washout before baseline). The primary endpoint was healing of rickets at Week 40 assessed by radiologists blinded to treatment using the Radiographic Global Impression of Change (RGI-C). The mean ± SE daily oral phosphate dose from baseline to Week 40 was 37.8 ± 3.2 mg/kg, with >99% compliance reported based on days of dosing. Compared with Pi/D, 40 weeks of burosumab resulted in a greater LS mean ± SE increase in serum phosphorus (0.92 ± 0.08 vs 0.20 ± 0.06 mg/dL), TmP/GFR (1.19 ± 0.11 vs -0.16 ± 0.05 mg/dL), and 1,25(OH)2D (30 ± 4 vs 19 ± 4 pg/mL). At Week 40, rickets improved in both groups; RGI-C global score was significantly higher in burosumab subjects than in Pi/D subjects (LS mean ± SE: +1.9 ± 0.1 vs +0.8 ± 0.1; p<0.0001). More burosumab subjects had substantial healing (RGI-C ≥+2.0), compared with Pi/D subjects (21/29, 72% vs 2/32, 6%; odds ratio of 39.1, p<0.0001). Improvement in the RGI-C lower limb deformity score was greater with burosumab than with Pi/D (+0.62 ± 0.12 vs +0.21 ± 0.12; p=0.02). Alkaline phosphatase decreased more with burosumab compared with Pi/D (-131 ± 13 vs 35 ± 19; p<0.0001). Consistent with decreases in rickets severity, burosumab improved growth and mobility. Standing height Z-score increased by a LS mean change (95% CI) of +0.15 (0.05, 0.25) for burosumab and +0.08 (-0.02, 0.19) for Pi/D. The 6 Minute Walk Test percent predicted distance increased with burosumab (Baseline to Week 40: 62% to 72%) and was unchanged with Pi/D (76% to 75%). Nephrocalcinosis score (range 0-4) shifted 0 in 20 Pi/D and 24 burosumab subjects; +1 in 3 Pi/D and 0 burosumab subjects; and -1 in 3 Pi/D and 2 burosumab subjects. Pre-defined adverse events (AEs) of interest, including hypersensitivity and injection site reactions, were higher in the burosumab group and were mild to moderate in severity overall. There were 4 serious AEs (3 burosumab, 1 Pi/D); none were treatment-related and all resolved. No subject discontinued study drug in either group. Data after 64 weeks of treatment will be available at the time of presentation. In this randomized Phase 3 trial, burosumab resulted in increases in growth and mobility, and significantly greater improvements in rickets than Pi/D in 1-12 year-old children with XLH

Patient-reported treatment satisfaction and budget impact with rivaroxaban vs. standard therapy in elective cardioversion of atrial fibrillation: a post hoc analysis of the X-VeRT trial.

AIMS: We compared patient-reported treatment satisfaction and the economic impact of anticoagulation therapy with rivaroxaban vs. vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation undergoing elective cardioversion procedures. METHODS AND RESULTS: The current study is a post hoc analysis of the prospective, multicentre X-VeRT (EXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in subjects with non-valvular aTrial fibrillation scheduled for cardioversion) trial. Patient-reported treatment satisfaction with anticoagulation therapy was assessed using the Treatment Satisfaction Questionnaire for Medication version II in seven countries (US, UK, Canada, Germany, France, Italy, and the Netherlands). An economic model was also developed to estimate the impact of postponed cardioversions for two countries (UK and Italy). This model estimated the total costs of cardioversion, taking into consideration the costs for drug therapy (including extended treatment duration due to cardioversion postponement), international normalized ratio monitoring of VKAs, the cardioversion procedure, and rescheduling the procedure. These costs were linked to the respective X-VeRT study data to estimate the total costs. Patients receiving rivaroxaban in the delayed cardioversion group had significantly higher scores for Convenience, Effectiveness, and Global satisfaction (81.74 vs. 65.78; 39.41 vs. 32.95; and 82.07 vs. 66.74, respectively; P < 0.0001). Based on the total patient population included in the treatment satisfaction substudy (n = 632) in the delayed cardioversion group in X-VeRT, the use of rivaroxaban was estimated to result in a saving of £421 and €360 per patient in UK and Italian settings, respectively. CONCLUSION: The use of rivaroxaban in the setting of cardioversion resulted in greater patient satisfaction and cost savings, compared with that of VKA

Enhancement of Low-field Magnetoresistance in Self-Assembled Epitaxial La0.67Ca0.33MnO3:NiO and La0.67Ca0.33MnO3:Co3O4 Composite Films via Polymer-Assisted Deposition

Polymer-assisted deposition method has been used to fabricate self-assembled epitaxial La(0.67)Ca(0.33)MnO(3):NiO and La(0.67)Ca(0.33)MnO(3):Co(3)O(4) films on LaAlO(3) substrates. Compared to pulsed-laser deposition method, polymer-assisted deposition provides a simpler and lower-cost approach to self-assembled composite films with enhanced low-field magnetoresistance effect. After the addition of NiO or Co(3)O(4), triangular NiO and tetrahedral Co(3)O(4) nanoparticles remain on the surface of La(0.67)Ca(0.33)MnO(3) films. This results in a dramatic increase in resistivity of the films from 0.0061 Ω•cm to 0.59 Ω•cm and 1.07 Ω•cm, and a decrease in metal-insulator transition temperature from 270 K to 180 K and 172 K by the addition of 10%-NiO and 10%-Co(3)O(4), respectively. Accordingly, the maximum absolute magnetoresistance value is improved from −44.6% to −59.1% and −52.7% by the addition of 10%-NiO and 10%-Co(3)O(4), respectively. The enhanced low-field magnetoresistance property is ascribed to the introduced insulating phase at the grain boundaries. The magnetism is found to be more suppressed for the La(0.67)Ca(0.33)MnO(3):Co(3)O(4) composite films than the La(0.67)Ca(0.33)MnO(3):NiO films, which can be attributed to the antiferromagnetic properties of the Co(3)O(4) phase. The solution-processed composite films show enhanced low-field magnetoresistance effect which are crucial in practical applications. We expect our polymer-assisted deposited films paving the pathway in the field of hole-doped perovskites with their intrinsic colossal magnetoresistance

Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin