Advanced Numerical Solver for Dam-Break Flow Application

In this paper, a HLL (Harten Lax van Leer) approximate Riemann solver with MUSCL scheme (Monotonic Upwind Schemes for Conservative Laws) is implemented in the presented FV (Finite Volume) model. The presented model is used to simulate different dam-break flow events to verify its capability. Four test cases are presented in this paper. In the first test case, a 1-Dimensional (1D) dambreak flow is simulated over a rectangular channel with different slope limiters of the FV model (namely Godunov, Superbee, Minmod, van Leer, and van Albada). The second test case consists of a simulation of shallow water discontinuous dam-break flow over a dry-downstream bed channel. The third test simulates the shallow water dam-break flow with the existence of bed slope and bed shear stress. Finally, in the last test, the HLL-MUSCL model used in this paper and some other solver models used in literature are compared against the referred exact solution in dam-break flow application. The presented HLL-MUSCL scheme is found to give the best agreement to the exact solution

Partial Confirmation of Single katG and katE Knockouts and Double katG/katE Knockouts Created from Isogenic Background of Escherichia coli K-12 Strains

Presumptive knockouts of katE and katG catalases were constructed from BW25113 E.coli K-12 strain background via Lambda Red recombination system to generate katE/katG double knockout for a better assessment of the roles of the individual catalases (Narita and Peng, JEMI, 16, 123-8, 2012). The kanamycin resistance cassettes were then removed through FLP-FRT recombination system for consistent antibiotic sensitivity across the laboratory strains. In this study, our goal was to confirm the genotype and phenotype of these knockout strains by PCR, and catalase activity assay with 30% or 2% hydrogen peroxide (H 2 O 2 ). The katG single knockout and double knockout strains, as expected, were catalase positive and negative, respectively. The katE single knockout strain was only catalase positive when the test was done with 2% hydrogen peroxide suggesting a threshold concentration of hydrogen peroxide required for katG expression. The PCR results confirmed the continued existence of katE knockout during the process of creating double knockouts. It also identified that the kanR gene insert is present in the presumptive double knockout strain PN11W-4a

Softening of First-Order Phase Transition on Quenched Random Gravity Graphs

We perform extensive Monte Carlo simulations of the 10-state Potts model on quenched two-dimensional $\Phi^3$ gravity graphs to study the effect of quenched coordination number randomness on the nature of the phase transition, which is strongly first order on regular lattices. The numerical data provides strong evidence that, due to the quenched randomness, the discontinuous first-order phase transition of the pure model is softened to a continuous transition, representing presumably a new universality class. This result is in striking contrast to a recent Monte Carlo study of the 8-state Potts model on two-dimensional Poissonian random lattices of Voronoi/Delaunay type, where the phase transition clearly stayed of first order, but is in qualitative agreement with results for quenched bond randomness on regular lattices. A precedent for such softening with connectivity disorder is known: in the 10-state Potts model on annealed Phi3 gravity graphs a continuous transition is also observed.Comment: Latex + 5 postscript figures, 10 pages of text, figures appende

Ising and Potts Models on Quenched Random Gravity Graphs

We report on single-cluster Monte Carlo simulations of the Ising, 4-state Potts and 10-state Potts models on quenched ensembles of planar, tri-valent random graphs. We confirm that the first-order phase transition of the 10-state Potts model on regular 2D lattices is softened by the quenched connectivity disorder represented by the random graphs and that the exponents of the Ising and 4-state Potts models are altered from their regular lattice counterparts. The behaviour of spin models on such graphs is thus more analogous to models with quenched bond disorder than to Poisonnian random lattices, where regular lattice critical behaviour persists. Using a wide variety of estimators we measure the critical exponents for all three models, and compare the exponents with predictions derived from taking a quenched limit in the KPZ formula for the Ising and 4-state Potts models. Earlier simulations suggested that the measured values for the 10-state Potts model were very close to the predicted quenched exponents of the {\it four}-state Potts models. The analysis here, which employs a much greater range of estimators and also benefits from greatly improved statistics, still supports these numerical values.Comment: 14 pages (latex) + 6 latex tables + 5 figure

Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab

AIM To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease. METHODS We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts: (1) the AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (any first-line regimen ± bevacizumab); and (3) two cancer centres in New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line regimen ± bevacizumab). For the AGITG MAX trial capecitabine was compared to the other two arms (capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases. Secondary endpoints included progression-free survival, chemotherapy duration, and overall survival. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS Eighty-four MAX, 179 TRACC and 69 NSWCC patients had peritoneal disease. There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone arm. In a further analysis of patients without peritoneal metastases in the TRACC registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group. The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64 (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37-0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32. Chemotherapy duration was similar across the groups. CONCLUSION Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone

Automated control of plasma ion-assisted electron beam-deposited TiO2 optical thin films

A hollow cathode plasma source has been operated automatically, demonstrating independent control of plasma ion energy and ion current density for plasma ion-assisted electron beam-deposited titania (TiO2). The lanthanum hexaboride hollow cathode design described in this work utilizes both the interior and exterior cathode surfaces, with the additional electrons generated removing the need for a separate neutralizing source. Automatic feedback control of plasma source cathode-to-anode accelerator voltage (AV-via argon gas flow to the anode and/or cathode plasma source areas) and accelerator current (AC-via an external high-current power supply) provides independent control of the ion energy distribution function and ion current density, respectively. Automated run-to-run reproducibility (over six separate deposition runs) in TiO2 refractive index (550 nm) was demonstrated as 2.416 ± 0.008 (spread quoted as one standard deviation), which is well within the required refractive index control for optical coating applications. Variation in refractive index is achievable through control of AV (ion energy) and/or AC (ion current density), directly influencing deposited TiO2 structural phase. Measured dependencies of TiO2 refractive index and extinction coefficient on AV and AC are described. Optimum plasma source parameters for assisted electron beam deposition of TiO2 optical thin-film applications are highlighted

The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits

The Hybrid Mouse Diversity Panel (HMDP) is a collection of approximately 100 well-characterized inbred strains of mice that can be used to analyze the genetic and environmental factors underlying complex traits. While not nearly as powerful for mapping genetic loci contributing to the traits as human genome-wide association studies, it has some important advantages. First, environmental factors can be controlled. Second, relevant tissues are accessible for global molecular phenotyping. Finally, because inbred strains are renewable, results from separate studies can be integrated. Thus far, the HMDP has been studied for traits relevant to obesity, diabetes, atherosclerosis, osteoporosis, heart failure, immune regulation, fatty liver disease, and host-gut microbiota interactions. High-throughput technologies have been used to examine the genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes of the mice under various environmental conditions. All of the published data are available and can be readily used to formulate hypotheses about genes, pathways and interactions

Smartphone electrocardiogram for detecting atrial fibrillation after a cerebral ischaemic event: a multicentre randomized controlled trial

Aims: Atrial fibrillation (AF) is a preventable cause of ischaemic stroke but it is often undiagnosed and undertreated. The utility of smartphone electrocardiogram (ECG) for the detection of AF after ischaemic stroke is unknown. The aim of this study is to determine the diagnostic yield of 30-day smartphone ECG recording compared with 24-h Holter monitoring for detecting AF ≥30 s. Methods and results: In this multicentre, open-label study, we randomly assigned 203 participants to undergo one additional 24-h Holter monitoring (control group, n = 98) vs. 30-day smartphone ECG monitoring (intervention group, n = 105) using KardiaMobile (AliveCor®, Mountain View, CA, USA). Major inclusion criteria included age ≥55 years old, without known AF, and ischaemic stroke or transient ischaemic attack (TIA) within the preceding 12 months. Baseline characteristics were similar between the two groups. The index event was ischaemic stroke in 88.5% in the intervention group and 88.8% in the control group (P = 0.852). AF lasting ≥30 s was detected in 10 of 105 patients in the intervention group and 2 of 98 patients in the control group (9.5% vs. 2.0%; absolute difference 7.5%; P = 0.024). The number needed to screen to detect one AF was 13. After the 30-day smartphone monitoring, there was a significantly higher proportion of patients on oral anticoagulation therapy at 3 months compared with baseline in the intervention group (9.5% vs. 0%, P = 0.002). Conclusions: Among patients ≥55 years of age with a recent cryptogenic stroke or TIA, 30-day smartphone ECG recording significantly improved the detection of AF when compared with the standard repeat 24-h Holter monitoring. Keywords: Anticoagulation; Atrial fibrillation; Cryptogenic stroke; Digital health; Smartphone electrocardiogram.

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure