High-definition velocity-space tomography of fast-ion dynamics

Velocity-space tomography of the fast-ion distribution function in a fusion plasma is usually a photon-starved tomography method due to limited optical access and signal-to-noise ratio of fast-ion Dα (FIDA) spectroscopy as well as the strive for high-resolution images. In high-definition tomography, prior information makes up for this lack of data. We restrict the target velocity space through the measured absence of FIDA light, impose phase-space densities to be non-negative, and encode the known geometry of neutral beam injection (NBI) sources. We further use a numerical simulation as prior information to reconstruct where in velocity space the measurements and the simulation disagree. This alternative approach is demonstrated for four-view as well as for two-view FIDA measurements. The high-definition tomography tools allow us to study fast ions in sawtoothing plasmas and the formation of NBI peaks at full, half and one-third energy by time-resolved tomographic movies

Deuterium temperature, drift velocity, and density measurements in non-Maxwellian plasmas at ASDEX Upgrade

We measure the deuterium density, the parallel drift velocity, and parallel and perpendicular temperatures (T∥, T⊥) in non-Maxwellian plasmas at ASDEX Upgrade. This is done by taking moments of the ion velocity distribution function measured by tomographic inversion of five simultaneously acquired spectra of Dα-light. Alternatively, we fit the spectra using a bi-Maxwellian distribution function. The measured kinetic temperatures (T∥ = 9 keV, T⊥ = 11 keV) reveal the anisotropy of the plasma and are substantially higher than the measured boron temperature (7 keV). The Maxwellian deuterium temperature computed with TRANSP (6 keV) is not uniquely measurable due to the fast ions. Nevertheless, simulated kinetic temperatures accounting for fast ions based on TRANSP (T∥= 8.3 keV, T⊥ = 10.4 keV) are in excellent agreement with the measurements. Similarly, the Maxwellian deuterium drift velocity computed with TRANSP (300 km s-1) is not uniquely measurable, but the simulated kinetic drift velocity accounting for fast ions agrees with the measurements (400 km s-1) and is substantially larger than the measured boron drift velocity (270 km s-1). We further find that ion cyclotron resonance heating elevates T∥ and T⊥ each by 2 keV without evidence for preferential heating in the Dα spectra. Lastly, we derive an expression for the 1D projection of an arbitrarily drifting bi-Maxwellian onto a diagnostic line-of-sight

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

Effective Cost-Sharing Models in Higher Education: Insights from Low-Income Students in Australian Universities

This study examines the global trend in shifting university costs from national governments to individual students and families, with a specific focus on the existing cost-sharing model in Australian higher education. The research examines the manner in which the availability of income-contingent loans (through the Higher Education Contribution Scheme, or HECS) enters into individual cost assessments and evaluative frameworks during the university exploration and search process of low-income Australian youth, and the resulting lessons that might be applied to other national contexts. Semi-structured interviews with 16 participants addressed a broad range of issues related to the development of educational aspirations, and how beliefs and attitudes about cost influenced participants’ understanding and decision-making regarding tertiary enrollment and post-graduate plans. A number of discreet and related themes emerged from analysis of the interviews, including motivations for attending university; pre-university cost considerations; self-assessments of skills, abilities, and personal traits and characteristics; general financial orientation; pre-university experiences and influences; and the role of others including family, peers, teachers and other school staff. The author concludes that the Australian system is worthy of consideration by other nations as a possible mechanism for enhancing access to higher education for individuals who might otherwise not possess the opportunity to participate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42840/1/10734_2004_Article_6373.pd

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Phase II randomised discontinuation trial of brivanib in patients with advanced solid tumours

Background: Brivanib is a selective inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signalling. We performed a phase II randomised discontinuation trial of brivanib in 7 tumour types (soft-tissue sarcomas [STS], ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer [NSCLC], gastric/esophageal cancer and transitional cell carcinoma [TCC]). Patients and methods: During a 12-week open-label lead-in period, patients received brivanib 800 mg daily and were evaluated for FGF2 status by immunohistochemistry. Patients with stable disease at week 12 were randomised to brivanib or placebo. A study steering committee evaluated week 12 response to determine if enrolment in a tumour type would continue. The primary objective was progression-free survival (PFS) for brivanib versus placebo in patients with FGF2-positive tumours. Results: A total of 595 patients were treated, and stable disease was observed at the week 12 randomisation point in all tumour types. Closure decisions were made for breast cancer, pancreatic cancer, NSCLC, gastric cancer and TCC. Criteria for expansion were met for STS and ovarian cancer. In 53 randomised patients with STS and FGF2-positive tumours, the median PFS was 2.8 months for brivanib and 1.4 months for placebo (hazard ratio [HR]: 0.58, p = 0.08). For all randomised patients with sarcomas, the median PFS was 2.8 months (95% confidence interval [CI]: 1.4–4.0) for those treated with brivanib compared with 1.4 months (95% CI: 1.3–1.6) for placebo (HR = 0.64, 95% CI: 0.38–1.07; p = 0.09). In the 36 randomised patients with ovarian cancer and FGF2-positive tumours, the median PFS was 4.0 (95% CI: 2.6–4.2) months for brivanib and 2.0 months (95% CI: 1.2–2.7) for placebo (HR: 0.56, 95% CI: 0.26–1.22). For all randomised patients with ovarian cancer, the median PFS in those randomised to brivanib was 4.0 months (95% CI: 2.6–4.2) and was 2.0 months (95% CI: 1.2–2.7) in those randomised to placebo (HR = 0.54, 95% CI: 0.25–1.17; p = 0.11). Conclusion: Brivanib demonstrated activity in STS and ovarian cancer with an acceptable safety profile. FGF2 expression, as defined in the protocol, is not a predictive biomarker of the efficacy of brivanib

The population history of northeastern Siberia since the Pleistocene

FGW – Publications without University Leiden contractDescriptive and Comparative Linguistic

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe