Abstract
Self-consistent modeling using the stability, transport, equilibrium, and pedestal (STEP) workflow in the OMFIT integrated modeling framework (predicting pedestal with EPED, core profiles ...with TGYRO, current profile with ONETWO, and EFIT for equilibrium) suggests ITER and future devices such as China Fusion Engineering Test Reactor (CFETR) Zhuang
et al
(2019
Nucl. Fusion
59
112010) will benefit from high-density operation (Greenwald limit fraction
f
g
w
≈
0.7−1.3). Regimes with an operational density near the Greenwald limit will likely need peaked density profiles so that the pedestal density remains below the Greenwald limit. Peaked density profiles can be achieved with the help of pellet injection. A flexible Pellet Ablation Module (PAM), which predicts the density source based on a comprehensive analytical pellet ablation model, has been developed for predicting pellet fueling for transport studies, and has been incorporated into the STEP workflow for predictive modeling. This workflow is applied to DIII-D and finds good agreement with experiments. On ITER the effect of pellet fueling is examined in an advanced inductive scenario, where a fusion gain of up to
Q
= 9 is predicted with strong central pellet fueling. On CFETR, with a mid-radius density source, an average of
1.5
×
10
22
electrons s
−1
are required to achieve the density and temperature profiles necessary for the 1000 MW advanced scenario with a tritium burn-up fraction of
∼
3
%
.
The development of potent, orally bioavailable, and selective series of 5-amino-3-hydroxy-
N(1-hydroxypropane-2-yl)isothiazole-4-carboxamidine inhibitors of MEK1 and MEK-2 kinase is described. ...Optimization of the carboxamidine and the phenoxyaniline group led to the identification of
55 which gave good potency as in vitro MEK1 inhibitors, and good oral exposure in rat.
Abstract Cost-effective strategies to maintain healthy active lifestyle in aging populations are required to address the global burden of age-related diseases. ASPREE will examine whether the ...potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals. Our primary hypothesis is that daily oral 100 mg enteric-coated aspirin will extend a composite primary endpoint termed ‘disability-free life’ including onset of dementia, total mortality, or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65 years and above (‘US minorities’) and 70 years and above (non-‘US minorities’). ASPREE is a double-blind, randomized, placebo-controlled trial of oral 100 mg enteric-coated acetyl salicylic acid (ASA) or matching placebo being conducted in Australian and US community settings on individuals free of dementia, disability and cardiovascular disease (CVD) events. Secondary endpoints are all-cause and cause specific mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer (excluding non-melanoma skin cancer), dementia, mild cognitive impairment, depression, physical disability, and clinically significant bleeding. To 20 September 2013 14,383 participants have been recruited. Recruitment and study completion are anticipated in July 2014 and December 2018 respectively. In contrast to other aspirin trials that have largely focused on cardiovascular endpoints, ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia.
We assessed the safety and immunogenicity of prime-boost vectors encoding the
Plasmodium falciparum circumsporozoite (CS) protein expressed either in the attenuated fowl-pox virus (FP9) or modified ...vaccinia virus Ankara (MVA). Thirty-two adult Gambians in groups of four to eight received one, two or three doses of FP9 CS and/or MVA CS. No serious adverse event was observed following vaccination. The most immunogenic regimen was two doses of FP9 followed by a single dose of MVA 4 weeks later (an average of 1000 IFN-γ spot forming units/million PBMCs). This level of effector T-cell responses appears higher than that seen in previously reported studies of CS-based candidate malaria vaccines.
A recombinant modified vaccinia virus Ankara expressing the antigen 85A gene from Mycobacterium tuberculosis (MVA85A) is being developed to enhance the immunogenicity and protective efficacy of BCG. ...2 This vaccine was recently designated an orphan drug by the European Commission.
.
Precise data for quasi-free photoproduction of
η
-mesons off the deuteron have been measured at the Bonn ELSA accelerator with the combined Crystal Barrel/TAPS detector for incident photon energies ...up to 2.5GeV. The
η
-mesons have been detected in coincidence with recoil protons and neutrons. Possible nuclear effects like Fermi motion and re-scattering can be studied via a comparison of the quasi-free reaction off the bound proton to
η
-production off the free proton. No significant effects beyond the folding of the free cross-section with the momentum distribution of the bound protons have been found. These Fermi motion effects can be removed by an analysis using the invariant mass of the
η
-nucleon pairs reconstructed from the final-state four-momenta of the particles. The total cross-section for quasi-free
η
-photoproduction off the neutron reveals even without correction for Fermi motion a pronounced bump-like structure around 1GeV of incident photon energy, which is not observed for the proton. This structure is even narrower in the invariant-mass spectrum of the
η
-neutron pairs. Position and width of the peak in the invariant-mass spectrum are
W
≈ 1665 MeV and FWHM
Γ
≈ 25 MeV. The data are compared to the results of different models.
Abstract
Background
Women are more susceptible to develop several forms of pulmonary hypertension, but they may have better survival rates than men. Sparse data are available concerning sex-specific ...differences in chronic thromboembolic pulmonary hypertension (CTEPH).
Purpose and methods
We investigated sex-specific differences in the clinical presentation of CTEPH, functional parameters, exposure to pulmonary endarterectomy (PEA), and survival.
Results
Women constituted half of the study population (N=679 treatment-naïve patients from the European CTEPH registry) and were characterized by a lower prevalence of some cardiovascular risk factors (e.g. prior acute coronary syndrome, smoking habit, chronic obstructive pulmonary disease), but more prevalent obesity, cancer, and thyroid diseases. Median age was 62 (IQR 50–73) years in women and 63 (IQR 53–70) in men. Women underwent PEA less often than men (54% vs 65%; Figure 1, Panel A) and were exposed to fewer additional cardiac procedures, notably coronary artery bypass graft surgery (0.5% vs. 9.5%). The prevalence of specific reasons for not being operated, including the patient's refusal and the proportion of proximal vs. distal lesions, did not differ between sexes. A total of 57 (17.0%) deaths in women and 70 (20.7%) in men were recorded over long-term follow-up. Female sex was positively associated with long-term survival (adjusted Hazard Ratio 0.66; 95% Confidence Interval 0.46–0.94). Short-term mortality was identical in the two groups (Figure 1, Panel B).
Conclusions
Women with CTEPH had a lower prevalence of cardiovascular risk factors and underwent PEA less frequently than men, who, in turn, were more often exposed to additional major cardiac surgery procedures. Women had more favorable long-term survival.
Acknowledgement/Funding
The CTEPH registry is supported by a research grant from Actelion Pharmaceuticals Ltd.
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