Channeltron Gain In Magnetic Fields

The gain and total count rate of electron channel multipliers depend strongly on applied magnetic fields. We report experimental results for Channeltrons operated in magnetic fields of up to 300 G, and find that the applied voltage must be increased to about 4000 V to maintain a sufficiently high gain. Slightly higher count rates are observed if the magnetic field is parallel to the plane of the Channeltron, as compared to perpendicular to that plane. © 1972 The American Institute of Physics

Lower activity of cholesteryl ester transfer protein (CETP) and the risk of dementia: A Mendelian randomization analysis

Background: Elevated concentrations of low-density lipoprotein cholesterol (LDL-C) are linked to dementia risk, and conversely, increased plasma concentrations of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein-A1 (Apo-A1) associate with decreased dementia risk. Inhibition of cholesteryl ester transfer protein (CETP) meaningfully affects the concentrations of these blood lipids and may therefore provide an opportunity to treat dementia. Methods: Drug target Mendelian randomization (MR) was employed to anticipate the on-target effects of lower CETP concentration (μg/mL) on plasma lipids, cardiovascular disease outcomes, autopsy confirmed Lewy body dementia (LBD), as well as Parkinson’s dementia. Results: MR analysis of lower CETP concentration recapitulated the blood lipid effects observed in clinical trials of CETP-inhibitors, as well as protective effects on coronary heart disease (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89; 0.96), heart failure, abdominal aortic aneurysm, any stroke, ischemic stroke, and small vessel stroke (0.90, 95%CI 0.85; 0.96). Consideration of dementia related traits indicated that lower CETP concentrations were associated higher total brain volume (0.04 per standard deviation, 95%CI 0.02; 0.06), lower risk of LBD (OR 0.81, 95%CI 0.74; 0.89) and Parkinson’s dementia risk (OR 0.26, 95%CI 0.14; 0.48). APOE4 stratified analyses suggested the LBD effect was most pronounced in APOE-ε4 + participants (OR 0.61 95%CI 0.51; 0.73), compared to APOE-ε4- (OR 0.89 95%CI 0.79; 1.01); interaction p-value 5.81 × 10− 4. Conclusions: These results suggest that inhibition of CETP may be a viable strategy to treat dementia, with a more pronounced effect expected in APOE-ε4 carriers.</p

An adaptive meta-search engine considering the user’s field of interest

AbstractExisting meta-search engines return web search results based on the page relevancy to the query, their popularity and content. It is necessary to provide a meta-search engine capable of ranking results considering the user’s field of interest. Social networks can be useful to find the users’ tendencies, favorites, skills, and interests. In this paper we propose MSE, a meta-search engine for document retrieval utilizing social information of the user. In this approach, each user is assumed to have a profile containing his fields of interest. MSE extracts main phrases from the title and short description of receiving results from underlying search engines. Then it clusters the main phrases by a Self-Organizing Map neural network. Generated clusters are then ranked on the basis of the user’s field of interest. We have compared the proposed MSE against two other meta-search engines. The experimental results show the efficiency and effectiveness of the proposed method

Variability and reproducibility of flow-mediated dilatation in a multicentre clinical trial

Aims The aim of this study was to assess the reproducibility of flow-mediated dilatation (FMD) in a multicentre setting. Methods and results This study was performed as part of the dal-VESSEL trial in which FMD was measured in 19 vascular imaging centres in six European countries. A subgroup of patients who were allocated in the placebo group and scanned twice at each trial time point (substudy) was analysed. Intra-sonographer variability was calculated from FMD measurements 48 h apart. Centre variability and short-, medium-, and long-term reproducibility of FMD were calculated at 48 h and at 3 and 9 months intervals, respectively. Intra- and inter-reader variability was assessed by re-analysing the FMD images by three certified readers at two time intervals, 7 days apart. Sixty-seven patients were included. Variability between centres was comparable at 48 h and 3 months interval but almost doubled at 9 months. The mean absolute difference in %FMD was 1.04, 0.99, and 1.45% at the three time intervals, respectively. Curves were generated to indicate the number of patients required for adequate power in crossover and parallel study designs. Conclusion This study demonstrates for the first time that in a multicentre setting reproducible FMD measurements can be achieved for short- and medium-term evaluation, which are comparable with those reported from specialized laboratories. These findings justify the use of FMD as an outcome measure for short- and medium-term assessment of pharmacological intervention

LDL-cholesterol lowering and clinical outcomes in hypercholesterolemic subjects with and without a familial hypercholesterolemia phenotype: Analysis from the secondary prevention 4S trial

Background and aims: Trial evidence for the benefits of cholesterol-lowering is limited for familial hypercho lesterolemia (FH) patients, since they have not been the focus of large outcome trials. We assess statin use in coronary artery disease (CAD) subjects with low-density lipoprotein cholesterol (LDL-C) ≥4.9 mmol/L with or without an FH phenotype. Methods: The 4S trial randomized hypercholesterolemic CAD patients to simvastatin or placebo. We first strat ified participants into baseline LDL-C <4.9 and ≥ 4.9 mmol/L; next, based on the DLCN criteria for FH, the latter group was stratified into four subgroups by presence of none, one or both of “premature CAD” and “family history of CAD”. Participants having both are defined as having an FH phenotype. Results: 2267 and 2164 participants had LDL-C <4.9 and ≥ 4.9 mmol/L, respectively. Mortality endpoints and major coronary events (MCE) were significantly reduced with simvastatin versus placebo in both groups over 5.4 years, but the latter derived greater absolute risk reductions (ARR) (4.1–4.3% for mortality endpoints, versus 2.5–2.8%). LDL-C reductions were similar among the 4 subgroups with levels ≥4.9 mmol/L. Participants with FH phenotype (n = 152) appeared to derive greater relative benefits with simvastatin than the other three subgroups (all-cause death: 84% relative risk reduction, p = 0.046; MCE: 55% reduction, p = 0.0297); statistical interaction was non significant. Participants with FH phenotype derived greater ARR than any other group with simvastatin versus placebo (all-cause mortality: 6.6% ARR; MCE 13.2%; versus 3.8% and 8.3%, respectively, among participants with LDL-C ≥4.9 mmol/L but without features suggestive of FH). Conclusions: The FH phenotype appeared to be associated with greater clinical benefits from a given magnitude of LDL-C reduction as compared to individuals without FH phenotype

Sustained changes in lipid profile and macrophage migration inhibitory factor levels after anti-tumour necrosis factor therapy in rheumatoid arthritis

BACKGROUND: Macrophage migration inhibitory factor (MIF) has recently emerged as an important cytokine possibly linking rheumatoid arthritis (RA) and atherogenesis. Because atherogenesis is accelerated in RA this study was conducted to investigate whether anti-tumour necrosis factor (TNF) therapy could lead to sustained downregulation of systemic MIF levels and improvement in lipid profiles. METHODS: Fifty RA patients with active disease (disease activity score in 28 joints (DAS28) >or=3.2), who started adalimumab therapy at 40 mg every other week, were included. At baseline, weeks 16 and 52 serum levels of MIF and lipids were assessed. In addition, the DAS28 and serum C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were determined. RESULTS: After 16 weeks of adalimumab therapy, both DAS28 and MIF levels were significantly decreased (p<0.001 and p = 0.020, respectively). This was sustained up to week 52 (p<0.001 and p = 0.012, respectively). CRP levels and ESR were significantly reduced after 16 and 52 weeks of adalimumab therapy (p<0.001). High-density lipoprotein cholesterol levels increased at week 16 (p<0.001), but returned to baseline at week 52. Apolipoprotein (apo) A-I levels increased at week 16 (p<0.001) and remained stable (p = 0.005). This resulted in an improved apo B/A-I ratio. CONCLUSIONS: The results underline the sustained downregulation of MIF as a potential new mechanism by which anti-TNF therapy might reduce vascular inflammation, and as such perhaps cardiovascular morbidity in RA patients. This hypothesis is supported by an improved apo B/A-I ratio as well as reduced CRP levels in these patient