High power semiconductor switches in the 12 kV, 50 kA pulse generator of the SPS beam dump kicker system

Horizontal deflection of the beam in the dump kicker system of the CERN SPS accelerator is obtained with a series of fast pulsed magnets. The high current pulses of 50 kA per magnet are generated with capacitor discharge type generators which, combined with a resistive free-wheel diode circuit, deliver a critically damped half-sine current with a rise-time of 25 ms. Each generator consists of two 25 kA units, connected in parallel to a magnet via a low inductance transmission line

Pseudospark Switch Development for the LHC Extraction Kicker Pulse Generator

CERN, the European Laboratory for Particle Physics, has started construction of the Large Hadron Collider (LHC), a superconducting accelerator that will collide protons at a center of mass energy of 14 TeV from the year 2005 onwards. The kicker magnet pulse generators of the LHC beam extraction system require fast high power switches. One possible type is the pseudospark switch (PSS) which has several advantages for this application. A PSS fulfilling most of the requirements has been developed in the past years. Two outstanding problems, prefiring at high operating voltages and sudden current interruptions (quenching) at low voltage could be solved recently. Prefiring can be avoided for this special application by conditioning the switch at two times the nominal voltage after each power pulse. Quenching can be suppressed by choosing an appropriate electrode geometry and by mixing Krypton to the D2 gas atmosphere. One remaining problem, related to the required large dynamic voltage range (1.7 kV to 30 kV) is under active investigation: steps in forward voltage during conduction, occurring at low operation voltage at irregular time instants and causing a pulse to pulse jitter of the peak current. This paper presents results of electrical measurements concerning prefiring and quenching and explains how these problems have been solved. Furthermore the plans to cure the forward voltage step problem will be discussed

Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms and Coronary Heart Disease

Single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor γ (PPARG) gene have been associated with cardiovascular risk factors, particularly obesity and diabetes. We assessed the relationship between 4 PPARG SNPs (C-681G, C-689T, Pro12Ala, and C1431T) and coronary heart disease (CHD) in the PRIME (249 cases/494 controls, only men) and ADVANCE (1,076 cases/805 controls, men or women) studies. In PRIME, homozygote individuals for the minor allele of the PPARG C-689T, Pro12Ala, and C1431T SNPs tended to have a higher risk of CHD than homozygote individuals for the frequent allele (adjusted OR [95% CI] = 3.43 [0.96–12.27], P = .058, 3.41 [0.95–12.22], P = .060 and 5.10 [0.99–26.37], P = .050, resp.). No such association could be detected in ADVANCE. Haplotype distributions were similar in cases and control in both studies. A meta-analysis on the Pro12Ala SNP, based on our data and 11 other published association studies (6,898 CHD cases/11,287 controls), revealed that there was no evidence for a significant association under the dominant model (OR = 0.99 [0.92–1.07], P = .82). However, there was a borderline association under the recessive model (OR = 1.29 [0.99–1.67], P = .06) that became significant when considering men only (OR = 1.73 [1.20–2.48], P = .003). In conclusion, the PPARG Ala12Ala genotype might be associated with a higher CHD risk in men but further confirmation studies are needed

Clinical research Are the Framingham and PROCAM coronary heart disease risk functions applicable to different European populations? The PRIME StudyM

Aims To assess whether the Framingham and PROCAM risk functions were applicable to men in Belfast and France. Methods and results We performed an external validation study within the PRIME (Prospective Epidemiological Study of Myocardial Infarction) cohort study. It comprised men recruited in Belfast (2399) and France (7359) who were aged 50 to 59 years, free of CHD at baseline (1991 to 1993) and followed over 5 years for CHD events (coronary death, myocardial infarction, angina pectoris). We compared the relative risks of CHD associated with the classic risk factors in PRIME with those in Framingham and PROCAM cohorts. We then compared the number of predicted and observed 5-year CHD events (calibration). Finally, we estimated the ability of the risk functions to separate high risk from low risk subjects (discrimination). The relative risk of CHD calculated for the various factors in the PRIME population were not statistically different from those published in the Framingham and PROCAM risk functions. The number of CHD events predicted by these risk functions however clearly overestimated those observed in Belfast and France. The two risk functions had a similar ability to separate high risk from low risk subjects in Belfast and France (c-statistic range: 0.61-0.68). Conclusion The Framingham and PROCAM risk functions should not be used to estimate the absolute CHD risk of middle-aged men in Belfast and France without any CHD history because of a clear overestimation. Specific population risk functions are needed

Heart Rate and Risk of Cancer Death in Healthy Men

BACKGROUND: Data from several previous studies examining heart-rate and cardiovascular risk have hinted at a possible relationship between heart-rate and non-cardiac mortality. We thus systematically examined the predictive value of heart-rate variables on the subsequent risk of death from cancer. METHODS: In the Paris Prospective Study I, 6101 asymptomatic French working men aged 42 to 53 years, free of clinically detectable cardiovascular disease and cancer, underwent a standardized graded exercise test between 1967 and 1972. Resting heart-rate, heart-rate increase during exercise, and decrease during recovery were measured. Change in resting heart-rate over 5 years was also available in 5139 men. Mortality including 758 cancer deaths was assessed over the 25 years of follow-up. FINDINGS: There were strong, graded and significant relationships between all heart-rate parameters and subsequent cancer deaths. After adjustment for age and tobacco consumption and, compared with the lowest quartile, those with the highest quartile for resting heart-rate had a relative risk of 2.4 for cancer deaths (95% confidence interval: 1.9-2.9, p<0.0001) This was similar after adjustment for traditional cardiovascular risk factors and was observed for the commonest malignancies (respiratory and gastrointestinal). Similarly, significant relationships with cancer death were observed between poor heart rate increase during exercise, poor decrease during recovery and greater heart-rate increase over time (p<0.0001 for all). INTERPRETATION: Resting and exercise heart rate had consistent, graded and highly significant associations with subsequent cancer mortality in men

The APOA5 Trp19 allele is associated with metabolic syndrome via its association with plasma triglycerides

<p>Abstract</p> <p>Background</p> <p>The goal of the present study was to assess the effect of genetic variability at the APOA5/A4/C3/A1 cluster locus on the risk of metabolic syndrome.</p> <p>Methods</p> <p>The <it>APOA5 </it>Ser19Trp, <it>APOA5 </it>-12,238T>C, <it>APOA4 </it>Thr347Ser, <it>APOC3 </it>-482C>T and <it>APOC3 </it>3238C>G (<it>Sst</it>I) polymorphisms were analyzed in a representative population sample of 3138 men and women from France, including 932 individuals with metabolic syndrome and 2206 without metabolic syndrome, as defined by the NCEP criteria.</p> <p>Results</p> <p>Compared with homozygotes for the common allele, the odds ratio (OR) [95% CI] for metabolic syndrome was 1.30 [1.03–1.66] (<it>p </it>= 0.03) for <it>APOA5 </it>Trp19 carriers, 0.81 [0.69–0.95] (<it>p </it>= 0.01) for <it>APOA5 </it>-12,238C carriers and 0.84 [0.70–0.99] (<it>p </it>= 0.04) for <it>APOA4 </it>Ser347 carriers. Adjustment for plasma triglycerides, (but not for waist girth, HDL, blood pressure or glycemia – the other components of metabolic syndrome) abolished these associations and suggests that triglyceride levels explain the association with metabolic syndrome. There was no association between the <it>APOC3 </it>-482C>T or <it>APOC3 </it>3238C>G polymorphisms and metabolic syndrome. The decreased risk of metabolic syndrome observed in <it>APOA5 </it>-12,238C and <it>APOA4 </it>Ser347 carriers merely reflected the fact that the <it>APOA5 </it>Trp19 allele was in negative linkage disequilibrium with the common alleles of <it>APOA5 </it>-12,238T>C and <it>APOA4 </it>Thr347Ser polymorphisms.</p> <p>Conclusion</p> <p>The <it>APOA5 </it>Trp19 allele increased susceptibility to metabolic syndrome via its impact on plasma triglyceride levels.</p