Response of a lithium fall to an inertially confined fusion microexplosion

One of the most difficult technology problems in an inertially confined fusion reactor is the survival of the structure from the repeated stresses caused by the microexplosion products. To mitigate the damage from the microexplosion products, a thick lithium fall can be circulated in front of the structure. This fall will absorb the short-ranged products and moderate and attenuate the neutrons. This paper discusses the response of the fall to the microexplosion products, and estimates the resulting loading and stresses in the first structural wall

Low‐Density Lipoprotein Cholesterol Attributable Cardiovascular Disease Risk Is Sex Specific

Background: Epidemiological studies show that women are generally at lower risk for cardiovascular disease than men. Here, we investigated the sex‐specific differential effect of genetically increased low‐density lipoprotein cholesterol (LDL‐C) on cardiovascular disease (CVD) and other lipid‐associated diseases. Methods and Results: This is a 2‐sample Mendelian randomization study that uses individual participant data from 425 043 participants from the UK Biobank, including 229 279 female participants. An 80‐variant LDL‐C weighted genetic score was generated. Linear and logistic regression models with interactions were used to identify differences between sex‐specific LDL‐C effects on lipids, carotid‐intima media thickness, and multiple cardiovascular outcomes such as CVD, ischemic heart disease, peripheral artery disease, heart failure, aortic valve disease, type 2 diabetes, atrial fibrillation, and aortic aneurysm and dissection. After correction for multiple testing, we observed that the genetically increased LDL‐C effect on CVD events was sex specific: per SD genetically increased LDL‐C, female participants had a higher LDL‐C increase but an attenuated CVD risk increase compared with male participants (LDL‐C: female participants 0.71 mmol/L, 95% CI, 0.70–0.72 and male participants 0.57 mmol/L, 95% CI, 0.56–0.59. P for interaction: 5.03×10−60; CVD: female participants: odds ratio [OR], 1.32; 95% CI 1.24–1.40 and male participants: OR, 1.52; 95% CI, 1.46–1.58. P for interaction: 9.88×10−5). We also observed attenuated risks for ischemic heart disease and (nominally for) heart failure in female participants, and genetically increased LDL‐C results in higher risk for aortic valve disease in female participants compared with male participants. Genetically increased LDL‐C was also associated with an attenuated carotid‐intima media thickness increase in female participants. We did not observe other significant attenuations. Sensitivity analyses with an unweighted genetic score and sex‐specific weighted genetic scores showed similar results. Conclusions: We found that genetically increased LDL‐C has a sex‐specific differential effect on the risk for cardiovascular disease, ischemic heart disease, heart failure, and aortic valve stenosis. Our observations provide evidence that LDL‐C might be a less important determinant of CVD in women compared with men, suggesting that male patients might benefit more from LDL‐C targeted therapies for CVD management than female patients and warranting investigations into the sex‐specific relative contribution of risk factors for CVD

Genetically Predicted Neutrophil-to-Lymphocyte Ratio and Coronary Artery Disease: Evidence From Mendelian Randomization.

Inflammation contributes to atherosclerosis and coronary artery disease (CAD). In order to help identify therapeutic targets, it is important to ascertain whether biomarkers associated with CAD risk are causal. In a recent meta-analysis of clinical trials, neutrophil-to lymphocyte ratio (NLR) was associated with increased cardiovascular risk 1 . We investigate a potential causal nature of this relationship by performing Mendelian randomization (MR) analyse

Real-World Identification Of European Patients With Statin-Associated Symptoms: Clinical Practice Compared With Clinical Guidelines

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Short-term obeticholic acid treatment does not impact cholangiopathy in Cyp2c70-deficient mice with a human-like bile acid composition

Cyp2c70-/- mice with a human-like bile acid (BA) composition, lacking hydrophilic muricholic acids (MCAs), have been reported to display cholangiopathy and biliary fibrosis with female preponderance that can be reversed by ursodeoxycholic acid (UDCA). Obeticholic acid (OCA), a steroidal BA-like FXR agonist, has been shown to improve liver function in patients with primary biliary cholangitis and is approved as second-line treatment for patients with an inadequate response or intolerance to UDCA. Here, we investigated the impact of OCA on BA hydrophobicity and cholangiopathy in Cyp2c70-/- mice. Male and female wild-type (WT) and Cyp2c70-/- mice were fed a chow diet with or without 10 mg/kg/day OCA for 4 weeks. OCA accounted for 1-5% of biliary BAs, with larger enrichments in Cyp2c70-/- than in WT mice. In WT mice, OCA induced a more hydrophilic, MCA-rich BA pool. In Cyp2c70-/- mice, however, BA pool became more hydrophobic with a larger proportion of chenodeoxycholic acid, attributable to a reduction of BA 12α-hydroxylation. OCA treatment reduced fecal BA excretion, indicating repression of hepatic BA synthesis in both WT and Cyp2c70-/- mice. OCA did, however, not impact on markers of liver (dys)function in plasma nor did it ameliorate cholangiopathy and fibrosis in male or female Cyp2c70-/- mice. OCA treatment also did not affect the expression of genes involved in fibrosis, inflammation and cellular senescence. In conclusion, 4 weeks of OCA treatment oppositely modulates the hydrophobicity of the BA pool in WT and Cyp2c70-/- mice, but does not improve or worsen the characteristic sex-dependent liver pathology in Cyp2c70-/- mice

Comparison of the design and costs of induction linac drivers for inertial fusion using ions of differing mass

An induction linear accelerator that produces an energetic (5 to 20 GeV) beam of heavy (130 to 238 amu) ions is a prime candidate as a driver for inertial fusion. The required accelerator output parameters for an ion species can be determined from the target requirements for a given fusion energy yield. The cost and efficiency of various accelerator configurations to produce the required output parameters can be determined to aid in the selection of the lowest cost accelerator design option. In this study, we compare the cost of various accelerator configurations that will produce various target fields and fusion powers using cesium 133 ions with those using mercury 200 ions, and report extensively on some 600 MJ target yield results

Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R

Aims: Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects. // Methods: We constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters. // Results: A 1 mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1 mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals. // Conclusions: IL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk

Comparison of the design and costs of induction linac drivers for inertial fusion using ions of mass 133 and 200

Optimized cost estimates for induction linac accelerators using mass 133 ions at a charge state of +2 producing inertial fusion target yields of 300, 600, and 1200 MJ are presented. The ions are injected into the accelerator at 3 MV, and accelerated to the required voltage appropriate to the desired target yield. A cost comparison of these drivers is made with drivers using mass 200, charge state +3 ions for several target yields and a fusion power of 3000 MW

Analysis of an induction linac driver system for inertial fusion

A linear induction accelerator that produces a beam of energetic (5 to 20 GeV) heavy (130 to 210 amu) ions is a prime candidate as a driver for inertial fusion. Continuing developments in sources for ions with charge state greater than unity allow a potentially large reduction in the driver cost and an increase in the driver efficiency. The use of high undepressed tunes (sigma/sub 0/ approx. = 85/sup 0/) and low depressed tunes (sigma approx. = 8.5/sup 0/) also contributes to a potentially large reduction in the driver cost. The efficiency and cost of the induction linac system are discussed as a function of output energy and pulse repetition frequency for several ion masses and charge states. The cost optimization code LIACEP, including accelerating module alternatives, transport modules, and scaling laws, is presented. Items with large cost-leverage are identified as a guide to future research activities and development of technology that can yield substantial reductions in the accelerator system cost and improvement in the accelerator system efficiency. Finally, a cost-effective strategy using heavy ion induction linacs in a development scenario for inertial fusion is presented. 34 refs., 6 figs., 7 tabs