Seismic radiation by magma injection: An anomalous seismic event near Tori Shima, Japan

The earthquake with a bodywave magnitude m_b=5.5, which occurred near Tori Shima, Japan, on June 13, 1984 (origin time: 0229:25.3 UT, 31.448°N, 140.036°E, depth of 10 km, m_b =5.5, M_S=5.5) is anomalous because it generated tsunamis which are disproportionately large for the magnitude of the earthquake. At Hachijo Island, 150 km from the epicenter, tsunamis were visually observed with peak-to-peak amplitude of 130 to 150 cm. Long-period seismic radiation is also anomalous. Love waves are almost absent, and Rayleigh waves are radiated with equal amplitude and phase in all directions. A simple double-couple model cannot explain these observations. With the assumption of no net volume change at the source, these data can be best explained with a compensated linear vector dipole (CLVD) with the principal tensional dipole in the vertical direction. The scalar moment of this dipole is 4×10^(24) dyn cm. Moment tensor inversions of long-period body waves and surface waves yield an almost identical solution. This CLVD source can be interpreted as horizontal fluid injection. The location of the event is in the Smith depression which is one of the nascent back arc basins just behind the Bonin arc. These basins are filled with thick sediments, and numerous young volcanoes are found near this site. Magmatic injection is most likely to occur in this tectonic environment. However, the time scale of the seismic event seems too short for magma injection to occur. A more likely mechanism involves water-magma interaction. The injection may be viewed as hydrofracturing driven by supercritical water heated by injected magma. The estimated volume of injected water is about 0.018 km^3 and that of basaltic magma is about 10% of this. This type of deformation is more efficient for tsunami generation than faulting with the same scalar moment

Association of RENAL nephrometry score with outcomes of minimally invasive partial nephrectomy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98294/1/iju3222.pd

Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2

Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

BackgroundCurrent treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.MethodsWe performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).ResultsRituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of$61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and$110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.ConclusionsOur results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug

Elevated Mechanical Loading When Young Provides Lifelong Benefits to Cortical Bone Properties in Female Rats Independent of a Surgically Induced Menopause

Exercise that mechanically loads the skeleton is advocated when young to enhance lifelong bone health. Whether the skeletal benefits of elevated loading when young persist into adulthood and after menopause are important questions. This study investigated the influence of a surgically induced menopause in female Sprague-Dawley rats on the lifelong maintenance of the cortical bone benefits of skeletal loading when young. Animals had their right forearm extrinsically loaded 3 d/wk between 4 and 10 weeks of age using the forearm axial compression loading model. Left forearms were internal controls and not loaded. Animals were subsequently detrained (restricted to cage activities) for 94 weeks (until age 2 years), with ovariectomy (OVX) or sham-OVX surgery being performed at 24 weeks of age. Loading enhanced midshaft ulna cortical bone mass, structure, and estimated strength. These benefits persisted lifelong and contributed to loaded ulnas having greater strength after detraining. Loading also had effects on cortical bone quality. The benefits of loading when young were not influenced by a surgically induced menopause because there were no interactions between loading and surgery. However, OVX had independent effects on cortical bone mass, structure, and estimated strength at early postsurgery time points (up to age 58 weeks) and bone quality measures. These data indicate skeletal loading when young had lifelong benefits on cortical bone properties that persisted independent of a surgically induced menopause. This suggests that skeletal loading associated with exercise when young may provide lifelong antifracture benefits by priming the skeleton to offset the cortical bone changes associated with aging and menopause

Navier-Stokes Analysis of a High Wing Transport High-Lift Configuration with Externally Blown Flaps

Insights and lessons learned from the aerodynamic analysis of the High Wing Transport (HWT) high-lift configuration are presented. Three-dimensional Navier-Stokes CFD simulations using the OVERFLOW flow solver are compared with high Reynolds test data obtained in the NASA Ames 12 Foot Pressure Wind Tunnel (PWT) facility. Computational analysis of the baseline HWT high-lift configuration with and without Externally Blown Flap (EBF) jet effects is highlighted. Several additional aerodynamic investigations, such as nacelle strake effectiveness and wake vortex studies, are presented. Technical capabilities and shortcomings of the computational method are discussed and summarized

Bioabsorbable metal zinc differentially affects mitochondria in vascular endothelial and smooth muscle cells

Zinc is an essential trace element having various structural, catalytic and regulatory interactions with an estimated 3000 proteins. Zinc has drawn recent attention for its use, both as pure metal and alloyed, in arterial stents due to its biodegradability, biocompatibility, and low corrosion rates. Previous studies have demonstrated that zinc metal implants prevent the development of neointimal hyperplasia, which is a common cause of restenosis following coronary intervention. This suppression appears to be smooth muscle cell-specific, as reendothelization of the neointima is not inhibited. To better understand the basis of zinc\u27s differential effects on rat aortic smooth muscle (RASMC) versus endothelial (RAENDO) cells, we conducted a transcriptomic analysis of both cell types following one-week continuous treatment with 5 µM or 50 µM zinc. This analysis indicated that genes whose protein products regulate mitochondrial functions, including oxidative phosphorylation and fusion/fission, are differentially affected by zinc in the two cell types. To better understand this, we performed Seahorse metabolic flux assays and quantitative imaging of mitochondrial networks in both cell types. Zinc treatment differently affected energy metabolism and mitochondrial structure/function in the two cell types. For example, both basal and maximal oxygen consumption rates were increased by zinc in RASMC but not in RAENDO. Zinc treatment increased apparent mitochondrial fusion in RASMC cells but increased mitochondrial fission in RAENDO cells. These results provide some insight into the mechanisms by which zinc treatment differently affects the two cell types and this information is important for understanding the role of zinc treatment in vascular cells and improving its use in biodegradable metal implants

p35, the non-cyclin activator of Cdk5, protects podocytes against apoptosis in vitro and in vivo

Cyclin-dependent kinase-5 is widely expressed and predominantly regulated by the non-cyclin activator p35. Since we recently showed that expression of p35 in the kidney is restricted to podocytes, we examined here its function in mice in which p35 was genetically deleted. The mice did not exhibit kidney abnormalities during glomerular development or during adult life. Conditionally immortalized cultured podocytes, derived from these null mice, did not have any change in their morphology, differentiation, or proliferation. However, when these cultured podocytes were exposed to UV-C irradiation, serum depletion, puromycin aminonucleoside, or transforming growth factor-β-1, they showed increased apoptosis compared to those from wild-type mice. Levels of Bcl-2 were decreased in these null podocytes but increased after transduction with human p35. Restoration of p35 or the ectopic expression of Bcl-2 reduced the susceptibility of p35-null podocytes to apoptosis. Experimental glomerulonephritis, characterized by podocyte apoptosis and subsequent crescent formation, was utilized to test these findings in vivo. Podocyte apoptosis was significantly increased in diseased p35-null compared with wild-type mice, accompanied by increased glomerulosclerosis and decreased renal function. Our study shows that p35 does not affect glomerulogenesis but controls podocyte survival following injury, in part, by regulating Bcl-2 expression

Effect of obesity on the population pharmacokinetics of meropenem in critically ill patients

Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m(2)), obese (30.0 to 39.9 kg/m(2)), and morbidly obese (>= 40 kg/m(2)). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean +/- standard deviation (SD) age, weight, and BMI were 49 +/- 15.9 years, 95 +/- 22.0 kg, and 33 +/- 7.0 kg/m(2), respectively. A two-compartment model described the data adequately. The mean +/- SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 +/- 6.0 liters/h; volume of distribution in the central compartment (V-1), 11.7 +/- 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 +/- 35.1 liters h(-1); and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 +/- 12.24 liters h(-1). Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V-1, dose adjustment based on CLCR appears to be more important than patient BMI