Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

Abstract Background: The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective: To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods: Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results: The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion: The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

Low autocorrelation sequences and flat polynomials

Magdeburg, Univ., Fak. für Mathematik, Habil.-Schr., 2014

Untersuchungen zum Verletzungspotential handelsüblicher Soft-Air-Waffen mit einer Geschossenergie zwischen 0,08 Joule und 0,5 Joule

Magdeburg, Univ., Med. Fak., Diss., 2015

Infaunal recruitment patterns in soft bottom habitats of the Patos Lagoon estuary, southern Brazil: influence of Chasmagnathus granulata (Brachyura, Grapsidae) disturbance

A comparative study of the infaunal recruitment patterns among disturbed surface sediment mounds around Chasmagnathus granulata Dana, 1851 burrows and undisturbed adjacent sediments was done in two intertidal soft bottom habitats (an upper and a lower mudflat zone) in an estuarine inlet of Patos Lagoon, southern Brazil. The most abundant infaunal organisms were recruits of the polychaete Laeonereis acuta Treadwell, 1923 and of the tanaid Kalliapseudes schubartii Mañé-Garzón, 1949. The densities of these species did not differ significantly between upper and lower mudflat habitats. These species showed lower densities around crab burrows than in adjacent areas, where differences in sediment characteristics were observed as well. The results indicate that C. granulata disturbances may play an important role in regulating the soft bottom benthic community by controlling infaunal recruitment in the estuarine intertidal mudflats of the Patos Lagoon.

Effects of both ecdysone and the acclimation to low temperature, on growth and metabolic rate of juvenile freshwater crayfish Cherax quadricarinatus (Decapoda, Parastacidae)

Growth, metabolic rate, and energy reserves of Cherax quadricarinatus (von Martens, 1868) juveniles were evaluated in crayfish acclimated for 16 weeks to either 25ºC (temperature near optimum) or 20ºC (marginal for the species). Additionally, the modulating effect of ecdsyone on acclimation was studied. After 12 weeks of exposure, weight gain of both experimental groups acclimated to 25ºC (control: C25, and ecdysone treated: E25) was significantly higher than that of those groups acclimated to 20ºC (C20 and E20). A total compensation in metabolic rate was seen after acclimation from 25ºC to 20ºC; for both the control group and the group treated with ecdysone. A Q10value significantly higher was only observed in the group acclimated to 20ºC and treated with ecdysone. A reduction of glycogen reserves in both hepatopancreas and muscle, as well as a lower protein content in muscle, was seen in both groups acclimated to 20ºC. Correspondingly, glycemia was always higher in these groups. Increased lipid levels were seen in the hepatopancreas of animals acclimated to 20ºC, while a higher lipid level was also observed in muscle at 20ºC, but only in ecdysone-treated crayfish.

The behavior of money velocity in low and high inflation countries

This paper presents a general equilibrium model of money demand where the velocity of money changes in response to endogenous fluctuations in the interest rate. The parameter space can be divided into two subsets: one where velocity is constant as in standard cash-in-advance models, and another one where velocity fluctuates as in Baumol (1952). The model provides an explanation of why, for a sample of 79 countries, the correlation between the velocity of money and the inflation rate appears to be low, unlike common wisdom would suggest. The reason is the diverse transaction technologies available in different economies.

Fabricació de Lents Zonals de Fresnel per aplicació als raigs X tous

Estudi elaborat a partir d’una estada al Paul Scherrer Institut del Maig a l’Octubre del 2006 amb l’ajuda i supervisió dels Dr. Konstantins Jefimovs i Dr. Christian David. Focalitzar raigs X tous és una necessitat essencial per al microanàlisis, la microscopia, i fer imatges en moltes Instal·lacions de Radiació Sincrotró. Les Lents Zonals de Fresnel (FZP, de la denominació anglesa “Fresnel Zone Plates”) han demostrat donar uns punts focals amb una resolució espacial destacada i una baixa il·luminació de fons. Tanmateix, la fabricació de FZP és complexa i no totalment reproduïble. A més a més, el temps de vida de les FZP és força curt, ja que estant situades sobre membranes de nitrur de silici molt fines i altament absorbents. Per tant, hem fet esforços per implementar FZP de silici, que s’espera que siguin més resistents. L’element està fet d’una oblia de cristall de silici poc absorbent, i no presenta cap interfase entre materials. Així doncs, aquestes lents són especialment adequades per a aguantar les extremes càrregues de radiació de les fonts de raigs X més brillants. Particularment, això és molt important per a les aplicacions a les pròximes generacions de fonts de raigs X, com els Làsers d’Electrons Lliures (FEL, de la denominació anglesa “Free Electron Laser”). El silici també garanteix que no hi hagi cap banda d’absorció en el rang d’energies de la finestra de l’aigua (200-520 eV), fent aquestes lents ideals per a fer imatges de mostres biològiques. En aquest informe, hi ha una descripció detallada de tots els passos involucrats en la fabricació de les Lents Zonals de Fresnel de silici. En resum, les estructures de FZP es modelen sobre una resina utilitzant litografia per feix d’electrons i llavors el patró es transmet al silici mitjançant un gravat d’ions reactius (RIE, de la denominació anglesa ‘Reactive Ion Etching’) utilitzant una fina (20 nm) màscara de Crintermitja. Les membranes de silici es poden aprimar després de la fabricació de les estructures per a garantir una transmissió suficient fins i tot a baixes energies. Aquest informe també inclou l’anàlisi i la discussió d’alguns experiments preliminars per avaluar el rendiment de les Si FZPs fets a la línia de llum PolLux del Swiss Ligth Source amb l’ajuda dels Dr. Jörg Raabe i Dr. George Tzvetkov.

Planificación de aplicaciones best-effort y soft real-time en NOWs

La aparición de nuevos tipos de aplicaciones, como vídeo bajo demanda, realidad virtual y videoconferencias entre otras, caracterizadas por la necesidad de cumplir sus deadlines. Este tipo de aplicaciones, han sido denominadas en la literatura aplicaciones soft-real time (SRT) periódicas. Este trabajo se centra en el problema de la planificación temporal de este nuevo tipo de aplicaciones en clusters no dedicados.

An 40Ar/39Ar, Rb/Sr, and stable isotope study of micas in low-grade fold-and-thrust belt: An example from the Swiss Helvetic Alps

White micas in carbonate-rich tectonites and a few other rock types of large thrusts in the Swiss Helvetic fold-and-thrust belt have been analyzed by Ar-40/Ar-39 and Rb/Sr techniques to better constrain the timing of Alpine deformation for this region. Incremental Ar-40/Ar-39 heating experiments of 25 weakly metamorphosed (anchizone to low greenschist) samples yield plateau and staircase spectra. We interpret most of the staircase release spectra result from variable mixtures of syntectonic (neoformed) and detrital micas. The range in dates obtained within individual spectra depends primarily on the duration of mica nucleation and growth, and relative proportions of neoformed and detrital mica. Rb/Sr analyses of 12 samples yield dates of ca. 10-39 Ma (excluding one anomalously young sample). These dates are slightly younger than the Ar-40/Ar-39 total gas dates obtained for the same samples. The Rb/ Sr dates were calculated using initial Sr-87/Sr-86 ratios obtained from the carbonate-dominated host rocks, which are higher than normal Mesozoic carbonate values due to exchange with fluids of higher Sr-87/Sr-86 ratios (and lower O-18/O-16 ratios). Model dates calculated using Sr-87/Sr-86 values typical of Mesozoic marine carbonates more closely approximate the Ar-40/Ar-39 total gas dates for most of the samples. The similarities of Rb/Sr and Ar-40/Ar-39 total gas dates are consistent with limited amounts of detrital mica in the samples. The delta(18)O values range from 24-15%. (VSMOW) for 2-6 mum micas and 27-16parts per thousand for the carbonate host rocks. The carbonate values are significantly lower than their protolith values due to localized fluid-rock interaction and fluid flow along most thrust surfaces. Although most calcite-mica pairs are not in oxygen isotope equilibrium at temperatures of ca. 200-400 degreesC, their isotopic fractionations are indicative of either 1) partial exchange between the minerals and a common external fluid, or 2) growth or isotopic exchange of the mica with the carbonate after the carbonate had isotopically exchanged with an external fluid. The geological significance of these results is not easily or uniquely determined, and exemplifies the difficulties inherent in dating very fine-grained micas of highly deformed tectonites in low-grade metamorphic terranes. Two generalizations can be made regarding the dates obtained from the Helvetic thrusts: 1) samples from the two highest thrusts (Mt. Gond and Sublage) have all of their Ar-40/Ar-39 steps above 20 Ma, and 2) most samples from the deepest Helvetic thrusts have steps (often accounting for more than 80% of Ar-39 release) between 15 and 25 Ma. These dates are consistent with the order of thrusting in the foreland-imbricating system and increase proportions of neoformed to detrital mica in the more metamorphosed hinterland and deeply buried portions of the nappe pile. Individual thrusts accommodated the majority of their displacement during their initial incorporation into the foreland-imbricating system, and some thrusts remained active or were reactivated down to 15 Ma.

Safe dissection of the distally based anterolateral thigh flap.

Background The distally based anterolateral thigh (ALT) flap is an interesting reconstructive solution for complex soft tissue defects of the knee. In spite of a low donor site morbidity and wide covering surface as well as arch of rotation, it has never gained popularity among reconstructive surgeons. Venous congestion and difficult flap dissection in the presence of a variable anatomy of the vascular pedicle are the possible reasons.Methods An anatomical study of 15 cadaver legs was performed to further clarify the blood supply of the distally based ALT. Our early experience with the use of preoperative angiography and a safe flap design modification that avoids distal intramuscular skeletonization of the vascular pedicle and includes a subcutaneous strip ranging from the distal end of the flap to the pivot point is presented.Results The distally based ALT presents a constant and reliable retrograde vascular contribution from the superior genicular artery. Preoperative angiography reliably identified and avoided critical Shieh Type II pedicled flaps. The preservation of a subcutaneous strip ranging from the distal flap end to the upper knee was associated with the absence of venous congestion in a short case series.Conclusions Preoperative angiography and a flap design modification are proposed to allow the safe transfer of the distally based ALT to reconstruct soft tissue defects of the knee.

Appropriateness criteria for surgery improve clinical outcomes in patients with low back pain and/or sciatica.

STUDY DESIGN: Prospective, controlled, observational outcome study using clinical, radiographic, and patient/physician-based questionnaire data, with patient outcomes at 12 months follow-up. OBJECTIVE: To validate appropriateness criteria for low back surgery. SUMMARY OF BACKGROUND DATA: Most surgical treatment failures are attributed to poor patient selection, but no widely accepted consensus exists on detailed indications for appropriate surgery. METHODS: Appropriateness criteria for low back surgery have been developed by a multispecialty panel using the RAND appropriateness method. Based on panel criteria, a prospective study compared outcomes of patients appropriately and inappropriately treated at a single institution with 12 months follow-up assessment. Included were patients with low back pain and/or sciatica referred to the neurosurgical department. Information about symptoms, neurologic signs, the health-related quality of life (SF-36), disability status (Roland-Morris), and pain intensity (VAS) was assessed at baseline, at 6 months, and at 12 months follow-up. The appropriateness criteria were administered prospectively to each clinical situation and outside of the clinical setting, with the surgeon and patients blinded to the results of the panel decision. The patients were further stratified into 2 groups: appropriate treatment group (ATG) and inappropriate treatment group (ITG). RESULTS: Overall, 398 patients completed all forms at 12 months. Treatment was considered appropriate for 365 participants and inappropriate for 33 participants. The mean improvement in the SF-36 physical component score at 12 months was significantly higher in the ATG (mean: 12.3 points) than in the ITG (mean: 6.8 points) (P = 0.01), as well as the mean improvement in the SF-36 mental component score (ATG mean: 5.0 points; ITG mean: -0.5 points) (P = 0.02). Improvement was also significantly higher in the ATG for the mean VAS back pain (ATG mean: 2.3 points; ITG mean: 0.8 points; P = 0.02) and Roland-Morris disability score (ATG mean: 7.7 points; ITG mean: 4.2 points; P = 0.004). The ATG also had a higher improvement in mean VAS for sciatica (4.0 points) than the ITG (2.8 points), but the difference was not significant (P = 0.08). The SF-36 General Health score declined in both groups after 12 months, however, the decline was worse in the ITG (mean decline: 8.2 points) than in the ATG (mean decline: 1.2 points) (P = 0.04). Overall, in comparison to ITG patients, ATG patients had significantly higher improvement at 12 months, both statistically and clinically. CONCLUSION: In comparison to previously reported literature, our study is the first to assess the utility of appropriateness criteria for low back surgery at 1-year follow-up with multiple outcome dimensions. Our results confirm the hypothesis that application of appropriateness criteria can significantly improve patient outcomes.

Low-Dose Vascular Photodynamic Therapy Decreases Tumor Interstitial Fluid Pressure, which Promotes Liposomal Doxorubicin Distribution in a Murine Sarcoma Metastasis Model.

INTRODUCTION: Solid tumors are known to have an abnormal vasculature that limits the distribution of chemotherapy. We have recently shown that tumor vessel modulation by low-dose photodynamic therapy (L-PDT) could improve the uptake of macromolecular chemotherapeutic agents such as liposomal doxorubicin (Liporubicin) administered subsequently. However, how this occurs is unknown. Convection, the main mechanism for drug transport between the intravascular and extravascular spaces, is mostly related to interstitial fluid pressure (IFP) and tumor blood flow (TBF). Here, we determined the changes of tumor and surrounding lung IFP and TBF before, during, and after vascular L-PDT. We also evaluated the effect of these changes on the distribution of Liporubicin administered intravenously (IV) in a lung sarcoma metastasis model. MATERIALS AND METHODS: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the lung of Fischer rats. Tumor/surrounding lung IFP and TBF changes induced by L-PDT were determined using the wick-in-needle technique and laser Doppler flowmetry, respectively. The spatial distribution of Liporubicin in tumor and lung tissues following IV drug administration was then assessed in L-PDT-pretreated animals and controls (no L-PDT) by epifluorescence microscopy. RESULTS: L-PDT significantly decreased tumor but not lung IFP compared to controls (no L-PDT) without affecting TBF. These conditions were associated with a significant improvement in Liporubicin distribution in tumor tissues compared to controls (P < .05). DISCUSSION: L-PDT specifically enhanced convection in blood vessels of tumor but not of normal lung tissue, which was associated with a significant improvement of Liporubicin distribution in tumors compared to controls.

Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of cancer-related venous thromboembolism.

Although extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was 149,865 dollars/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of 15,329 dollars. Overall, 46% (7108 dollars) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of 7,609 dollars. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin.