Scaling relations between trabecular bone volume fraction and microstructure at different skeletal sites

In this study, we investigated the scaling relations between trabecular bone volume fraction (BV/TV) and parameters of the trabecular microstructure at different skeletal sites. Cylindrical bone samples with a diameter of 8mm were harvested from different skeletal sites of 154 human donors in vitro: 87 from the distal radius, 59/69 from the thoracic/lumbar spine, 51 from the femoral neck, and 83 from the greater trochanter. μCT images were obtained with an isotropic spatial resolution of 26μm. BV/TV and trabecular microstructure parameters (TbN, TbTh, TbSp, scaling indices (< > and σ of α and αz), and Minkowski Functionals (Surface, Curvature, Euler)) were computed for each sample. The regression coefficient β was determined for each skeletal site as the slope of a linear fit in the double-logarithmic representations of the correlations of BV/TV versus the respective microstructure parameter. Statistically significant correlation coefficients ranging from r=0.36 to r=0.97 were observed for BV/TV versus microstructure parameters, except for Curvature and Euler. The regression coefficients β were 0.19 to 0.23 (TbN), 0.21 to 0.30 (TbTh), −0.28 to −0.24 (TbSp), 0.58 to 0.71 (Surface) and 0.12 to 0.16 (<α>), 0.07 to 0.11 (<αz>), −0.44 to −0.30 (σ(α)), and −0.39 to −0.14 (σ(αz)) at the different skeletal sites. The 95% confidence intervals of β overlapped for almost all microstructure parameters at the different skeletal sites. The scaling relations were independent of vertebral fracture status and similar for subjects aged 60–69, 70–79, and >79years. In conclusion, the bone volume fraction–microstructure scaling relations showed a rather universal character.

C-reactive protein predicts mortality in patients referred for coronary angiography and symptoms of heart failure with preserved ejection fraction

AIMS Heart failure with preserved ejection fraction (HFpEF) has a different pathophysiological background compared to heart failure with reduced ejection fraction (HFrEF). Tailored risk prediction in this separate heart failure group with a high mortality rate is of major importance. Inflammation may play an important role in the pathogenesis of HFpEF because of its significant contribution to myocardial fibrosis. We therefore aimed to assess the predictive value of C-reactive protein (CRP) in patients with HFpEF. METHODS AND RESULTS Plasma levels of CRP were determined in 459 patients with HFpEF in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study using a high-sensitivity assay. During a median follow-up of 9.7 years 40% of these patients died. CRP predicted all-cause mortality with an adjusted hazard ratio (HR) of 1.20 [95% confidence interval (CI) 1.02-1.40, P = 0.018] and cardiovascular mortality with a HR of 1.32 (95% CI 1.08-1.62, P = 0.005) per increase of one standard deviation. CRP was a significantly stronger mortality predictor in HFpEF patients than in a control group of 522 HFrEF patients (for interaction, P = 0.015). Furthermore, CRP added prognostic value to N-terminal pro B-type natriuretic peptide (Nt-proBNP): the lowest 5-year mortality rate of 6.8% was observed for patients in the lowest tertile of Nt-proBNP as well as CRP. The mortality risk peaked in the group combining the highest values of Nt-proBNP and CRP with a 5-year rate of 36.5%. CONCLUSION It was found that CRP was an independent and strong predictor of mortality in HFpEF. This observation may reflect immunological processes with an adverse impact on the course of HFpEF.

Bone Volume Fraction and Fabric Anisotropy Are Better Determinants of Trabecular Bone Stiffness than Other Morphological Variables

As our population ages, more individuals suffer from osteoporosis. This disease leads to impaired trabecular architecture and increased fracture risk. It is essential to understand how morphological and mechanical properties of the cancellous bone are related. Morphologyelasticity relationships based on bone volume fraction (BV/TV) and fabric anisotropy explain up to 98% of the variation in elastic properties. Yet, other morphological variables such as individual trabeculae segmentation (ITS) and trabecular bone score (TBS) could improve the stiffness predictions. A total of 743 micro-computed tomography reconstructions of cubic trabecular bone samples extracted from femur, radius, vertebrae and iliac crest were analysed. Their morphology was assessed via 25 variables and their stiffness tensor (inline image) was computed from six independent load cases using micro finite element analyses. Variance inflation factors were calculated to evaluate collinearity between morphological variables and decide upon their inclusion in morphology-elasticity relationships. The statistically admissible morphological variables were included in a multi-linear regression modelling the dependent variable inline image. The contribution of each independent variable was evaluated (ANOVA). Our results show that BV/TV is the best determinant of inline image (inline image=0.889), especially in combination with fabric (inline image=0.968). Including the other independent predictors hardly affected the amount of variance explained by the model (inline image=0.975). Across all anatomical sites, BV/TV explained 87% of the variance of the bone elastic properties. Fabric further described 10% of the bone stiffness, but the improvement in variance explanation by adding other independent factors was marginal (<1%). These findings confirm that BV/TV and fabric are the best determinants of trabecular bone stiffness and show, against common belief, that other morphological variables do not bring any further contribution. These overall conclusions remain to be confirmed for specific bone diseases and post-elastic properties.

Von Willebrand Factor Improves Risk Prediction in Addition to N-Terminal Pro-B-type Natriuretic Peptide in Patients Referred to Coronary Angiography and Signs and Symptoms of Heart Failure and Preserved Ejection Fraction.

BACKGROUND Heart failure with preserved ejection fraction (HFpEF) represents a growing health burden associated with substantial mortality and morbidity. Consequently, risk prediction is of highest importance. Endothelial dysfunction has been recently shown to play an important role in the complex pathophysiology of HFpEF. We therefore aimed to assess von Willebrand factor (vWF), a marker of endothelial damage, as potential biomarker for risk assessment in patients with HFpEF. METHODS AND RESULTS Concentrations of vWF were assessed in 457 patients with HFpEF enrolled as part of the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. All-cause mortality was observed in 40% of patients during a median follow-up time of 9.7 years. vWF significantly predicted mortality with a hazard ratio (HR) per increase of 1 SD of 1.45 (95% confidence interval, 1.26-1.68; P<0.001) and remained a significant predictor after adjustment for age, sex, body mass index, N-terminal pro-B-type natriuretic peptide (NT-proBNP), renal function, and frequent HFpEF-related comorbidities (adjusted HR per 1 SD, 1.22; 95% confidence interval, 1.05-1.42; P=0.001). Most notably, vWF showed additional prognostic value beyond that achievable with NT-proBNP indicated by improvements in C-Statistic (vWF×NT-proBNP: 0.65 versus NT-proBNP: 0.63; P for comparison, 0.004) and category-free net reclassification index (37.6%; P<0.001). CONCLUSIONS vWF is an independent predictor of long-term outcome in patients with HFpEF, which is in line with endothelial dysfunction as potential mediator in the pathophysiology of HFpEF. In particular, combined assessment of vWF and NT-proBNP improved risk prediction in this vulnerable group of patients.

Impact of mitral regurgitation on clinical outcomes of patients with low-ejection fraction, low-gradient severe aortic stenosis undergoing transcatheter aortic valve implantation.

BACKGROUND Up to 1 in 6 patients undergoing transcatheter aortic valve implantation (TAVI) present with low-ejection fraction, low-gradient (LEF-LG) severe aortic stenosis and concomitant relevant mitral regurgitation (MR) is present in 30% to 55% of these patients. The effect of MR on clinical outcomes of LEF-LG patients undergoing TAVI is unknown. METHODS AND RESULTS Of 606 consecutive patients undergoing TAVI, 113 (18.7%) patients with LEF-LG severe aortic stenosis (mean gradient ≤40 mm Hg, aortic valve area <1.0 cm(2), left ventricular ejection fraction <50%) were analyzed. LEF-LG patients were dichotomized into ≤mild MR (n=52) and ≥moderate MR (n=61). Primary end point was all-cause mortality at 1 year. No differences in mortality were observed at 30 days (P=0.76). At 1 year, LEF-LG patients with ≥moderate MR had an adjusted 3-fold higher rate of all-cause mortality (11.5% versus 38.1%; adjusted hazard ratio, 3.27 [95% confidence interval, 1.31-8.15]; P=0.011), as compared with LEF-LG patients with ≤mild MR. Mortality was mainly driven by cardiac death (adjusted hazard ratio, 4.62; P=0.005). As compared with LEF-LG patients with ≥moderate MR assigned to medical therapy, LEF-LG patients with ≥moderate MR undergoing TAVI had significantly lower all-cause mortality (hazard ratio, 0.38; 95% confidence interval, 0.019-0.75) at 1 year. CONCLUSIONS Moderate or severe MR is a strong independent predictor of late mortality in LEF-LG patients undergoing TAVI. However, LEF-LG patients assigned to medical therapy have a dismal prognosis independent of MR severity suggesting that TAVI should not be withheld from symptomatic patients with LEF-LG severe aortic stenosis even in the presence of moderate or severe MR.

De oudste Synagogen der hoodguitsch-joodsche gemeende te Amsterdam (1635-1671) : Ordre van den dienst po woensdag 12 Nisan 5681 (20. April 1921) bij de plechtige overdracht van het feest-geschenk ter herdenking van het 250-jarig bestaan der groote Synagoge van de Nederl. Israel. Hoofdsynagoge te Amsterdam ...

door D. M. Sluys

Chandrayaan-1 observations of backscattered solar wind protons from the lunar regolith: Dependence on the solar wind speed

We study the backscattering of solar wind protons from the lunar regolith using the Solar Wind Monitor of the Sub-keV Atom Reflecting Analyzer on Chandrayaan-1. Our study focuses on the component of the backscattered particles that leaves the regolith with a positive charge. We find that the fraction of the incident solar wind protons that backscatter as protons, i.e., the proton-backscattering efficiency, has an exponential dependence on the solar wind speed that varies from ~0.01% to ~1% for solar wind speeds of 250 km/s to 550 km/s. We also study the speed distribution of the backscattered protons in the fast (~550 km/s) solar wind case and find both a peak speed at ~80% of the solar wind speed and a spread of ~85 km/s. The observed flux variations and speed distribution of the backscattered protons can be explained by a speed-dependent charge state of the backscattered particles.

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at √s=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton-proton collision data at s√=8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t~→tχ~01 or t~→bχ~±1→bW(∗)χ~01, where χ~01 (χ~±1) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t~→tχ~01. For a branching fraction of 100%, top squark masses in the range 270-645 GeV are excluded for χ~01 masses below 30 GeV. For a branching fraction of 50% to either t~→tχ~01 or t~→bχ~±1, and assuming the χ~±1 mass to be twice the χ~01 mass, top squark masses in the range 250-550 GeV are excluded for χ~01 masses below 60 GeV.

Seasonal variation of high-molecular-weight compounds in the water-soluble fraction of organic urban aerosols

Aerosol samples were collected in Zurich, Switzerland, at an urban background site and were analyzed with size exclusion chromatography (SEC) and laser/desorption ionization mass spectrometry (LDI-MS) for water-soluble organic compounds with high molecular weight. Daily samples were collected during two campaigns in winter and summer, for 1 month each. The concentration of high-molecular-weight compounds (humic-like substances (HULIS)) was between 0.4 and 4 μg/m3 in winter and summer. The most intense signals in the LDI-MS mass spectra were measured between m/z150 and 500, comparing well with the mode of the two main high mass peaks determined with SEC corresponding to masses between 200 and 600 Da. For the maximum molecular weight, however, different results were obtained by the two techniques: whereas a maximum molecular weight between 1300 and 3300 Da was found with SEC, hardly any peaks above m/z700 were measured with LDI-MS. During summer the maximum molecular weight of HULIS (determined with SEC) correlates positively with several parameters such as ozone and increased temperature indicative of enhanced atmospheric photo-oxidation. The HULIS concentration also correlates positively with the oxalic acid concentration in the particles. This suggests that HULIS are generated by secondary processes in summer. The lack of such correlations during winter suggests that other sources and processes might be important during colder seasons.

Das Ministerium Brandenburg und die Fraction Unruh, und Eiserner Bestand an Regierungs-Rechten, ohne welche ein Staat überhaupt nicht lebensfähig ist

Boberach: Weil Völker nicht selten an ihren politischen Ideen zugrundegehen, war auch Preußen durch die Politik der Linken bedroht und das Ministerium hat die dem Staat gebührenden Regierungsfunktionen mit Recht in Anspruch genommen

Hepatocellular Carcinoma Screening With Computed Tomography Using the Arterial Enhancement Fraction With Radiologic-Pathologic Correlation.

OBJECTIVE The aim of this study was to investigate the performance of the arterial enhancement fraction (AEF) in multiphasic computed tomography (CT) acquisitions to detect hepatocellular carcinoma (HCC) in liver transplant recipients in correlation with the pathologic analysis of the corresponding liver explants. MATERIALS AND METHODS Fifty-five transplant recipients were analyzed: 35 patients with 108 histologically proven HCC lesions and 20 patients with end-stage liver disease without HCC. Six radiologists looked at the triphasic CT acquisitions with the AEF maps in a first readout. For the second readout without the AEF maps, 3 radiologists analyzed triphasic CT acquisitions (group 1), whereas the other 3 readers had 4 contrast acquisitions available (group 2). A jackknife free-response reader receiver operating characteristic analysis was used to compare the readout performance of the readers. Receiver operating characteristic analysis was used to determine the optimal cutoff value of the AEF. RESULTS The figure of merit (θ = 0.6935) for the conventional triphasic readout was significantly inferior compared with the triphasic readout with additional use of the AEF (θ = 0.7478, P < 0.0001) in group 1. There was no significant difference between the fourphasic conventional readout (θ = 0.7569) and the triphasic readout (θ = 0.7615, P = 0.7541) with the AEF in group 2. Without the AEF, HCC lesions were detected with a sensitivity of 30.7% (95% confidence interval [CI], 25.5%-36.4%) and a specificity of 97.1% (96.0%-98.0%) by group 1 looking at 3 CT acquisition phases and with a sensitivity of 42.1% (36.2%-48.1%) and a specificity of 97.5% (96.4%-98.3%) in group 2 looking at 4 CT acquisition phases. Using the AEF maps, both groups looking at the same 3 acquisition phases, the sensitivity was 47.7% (95% CI, 41.9%-53.5%) with a specificity of 97.4% (96.4%-98.3%) in group 1 and 49.8% (95% CI, 43.9%-55.8%)/97.6% (96.6%-98.4%) in group 2. The optimal cutoff for the AEF was 50%. CONCLUSION The AEF is a helpful tool to screen for HCC with CT. The use of the AEF maps may significantly improve HCC detection, which allows omitting the fourth CT acquisition phase and thus making a 25% reduction of radiation dose possible.

Inhalation anesthesia of rats: influence of the fraction of inspired oxygen on limb ischemia/reperfusion injury

Inhalation anesthesia with isoflurane is a well-established and safe method used in small laboratory animals. In most cases oxygen is used as a carrier gas for isoflurane, but room air or mixtures of oxygen with air or nitrous oxide are also being used. Anesthesia is therefore administered using different fractions of inspired oxygen (FiO2), and this may have consequences for the outcome of experiments. The aim of the present study was to investigate the influence of FiO2 on rat hind limb ischemia/reperfusion injury and to refine the used inhalation anesthesia. Male Wistar rats were subjected to 3.5 h of ischemia and 2 h of reperfusion, and divided into three groups according to FiO2 in the O2/air/isoflurane anesthesia gas mixture: 40%, 60%, and 100% O2. Normal, healthy rats were used as controls. Muscle edema and creatine kinase MM, a marker for myocyte necrosis, were significantly increased with 40% FiO2 as compared with 100% FiO2 (P<0.05). Partial pressure of oxygen, oxygen saturation, and oxyhemoglobin were significantly higher in the 100% O2 group as compared with 40% O2. No significant differences were detected for other parameters, such as the oxidative stress markers malondialdehyde and superoxide dismutase. We conclude that a refined inhalation anesthesia setting using 40% FiO2, reflecting more or less the clinical situation, leads to a more severe and more physiologically relevant reperfusion injury than higher FiO2. Oxidative stress did not correlate with FiO2 and seemed to have no influence on reperfusion injury.