A randomized controlled trial

Objective We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. Methods This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. Results 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). Conclusions In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation

Video-based, student tutor- versus faculty staff-led ultrasound course for medical students - a prospective randomized study

Background Ultrasound education is propagated already during medical school due to its diagnostic importance. Courses are usually supervised by experienced faculty staff (FS) with patient bedside examinations or students among each other but often overbooked due to limited FS availability. To overcome this barrier, use of teaching videos may be advantageous. Likewise, peer teaching concepts solely with trained student tutors have shown to be feasible and effective. The aim was to evaluate 1) objective learning outcomes of a combined video-based, student-tutor (ViST) as compared to a FS-led course without media support, 2) acceptance and subjective learning success of the videos. Methods Two ultrasound teaching videos for basic and advanced abdominal ultrasound (AU) and transthoracic echocardiography (TTE) were produced and six students trained as tutors. Fourth-year medical students (N = 96) were randomized to either the ViST- or FS course (6 students per tutor). Learning objectives were defined equally for both courses. Acquired practical basic and advanced ultrasound skills were tested in an objective structured clinical examination (OSCE) using modified validated scoring sheets with a maximum total score of 40 points. Acceptance and subjective learning success of both videos were evaluated by questionnaires based on Kirkpatrick's evaluation model with scale-rated closed and open questions. Results 79 of 96 medical students completed the OSCE and 77 could be finally analyzed. There was no significant difference in the mean total point score of 31.3 in the ViST (N = 42) and 32.7 in the FS course (N = 35, P = 0.31) or in any of the examined basic or advanced ultrasound skill subtasks. Of the 42 ViST participants, 29 completed the AU and 27 the TTE video questionnaire. Acceptance and subjective learning success of both videos was rated positively in 14-52% and 48-88% of the rated responses to each category, respectively. Attendance of either the student or faculty tutor was deemed necessary in addition to the videos. Conclusions A ViST versus FS teaching concept was able to effectively teach undergraduate students in AU and TTE, albeit acceptance of the teaching videos alone was limited. However, the ViST concept has the potential to increase course availability and FS resource allocation

"Women's rights, the European Court and Supranational Constitutionalism"

This analysis examines supranational constitutionalism in the European Union. In particular, the study focuses on the role of the European Court of Justice in the creation of women’s rights. I examine the interaction between the Court and member state governments in legal integration, and also the integral role that women’s advocates – both individual activists and groups – have played in the development of EU social provisions. The findings suggest that this litigation dynamic can have the effect of fueling the integration process by creating new rights that may empower social actors and EU organizations, with the ultimate effect of diminishing member state government control over the scope and direction of EU law. This study focuses specifically on gender equality law, yet provides a general framework for examining the case law in subsequent legal domains, with the purpose of providing a more nuanced understanding of supranational governance and constitutionalism

Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma

BACKGROUND: Recent evidence suggests that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that tumorous tissues have higher 5α-reductase (5αR) and lower 3α-hydroxysteroid oxidoreductase (3α-HSO) and 20α-HSO activities. The resulting higher levels of 5α-reduced progesterone metabolites such as 5α-pregnane-3,20-dione (5αP) in tumorous tissue promote cell proliferation and detachment, whereas the 4-pregnene metabolites, 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αDHP), more prominent in normal tissue, have the opposite (anti-cancer-like) effects. The aim of this study was to determine if the differences in enzyme activities between tumorous and nontumorous breast tissues are associated with differences in progesterone metabolizing enzyme gene expression. METHODS: Semi-quantitative RT-PCR was used to compare relative expression (as a ratio of 18S rRNA) of 5αR type 1 (SRD5A1), 5αR type 2 (SRD5A2), 3α-HSO type 2 (AKR1C3), 3α-HSO type 3 (AKR1C2) and 20α-HSO (AKR1C1) mRNAs in paired (tumorous and nontumorous) breast tissues from 11 patients, and unpaired tumor tissues from 17 patients and normal tissues from 10 reduction mammoplasty samples. RESULTS: Expression of 5αR1 and 5αR2 in 11/11 patients was higher (mean of 4.9- and 3.5-fold, respectively; p < 0.001) in the tumor as compared to the paired normal tissues. Conversely, expression of 3α-HSO2, 3α-HSO3 and 20α-HSO was higher (2.8-, 3.9- and 4.4-fold, respectively; p < 0.001) in normal than in tumor sample. The mean tumor:normal expression ratios for 5αR1 and 5αR2 were about 35–85-fold higher than the tumor:normal expression ratios for the HSOs. Similarly, in the unmatched samples, the tumor:normal ratios for 5αR were significantly higher than the ratios for the HSOs. CONCLUSIONS: The study shows changes in progesterone metabolizing enzyme gene expression in human breast carcinoma. Expression of SRD5A1 (5αR1) and SRD5A2 (5αR2) is elevated, and expression of AKR1C1 (20α-HSO), AKR1C2 (3α-HSO3) and AKR1C3 (3α-HSO2) is reduced in tumorous as compared to normal breast tissue. The changes in progesterone metabolizing enzyme expression levels help to explain the increases in mitogen/metastasis inducing 5αP and decreases in mitogen/metastasis inhibiting 3αHP progesterone metabolites found in breast tumor tissues. Understanding what causes these changes in expression could help in designing protocols to prevent or reverse the changes in progesterone metabolism associated with breast cancer

Pathogen Entrapment by Transglutaminase—A Conserved Early Innate Immune Mechanism

Clotting systems are required in almost all animals to prevent loss of body fluids after injury. Here, we show that despite the risks associated with its systemic activation, clotting is a hitherto little appreciated branch of the immune system. We compared clotting of human blood and insect hemolymph to study the best-conserved component of clotting systems, namely the Drosophila enzyme transglutaminase and its vertebrate homologue Factor XIIIa. Using labelled artificial substrates we observe that transglutaminase activity from both Drosophila hemolymph and human blood accumulates on microbial surfaces, leading to their sequestration into the clot. Using both a human and a natural insect pathogen we provide functional proof for an immune function for transglutaminase (TG). Drosophila larvae with reduced TG levels show increased mortality after septic injury. The same larvae are also more susceptible to a natural infection involving entomopathogenic nematodes and their symbiotic bacteria while neither phagocytosis, phenoloxidase or—as previously shown—the Toll or imd pathway contribute to immunity. These results firmly establish the hemolymph/blood clot as an important effector of early innate immunity, which helps to prevent septic infections. These findings will help to guide further strategies to reduce the damaging effects of clotting and enhance its beneficial contribution to immune reactions

Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat.

In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1) x day(-1)), with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1) x day(-1) and 100 mg x kg(-1) x day(-1), respectively), on postnatal days 1-6 (P1-6). Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3) vs. 564.0±20.0 mm(3)), the soma volume of neurons in the CA1 (1172.6±30.4 µm(3) vs. 1002.4±11.8 µm(3)) and in the dentate gyrus (525.9±27.2 µm(3) vs. 421.5±24.6 µm(3)) of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%). Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3)), and soma volume of neurons in the CA1 (1157.5±42.4 µm(3)) and the dentate gyrus (536.1±27.2 µm(3)). Hsp70 protein expression was unaltered in the cortex (+9%), however, 4-HNE (+95%) and NT (+24%) protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22%) and in the hippocampus (NT: +35%). Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio