@article{VandenbergChahoudHeindeletal.2012, author = {Vandenberg, Laura N. and Chahoud, Ibrahim and Heindel, Jerrold J. and Padmanabhan, Vasantha and Paumgartten, Francisco J. R. and Sch{\"o}nfelder, Gilbert}, title = {Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A}, series = {Ci{\^e}ncia \& Sa{\´u}de Coletiva}, volume = {17}, journal = {Ci{\^e}ncia \& Sa{\´u}de Coletiva}, number = {2}, doi = {10.1289/ehp.0901716}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134332}, pages = {407-434}, year = {2012}, abstract = {Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.}, language = {en} } @article{StoeltingWiesnervanVlietetal.2012, author = {St{\"o}lting, Miriam and Wiesner, Christiane and van Vliet, Vanessa and Butt, Elke and Pavenst{\"a}dt, Hermann and Linder, Stefan and Kremerskothen, Joachim}, title = {Lasp-1 Regulates Podosome Function}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {4}, doi = {10.1371/journal.pone.0035340}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134315}, pages = {e35340}, year = {2012}, abstract = {Eukaryotic cells form a variety of adhesive structures to connect with their environment and to regulate cell motility. In contrast to classical focal adhesions, podosomes, highly dynamic structures of different cell types, are actively engaged in matrix remodelling and degradation. Podosomes are composed of an actin-rich core region surrounded by a ring-like structure containing signalling molecules, motor proteins as well as cytoskeleton-associated proteins. Lasp-1 is a ubiquitously expressed, actin-binding protein that is known to regulate cytoskeleton architecture and cell migration. This multidomain protein is predominantely present at focal adhesions, however, a second pool of Lasp-1 molecules is also found at lamellipodia and vesicle-like microdomains in the cytosol. In this report, we show that Lasp-1 is a novel component and regulator of podosomes. Immunofluorescence studies reveal a localization of Lasp-1 in the podosome ring structure, where it colocalizes with zyxin and vinculin. Life cell imaging experiments demonstrate that Lasp-1 is recruited in early steps of podosome assembly. A siRNA-mediated Lasp-1 knockdown in human macrophages affects podosome dynamics as well as their matrix degradation capacity. In summary, our data indicate that Lasp-1 is a novel component of podosomes and is involved in the regulation of podosomal function.}, language = {en} } @article{PruggerHeidrichWellmannetal.2012, author = {Prugger, Christof and Heidrich, Jan and Wellmann, J{\"u}rgen and Dittrich, Ralf and Brand, Stefan-Martin and Telgmann, Ralph and Breithardt, G{\"u}nter and Reinecke, Holger and Scheld, Hans and Kleine-Katth{\"o}fer, Peter and Heuschmann, Peter U. and Keil, Ulrich}, title = {Trends in Cardiovascular Risk Factors Among Patients With Coronary Heart Disease : Results From the EUROASPIRE I, II, and III Surveys in the M{\"u}nster Region}, series = {Deutsches {\"A}rzteblatt International}, volume = {109}, journal = {Deutsches {\"A}rzteblatt International}, number = {17}, doi = {10.3238/arztebl.2012.0303}, pages = {303-U21}, year = {2012}, abstract = {Background: Target values for cardiovascular risk factors in patients with coronary heart disease (CHD) are stated in guidelines for the prevention of cardiovascular disease. We studied secular trends in risk factors over a 12-year period among CHD patients in the region of Munster, Germany. Methods: The cross-sectional EUROASPIRE I, II and III surveys were performed in multiple centers across Europe. For all three, the Munster region was the participating German region. In the three periods 1995/96, 1999/2000, and 2006/07, the surveys included (respectively) 392, 402 and 457 <= 70-year-old patients with CHD in Munster who had sustained a coronary event at least 6 months earlier. Results: The prevalence of smoking remained unchanged, with 16.8\% in EUROASPIRE I and II and 18.4\% in EUROASPIRE III (p=0.898). On the other hand, high blood pressure and high cholesterol both became less common across the three EUROASPIRE studies (60.7\% to 69.4\% to 55.3\%, and 94.3\% to 83.4\% to 48.1\%, respectively; p<0.001 for both). Obesity became more common (23.0\% to 30.6\% to 43.1\%, p<0.001), as did treatment with antihypertensive and lipid-lowering drugs (80.4\% to 88.6\% to 94.3\%, and 35.0\% to 67.4\% to 87.0\%, respectively; p<0.001 for both). Conclusion: The observed trends in cardiovascular risk factors under-score the vital need for better preventive strategies in patients with CHD.}, language = {en} } @article{RahimiBhalaKamphuisenetal.2012, author = {Rahimi, Kazem and Bhala, Neeraj and Kamphuisen, Pieter and Emberson, Jonathan and Biere-Rafi, Sara and Krane, Vera and Robertson, Michele and Wikstrand, John and McMurray, John}, title = {Effect of Statins on Venous Thromboembolic Events: A Meta-analysis of Published and Unpublished Evidence from Randomised Controlled Trials}, series = {PLoS Medicine}, volume = {9}, journal = {PLoS Medicine}, number = {9}, doi = {10.1371/journal.pmed.1001310}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134279}, pages = {e1001310}, year = {2012}, abstract = {Background: It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins. Methods and Findings: We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9\%] statin versus 521 [1.0\%] control, odds ratio [OR] = 0.89, 95\% CI 0.78-1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95\% CI 0.72-1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95\% CI 0.76-1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9\%] versus 461 [1.0\%], OR = 0.93 [95\% CI 0.82-1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0\%] versus 202 [1.0\%], OR = 0.98, 95\% CI 0.80-1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Conclusions: The findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out. Please see later in the article for the Editors' Summary.}, language = {en} } @article{KotteLoewHuberetal.2012, author = {Kotte, K. and L{\"o}w, F. and Huber, S. G. and Krause, T. and Mulder, I. and Sch{\"o}ler, H. F.}, title = {Organohalogen emissions from saline environments - spatial extrapolation using remote sensing as most promising tool}, series = {Biogeosciences}, volume = {9}, journal = {Biogeosciences}, number = {3}, doi = {10.5194/bg-9-1225-2012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134265}, pages = {1225-1235}, year = {2012}, abstract = {Due to their negative water budget most recent semi-/arid regions are characterized by vast evaporates (salt lakes and salty soils). We recently identified those hyper-saline environments as additional sources for a multitude of volatile halogenated organohalogens (VOX). These compounds can affect the ozone layer of the stratosphere and play a key role in the production of aerosols. A remote sensing based analysis was performed in the Southern Aral Sea basin, providing information of major soil types as well as their extent and spatial and temporal evolution. VOX production has been determined in dry and moist soil samples after 24 h. Several C1- and C2 organohalogens have been found in hyper-saline topsoil profiles, including CH3Cl, CH3Br, CHBr3 and CHCl3. The range of organohalogens also includes trans-1,2-dichloroethene (DCE), which is reported here to be produced naturally for the first time. Using MODIS time series and supervised image classification a daily production rate for DCE has been calculated for the 15 000 km\(^2\) ranging research area in the southern Aralkum. The applied laboratory setup simulates a short-term change in climatic conditions, starting from dried-out saline soil that is instantly humidified during rain events or flooding. It describes the general VOX production potential, but allows only for a rough estimation of resulting emission loads. VOX emissions are expected to increase in the future since the area of salt affected soils is expanding due to the regressing Aral Sea. Opportunities, limits and requirements of satellite based rapid change detection and salt classification are discussed.}, language = {en} } @article{SchwitterWackerWilkeetal.2012, author = {Schwitter, Juerg and Wacker, Christian M. and Wilke, Norbert and Al-Saadi, Nidal and Sauer, Ekkehart and Huettle, Kalman and Sch{\"o}nberg, Stefan O. and Debl, Kurt and Strohm, Oliver and Ahlstrom, Hakan and Dill, Thorsten and Hoebel, Nadja and Simor, Tamas}, title = {Superior diagnostic performance of perfusion-cardiovascular magnetic resonance versus SPECT to detect coronary artery disease: The secondary endpoints of the multicenter multivendor MR-IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary Artery Disease Trial)}, series = {Journal of Cardiovascular Magnetic Resonance}, volume = {14}, journal = {Journal of Cardiovascular Magnetic Resonance}, number = {61}, organization = {MR-IMPACT investigators}, doi = {10.1186/1532-429X-14-61}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134256}, year = {2012}, abstract = {Background: Perfusion-cardiovascular magnetic resonance (CMR) is generally accepted as an alternative to SPECT to assess myocardial ischemia non-invasively. However its performance vs gated-SPECT and in sub-populations is not fully established. The goal was to compare in a multicenter setting the diagnostic performance of perfusion-CMR and gated-SPECT for the detection of CAD in various populations using conventional x-ray coronary angiography (CXA) as the standard of reference. Methods: In 33 centers (in US and Europe) 533 patients, eligible for CXA or SPECT, were enrolled in this multivendor trial. SPECT and CXA were performed within 4 weeks before or after CMR in all patients. Prevalence of CAD in the sample was 49\% and 515 patients received MR contrast medium. Drop-out rates for CMR and SPECT were 5.6\% and 3.7\%, respectively (ns). The study was powered for the primary endpoint of non-inferiority of CMR vs SPECT for both, sensitivity and specificity for the detection of CAD (using a single-threshold reading), the results for the primary endpoint were reported elsewhere. In this article secondary endpoints are presented, i.e. the diagnostic performance of CMR versus SPECT in subpopulations such as multi-vessel disease (MVD), in men, in women, and in patients without prior myocardial infarction (MI). For diagnostic performance assessment the area under the receiver-operator-characteristics-curve (AUC) was calculated. Readers were blinded versus clinical data, CXA, and imaging results. Results: The diagnostic performance (= area under ROC = AUC) of CMR was superior to SPECT (p = 0.0004, n = 425) and to gated-SPECT (p = 0.018, n = 253). CMR performed better than SPECT in MVD (p = 0.003 vs all SPECT, p = 0.04 vs gated-SPECT), in men (p = 0.004, n = 313) and in women (p = 0.03, n = 112) as well as in the non-infarct patients (p = 0.005, n = 186 in 1-3 vessel disease and p = 0.015, n = 140 in MVD). Conclusion: In this large multicenter, multivendor study the diagnostic performance of perfusion-CMR to detect CAD was superior to perfusion SPECT in the entire population and in sub-groups. Perfusion-CMR can be recommended as an alternative for SPECT imaging.}, language = {en} } @article{ReuterSparwasserHuenigetal.2012, author = {Reuter, Dajana and Sparwasser, Tim and H{\"u}nig, Thomas and Schneider-Schaulies, J{\"u}rgen}, title = {Foxp3\(^+\) Regulatory T Cells Control Persistence of Viral CNS Infection}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {3}, doi = {10.1371/journal.pone.0033989}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134248}, pages = {e33989}, year = {2012}, abstract = {We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified) mice and recombinant measles virus (MV). Using this model infection we investigated the role of regulatory T cells (Tregs) as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4\(^+\) CD25\(^+\) Foxp3\(^+\) Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8\(^+\) T cells predominantly recognising the H-2D(b)-presented viral hemagglutinin epitope MV-H22-30 (RIVINREHL) were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p.) application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT) in DEREG (depletion of regulatory T cells)-mice induced an increase of virus-specific CD8\(^+\) effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.}, language = {en} } @article{JinAllisonKaufmannetal.2012, author = {Jin, Jing and Allison, Brendan Z. and Kaufmann, Tobias and K{\"u}bler, Andrea and Zhang, Yu and Wang, Xingyu and Cichocki, Andrzej}, title = {The Changing Face of P300 BCIs: A Comparison of Stimulus Changes in a P300 BCI Involving Faces, Emotion, and Movement}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {11}, doi = {10.1371/journal.pone.0049688}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134173}, pages = {e49688}, year = {2012}, abstract = {Background: One of the most common types of brain-computer interfaces (BCIs) is called a P300 BCI, since it relies on the P300 and other event-related potentials (ERPs). In the canonical P300 BCI approach, items on a monitor flash briefly to elicit the necessary ERPs. Very recent work has shown that this approach may yield lower performance than alternate paradigms in which the items do not flash but instead change in other ways, such as moving, changing colour or changing to characters overlaid with faces. Methodology/Principal Findings: The present study sought to extend this research direction by parametrically comparing different ways to change items in a P300 BCI. Healthy subjects used a P300 BCI across six different conditions. Three conditions were similar to our prior work, providing the first direct comparison of characters flashing, moving, and changing to faces. Three new conditions also explored facial motion and emotional expression. The six conditions were compared across objective measures such as classification accuracy and bit rate as well as subjective measures such as perceived difficulty. In line with recent studies, our results indicated that the character flash condition resulted in the lowest accuracy and bit rate. All four face conditions (mean accuracy >91\%) yielded significantly better performance than the flash condition (mean accuracy = 75\%). Conclusions/Significance: Objective results reaffirmed that the face paradigm is superior to the canonical flash approach that has dominated P300 BCIs for over 20 years. The subjective reports indicated that the conditions that yielded better performance were not considered especially burdensome. Therefore, although further work is needed to identify which face paradigm is best, it is clear that the canonical flash approach should be replaced with a face paradigm when aiming at increasing bit rate. However, the face paradigm has to be further explored with practical applications particularly with locked-in patients.}, language = {en} } @article{ZwinkJenetzkySchmiedekeetal.2012, author = {Zwink, Nadine and Jenetzky, Ekkehart and Schmiedeke, Eberhard and Schmidt, Dominik and M{\"a}rzheuser, Schmidt and Grasshoff-Derr, Sabine and Holland-Cunz, Stefan and Weih, Sandra and Hosie, Stuart and Reifferscheid, Peter and Ameis, Helen and Kujath, Christina and Rissmann, Anke and Obermayr, Florian and Schwarzer, Nicole and Bartels, Enrika and Reutter, Heiko and Brenner, Hermann}, title = {Assisted reproductive techniques and the risk of anorectal malformations: a German case-control study}, series = {Orphanet Journal of Rare Diseases}, volume = {7}, journal = {Orphanet Journal of Rare Diseases}, number = {65}, organization = {CURE-Net Consortium}, doi = {10.1186/1750-1172-7-65}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134036}, year = {2012}, abstract = {Background: The use of assisted reproductive techniques (ART) for treatment of infertility is increasing rapidly worldwide. However, various health effects have been reported including a higher risk of congenital malformations. Therefore, we assessed the risk of anorectal malformations (ARM) after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Methods: Data of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (95\% confidence intervals) were determined to quantify associations using multivariable logistic regression accounting for potential confounding or interaction by plurality of births. Results: In total, 295 ARM patients born between 1997 and 2011 in Germany, who were recruited through participating pediatric surgeries from all over Germany and the German self-help organisation SoMA, were included. Controls were all German live-births (n = 10,069,986) born between 1997 and 2010. Overall, 30 cases (10\%) and 129,982 controls (1\%) were born after IVF or ICSI, which translates to an odds ratio (95\% confidence interval) of 8.7 (5.9-12.6) between ART and ARM in bivariate analyses. Separate analyses showed a significantly increased risk for ARM after IVF (OR, 10.9; 95\% CI, 6.2-19.0; P < 0.0001) as well as after ICSI (OR, 7.5; 95\% CI, 4.6-12.2; P < 0.0001). Furthermore, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed strong associations with ART (ORs 4.9, 11.9 and 7.9, respectively). After stratification for plurality of birth, the corresponding odds ratios (95\% confidence intervals) were 7.7 (4.6-12.7) for singletons and 4.9 (2.4-10.1) for multiple births. Conclusions: There is a strongly increased risk for ARM among children born after ART. Elevations of risk were seen after both IVF and ICSI. Further, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed increased risks in each group. An increased risk of ARM was also seen among both singletons and multiple births.}, language = {en} } @article{TempelVeitAssmannetal.2012, author = {Tempel, Jean-Sebastian and Veit, Tempel and Assmann, Marc and Kreilkamp, Lars Erik and H{\"o}fling, Sven and Kamp, Martin and Forchel, Alfred and Bayer, Manfred}, title = {Temperature dependence of pulsed polariton lasing in a GaAs microcavity}, series = {New Journal of Physics}, volume = {14}, journal = {New Journal of Physics}, number = {083014}, doi = {10.1088/1367-2630/14/8/083014}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134022}, year = {2012}, abstract = {The second-order correlation function g\(^2\)(\(\tau\) = 0), input-output curves and pulse duration of the emission from a microcavity exciton-polariton system subsequent to picosecond-pulsed excitation are measured for different temperatures. At low temperatures a two-threshold behaviour emerges, which has been attributed to the onset of polariton lasing and conventional lasing at the first and the second threshold, respectively. We observe that polariton lasing is stable up to temperatures comparable with the exciton binding energy. At higher temperatures a single threshold displays the direct transition from thermal emission to photon lasing.}, language = {en} }