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Contains fulltext : 290373.pdf (Publisher’s version ) (Open Access) 43 p.

The collective structure of $^{106}$Cd is elucidated by multi-step Coulomb excitation of a 3.849 MeV/$A$ beam of $^{106}$Cd on a 1.1 mg/cm$^2$ $^{208}$Pb target using GRETINA-CHICO2 at ATLAS. Fourteen $E2$ matrix elements were obtained. The nucleus $^{106}$Cd is a prime example of emergent collectivity that possesses a simple structure: it is free of complexity caused by shape coexistence and has a small, but collectively active number of valence nucleons. This work follows in a long and currently active quest to answer the fundamental question of the origin of nuclear collectivity and deformation, notably in the cadmium isotopes. The results are discussed in terms of phenomenological models, the shell model, and Kumar-Cline sums of $E2$ matrix elements. The ${\langle 0_2^+ ||E2||2_1^+ \rangle}$ matrix element is determined for the first time, providing a total, converged measure of the electric quadrupole strength, $\langle Q^2 \rangle$, of the first-excited $2_1^+$ level relative to the $0_1^+$ ground state, which does not show an increase as expected of harmonic and anharmonic vibrations. Strong evidence for triaxial shapes in weakly collective nuclei is indicated; collective vibrations are excluded. This is contrary to the only other cadmium result of this kind in $^{114}$Cd by C. Fahlander et al., Nucl. Phys. A485, 327 (1988), which is complicated by low-lying shape coexistence near midshell., 7 pages, 4 figures

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Radioactive $^{129}$Sb, which can be treated as a proton plus semi-magic $^{128}$Sn core within the particle-core coupling scheme, was studied by Coulomb excitation. Reduced electric quadrupole transition probabilities, $B(E2)$, for the $2^+$ $\times$ $\pi g_{{7/2}}$ multiplet members and candidate $\pi d_{{5/2}}$ state were measured. The results indicate that the total electric quadrupole strength of $^{129}$Sb is a factor of 1.39(11) larger than the $^{128}$Sn core, which is in stark contrast to the expectations of the empirically successful particle-core coupling scheme. Shell-model calculations performed with two different sets of nucleon-nucleon interactions suggest that this enhanced collectivity is due to constructive quadrupole coherence in the wavefunctions stemming from the proton-neutron residual interactions, where adding one nucleon to a core near a double-shell closure can have a pronounced effect. The enhanced electric quadrupole strength is an early signal of the emerging nuclear collectivity that becomes dominant away from the shell closure., Comment: Accepted, Physical Review Letters

Supplemental material, sj-docx-1-jdr-10.1177_00220345211034766 for Robert Frank: A Pioneer and Visionary Scientist in Oral Medicine by C. Taddei-Gross, A.M. Musset, Y. Haikel and A. Bloch-Zupan in Journal of Dental Research

Item does not contain fulltext 24 november 2021

In magnetic resonance imaging (MRI) examinations, moderate to severe changes of the distal sesamoidean impar ligament (DSIL) were found in horses with lameness localized to their feet. Histologic abnormalities were detected more commonly in lame horses. Because of its heterogeneity and small thickness, evaluation of the DSIL in MRI can be challenging. The aim of the study was to determine the optimal sequence and the ideal transverse perpendicular angle for visualization of the DSIL before and after arthrography of the distal interphalangeal joint (DIPJ). Twenty-five cadaver forelimbs were examined with low-field MRI. Sagittal, frontal, and three different angled transverse planes were obtained before and after arthrography of the DIPJ. All planes were acquired in T1w (weighted) Gradient Recall Echo (GRE), T2∗w GRE, T2w Fast Spin Echo (FSE), and Short Tau Inversion Recovery (STIR) FSE and visualization of the DSIL was scored by two observers. Visualization of the DSIL was best on sagittal T2w FSE and STIR FSE images. All transverse planes were inferior compared with sagittal sequences. After arthrography of the DIPJ, visualization of the DSIL origin improved in sagittal T2w FSE sequences, and agreement between observers increased for sagittal T2w FSE and STIR FSE images. Sagittal T2w FSE and STIR FSE images allowed good visualization of the DSIL in low-field MRI. Visualization of the DSIL did not improve for altered angled transverse sequences but increased with arthrography of the DIPJ. Subjective influence between different observers was found but decreased with DIPJ arthrography.

Illuminating the functional part of the genome of livestock species has the potential to facilitate precision breeding and to accelerate improvements. Identifying functional and potentially deleterious mutations can provide breeders with crucial information to tackle inbreeding depression or to increase the overall health of their populations and animal welfare. By performing Genome Wide Association Studies (GWAS) the genome can be interrogated for mutations that co-occur with a phenotype of interest. However, every GWAS delivers a large number of potentially functionally important single nucleotide polymorphisms (SNPs). The exact effect of each of these SNPs is often not known, especially for SNPs in noncoding sequences. Investigating each candidate SNP variantin detail is laborious and, eventually, infeasible, given the sheer number of variants. Thus, there is a strong need for approaches to select the most promising SNP candidates. Prioritizing variants, in particular, SNPs, has seen major developments in recent years which led to several discoveries and insights inheritable diseases of humans. Despite their great economical value, for livestock and other non-human species, this development is lagging behind.A major contributing factor to the deficit in prioritization tools for non-human species is a lack of genomic annotations. In this thesis, we translated one of the currently popular SNP prioritization tools, CADD (Combined Annotation-Dependent Depletion), to mouse (mCADD) and performed an experiment in which we simulated a decrease in the number of available genomic annotations.These results showed that following the CADD approach to predict the putative deleteriousness of SNPs is meaningful in a non-human species, even when fewer genomic annotations are available than for the human case. This motivated us to build various CADD-like SNP prioritization tools for livestock species, in particular for pig (pCADD) and chicken (chCADD). We validated the pig prioritization tool on a set of well-known functional pig variants. Further, we showed how functional and non-functional parts of the pig genome are scored differently by pCADD. In collaboration with the breeding industry, we built upon the pCADD scores and implemented them in a pipeline to identify likely causal variants in GWAS. To this end, we utilized SNPs that were found significant in GWAS based on SNP-array data and found variants with high pCADD scores in whole genome sequence data that are in linkage disequilibrium with high GWAS-scoring SNPs. Thus, these pCADD-identified SNPs are likely (causal) functional candidates for the phenotypes tested. We also identified several expression quantitative loci (eQTL) variants, SNPs that explain observed differences in gene expression, which we were able to validate using RNA-seq data. This demonstrated the power of this new tool and its usefulness in identifying novel, functional variants. For chicken, we used the chCADD to interrogate highly conserved elements in the chicken genome. Here we found that, despite being highly conserved, not all parts of these elements might be functionally active. chCADD differentiates between regions within each conserved element that are predicted to be functionally different. Taken together, the results presented in this thesis demonstrate SNP prioritization can successfully be done in non-human species, which can greatly assist breeders and animal geneticists in their work to illuminate the functional genome.

ZusammenfassungDie neue S3-Leitlinie Colitis stellt aktuelle und evidenzbasierte Empfehlungen zur Behandlung der Colitis ulcerosa zur Verfügung. Sie ersetzt damit die Vorläuferversion von 2011. Neben den neuesten Erkenntnissen zu Diagnostik und Therapie werden insbesondere infektiologische Probleme, chirurgische und Ernährungsmaßnahmen aufgegriffen. Unter der Federführung der DGVS wurde die Leitlinie gemeinsam mit 10 weiteren Fachgesellschaften und Patientenvertretern erarbeitet mit dem Ziel, eine optimale interdisziplinäre Versorgung der Patienten zu gewährleisten.

Mark D Mifflin,1 Xavier M Mortensen,1 Brent S Betts,1 Cole Gross,2 Brian Zaugg1 1Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City, UT, 2University of Nevada School of Medicine, Reno, NV, USA Purpose: To study the accuracy and reliability of optical pachymetry using the Alcon WaveLight EX500 during laser-assisted in situ keratomileusis (LASIK). Materials and methods: This was a retrospective chart review of 90 eyes from 45 patients who had undergone LASIK (mean age 35.2±8.2 years; 19 males, 26 females). The WaveLight FS200 femtosecond laser was programmed to cut LASIK flaps at a desired depth of 120 µm. Optical low-coherence reflectometry (WaveLight EX500) was used to measure central corneal thickness prior to lifting the flap, and the residual stromal bed immediately after excimer ablation. Flap thickness (FT) was calculated using simple subtraction. Optical coherence tomography (OCT) was used to measure central corneal thickness, flap thickness, and residual stromal bed in the postoperative period and the results compared to intraoperative measurements. Results: Mean programmed FS200 FT was 119 µm. Mean FT using EX500 optical pachymetry was 109 µm. The difference between FS200- programmed and EX500-measured FT was 9 µm (P

BACKGROUND: Spatial memory and navigation have been widely studied using animal models, most of them were performed with rodents and only few of them with non-human primates. Also, most of these studies were achieved in simple and small-scale mazes. NEW METHOD: In order to test navigation strategy in macaque monkeys, we used a double-cross virtual maze in which they could freely move using a joystick and a procedure adapted from previous studies with rodents. The monkeys had first to learn several routes from a specific starting point to reach separate positions, each one containing distinct symbols, and then to associate each route with these symbols. After this phase, the monkeys had to reach these targets from a second starting point positioned at the other end of the maze, requiring the use an allocentric strategy. In order to evaluate monkey's strategy, we analyzed monkey's first choice as a function of the symbol presented. RESULTS: The monkeys were able to learn routes and to associate routes with symbols but were not able to use an allocentric strategy. They also did not use the procedural strategy and seemed disoriented or adopted a stereotypical behavior. COMPARISON WITH EXISTING METHOD(S): Contrary to the few studies using small-scale environments, the monkeys seemed unable to solve the allocentric task. The studies using virtual mazes seemed not to specifically analyze monkey's navigation strategy. CONCLUSIONS: Supplementary experiments will be necessary to explain the origin of the monkey's inability to use an allocentric strategy. Modified learning conditions could also incite the monkeys to develop an allocentric representation.

A search for superallowed α decay of N=Z nuclei Te104 and Xe108 was carried out using a novel recoil-decay scintillator detector at the tandem accelerator facility at the Japan Atomic Energy Agency (JAEA). Inorganic crystal scintillation material YAP:Ce (yttrium aluminum perovskite) coupled to a position-sensitive photomultiplier tube (PSPMT) was implemented for the first time in a radioactive decay experiment. Residues from the fusion-evaporation reaction Ni58+Fe54→Xe∗112 were separated by the JAEA Recoil Mass Separator (RMS) and implanted into the YAP:Ce crystal. α decays of neutron-deficient tellurium isotopes were identified and proton emission of I109 was observed. The α-decay chain Xe109→Te105→Sn101 was recorded with a time interval of 960 ns between two α pulses. Position localization in the crystal for decays and ions in the energy range from hundreds of keV to 60 MeV was achieved with an accuracy of 0.67 mm, proving that this detector is capable of making temporal and spatial correlations for fast decay events. No conclusive evidence was found for the decay chain Xe108→Te104→Sn100 within 3 days of experiment. However, two events were observed with properties consistent with the reported observation at the Fragment Mass Analyzer (FMA), but with a separation between signals of less than 4 ns. The cross section limit of 130 pb was obtained for production of two events of Xe108, about an order of magnitude below the expectation based on earlier cross section measurements and the hivap fusion-evaporation code.

Microglia participate in synapse remodeling in the cortex and hippocampus during mouse postnatal development. Although sex differences in microglia activity during embryonic development have been reported in these regions, it remains unexplored whether microglia show sexually dimorphic features during the early postnatal period, a critical window for synapse formation and maturation. Here, we investigated morphological and functional features of microglia across early postnatal development as well as morphological features of both pre‐ and postsynaptic neuronal compartments in the mouse hippocampus. We found a sex‐dependent shift in microglia volume and phagocytic capacity across the first four postnatal weeks. Measurements of synaptic features revealed sex differences in the density of synaptic spines and boutons during the second postnatal week. These data are consistent with a precocious development of both microglia and synapses in the female brain. We further hypothesize that this bias may contribute to sex‐specific brain wiring.

Genetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all, studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioral traits, we set out to develop a mouse model of the human 5-HTT-LPR. Here we describe the creation and characterization of a set of mouse lines with single-copy human transgenes carrying the short and long 5-HTT-LPR variants. Although we were not able to detect differences in expression between the short and long variants, we encountered several technical issues concerning the design of our humanized mice that are likely to have influenced our findings. Our study serves as a cautionary note for future studies aimed at studying human transgene regulation in the context of the living mouse.

An autoimmune-mediated process in the pathophysiology of narcolepsy type 1 (NT1) is highly suspicious, if this pathomechanism is transferable to other types of central disorders of hypersomnolence (CDH), is still controversial. The association of NT1 with HLA-class-II system implicates a T-cell-mediated autoimmunity, in which helper CD4+ T-cells and cytotoxic CD8+ T-cells may be pathogenic.This study aimed to identify specific immune profiles in peripheral blood (PB) and cerebrospinal fluid (CSF) in different types of CDH.Forty-three patients with polysomnographically confirmed CDH (24 idiopathic hypersomnia (IH), 12 NT1, 7 NT2) were compared to 24 healthy controls (HC). PB and CSF were analysed with multiparameter flow cytometry to distinguish between subclasses of peripheral and intrathecal immune cells and specific surface markers of T-cells.The overall proportion of helper CD4+ T-cells and cytotoxic CD8+ T-cells in PB and CSF did not differ between the patients and HC. Activated HLA-DR+ CD4+T-cells and HLA-DR+ CD8+T-cells in PB and CSF both in NT1, NT2 and IH were significant increased compared to HC. A significant correlation of HLA-DR+ CD4+ - and HLA-DR+ CD8+ T-cells with higher amounts of excessive daytime sleepiness was found in the NT1- and IH groups, indicating an association of activated T-cells in the CNS with increased of sleepiness.These findings provide further evidence of a T-cell-mediated autoimmunity not only in NT1, but in NT2 and IH as well. Moreover, the identification of activated cytotoxic CD8+ T-cells further supports the evidence of T cell-mediated neuronal damage, which has previously been suggested in NT1.

BACKGROUND: A point-prevalence survey that was conducted in the United States in 2011 showed that 4% of hospitalized patients had a health care–associated infection. We repeated the survey in 2015 to assess changes in the prevalence of health care–associated infections during a period of national attention to the prevention of such infections. METHODS: At Emerging Infections Program sites in 10 states, we recruited up to 25 hospitals in each site area, prioritizing hospitals that had participated in the 2011 survey. Each hospital selected 1 day on which a random sample of patients was identified for assessment. Trained staff reviewed medical records using the 2011 definitions of health care–associated infections. We compared the percentages of patients with health care–associated infections and performed multivariable log-binomial regression modeling to evaluate the association of survey year with the risk of health care–associated infections. RESULTS: In 2015, a total of 12,299 patients in 199 hospitals were surveyed, as compared with 11,282 patients in 183 hospitals in 2011. Fewer patients had health care–associated infections in 2015 (394 patients [3.2%; 95% confidence interval {CI}, 2.9 to 3.5]) than in 2011 (452 [4.0%; 95% CI, 3.7 to 4.4]) (P

Continuous flow left ventricular assist devices (cfLVADS) result in a significant reduction in aortic valve (AV) opening, which has been associated with several complications. Reliable monitoring of AV opening is needed to determine whether pump speed adjustment may be able to minimize adverse outcomes. We assessed AV status continuously by echocardiography for 4 minutes in 3 states in 18 HeartWare HVAD patients: 2 minutes at rest, and 1 minute each following Valsalva maneuver and supine leg-raising. Using a previously described algorithm, beat-to-beat AV status was compared with the area under the curve of the normalized power spectral density analysis (PSD-AUC) for the corresponding beats of the pump speed waveform. Five thousand five hundred twenty-seven beats were analyzed. AV opening varied between 0% and 100% for the cohort with the median AV opening frequency 21.5%, and median duration of opening of 124 msec (range 0-279). The receiver operating characteristic (ROC) curve area for AV opening by the PSD-AUC algorithm was 0.95 (P

Short-lived α-decaying nuclei "northeast" of 208Pb in the chart of nuclides were studied using the reaction 48Ca+243Am with the decay station TASISpec at TASCA, GSI Darmstadt. Decay energies and times from pile-up events were extracted with a tailor-made pulse-shape analysis routine and specific α-decay chains were identified in a correlation analysis. Decay chains starting with the even-even 220Ra and its odd-A neighbors, 219Fr, and 219,221Ra, with a focus on the 219Ra→215Rn decay, were studied by means of α-γ spectroscopy. A revised α-decay scheme of 219Ra is proposed, including a new decay branch from a previously not considered isomeric state at 17 keV excitation energy. Conclusions on nuclear structure are drawn from the experimental data, aided by Geant4 simulations and a discussion on theoretical calculations.

Neukum Crater, located at about 28°E/45°S at Noachis Terra on Mars, contains various geomorphological features that indicate a diverse geological history forming the crater during the past up to 4 Ga years. Most prominent features of this 102 km-crater are the large dark dune field and the two pits on its floor. The basaltic composition of the dunes sands, enriched in high-calcium pyroxenes, does not differ from the overall composition of the dark dunes found in various places elsewhere on Mars. Avalanches of the dune slip faces evidence recent seasonal mass movement processes within the dune field. Aeolian processes also left its traces in the form of countless dust devil tracks widespread on the crater floor as well as in the form of transverse aeolian ridges within the pits. These pits, also found in some neighbouring craters, act as geological windows to the subsurface and might have contributed as sources of the dark dune materials of this region. Moraine-like features and mass movements in smoothed terrain along the crater wall whiteness an era of active glacial and periglacial processes at Neukum crater. Superposed ejecta onto these landforms allow determining the minimum age of the features and constraining the timing of geological processes.

Item does not contain fulltext 121 p.

The lysis‐lysogeny decision made by bacteriophage lambda is one of the classic problems of molecular biology. Shortly after infecting a cell, the virus can either go down the lytic pathway and make more viruses, or go down the lysogenic pathway and integrate itself into the host genome. While much is known about how this decision takes place, the extent to which host physiology influences this decision and the mechanisms by which this influence takes place has remained mysterious. To answer this question, we performed a forward genetic screen to systematically identify all of the genes in E. coli that influence the lysis‐lysogeny decision. Our results demonstrate previously unknown links between host physiology and viral decision making and shed new light on this classic system.

Contains fulltext : 144854.pdf (Publisher’s version ) (Closed access) This study draws on an active audience perspective to develop a better understanding of mass audiences' attraction towards popular management ideas. It focuses on audience members' own experiences and, in particular, what audience activities actually play a role in shaping mass attraction, and how the deployment of these activities may vary. Analysing 65 in-depth interviews with management practitioners in their role as audience members of guru seminars, the authors identify different key consumption activities, and explain how individual management practitioners may shift in consumption orientation throughout the communication process. This paper argues that such a broader and more dynamic understanding of consumption activity is essential in understanding the success and impact of management ideas, and opens several fruitful research directions. 25 december 2014 19 p.

Products of the fusion-evaporation reaction 48Ca + 243Am were studied with the TASISpec set-up at the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany. Amongst the detected thirty correlated α-decay chains associated with the production of element Z=115, two recoil-α-fission and five recoil-α-α-fission events were observed. The latter five chains are similar to four such events reported from experiments performed at the Dubna gas-filled separator, and three such events reported from an experiment at the Berkeley gas-filled separator. The four chains observed at the Dubna gas-filled separator were assigned to start from the 2n-evaporation channel 289115 due to the fact that these recoil-α-α-fission events were observed only at low excitation energies. Contrary to this interpretation, we suggest that some of these recoil-α-α-fission decay chains, as well as some of the recoil-α-α-fission and recoil-α-fission decay chains reported from Berkeley and in this article, start from the 3n-evaporation channel 288115.

Products of the fusion-evaporation reaction Ca-48 + Am-243 were studied with the TASISpec set-up at the gas-filled separator TASCA at the GSI Helmholtzzentrum f\"ur Schwerionenforschung. Amongst the detected thirty correlated alpha-decay chains associated with the production of element Z=115, two recoil-alpha-fission and five recoil-alpha-alpha-fission events were observed. The latter are similar to four such events reported from experiments performed at the Dubna gas-filled separator. Contrary to their interpretation, we propose an alternative view, namely to assign eight of these eleven decay chains of recoil-alpha(-alpha)-fission type to start from the 3n-evaporation channel 115-288. The other three decay chains remain viable candidates for the 2n-evaporation channel 115-289., Comment: 15 pages. Article: 9 pages, 3 tables, 3 figures. Supplemental material: 6 pages, 7 tables, 1 figure. Submitted to PRC

The aim of this chapter is to investigate the relationship between tracking and migrant student performance and compare the results of native-born people, and first and second generation migrants. We combine two insights: the need to take into account school level variables when estimating the strength of the relationship between education systems and student performance and the need to include country of origin to correctly estimate models for migrant students. We use pisa 2009 data for 15 oecd countries, running analyses for native-born students, first and second generation migrants. We find that both first and second generation migrant students in educational systems with many tracks have equal or higher scores than students in systems with only one track. In an extended sample, the influence of the educational system on migrant students is absent, while for native-born students the influence remains substantial.

Impacts on Mars play an important global role in exposing ancient phyllosilicates from buried Noachian rocks and may have also provided localized aqueous alteration. Current studies are investigating the extent of impact-induced alteration on Mars.

Educational systems differ in at least three dimensions: the timing and form of tracking students, the extent to which a system provides vocationally specific skills, and the extent to which an educational system is standardised nationwide. Existing conceptualisations of these three dimensions are rather fragmented, and in this chapter we develop new indicators for a large number of countries, based on various sources of data (OECD, UNESCO, TIMSS, PISA and Eurydice). With our new indicators we examine how educational systems affect four core functions of schooling: equality of opportunity, the optimisation of student skills, the allocation of students to the labour market, and the preparation for active participation in society at large.

Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of ≥100 points or a CDAI score150). The primary end point for the maintenance trial was remission at week 44 (CDAI score150).The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P=0.005 and P=0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups.Among patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329 , NCT01369342 , and NCT01369355 .).

86 patients with significant main coronary artery stenosis (greater than 50%) were divided into 61 with stable and 25 with unstable angina pectoris. The coronary morphology (isolated main coronary artery stenosis, degree of stenosis, additional vessel disease) and the left ventricular function (ejection fraction, left ventricular end-diastolic pressure) were the same in both groups. Deaths due to coronary angiography amounted to 2.3% and involved two patients with unstable angina. 82% (n = 50) of the patients with stable angina and 83% (n = 19) with unstable angina were considered operable. 69% of the stable and 74% of the unstable group were actually revascularised. Operative deaths amounted to 3.4% and again involved two patients with unstable angina. During an average post-operative follow-up period of 38 months 5% of the operated and 28% of the non-operated patients died (P less than 0.05). The investigation demonstrated that for patients with main coronary artery stenosis operability in stable angina is no different from that in unstable angina. Angiographic and operative deaths in patients with unstable symptomatology, however, were markedly higher than in those with stable angina.

GSI Scientific Report 2014 - GSI Report 2015-1

Hintergrund. Das Auftreten einer Hamolyse bei alkoholtoxischem Leberschaden in Verbindung mit einer sekundaren Hyperlipidamie wird als Zieve-Syndrom bezeichnet. Uber damit in Zusammenhang stehende Netzhautveranderungen wurde bisher nicht berichtet. Patient. Ein 44-jahriger Diabetiker stellte sich zur Routinekontrolle beim Augenarzt vor. Die Sehscharfe war beidseitig gut (1,0/0,8). Ophthalmoskopisch imponierte beidseitig eine ausgepragte Lipaemia retinalis mit cremefarbenen Netzhautgefasen sowie peripapillaren Cotton-wool-Herden mit vereinzelten Blutungen. Anamnestisch bekannt war eine Fettleberhepatitis bei jahrelangem Athanolabusus. Seit einem Monat bestand eine vermehrte Ubelkeit mit Erbrechen. Paraklinisch waren eine gemischte Hyperlipidamie mit hochgradig lipamischem Serum und eine schwere Anamie auffallig. Der Patient wurde zur weiteren Diagnostik und Therapie stationar in der Inneren Klinik aufgenommen. Hier erfolgte wegen der Anamie eine Bluttransfusion. Die extrem erhohten Cholesterin- und Triglyzeridwerte im Serum konnten durch medikamentose Einstellung der Hyperlipidamie deutlich reduziert werden. Die Kontrolluntersuchung des Augenhintergrundes 3 Wochen nach Therapiebeginn zeigte eine regelrechte Gefasfullung und in Ruckbildung befindliche Cotton-wool-Herde. Einen Monat spater lies sich kein pathologischer Netzhautbefund mehr feststellen. Schlussfolgerungen. Die beobachteten Netzhautveranderungen sind auf die Kombination von schwerer Anamie und Hyperlipidamie zuruckzufuhren und waren wegweisend fur die weitere internistische Diagnostik. Nach Behandlung der Grunderkrankung waren die Veranderungen ohne funktionelle Beeintrachtigung komplett reversibel.

Background: The actin-bundling protein Fascin (FSCN1) is a tumor marker that is highly expressed in numerous types of cancer including lymphomas and is important for migration and metastasis of tumor cells. Fascin has also been detected in B lymphocytes that are freshly-infected with Epstein-Barr virus (EBV), however, both the inducers and the mechanisms of Fascin upregulation are still unclear. Results: Here we show that the EBV-encoded oncoprotein latent membrane protein 1 (LMP1), a potent regulator of cellular signaling and transformation, is sufficient to induce both Fascin mRNA and protein in lymphocytes. Fascin expression is mainly regulated by LMP1 via the C-terminal activation region 2 (CTAR2). Block of canonical NF-κB signaling using a chemical inhibitor of IκB kinase β (IKKβ) or cotransfection of a dominant-negative inhibitor of IκB (NFKBIA) reduced not only expression of p100, a classical target of the canonical NF-κB-pathway, but also LMP1-induced Fascin expression. Furthermore, chemical inhibition of IKKβ reduced both Fascin mRNA and protein levels in EBV-transformed lymphoblastoid cell lines, indicating that canonical NF-κB signaling is required for LMP1-mediated regulation of Fascin both in transfected and transformed lymphocytes. Beyond that, chemical inhibition of IKKβ significantly reduced invasive migration of EBV-transformed lymphoblastoid cells through extracellular matrix. Transient transfection experiments revealed that Fascin contributed to LMP1-mediated enhancement of invasive migration through extracellular matrix. While LMP1 enhanced the number of invaded cells, functional knockdown of Fascin by two different small hairpin RNAs resulted in significant reduction of invaded, non-attached cells. Conclusions: Thus, our data show that LMP1-mediated upregulation of Fascin depends on NF-κB and both NF-κB and Fascin contribute to invasive migration of LMP1-expressing lymphocytes.