Alterations of the CARD15/NOD2 gene and the impact on management and treatment of Crohn's disease patients

The recent identification of the CARD15/NOD2 gene as a susceptibility locus for Crohn's disease represents an important step towards the delineation of the immuno-pathogenesis of inflammatory bowel disease. CARD15 functions as an intracellular receptor for bacterial components and thus represents an important link between inflammatory bowel disease and innate immunity. Three major CARD15/NOD2 gene mutations have been associated with Crohn's disease in Caucasians in several independent studies. Together, they explain about 20% of the genetic susceptibility for Crohn's disease. Genotype-phenotype analyses demonstrated an association of these mutations with ileum-specific disease, an increased incidence of the fibrostenotic phenotype and an earlier age of disease onset. Beside these associations, no other relationship between the CARD15/NOD2 genotype and disease behavior or response to treatment has been detailed so far. Thus, the clinical impact of knowing the patient's genotype is limited at this time. Screening for CARD15 mutations in order to identify high-risk individuals or to introduce an individualized disease management is therefore currently not recommended. Copyright (C) 2003 S. Karger AG, Basel

Het uitbesteden vanonderhoudswerk; de invloed van het uitbesteden van onderhoudswerk op de organisatie van het werk

Er is een inventarisatie gemaakt naar de invloed die het uitbesteden van onderhoudswerk heeft op de verdeling van werk in een organisatie in het bijzonder op de verdeling van werkzaamheden in de onderhouds-en productie-afdeling. De aanleiding voor het onderzoek is de tendens, die in de afgelopen 20 jaar binnen organisaties is ontstaan om steeds meer werk dat niet tot de kernactiviteiten behoort, uit te besteden. Dit geldt ook voor de onderhoudsactiviteiten. Onderhoud aan productiemiddelen behoort weliswaar niet tot de kernactiviteiten van een organisatie, maar het goed uitvoeren van onderhoud is wel een belangrijke voorwaarde voor het efficiënt functioneren van de productie binnen het primaire proces. De vraagstelling is gericht op het onderzoeken van de relatie tussen het uitbesteden van onderhoudswerk en de organisatie van het werk in de onderhouds-en productie-afdeling. Bij bestudering van de literatuur bleek dat er vrij veel onderzoek is verricht naar de wijze waarop de beslissing om onderhoudswerkzaamheden uit te besteden tot stand komt. Er is echter weinig bekend over de gevolgen van die beslissing voor de organisatie van het werk. Uitbesteding wordt meestal gezien als een mogelijkheid tot kostenbesparing. Bovendien geldt dat in organisaties ook mogelijkheden worden gezocht om niet-kernactiviteiten, die relatief veel managementaandacht opeisen, uit te besteden. Eén van deze activiteiten is het onderhoud aan productiemiddelen. In dit rapport zijn de taken in het onderhoud in kaart gebracht. Daarna zijn de mogelijke keuzen in vormen van uitbesteding beschreven. De vijf mogelijke vormen zijn: inhuren van personeel, uitbesteden op specificatie, uitbesteden van de organisatie van het onderhoud, verzelfstandigen van de onderhoudsafdeling en operational lease van productiemiddelen. Het onderhoud aan productiemiddelen is meestal ondergebracht in een apart organisatiedeel, de onderhoudsafdeling. Er is echter ook een tendens ontstaan, waarin een deel van het preventief onderhoud ondergebracht wordt bij de productiemedewerkers (Total Productive Maintenance, TPM). In veel literatuur wordt beargumenteerd, dat dit een zeer efficiënte werkwijze is. De relatie tussen het uitbesteden van onderhoud en deze praktijk is tot nu toe echter niet of slechts zijdelings beschreven. Aanvullend op het literatuuronderzoek is een praktijkonderzoek verricht. Teneinde de actuele situatie in organisaties in kaart te brengen is gekozen voor een meervoudige case-study. Er zijn vier organisaties onderzocht. Het streven was om vier organisaties te vinden met verschillende karakteristieken van TPM die bovendien verschilden in de relatieve omvang van uitbesteding van de onderhoudswerkzaamheden. Dit om een breed inzicht in verschillende situaties te bewerkstelligen. Uit de interviews bleek dat het percentage van de uitbestede onderhoudswerkzaamheden, ten opzichte van de totale onderhoudsinspanning, slechts op hoofdlijnen bekend was. Dit varieerde van ongeveer 10% (Ned-Car) tot rond 60% (Corus). Bij slechts één van de vier organisaties werd beoogd dit percentage in de nabije toekomst te verhogen. Alleen bij Electrabel werd verwacht, dat het percentage uitbesteding in de toekomst zou toenemen. Dit in tegenstelling tot de tendens in de literatuur, waarin een grote toename van de uitbestedingspraktijk wordt voorzien

Anti-Saccharomyces cerevisiae antibodies in patients with inflammatory bowel disease and their first-degree relatives: Potential clinical value

Anti-Saccharomyces cerevisiae antibodies (ASCA) have been described as specific markers in Crohn's disease and their healthy first-degree relatives. 171 patients with Crohn's disease, their 105 first-degree relatives, 145 patients with ulcerative colitis and 101 first-degree relatives of patients with ulcerative colitis, 50 patients with infectious enterocolitis and 100 healthy controls were tested for ASCA employing the ELISA technique. When compared with the healthy controls (p < 0.0001) and patients with infectious enterocolitis (p < 0.0001) the prevalence of ASCA was significantly increased in patients with Crohn's disease and their first-degree relatives (p < 0.01). Further significant differences concerning the frequency of ASCA within the different groups of our study population were not observed. In particular, ASCA were not found in increased prevalence in infectious enterocolitis. These observations are compatible with a role of ASCA as a marker of genetic predisposition to Crohn's disease. Copyright (C) 2002 S. Karger AG, Basel

Inflammatory bowel disease-specific autoantibodies in HLA-B27-associated spondyloarthropathies: Increased prevalence of ASCA and pANCA

Aims: An association between inflammatory bowel disease (IBD) and spondyloarthropathies (SpA) has repeatedly been reported. The aim of the present study was to investigate whether serologic markers of IBD, e. g. antibodies against Saccharomyces cerevisiae (ASCA), antibodies against exocrine pancreas (PAB) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) are present in HLA-B27-associated SpA. Methods: 87 patients with HLA-B27-positive SpA and 145 controls were tested for ASCA, PAB and pANCA employing ELISA or indirect immunofluorescence, respectively. Antibody-positive patients were interviewed regarding IBD-related symptoms using a standardized questionnaire. Results/Conclusion: When compared to the controls, ASCA IgA but not ASCA IgG levels were significantly increased in patients with SpA, in particular in ankylosing spondylitis (AS) and undifferentiated SpA (uSpA). pANCA were found in increased frequency in patients with SpA whereas PAB were not detected. The existence of autoantibodies was not associated with gastrointestinal symptoms but sustains the presence of a pathophysiological link between bowel inflammation and SpA. Copyright (C) 2004 S. Karger AG, Basel

Buried dislocation networks designed to organize the growth of III-V semiconductor nanostructures

We first report a detailed transmission electron microscopy study of dislocation networks (DNs) formed at shallowly buried interfaces obtained by bonding two GaAs crystals between which we establish in a controlled manner a twist and a tilt around a k110l direction. For large enough twists, the DN consists of a twodimensional network of screw dislocations accommodating mainly the twist and of a one-dimensional network of mixed dislocations accommodating mainly the tilt. We show that in addition the mixed dislocations accommodate part of the twist and we observe and explain slight unexpected disorientations of the screw dislocations with respect to the k110l directions. By performing a quantitative analysis of the whole DN, we propose a coherent interpretation of these observations which also provides data inaccessible by direct experiments. When the twist is small enough, one screw subnetwork vanishes. The surface strain field induced by such DNs has been used to pilot the lateral ordering of GaAs and InGaAs nanostructures during metal-organic vapor phase epitaxy. We prove that the dimensions and orientations of the nanostructures are correlated with those of the cells of the underlying DN and explain how the interface dislocation structure governs the formation of the nanostructures

Response to combination therapy with interferon alfa-2a and ribavirin in chronic hepatitis C according to a TNF-alpha promoter polymorphism

Background. Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of chronic active hepatitis C. Polymorphisms in the promoter region of the TNF-alpha gene can alter the TNF-alpha expression and modify the host immune response. The present study aimed at the correlation of the G308A TNF-alpha polymorphism with the response to antiviral combination therapy in chronic hepatitis C. Patients and Methods: 62 patients with HCV and 119 healthy unrelated controls were genotyped for the G308A TNF-alpha promoter polymorphism. The patients received 3 x 3 million units of interferon alfa-2a and 1,0001,200 mg ribavirin daily according to their body weight. A response was defined as absence of HCV-RNA and normalization of S-ALT after 6 months of combination therapy. Results:With respect to the allele and genotype frequency, a significant difference was not observed between controls and patients with chronic hepatitis C. Furthermore, such a difference was also not observed if responders and non-responders to antiviral therapy were compared. Conclusions: The promoter polymorphism of the TNF-alpha gene investigated herein is equally distributed in healthy individuals and patients with hepatitis C and does not seem to predict the response to therapy with interferon alfa-2a and ribavirin. Copyright (C) 2003 S. Karger AG, Basel

Spaced training enhances memory and prefrontal ensemble stability in mice

It is commonly acknowledged that memory is substantially improved when learning is distributed over time, an effect called the "spacing effect". So far it has not been studied how spaced learning affects the neuronal ensembles presumably underlying memory. In the present study, we investigate whether trial spacing increases the stability or size of neuronal ensembles. Mice were trained in the "everyday memory"task, an appetitive, naturalistic, delayed matching-to-place task. Spacing trials by 60 min produced more robust memories than training with shorter or longer intervals. c-Fos labeling and chemogenetic inactivation established the involvement of the dorsomedial prefrontal cortex (dmPFC) in successful memory storage. In vivo calcium imaging of excitatory dmPFC neurons revealed that longer trial spacing increased the similarity of the population activity pattern on subsequent encoding trials and upon retrieval. Conversely, trial spacing did not affect the size of the total neuronal ensemble or the size of subpopulations dedicated to specific task-related behaviors and events. Thus, spaced learning promotes reactivation of prefrontal neuronal ensembles processing episodic-like memories

Determination of the local concentrations of Mn interstitials and antisite defects in GaMnAs

We present a method for the determination of the local concentrations of interstitial and substitutional Mn atoms and As antisite defects in GaMnAs. The method relies on the sensitivity of the structure factors of weak reflections to the concentrations and locations of these minority constituents. High spatial resolution is obtained by combining structure factor measurement and X-ray analysis in a transmission electron microscope. We demonstrate the prevalence of interstitials with As nearest neighbors in as-grown layers.Comment: 10 pages, 4 figure

Elevated CO2 emissions during magmatic-hydrothermal degassing at Awu Volcano, Sangihe Arc, Indonesia

Awu is a remote and little known active volcano of Indonesia located in the northern part of Molucca Sea. It is the northernmost active volcano of the Sangihe arc with 18 eruptions in less than 4 centuries, causing a cumulative death toll of 11,048. Two of these eruptions were classified with a Volcanic Explosivity Index (VEI) of 4. Since 2004, a lava dome has occupied the centre of Awu crater, channelling the fumarolic gas output along the crater wall. A combined Differential Optical Absorption Spectroscopy (DOAS) and Multi-component Gas Analyzer System (Multi-GAS) study highlight a relatively small SO2 flux (13 t/d) sustained by mixed magmatic–hydrothermal emissions made-up of 82 mol.% H2O, 15 mol.% CO2, 2.55 mol.% total S (ST) and 0.02 mol.% H2. The CO2 emission budget, as observed during a short observation period in 2015, corresponds to a daily contribution to the atmosphere of 2600 t/d, representing 1% of the global CO2 emission budget from volcanoes. The gas CO2/ST ratio of 3.7 to 7.9 is at the upper limit of the Indonesian gas range, which is ascribed to (i) some extent of S loss during hydrothermal processing, and perhaps (ii) a C-rich signature of the feeding magmatic gas phase. The source of this high CO2 signature and flux is yet to be fully understood; however, given the peculiar geodynamic context of the region, dominated by the arc-to-arc collision, this may result from either the prolonged heating of the slab and consequent production of carbon-rich fluids, or the recycling of crustal carbon