StratIT– Ein Rahmenwerk zu den Inhalten von ITStrategien. Grundlegung und methodische Fundierung

Bis heute ist kein Konsens über die Inhalte von IT-Strategien vorhan-den. Daraus folgt eine gewisse Unsicherheit, wenn es gilt, die Themenbereiche einer IT-Strategie festzulegen. Dieser Missstand soll durch den Entwurf eines Rahmenwerks/Frameworks behoben werden. Die Fachgruppe Strategisches In-formationsmanagement der Gesellschaft für Informatik (GI-Fachgruppe SIM) hat sich zum Ziel gesetzt, ein entsprechendes Rahmenwerk zu entwickeln. Dieses dient dazu, die Erstellung von IT-Strategien zu unterstützen. Der vorlie-gende Beitrag beschreibt den aktuellen Stand der Arbeit und zeigt im Sinne einer Diskussionsgrundlage auf, in welche thematischen Perspektiven, Domä-nen und Elemente sich IT-Strategien gliedern lassen. Darüber hinaus werden die methodische und wissenschaftstheoretische Fundierung sowie der „modus operandi“ der Arbeitsgruppe beschrieben. Das Rahmenwerk „StratIT“ entsteht in Zusammenarbeit von Forschern und Praktikern

Functional Contribution of Elevated Circulating and Hepatic Non-Classical CD14+CD16+ Monocytes to Inflammation and Human Liver Fibrosis

BACKGROUND: Monocyte-derived macrophages critically perpetuate inflammatory responses after liver injury as a prerequisite for organ fibrosis. Experimental murine models identified an essential role for the CCR2-dependent infiltration of classical Gr1/Ly6C(+) monocytes in hepatic fibrosis. Moreover, the monocyte-related chemokine receptors CCR1 and CCR5 were recently recognized as important fibrosis modulators in mice. In humans, monocytes consist of classical CD14(+)CD16(-) and non-classical CD14(+)CD16(+) cells. We aimed at investigating the relevance of monocyte subpopulations for human liver fibrosis, and hypothesized that 'non-classical' monocytes critically exert inflammatory as well as profibrogenic functions in patients during liver disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed circulating monocyte subsets from freshly drawn blood samples of 226 patients with chronic liver disease (CLD) and 184 healthy controls by FACS analysis. Circulating monocytes were significantly expanded in CLD-patients compared to controls with a marked increase of the non-classical CD14(+)CD16(+) subset that showed an activated phenotype in patients and correlated with proinflammatory cytokines and clinical progression. Correspondingly, CD14(+)CD16(+) macrophages massively accumulated in fibrotic/cirrhotic livers, as evidenced by immunofluorescence and FACS. Ligands of monocyte-related chemokine receptors CCR2, CCR1 and CCR5 were expressed at higher levels in fibrotic and cirrhotic livers, while CCL3 and CCL4 were also systemically elevated in CLD-patients. Isolated monocyte/macrophage subpopulations were functionally characterized regarding cytokine/chemokine expression and interactions with primary human hepatic stellate cells (HSC) in vitro. CD14(+)CD16(+) monocytes released abundant proinflammatory cytokines. Furthermore, CD14(+)CD16(+), but not CD14(+)CD16(-) monocytes could directly activate collagen-producing HSC. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the expansion of CD14(+)CD16(+) monocytes in the circulation and liver of CLD-patients upon disease progression and suggest their functional contribution to the perpetuation of intrahepatic inflammation and profibrogenic HSC activation in liver cirrhosis. The modulation of monocyte-subset recruitment into the liver via chemokines/chemokine receptors and their subsequent differentiation may represent promising approaches for therapeutic interventions in human liver fibrosis

Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

<p>Abstract</p> <p>Background</p> <p>Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases.</p> <p>Methods</p> <p>We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation.</p> <p>Results</p> <p>We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients.</p> <p>Conclusions</p> <p>Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should therefore be evaluated in larger prospective studies.</p

Small intestinal mucosa expression of putative chaperone fls485

<p>Abstract</p> <p>Background</p> <p>Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. <it>fls485 </it>coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze <it>fls48</it>5 expression in human small intestinal mucosa.</p> <p>Methods</p> <p><it>fls485 </it>expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several <it>in situ </it>techniques and usage of newly synthesized mouse monoclonal antibodies.</p> <p>Results</p> <p>fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c.</p> <p>Conclusions</p> <p>Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.</p

Habitat Composition and Connectivity Predicts Bat Presence and Activity at Foraging Sites in a Large UK Conurbation

Background: Urbanization is characterized by high levels of sealed land-cover, and small, geometrically complex, fragmented land-use patches. The extent and density of urbanized land-use is increasing, with implications for habitat quality, connectivity and city ecology. Little is known about densification thresholds for urban ecosystem function, and the response of mammals, nocturnal and cryptic taxa are poorly studied in this respect. Bats (Chiroptera) are sensitive to changing urban form at a species, guild and community level, so are ideal model organisms for analyses of this nature. Methodology/Principal Findings: We surveyed bats around urban ponds in the West Midlands conurbation, United Kingdom (UK). Sites were stratified between five urban land classes, representing a gradient of built land-cover at the 1 km 2 scale. Models for bat presence and activity were developed using land-cover and land-use data from multiple radii around each pond. Structural connectivity of tree networks was used as an indicator of the functional connectivity between habitats. All species were sensitive to measures of urban density. Some were also sensitive to landscape composition and structural connectivity at different spatial scales. These results represent new findings for an urban area. The activity of Pipistrellus pipistrellus (Schreber 1774) exhibited a non-linear relationship with the area of built land-cover, being much reduced beyond the threshold of,60 % built surface. The presence of tree networks appears to mitigate the negative effects of urbanization for this species

Assessing anti-rabies baiting – what happens on the ground?

BACKGROUND: Rabies is one of the most hazardous zoonoses in the world. Oral mass vaccination has developed into the most effective management method to control fox rabies. The future need to control the disease in large countries (i.e. Eastern Europe and the Americas) forces cost-benefit discussions. The 'Increase bait density' option refers to the usual management assumption that more baits per km(2 )could compensate for high fox abundance and override the imperfect supply of bait pieces to the individual fox. METHODS: We use a spatial simulation, which combines explicitly fox space use (tessellation polygons) and aeroplane flight lines (straight lines). The number of baits actually falling into each polygon is measured. The manager's strategic options are converted into changes of the resulting bait distribution on the ground. The comparison enables the rating of the options with respect to the management aim (i.e. accessibility of baits). RESULTS: Above 5% (approx. 10%) of all fox groups without any bait (at most 5 baits) relate to the baiting strategy applied in the field (1 km spaced parallel flight lines, 20 baits per km(2 )distributed) under habitat conditions comparable to middle and western Europe (fox group home-range 1 km(2), 2.5 adults; reference strategy). Increasing the bait density on the same flight-line pattern neither reduces the number of under-baited fox group home-ranges, nor improves the management outcome and hence wastes resources. However, reducing the flight line distance provides a more even bait distribution and thus compensates for missed fox groups or extra high fox density. The reference strategy's bait density can be reduced when accounting for the missed fox groups. The management result with the proper strategy is likely the same but with reduced costs. CONCLUSION: There is no overall optimal strategy for the bait distribution in large areas. For major parts of the landscape, the reference strategy will be more competitive. In situations where set backs are attributed to non-homogeneous bait accessibility the distribution scheme has to be refined zone-based (i.e. increase of the flight line length per unit area). However, increase in bait density above the reference strategy appears inappropriate at least for non-urban abundance conditions of the red fox

Emergency vaccination of rabies under limited resources – combating or containing?

BACKGROUND: Rabies is the most important viral zoonosis from a global perspective. Worldwide efforts to combat the disease by oral vaccination of reservoirs have managed to eradicate wildlife rabies in large areas of central Europe and North-America. Thus, repeated vaccination has been discontinued recently on a geographical scale. However, as rabies has not yet been eradicated globally, a serious risk of re-introduction remains. What is the best spatial design for an emergency vaccination program – particularly if resources are limited? Either, we treat a circular area around the detected case and run the risk of infected hosts leaving the limited control area, because a sufficient immunisation level has not yet been built up. Or, initially concentrate the SAME resources in order to establish a protective ring which is more distant from the infected local area, and which then holds out against the challenge of the approaching epidemic. METHODS: We developed a simulation model to contrast the two strategies for emergency vaccination. The spatial-explicit model is based on fox group home-ranges, which facilitates the simulation of rabies spread to larger areas relevant to management. We used individual-based fox groups to follow up the effects of vaccination in a detailed manner. Thus, regionally – bait distribution orientates itself to standard schemes of oral immunisation programs and locally – baits are assigned to individual foxes. RESULTS: Surprisingly, putting the controlled area ring-like around the outbreak does not outperform the circular area of the same size centred on the outbreak. Only during the very first baitings, does the ring area result in fewer breakouts. But then as rabies is eliminated within the circle area, the respective ring area fails, due to the non-controlled inner part. We attempt to take advantage of the initially fewer breakouts beyond the ring when applying a mixed strategy. Therefore, after a certain number of baitings, the area under control was increased for both strategies towards the same larger circular area. The circle-circle strategy still outperforms the ring-circle strategy and analysis of the spatial-temporal disease spread reveals why: improving control efficacy by means of a mixed strategy is impossible in the field, due to the build-up time of population immunity. CONCLUSION: For practical emergency management of a new outbreak of rabies, the ring-like application of oral vaccination is not a favourable strategy at all. Even if initial resources are substantially low and there is a serious risk of rabies cases outside the limited control area, our results suggest circular application instead of ring vaccination

Immigration Rates in Fragmented Landscapes – Empirical Evidence for the Importance of Habitat Amount for Species Persistence

BACKGROUND: The total amount of native vegetation is an important property of fragmented landscapes and is known to exert a strong influence on population and metapopulation dynamics. As the relationship between habitat loss and local patch and gap characteristics is strongly non-linear, theoretical models predict that immigration rates should decrease dramatically at low levels of remaining native vegetation cover, leading to patch-area effects and the existence of species extinction thresholds across fragmented landscapes with different proportions of remaining native vegetation. Although empirical patterns of species distribution and richness give support to these models, direct measurements of immigration rates across fragmented landscapes are still lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using the Brazilian Atlantic forest marsupial Gray Slender Mouse Opossum (Marmosops incanus) as a model species and estimating demographic parameters of populations in patches situated in three landscapes differing in the total amount of remaining forest, we tested the hypotheses that patch-area effects on population density are apparent only at intermediate levels of forest cover, and that immigration rates into forest patches are defined primarily by landscape context surrounding patches. As expected, we observed a positive patch-area effect on M. incanus density only within the landscape with intermediate forest cover. Density was independent of patch size in the most forested landscape and the species was absent from the most deforested landscape. Specifically, the mean estimated numbers of immigrants into small patches were lower in the landscape with intermediate forest cover compared to the most forested landscape. CONCLUSIONS/SIGNIFICANCE: Our results reveal the crucial importance of the total amount of remaining native vegetation for species persistence in fragmented landscapes, and specifically as to the role of variable immigration rates in providing the underlying mechanism that drives both patch-area effects and species extinction thresholds

Analysing the eosinophil cationic protein - a clue to the function of the eosinophil granulocyte

Eosinophil granulocytes reside in respiratory mucosa including lungs, in the gastro-intestinal tract, and in lymphocyte associated organs, the thymus, lymph nodes and the spleen. In parasitic infections, atopic diseases such as atopic dermatitis and asthma, the numbers of the circulating eosinophils are frequently elevated. In conditions such as Hypereosinophilic Syndrome (HES) circulating eosinophil levels are even further raised. Although, eosinophils were identified more than hundred years ago, their roles in homeostasis and in disease still remain unclear. The most prominent feature of the eosinophils are their large secondary granules, each containing four basic proteins, the best known being the eosinophil cationic protein (ECP). This protein has been developed as a marker for eosinophilic disease and quantified in biological fluids including serum, bronchoalveolar lavage and nasal secretions. Elevated ECP levels are found in T helper lymphocyte type 2 (atopic) diseases such as allergic asthma and allergic rhinitis but also occasionally in other diseases such as bacterial sinusitis. ECP is a ribonuclease which has been attributed with cytotoxic, neurotoxic, fibrosis promoting and immune-regulatory functions. ECP regulates mucosal and immune cells and may directly act against helminth, bacterial and viral infections. The levels of ECP measured in disease in combination with the catalogue of known functions of the protein and its polymorphisms presented here will build a foundation for further speculations of the role of ECP, and ultimately the role of the eosinophil