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  • 1
    Keywords: MODELS ; INFORMATION ; LUNG-CANCER ; GENES ; REGRESSION ; SNPs ; RHEUMATOID-ARTHRITIS ; COMPLEX DISEASES ; SETS
    Abstract: Biological pathways provide rich information and biological context on the genetic causes of complex diseases. The logistic kernel machine test integrates prior knowledge on pathways in order to analyze data from genome-wide association studies (GWAS). In this study, the kernel converts the genomic information of 2 individuals into a quantitative value reflecting their genetic similarity. With the selection of the kernel, one implicitly chooses a genetic effect model. Like many other pathway methods, none of the available kernels accounts for the topological structure of the pathway or gene-gene interaction types. However, evidence indicates that connectivity and neighborhood of genes are crucial in the context of GWAS, because genes associated with a disease often interact. Thus, we propose a novel kernel that incorporates the topology of pathways and information on interactions. Using simulation studies, we demonstrate that the proposed method maintains the type I error correctly and can be more effective in the identification of pathways associated with a disease than non-network-based methods. We apply our approach to genome-wide association case-control data on lung cancer and rheumatoid arthritis. We identify some promising new pathways associated with these diseases, which may improve our current understanding of the genetic mechanisms. (c) 2014 S. Karger AG, Basel.
    Type of Publication: Journal article published
    PubMed ID: 24434848
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  • 2
  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS German Medical Science; VOL: 8; DOC13 /20100615/
    Publication Date: 2010-06-16
    Description: Extended traumatic wounds require extended reconstructive operations and are accompanied by long hospitalizations and risks of infection, thrombosis and flap loss. In particular, the frequently used Topical Negative Pressure (TNP) Therapy is regarded as cost-intensive. The costs of TNP in the context of traumatic wounds is analyzed using the method of health economic evaluation. All patients (n=67: 45 male, 22 female; average age 54 y) with traumatically acquired wounds being treated with TNP at the university hospital of Goettingen in the period 01/01/2005-31/12/2007 comprise the basis for this analysis. The concept of activity-based costing based on clinical pathways according to InEK (National Institute for the Hospital Remuneration System) systematic calculations was chosen for cost accounting. In addition, a special module system adaptable for individual courses of disease was developed. The treated wounds were located on a lower extremity in 83.7% of cases (n=56) and on an upper extremity in 16.3% of cases (n=11). The average time of hospitalization of the patients was 54 days. Twenty-five patients (37.31%) exceeded the "maximum length of stay" of their associated DRG (Diagnosis Related Groups). The total PCCL (patient clinical complexity level = patient severity score) of 2.99 reflects the seriousness of disease. For the treatment of the 67 patients, total costs were $1,729,922.32 (1,249,176.91 Euro). The cost calculation showed a financial deficit of $-210,932.50 (-152,314.36 Euro). Within the entire treatment costs of $218,848.07 (158,030.19 Euro), 12.65% per case were created by TNP with material costs of $102,528.74 (74,036 Euro), representing 5.92% of entire costs. The cost of TNP per patient averaged $3,266.39 (2,358.66 Euro). The main portion of the costs was not - as is often expected - due to high material costs of TNP but instead to long-term treatments. Because of their complexity, the cases are insufficiently represented in the lump-sum calculation of the InEK. A differentiated integration of complex TNP-treatment in the DRG system (e.g., as an expanded DRG I98Z) would be a step towards cost recovery. In addition, the refunding of outpatient TNP-treatment would lead to enhanced quality of life for the patients and to a reduction of hospital costs and length of stay.
    Description: Ausgedehnte traumatische Weichteildefekte erfordern aufwändige rekonstruktive Operationsverfahren und sind von langen Liegezeiten und Risiken wie Infektion, Thrombose und Lappenverlusten gekennzeichnet. Die Vakuumtherapie (VAC) stellt dabei eine wesentliche und häufig angewandte Therapie dar, die als kostenintensiv angesehen wird. Die Kosten dieser Vakuumtherapie in der Behandlung des traumatischen Weichteildefekts werden in der vorliegenden Arbeit mit der Methodik der gesundheitsökonomischen Evaluation analysiert. Alle Patienten (n=67: 45 m, 22 w; Ø 54 J.) mit traumatischem Weichteildefekt, die zwischen 01/01/2005-31/12/2007 an der Universitätsklinik Göttingen mit VAC behandelt wurden, wurden in die Evaluation eingeschlossen. Die Methode der Prozesskostenrechnung anhand Klinischer Pfade, welche sich an der InEK (Institut für das Entgeltsystem im Krankenhaus)-Systematik orientiert, war Grundlage dieser Kalkulation. Zusätzlich wurde ein neues Modulsystem entwickelt, welches es ermöglichte, individuelle Patientenkarrieren exakt abzubilden. Die behandelten Weichteildefekte waren in 83,7% der Fälle (n=56) an der oberen Extremität und in 16,3% der Fälle (n=11) an der unteren Extremität lokalisiert. Die durchschnittliche Liegezeit betrug 54 Tage. 25 Patienten (37,31%) überschritten die obere Grenzverweildauer ihrer assoziierten DRG (Diagnosebezogene Fallgruppen). Der PCCL (patientenbezogener Gesamtschweregrad)-Wert von 2.99 zeigt den hohen Schweregrad dieses Kollektivs an. Für die Behandlung dieser 67 Patienten entstanden Kosten von 1.249.176,91 Euro. Die Kosten-Erlöskalkulation zeigte eine Negativbilanz von -152.314,36 Euro. Die Kosten für die VAC Behandlung betrugen 158,030.19 Euro (12,65%) mit Materialkostenanteil von 5,92% (74.036 Euro). Die Gesamtkosten pro Patient für die VAC Therapie betrugen 2.358,66 Euro. Der Hauptanteil der entstehenden Behandlungskosten bestand nicht, wie häufig angenommen, aus den Materialkosten für die VAC Behandlung, sondern in den langen Liegezeiten dieser Patienten. Aufgrund ihrer Komplexität sind diese Fälle nicht adäquat in der Fallpauschalenkalkulation des InEK abgebildet. Eine differenzierte Integration der komplexen Vakuumbehandlung in das DRG-System (z.B. als erweiterte DRG I98Z) würde die Erlössituation sachgerechter abbilden. Auch die Erstattung ambulanter VAC Therapie würde, neben erhöhter Lebensqualität für die Patienten, die Behandlungskosten und stationären Liegezeiten reduzieren.
    Keywords: topical negative pressure therapy (TNP) ; traumatic wound ; economic evaluation ; cost analysis ; vacuum assisted closure (VAC) ; Vakuumtherapie (VAC) ; traumatischer Weichteildefekt ; ökonomische Evaluation ; Kostenanalyse ; ddc: 610
    Language: English
    Type: article
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  • 4
    ISSN: 1435-1463
    Keywords: Keywords: Alzheimer's disease ; Cerebrolysin ; neurotrophic therapy ; disease progression.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The present study is an extension of the work of Rüther et al. (1994). 101 patients suffering from DAT were evaluated 6 months after completion of a 4 week (5 days per week) therapy with either 30 ml Cerebrolysin or placebo. The significant and clinically relevant improvements in the global rating (CGI), clinical symptomatology (SCAG), cognitive performance (ZVT-G) as primary efficacy variables, as well as the improvements in the secondary efficacy variables activities of daily living (NAI) and wellbeing (Bf-S), achieved in the Cerebrolysin group after only 4 weeks of active therapy, were maintained to a large extent during the follow-up period. Although there was a moderate tendency in the drug group towards loss of improvement, the differences between baseline and follow-up examination, as well as the differences between the verum and the placebo group, clearly document a sustained improvement in patients treated with Cerebrolysin in the first 4 weeks of the study period. It can be speculated that relatively short treatment courses with Cerebrolysin in patients suffering from neurodegenerative dementia can lead to long term influence on disease progression, which is in accordance with the proposed neurotrophic – nerve growth factor like – mode of action.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1615-6102
    Keywords: Rust fungi ; Uromyces ; Infection structures ; Lectins ; Cell wall architecture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Uredospores ofUromyces viciae-fabae differentiate to form germ tubes, appressoria, infection hyphae and haustorial mother cells on oil-containing collodion membranes. The cell walls of these infection structures were studied with the electron microscope and with FITC-labeled lectins before and after treatment with enzymes and inorganic solvents. Binding of the FITC-labeled lectins was measured with a microscope photometer. The enzymes pronase E, laminarinase, chitinase and lipase had different effects on each infection structure. Pronase treatment uncovered the chitin of germ tubes, appressoria and haustorial mother cells, but not of substomatal vesicles and infection hyphae. A mixture of α- and β-1,3-glucanase which also contained chitinase activity dissolved germ tubes and appressoria completely, but not infection pegs, substomatal vesicles, infection hyphae and haustorial mother cells. After treatment with laminarinase or lipase, an additional layer, which is especially obvious over the substomatal vesicle, infection hypha and haustorial mother cell, bound to LCA-FITC. In the wall of the haustorial mother cell, a ring, which surrounds the presumed infection peg, had strong affinity for WGA after protease and sodium hydroxide treatment. The infection structures have a fibrillar skeleton. The main constituent seems to be chitin. This skeleton is more dense or has a higher chitin content in the walls of appressoria and haustorial mother cells. The fibrils of the skeleton extend throughout the cell wall of the germ tube and appressorium. They are embedded within amorphous material of complex chemical composition (α-1,3-glucan, β-1,3-glucan, glycoprotein). The chitin of the infection peg, substomatal vesicle, infection hypha and haustorial mother cell is covered completely with this amorphous material. These results show, that each infection structure has distinct surface and wall characteristics. They may reflect the different tasks of the infection structures during host recognition and leaf penetration.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0147-5975
    Keywords: [idt] Uromyces ; [idt] basidiospores ; [idt] infection structures ; [idt] rust fungi
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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