23 research outputs found

    Approximate Query Answering and Result Refinement on XML Data

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    Today, many economic decisions are based on the fast analysis of XML data. Yet, the time to process analytical XML queries is typically high. Although current XML techniques focus on the optimization of query processing, none of these support early approximate feedback as possible in relational Online Aggregation systems. In this paper, we introduce a system that provides fast estimates to XML aggregation queries. While processing, these estimates and the assigned confidence bounds are constantly improving. In our evaluation, we show that without significantly increasing the overall execution time our system returns accurate guesses of the final answer long before traditional systems are able to produce output

    Throat Swabs and Sputum Culture as Predictors of P. aeruginosa or S. aureus Lung Colonization in Adult Cystic Fibrosis Patients

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    Background: Due to frequent infections in cystic fibrosis (CF) patients, repeated respiratory cultures are obtained to inform treatment. When patients are unable to expectorate sputum, clinicians obtain throat swabs as a surrogate for lower respiratory cultures. There is no clear data in adult subjects demonstrating the adequacy of throat swabs as a surrogate for sputum or BAL. Our study was designed to determine the utility of throat swabs in identifying lung colonization with common organisms in adults with CF. Methods: Adult CF subjects (n = 20) underwent bronchoscopy with BAL. Prior to bronchoscopy, a throat swab was obtained. A sputum sample was obtained from subjects who were able to spontaneously expectorate. All samples were sent for standard microbiology culture. Results: Using BAL as the gold standard, we found the positive predictive value for Pseudomonas aeruginosa to be 100% in both sputum and throat swab compared to BAL. However, the negative predictive value for P. aeruginosa was 60% and 50% in sputum and throat swab, respectively. Conversely, the positive predictive value for Staphylococcus aureus was 57% in sputum and only 41% in throat swab and the negative predictive value of S. aureus was 100% in sputum and throat swab compared to BAL. Conclusions: Our data show that positive sputum and throat culture findings of P. aeruginosa reflect results found on BAL fluid analysis, suggesting these are reasonable surrogates to determine lung colonization with P. aeruginosa. However, sputum and throat culture findings of S. aureus do not appear to reflect S. aureus colonization of the lung

    Genetic screens identify a context-specific PI3K/p27Kip1 node driving extrahepatic biliary cancer

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    Biliary tract cancer ranks among the most lethal human malignancies, representing an unmet clinical need. Its abysmal prognosis is tied to an increasing incidence and a fundamental lack of mechanistic knowledge regarding the molecular basis of the disease. Here, we show that the Pdx1-positive extrahepatic biliary epithelium is highly susceptible toward transformation by activated PIK3CAH1047R but refractory to oncogenic KrasG12D. Using genome-wide transposon screens and genetic loss-of-function experiments, we discover context-dependent genetic interactions that drive extrahepatic cholangiocarcinoma (ECC) and show that PI3K signaling output strength and repression of the tumor suppressor p27Kip1 are critical context-specific determinants of tumor formation. This contrasts with the pancreas, where oncogenic Kras in concert with p53 loss is a key cancer driver. Notably, inactivation of p27Kip1 permits KrasG12D-driven ECC development. These studies provide a mechanistic link between PI3K signaling, tissue-specific tumor suppressor barriers, and ECC pathogenesis, and present a novel genetic model of autochthonous ECC and genes driving this highly lethal tumor subtype

    Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes.

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    The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRAS in human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest KrasMUTlevels underlying aggressive undifferentiated phenotypes. We also identify alternative oncogenic gains (Myc, Yap1 or Nfkb2), which collaborate with heterozygous KrasMUTin driving tumorigenesis, but have lower metastatic potential. Mechanistically, different oncogenic gains and dosages evolve along distinct evolutionary routes, licensed by defined allelic states and/or combinations of hallmark tumour suppressor alterations (Cdkn2a, Trp53, Tgfβ-pathway). Thus, evolutionary constraints and contingencies direct oncogenic dosage gain and variation along defined routes to drive the early progression of PDAC and shape its downstream biology. Our study uncovers universal principles of Ras-driven oncogenesis that have potential relevance beyond pancreatic cancer.The work was supported by the German Cancer Consortium Joint Funding Program, the Helmholtz Gemeinschaft (PCCC Consortium), the German Research Foundation (SFB1243; A13/A14) and the European Research Council (ERC CoG number 648521)

    Konzept zur Einführung des Expertenstandards Ernährungsmanagement : Entwurf zur Umsetzung der Standardebenen 1-3 in der Alterstraumatologie mit anschließender geriatrischer Rehabilitation

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    Das Ziel der Arbeit ist die Erstellung eines Konzeptes zur Einführung des Expertenstandards ‚Ernährungsmanagement zur Sicherung und Förderung der oralen Ernährung in der Pflege‘. Es wird ein Entwurf zur Umsetzung der Standardebenen 1-3 erstellt, welcher sich auf geriatrische Patienten bezieht, die sich zunächst auf einer alterstraumatologischen Station befinden und darauffolgend eine geriatrische Rehabilitation anschließt. Dazu wird zur Prozessdarstellung ein Ablaufdiagramm erstellt. Die Grundlage für dieses Konzept ist die Literaturrecherche zum Theorieteil, welche die genauere Betrachtung der Mangelernährung beim geriatrischen Patienten sowie eine Übersicht zum oben genannten Expertenstandard beinhaltet. Die Erkenntnisse aus dem Theorieteil fließen in das Konzept ein. Dieses besteht aus drei Prozessphasen. Die erste Phase, Aufnahme und Aufenthalt in der Alterstraumatologie, beinhaltet das Aufnahme-Screening sowie zeitnahe ernährungstherapeutische Maßnahmen bei auffälligem Befund. In der zweiten Phase schließt ein vertieftes Assessment an. Nach Diagnosestellung des Arztes und Feststellung der Ursachen für die drohende oder bestehende Mangelernährung schließen sich auch hier durch einen multidisziplinären Austausch verschiedene therapeutische Maßnahmen an. Die dritte Phase ist gekennzeichnet durch ein ernährungstherapeutisches Entlassungsmanagement.The aim of the work is to develop a concept for the introduction of the experts’ standard ‘Nutrition management to ensure and promote oral nutrition in nursing’. A draft for the implementation of the standard levels 1-3 is created, which refers to geriatric patients who are initially on a geriatric trauma ward and subsequently undergo geriatric rehabilitation. For this purpose, a flow chart is created to illustrate the process. The basis for this concept is the literature research for the theory part, which includes a closer look at malnutrition in geriatric patients as well as an overview of the above-mentioned expert standard. The findings from the theoretical part flow into the concept. This consists of three process phases. The first phase, admission and stay on a geriatric trauma ward, includes the admission screening as well as prompt nutritional therapy measures in case of conspicuous findings. The second phase is followed by an admission assessment. After the doctor has made a diagnosis and determined the causes of the threatening or existing malnutrition, various therapeutic measures follow through a multidisciplinary exchange. The third phase is characterised by a nutritional therapy discharge management

    Throat Swabs and Sputum Culture as Predictors of P. aeruginosa or S. aureus Lung Colonization in Adult Cystic Fibrosis Patients.

    No full text
    Due to frequent infections in cystic fibrosis (CF) patients, repeated respiratory cultures are obtained to inform treatment. When patients are unable to expectorate sputum, clinicians obtain throat swabs as a surrogate for lower respiratory cultures. There is no clear data in adult subjects demonstrating the adequacy of throat swabs as a surrogate for sputum or BAL. Our study was designed to determine the utility of throat swabs in identifying lung colonization with common organisms in adults with CF.Adult CF subjects (n = 20) underwent bronchoscopy with BAL. Prior to bronchoscopy, a throat swab was obtained. A sputum sample was obtained from subjects who were able to spontaneously expectorate. All samples were sent for standard microbiology culture.Using BAL as the gold standard, we found the positive predictive value for Pseudomonas aeruginosa to be 100% in both sputum and throat swab compared to BAL. However, the negative predictive value for P. aeruginosa was 60% and 50% in sputum and throat swab, respectively. Conversely, the positive predictive value for Staphylococcus aureus was 57% in sputum and only 41% in throat swab and the negative predictive value of S. aureus was 100% in sputum and throat swab compared to BAL.Our data show that positive sputum and throat culture findings of P. aeruginosa reflect results found on BAL fluid analysis, suggesting these are reasonable surrogates to determine lung colonization with P. aeruginosa. However, sputum and throat culture findings of S. aureus do not appear to reflect S. aureus colonization of the lung

    HCF164 Encodes a Thioredoxin-Like Protein Involved in the Biogenesis of the Cytochrome b(6)f Complex in Arabidopsis

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    To understand the biogenesis of the plastid cytochrome b(6)f complex and to identify the underlying auxiliary factors, we have characterized the nuclear mutant hcf164 of Arabidopsis and isolated the affected gene. The mutant shows a high chlorophyll fluorescence phenotype and is severely deficient in the accumulation of the cytochrome b(6)f complex subunits. In vivo protein labeling experiments indicated that the mutation acts post-translationally by interfering with the assembly of the complex. Because of its T-DNA tag, the corresponding gene was cloned and its identity confirmed by complementation of homozygous mutant plants. HCF164 encodes a thioredoxin-like protein that possesses disulfide reductase activity. The protein was found in the chloroplast, where it is anchored to the thylakoid membrane at its lumenal side. HCF164 is closely related to the thioredoxin-like protein TxlA of Synechocystis sp PCC6803, most probably reflecting its evolutionary origin. The protein also shows a limited similarity to the eubacterial CcsX and CcmG proteins, which are required for the maturation of periplasmic c-type cytochromes. The putative roles of HCF164 for the assembly of the cytochrome b(6)f complex are discussed

    Comparison of Methods for Determining Bacterial Colonization.

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    <p>Clinical samples were obtained from CF subjects (n = 20 for BAL and throat swab and n = 12 for sputum). The phi coefficient was used to measure the degree of association between positive and negative cultures for <i>P</i>. <i>aeruginosa</i> and <i>S</i>. <i>aureus</i> in BAL fluid, sputum and throat swabs. Throat swabs and sputum were significantly correlated for both pathogens, as were BAL fluid and sputum for <i>P</i>. <i>aeruginosa</i> (p < 0.05 as determined with Fisher’s Exact Test and indicated by an asterisk).</p
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