Simulating Light-Weight Personalised Recommender Systems in Learning Networks: A Case for Pedagogy-Oriented and Rating-Based Hybrid Recommendation Strategies

Recommender systems for e-learning demand specific pedagogy-oriented and hybrid recommendation strategies. Current systems are often based on time-consuming, top down information provisioning combined with intensive data-mining collaborative filtering approaches. However, such systems do not seem appropriate for Learning Networks where distributed information can often not be identified beforehand. Providing sound way-finding support for lifelong learners in Learning Networks requires dedicated personalised recommender systems (PRS), that offer the learners customised advise on which learning actions or programs to study next. Such systems should also be practically feasible and be developed with minimized effort. Currently, such so called light-weight PRS systems are scarcely available. This study shows that simulation studies can support the analysis and optimisation of PRS requirements prior to starting the costly process of their development, and practical implementation (including testing and revision) during field experiments in real-life learning situations. This simulation study confirms that providing recommendations leads towards more effective, more satisfied, and faster goal achievement. Furthermore, this study reveals that a light-weight hybrid PRS-system based on ratings is a good alternative for an ontology-based system, in particular for low-level goal achievement. Finally, it is found that rating-based light-weight hybrid PRS-systems enable more effective, more satisfied, and faster goal attainment than peer-based light-weight hybrid PRS-systems (incorporating collaborative techniques without rating).Recommendation Strategy; Simulation Study; Way-Finding; Collaborative Filtering; Rating

PCN94 - Cost-effectiveness and preference for follow-up scenarios following breast cancer

OBJECTIVES: About one in every eight women in The Netherlands develops breast cancer. Every year, 11,000 new cases are registered and about 3500 women die of breast cancer. Prognosis after primary treatment for patients with breast cancer is improving. This leads to an increased number of patients in follow-up, which leads to increased workload. One of the main goals of follow-up is to improve the survival of patients. This study aims to determine a more individualized follow-up by modelling costeffectiveness of various follow-up scenarios and by determining individual preferences by using a discrete choice experiment (DCE). METHODS: A discrete-event state-transition model was developed to estimate the cost-effectiveness of all scenarios for all patient groups. In addition, a discrete choice experiment (DCE) was designed to establish patient preferences. The DCE incorporated three process attributes (duration of follow-up, frequency and type of consult) and data were collected in a sample of 125 breast cancer patients. Patients had to complete all 18 choice sets that were generated from the three attributes. RESULTS: The modelling study revealed recommendations for follow-up in different age categories. Patients younger than 40 and patients with unfavorable tumor characteristics (>3 lymph nodes, tumor size >2 cm) can benefit from a more intensive follow-up of five or possibly ten years. Patients older than 40 but younger than 70 years old sometimes benefit from a more intensive follow-up; e.g. when younger than 50 and tumor size >2 cm. The DCE, however, showed that patients chose maximum levels of follow-up independent from age and their individual clinical risk profile. Duration of follow-up and type of consult (either hospital visit or telephone) weighted approximately 0.43 and 0.50 respectively. The frequency of follow-up (either once or twice a year) was least important (0.07). CONCLUSIONS: The model showed that follow-up may be individualized according to risk profile and age. However, patients preferred long and intensive follow-up strategies after breast cancer treatment. Taking into account individual patient preferences it may be recommended to reduce the frequency of follow-up to once a year. The service delivery by nurse practioners is well appreciated and another means for improving cost-effective follow-up

Beiträge zur Geschichte des Landkreises Regensburg 24

24 Marginalien von 18 Autoren; darin: Werner, Hannsjürgen: Ein endneolithisches Körpergrab bei Moosham (S. 4); Fischer, T.: Die vor 110 Jahren erwähnt Burg Langenerling (S. 8); Bößl, Karl: Als Kareth zur freien Reichsstadt Regensburg gehörte (S. 10); Hummel, Franz: Der Hermann-, German- und Gerhof in der Gemeinde Wolfsegg (S. 12); Hemrich, Hans: Die letzte Ritterschlacht wurde bei Wenzenbach geschlagen (S. 14); Unterstöger, A.: Die Wallfahrtskirche St. Salvator in Donaustauf (S. 16); Daxl, Petra: Die Besiedlung der Hohengebrachinger Heide (S. 18); Neumann, Wenzel: Die Mötzinger Votivtafeln von 1775 und 1815 (S. 20); Schön, M.: Napoleon in Alteglofsheim (S. 22); Geser, Werner: Zum Alter der Wolfgangskapelle Klausen bei Thalmassing (S. 24); Jörgl, Fritz: Interessantes aus alten Geislinger Rechnungen (S. 25); Bösl, Hans-Josef: Die Heilung eines Taubstummen in der Wallfahrtskirche Mariae Schnee (S. 28); Fendl, Josef: Soll die Egglfinger Kirche verfallen? ( S. 30); Ebner, Karl: Aus der Geschichte des Schützenvereins Pfatter (S. 32); Staudigl, Franz Xaver: Beratzhausen in der Literatur (S. 34); Besenreiter, J.: Handwerk und Gewerbe in Aufhausen im Wandel der Zeit (S. 36); Forster, Fritz: Der Thurn- und Taxis´sche Wildpark (S. 38

Laboratory evolution of Pyrococcus furiosus alcohol dehydrogenase to improve the production of (2S,5S)-hexanediol at moderate temperatures

There is considerable interest in the use of enantioselective alcohol dehydrogenases for the production of enantio- and diastereomerically pure diols, which are important building blocks for pharmaceuticals, agrochemicals and fine chemicals. Due to the need for a stable alcohol dehydrogenase with activity at low-temperature process conditions (30°C) for the production of (2S,5S)-hexanediol, we have improved an alcohol dehydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus (AdhA). A stable S-selective alcohol dehydrogenase with increased activity at 30°C on the substrate 2,5-hexanedione was generated by laboratory evolution on the thermostable alcohol dehydrogenase AdhA. One round of error-prone PCR and screening of ∼1,500 mutants was performed. The maximum specific activity of the best performing mutant with 2,5-hexanedione at 30°C was tenfold higher compared to the activity of the wild-type enzyme. A 3D-model of AdhA revealed that this mutant has one mutation in the well-conserved NADP(H)-binding site (R11L), and a second mutation (A180V) near the catalytic and highly conserved threonine at position 183

Preamplification techniques for real-time RT-PCR analyses of endomyocardial biopsies

<p>Abstract</p> <p>Background</p> <p>Due to the limited RNA amounts from endomyocardial biopsies (EMBs) and low expression levels of certain genes, gene expression analyses by conventional real-time RT-PCR are restrained in EMBs. We applied two preamplification techniques, the TaqMan^®PreAmp Master Mix (T-PreAmp) and a multiplex preamplification following a sequence specific reverse transcription (SSRT-PreAmp).</p> <p>Results</p> <p>T-PreAmp encompassing 92 gene assays with 14 cycles resulted in a mean improvement of 7.24 ± 0.33 Ct values. The coefficients for inter- (1.89 ± 0.48%) and intra-assay variation (0.85 ± 0.45%) were low for all gene assays tested (<4%). The PreAmp uniformity values related to the reference gene CDKN1B for 91 of the investigated gene assays (except for CD56) were -0.38 ± 0.33, without significant differences between self-designed and ABI inventoried Taqman^®gene assays. Only two of the tested Taqman^®ABI inventoried gene assays (HPRT-ABI and CD56) did not maintain PreAmp uniformity levels between -1.5 and +1.5. In comparison, the SSRT-PreAmp tested on 8 self-designed gene assays yielded higher Ct improvement (9.76 ± 2.45), however was not as robust regarding the maintenance of PreAmp uniformity related to HPRT-CCM (-3.29 ± 2.40; p < 0.0001), and demonstrated comparable intra-assay CVs (1.47 ± 0.74), albeit higher inter-assay CVs (5.38 ± 2.06; p = 0.01). Comparing EMBs from each 10 patients with dilated cardiomyopathy (DCM) and inflammatory cardiomyopathy (DCMi), T-PreAmp real-time RT-PCR analyses revealed differential regulation regarding 27 (30%) of the investigated 90 genes related to both HPRT-CCM and CDKN1B. Ct values of HPRT and CDKN1B did not differ in equal RNA amounts from explanted DCM and donor hearts.</p> <p>Conclusion</p> <p>In comparison to the SSRT-PreAmp, T-PreAmp enables a relatively simple workflow, and results in a robust PreAmp of multiple target genes (at least 92 gene assays as tested here) by a mean Ct improvement around 7 cycles, and in a lower inter-assay variance in RNA derived from EMBs. Preliminary analyses comparing EMBs from DCM and DCMi patients, revealing differential regulation regarding 30% of the investigated genes, confirm that T-PreAmp is a suitable tool to perform gene expression analyses in EMBs, expanding gene expression investigations with the limited RNA/cDNA amounts derived from EMBs. CDKN1B, in addition to its function as a reference gene for the calculation of PreAmp uniformity, might serve as a suitable housekeeping gene for real-time RT-PCR analyses of myocardial tissues.</p

EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas

Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer genotype-directed therapy, we developed a screening assay for EZH2 codon 641 mutations amenable for testing formalin-fixed clinical specimens, based on the sensitive SNaPshot single nucleotide extension technology. We detected EZH2 mutations in 12/55 (22%) follicular lymphomas (FL), 5/35 (14%) diffuse large B cell lymphomas with a germinal center immunophenotype (GCB-DLBCL), and 2/11 (18%) high grade B cell lymphomas with concurrent rearrangements of BCL2 and MYC. No EZH2 mutations were detected in cases of Burkitt lymphoma (0/23). EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003). We confirmed gain-of-function activity for all previously reported EZH2 codon 641 mutation variants. Our findings suggest that EZH2 mutations constitute an additional genetic “hit” in many BCL2-rearranged germinal center B cell lymphomas. Our work may be helpful in the selection of lymphoma patients for future trials of pharmacologic agents targeting EZH2 and EZH2-regulated pathways

MicroRNA signatures in B-cell lymphomas

Accurate lymphoma diagnosis, prognosis and therapy still require additional markers. We explore the potential relevance of microRNA (miRNA) expression in a large series that included all major B-cell non-Hodgkin lymphoma (NHL) types. The data generated were also used to identify miRNAs differentially expressed in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) samples. A series of 147 NHL samples and 15 controls were hybridized on a human miRNA one-color platform containing probes for 470 human miRNAs. Each lymphoma type was compared against the entire set of NHLs. BL was also directly compared with DLBCL, and 43 preselected miRNAs were analyzed in a new series of routinely processed samples of 28 BLs and 43 DLBCLs using quantitative reverse transcription-polymerase chain reaction. A signature of 128 miRNAs enabled the characterization of lymphoma neoplasms, reflecting the lymphoma type, cell of origin and/or discrete oncogene alterations. Comparative analysis of BL and DLBCL yielded 19 differentially expressed miRNAs, which were confirmed in a second confirmation series of 71 paraffin-embedded samples. The set of differentially expressed miRNAs found here expands the range of potential diagnostic markers for lymphoma diagnosis, especially when differential diagnosis of BL and DLBCL is required

Three-Dimensional In Vivo Imaging of the Murine Liver: A Micro-Computed Tomography-Based Anatomical Study

Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver