Cooperative Development of Web-based Mass Information Systems

This paper describes a research framework which led to the development of industry-specific reference models for mass information systems (mass IS). As one of the primary means of standardized communication, these models provide an invaluable opportunity to strengthen the ties between academic research and industry practice. By avoiding structural inconsistencies and mistakes, companies are able to improve the quality of their systems, usually at low costs compared to acquiring the required know-how from external commercial organizations. Researchers, on the other hand, are able to test hypotheses about the success factors of mass IS in different industries. For this reason the extended World Wide Web Design Technique (eW3DT) was developed and - in cooperation with renowned Austrian and German companies—applied to a number of Web- based prototypes

THE MODEL GENERATOR: A CRUCIAL ELEMENT OF THE MODEL DEVELOPMENT ENVIRONMENT

This report documents development of a prototype model generator. The model generator is designed to assist a discrete event simulation modeler in converting this conceptual model to a representation which can be communicated to other persons (the communicative model). The current version uses English phrases to represent the communicative model. The model generator is one of the tools of the Model Development Environment, which is a toolset being developed at VPI & SU. The Model Development Environment is envisioned as a complete set of tools designed to provide integrated support to the modeler throughout the mode! life cycle. The governing concepts of the model generator are based on the Conical Methodology of Nance. With that underpinning, the prototype model generator provides a tool of moderately general applicability for the construction of hierarchical models. The report includes a brief review of applicable previous efforts, design criteria for the model generator, a description of the model generator computer program, and a user manual

Baseline anti-NS4a antibodies in combination with on-treatment quantitative HCV-RNA reliably identifies nonresponders to pegylated interferon-ribavirin combination therapy after 4 weeks of treatment

Background Early detection of nonresponders to hepatitis C therapy limits unnecessary exposure to treatment and its side-effects. A recent algorithm combining baseline anti-NS4a antibodies and on-treatment quantitative PCR identified nonresponders to a combination of interferon and ribavirin after 1 week of treatment. Aim To validate a stopping rule based on baseline anti-NS4a antibody levels and early on-treatment virological response in treatment-naive genotype 1 chronic hepatitis C patients treated with the current standard pegylated interferon and ribavirin combination therapy. Methods Eighty-nine genotype 1 patients from the Dynamically Individualized Treatment of hepatitis C Infection and Correlates of Viral/Host dynamics Study treated for 48 weeks with standard 180 mu g pegylated interferon (PEG-IFN)-alpha-2a (weekly) and ribavirin 1000-1200mg (daily) were analysed. Baseline anti-NS4a antibody enzyme-linked immunosorbent assay (NS4a AA 1687-1718) was performed on pretreatment serum. Hepatitis C virus-RNA was assessed at days 0, 1, 4, 7, 8, 15, 22, 29, weeks 6, 7, 8, 10, 12 and 6 weekly thereafter until end of treatment. Multiple regression logistic analysis was performed. Results Overall 54 of 89 (61%) patients achieved sustained virological response. A baseline anti-NS4a antibody titre less than 1/1250 correlated with absence of favourable initial viral decline according to variable response types (P=0.015). The optimal algorithm was developed using the combination of the absence of anti-NS4a Ab (= 100.000 IU/ml at week 4. This algorithm has a specificity of 43% and negative predictive value of 100% to detect nonresponse to standard PEG-IFN-alpha-2a and ribavirin therapy at fourth week of therapy (intention-to-treat analysis). Conclusion The decision to stop the therapy in genotype 1 chronic hepatitis C patients treated with PEG-IFN-alpha-2a and ribavirin can be confidently made after 4 weeks of treatment based on the absence of baseline anti-NS4a Ab and a week-4 hepatitis C virus-RNA above 100.000 IU/ml. Eur J Gastroenterol Hepatol 22:1443-1448 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Identification of the UBP1 Locus as a Critical Blood Pressure Determinant Using a Combination of Mouse and Human Genetics

Hypertension is a major health problem of largely unknown genetic origins. To identify new genes responsible for hypertension, genetic analysis of recombinant inbred strains of mice followed by human association studies might prove powerful and was exploited in our current study. Using a set of 27 recombinant BXD strains of mice we identified a quantitative trait locus (QTL) for blood pressure (BP) on distal chromosome 9. The association analysis of markers encompassing the syntenic region on human chromosome 3 gave in an additive genetic model the strongest association for rs17030583 C/T and rs2291897 G/A, located within the UBP1 locus, with systolic and diastolic BP (rs17030583: 1.3±0.4 mmHg p<0.001, 0.8±0.3 mmHg p = 0.006, respectively and rs2291897: 1.5±0.4 mmHg p<0.001, 0.8±0.3 mmHg p = 0.003, respectively) in three separate studies. Our study, which underscores the marked complementarities of mouse and human genetic approaches, identifies the UBP1 locus as a critical blood pressure determinant. UBP1 plays a role in cholesterol and steroid metabolism via the transcriptional activation of CYP11A, the rate-limiting enzyme in pregnenolone and aldosterone biosynthesis. We suggest that UBP1 and its functional partners are components of a network controlling blood pressure

Relative performance of machine learning and linear regression in predicting quality of life and academic performance of school children in Norway : data analysis of a quasi-experimental study

Background: Machine learning (ML) approaches are increasingly being used in health research. It is not clear how useful these approaches are for modelling continuous health outcomes. Child quality of life (QoL) is associated with parental socioeconomic status and child activity levels, and may be associated with aerobic fitness and strength. It is not clear whether diet, or academic performance (AP) is associated with QoL. Objective: To compare predictive performances of ML approaches with linear regression for modelling QoL and AP using parental education and lifestyle data. Methods: We modelled data from children attending nine schools in a quasi-experimental study (NCT02495714). We split data randomly into training and validation sets, and simulated curvilinear, non-linear, and heteroscedastic variables. We examined relative performance of ML approaches using R2, making comparisons to mixed and fixed models, and regression with splines, with and without imputation. We also examined the effect of training set size on overfitting. Results: We had 1,711 cases. Using real data, our regression models explained 24% of AP variance in the complete-case validation set, and up to 15% of QoL variance. While ML models explained high proportions of variance in training sets, in validation sets these explained ~0% of AP and between 3% and 8% of QoL. Following imputation, ML models improved up to 15% for AP. ML models outperformed regression for modelling simulated non-linear and heteroscedastic variables only. A smaller training set did not lead to increased overfitting. The best predictors of QoL were 7-point self-reported activity (P<.001; ß=1.09 (95% CI 0.53 to 1.66)) and TV/computer use (P=.002; ß=-0.95 (-1.55 to -0.36)). For AP, these were mother having master’s-level education (P<.001; ß=1.98 (0.25 to 3.71)) and dichotomised self-reported activity (P=.001; ß=2.47 (1.08 to 3.87)). Adjusted academic performance was associated with QoL (P=.02; ß=0.12 (0.02 to 0.22)). Conclusions: Exercising to cause sweat once per week and 2 hours per day of TV or computer use are associated with small-to-medium increases and decreases in child QoL, respectively. An increase in AP of 20 units is associated with a small increase in QoL. A mother having higher and master’s-level education, 2 hours per day of TV or computer use, and taking at least 2 hours of exercise, are each associated with small-to-medium increases in AP. Differences between effects of computer/TV use for work/leisure needs further investigation. Linear regression is less prone to overfitting and performs better than ML in predicting continuous health outcomes in a dataset containing missing data. Imputation improves ML performance but not enough to outperform regression. ML outperformed regression with non-linear and heteroscedastic data and may be of use when such relationships exist, and where imputation is sensible or there are no missing data. Clinical Trial: The data are from a quasi-experimental design and not an RCT but nevertheless the study from which the data are from does have a registration: NCT0249571

Identification and evolution of a plant cell wall specific glycoprotein glycosyl transferase, ExAD

Extensins are plant cell wall glycoproteins that act as scaffolds for the deposition of the main wall carbohydrate polymers, which are interlocked into the supramolecular wall structure through intra- and inter-molecular iso-di-tyrosine crosslinks within the extensin backbone. In the conserved canonical extensin repeat, Ser-Hyp(4), serine and the consecutive C4-hydroxyprolines (Hyps) are substituted with an α-galactose and 1–5 β- or α-linked arabinofuranoses (Arafs), respectively. These modifications are required for correct extended structure and function of the extensin network. Here, we identified a single Arabidopsis thaliana gene, At3g57630, in clade E of the inverting Glycosyltransferase family GT47 as a candidate for the transfer of Araf to Hyp-arabinofuranotriose (Hyp-β1,4Araf-β1,2Araf-β1,2Araf) side chains in an α-linkage, to yield Hyp-Araf(4) which is exclusively found in extensins. T-DNA knock-out mutants of At3g57630 showed a truncated root hair phenotype, as seen for mutants of all hitherto characterized extensin glycosylation enzymes; both root hair and glycan phenotypes were restored upon reintroduction of At3g57630. At3g57630 was named Extensin Arabinose Deficient transferase, ExAD, accordingly. The occurrence of ExAD orthologs within the Viridiplantae along with its’ product, Hyp-Araf(4), point to ExAD being an evolutionary hallmark of terrestrial plants and charophyte green algae

Retreatment of hepatitis C non-responsive to Interferon. A placebo controlled randomized trial of Ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378]

BACKGROUND: Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published untill now. METHODS: One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%), HCV RNA above 2 × 10(6 )copies/ml (55%) and cirrhosis (38%). Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw) and ribavirin (1000–1200 mg / day), 6 months ribavirin monotherapy (1000–1200 mg / day) or 6 months ribavirin placebo. The study was double blinded for the ribavirin / placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis. RESULTS: At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin. During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin monotherapy (p = 0.76). End of treatment WBC was significantly lower in patients treated with combination therapy, compared to ribavirin (p < 0.01) as well as for patients treated with ribavirin monotherapy compared to placebo (p < 0.01). DISCUSSION: This belated report on the only placebo controlled study of interferon ribavirin combination therapy in non responders to standard doses of interferon monotherapy documents the effectiveness, be it limited, of this approach as well as the dynamics of the effects on blood counts

THE K2-ESPRINT PROJECT. V. A SHORT-PERIOD GIANT PLANET ORBITING A SUBGIANT STAR

We report on the discovery and characterization of the transiting planet K2-39b (EPIC 206247743b). With an orbital period of 4.6 days, it is the shortest-period planet orbiting a subgiant star known to date. Such planets are rare, with only a handful of known cases. The reason for this is poorly understood but may reflect differences in planet occurrence around the relatively high-mass stars that have been surveyed, or may be the result of tidal destruction of such planets. K2-39 (EPIC 206247743) is an evolved star with a spectroscopically derived stellar radius and mass of 3.88 [subscript -0.42] [superscript +0.48] R [subscript ⊙] and 1.53[subscript-0.12] [superscript +0.13] M[subscript ⊙], respectively, and a very close-in transiting planet, with a/R [subscript asterisk]= 3.4 Radial velocity (RV) follow-up using the HARPS, FIES, and PFS instruments leads to a planetary mass of 50.3 [subscript -9.4] [superscript +9.7] M [subscript ⊙]. In combination with a radius measurement of 8.3 ± 1.1 R [subscript oplus], this results in a mean planetary density of 0.50 [subscript -0.17] [superscript +0.29] g cm [superscript -3]. We furthermore discover a long-term RV trend, which may be caused by a long-period planet or stellar companion. Because K2-39b has a short orbital period, its existence makes it seem unlikely that tidal destruction is wholly responsible for the differences in planet populations around subgiant and main-sequence stars. Future monitoring of the transits of this system may enable the detection of period decay and constrain the tidal dissipation rates of subgiant stars