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Background and aimsDetailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.Approach and resultsA targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p

Aims: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is undertaking a new cohort study in LURN II including cases and controls. Methods: This new cohort was enrolled to specifically study urinary urgency and urgency urinary incontinence, lower urinary tract symptoms (LUTSs) that are often difficult to treat due to a lack of understanding of their phenotypes and pathophysiologies. Results: This paper will focus on the motivation for the second iteration of LURN and highlight the new research techniques and plans for more thorough phenotyping of this population. Conclusions: This paper will outline the gaps in understanding in treating LUTSs, specifically urinary urgency. [ABSTRACT FROM AUTHOR]

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indices approach. Data domains only available on a subset of the cohort were integrated using a semi-supervised clustering approach. Novel contrast criterion for determination of the optimal number of clusters in consensus clustering was introduced and compared with existing criteria. Distinctiveness of the clusters was confirmed by using multiple criteria for cluster quality, and by testing for significantly different variables in pairwise comparisons of the clusters. Cluster dynamics were explored by analyzing longitudinal data at 3- and 12-month follow-up. Five clusters of women with LUTS were identified using the developed methodology. None of the clusters could be characterized by a single symptom, but rather by a distinct combination of symptoms with various levels of severity. Targeted proteomics of serum samples demonstrated that differentially abundant proteins and affected pathways are different across the clusters. The clinical relevance of the identified clusters is discussed and compared with the current conventional approaches to the evaluation of LUTS patients. The rationale and thought process are described for the selection of procedures for data preprocessing, clustering, and cluster evaluation. Suggestions are provided for minimum reporting requirements in publications utilizing clustering methodology with multiple heterogeneous data domains. [ABSTRACT FROM AUTHOR]

A new denoising and peak picking algorithm (MEND, matched filtration with experimental noise determination) for analysis of LC--MS data is described. The algorithm minimizes both random and chemical noise in order to determine MS peaks corresponding to sample components. Noise characteristics in the data set are experimentally determined and used for efficient denoising. MEND is shown to enable low-intensity peaks to be detected, thus providing additional useful information for sample analysis. The process of denoising, performed in the chromatographic time domain, does not distort peak shapes in the m/z domain, allowing accurate determination of MS peak centroids, including low-intensity peaks. MEND has been applied to denoising of LC-MALDI-TOF-MS and LC-ESI-TOF-MS data for tryptic digests of protein mixtures. MEND is shown to suppress chemical and random noise and baseline fluctuations, as well as filter out false peaks originating from the matrix (MALDI) or mobile phase (ESI). In addition, MEND is shown to be effective for protein expression analysis by allowing selection of a large number of differentially expressed ICAT pairs, due to increased signal-to-noise ratio and mass accuracy.

Aims: Lower urinary tract symptoms (LUTS) are diverse in type and variable in severity. We examined symptom change within the Symptoms of the Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort study identified clusters over time and tested associations with treatments received. Methods: Patient‐reported LUTS and treatment data were collected at multiple time points between baseline and 12 months from the LURN Observational Cohort study. LUTS severity scores were calculated to summarize changes in symptom reporting over time in previously identified LURN clusters. Repeated measures linear regression models tested adjusted associations between cluster membership and severity scores. Results: Four‐hundred seventeen men and 396 women were classified into improved, unchanged, and worsened symptoms between baseline and 12 months (men: 44.1%, 40.5%, and 15.3%; women: 55.8%, 33.1%, 11.1%, respectively). Improvement in LUTS severity scores varied by cluster (estimated adjusted mean change from baseline range: −.04 change in standard deviations of severity scores (ΔSD) to −.67 ΔSD). Prostate surgery was associated with improved severity scores (−.63 ΔSD) in men, while stress incontinence surgery was associated with improved severity scores (−.88 ΔSD) in women. Conclusion: Symptom improvement varied by cluster indicating response to therapy differs amongst subtypes of patients with LUTS. The differential improvement of patients in clusters suggests mechanistic differences between clusters and may aid in selecting more targeted treatments in the future. [ABSTRACT FROM AUTHOR]

Aims: The aims of this study were to assess the completeness of voiding diaries in a research context and to correlate diary data with patient‐reported questionnaires. Methods: Men and women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) were given a 3‐day voiding and fluid‐intake diary to fill‐out. Diaries were assessed for completeness and intake‐output imbalances. They were assigned to one of four categories based on a percentage of missing data and fluid imbalance: no diary submitted, unusable (>40% missing void or intake volumes, or unphysiological fluid imbalance), usable but not complete, and complete. Results: A total of 1064 participants were enrolled and 85% (n = 902) returned the bladder diary. Of the diaries returned, 94% (n = 845) had data on three separate days, 87% (n = 786) had no missing intake volumes, 61% (n = 547) had no missing voided volumes, and 70% (n = 635) had a fluid imbalance within 3 L across the 3‐day time period, resulting in 50% (n = 448) of participants with 100% complete diaries. Younger age was associated with a higher likelihood of not submitting a diary, or submitting an unusable diary. Women had a higher likelihood of submitting an unusable diary or a usable but incomplete diary. Conclusion: Overall, 50% of LURN participants returned voiding diaries with perfectly complete data. Incomplete data for voided volumes was the most common deficiency. There was only a moderate correlation between diary data and questionnaire responses, indicating that diaries are a source of unique information. [ABSTRACT FROM AUTHOR]

Electroinjection analysis has been demonstrated to provide reaction kinetics information. Reactants are injected continuously from opposite ends of the capillary for the duration of the experiment, and reaction product formation occurs at the boundary where the zones merge. The width of the product signal measured by the detector depends on the ratio of the fluxes of reactants. The boundary moves toward the detector where the products are measured. A sharp peak at the edge of the main flat product signal peak was observed and most probably corresponds to the metastable intermediate product of reaction, a unique capability of this technique. A theoretical explanation and an experimental verification of the possibile use of electroinjection analysis for the study of reaction kinetics is given.

Abstract: Based on analysis of data flows and functional structure of information – measuring and control systems of mobile robots with supervisory control, proposed a combined approach to designing this systems and multi-camera computer vision. This approach is based on network technologies and our analysis of data flows and suggested functional structure of main types of mobile robots with supervisory control. [Copyright &y& Elsevier]