TIGA-CUB-manualised psychoanalytic child psychotherapy versus treatment as usual for children aged 5-11 with treatment-resistant conduct disorders and their primary carers: results from a randomised controlled feasibility trial.

Background: Parenting programmes are recommended for conduct disorders in 5-11 year olds, but ineffective for 25-33%. A feasibility trial was needed to determine whether a confirmatory trial of second-line, manualised short-term psychoanalytic child psychotherapy (mPCP) versus treatment as usual (TaU) is practicable.

Method: This was a two-arm, pragmatic, parallel-group, multi-centre, individually-randomised controlled feasibility trial with blinded outcome assessment.

TIGA-CUB - manualised psychoanalytic child psychotherapy versus treatment as usual for children aged 5-11 years with treatment-resistant conduct disorders and their primary carers: study protocol for a randomised controlled feasibility trial.

Background: The National Institute for Health and Care Excellence (NICE) recommends evidence-based parenting programmes as a first-line intervention for conduct disorders (CD) in children aged 5-11 years. As these are not effective in 25-33% of cases, NICE has requested research into second-line interventions. Child and Adolescent Psychotherapists (CAPTs) address highly complex problems where first-line treatments have failed and there have been small-scale studies of Psychoanalytic Child Psychotherapy (PCP) for CD.

Does integration of various ion channel measurements improve diagnostic performance in cystic fibrosis?

Rationale: The diagnosis of cystic fibrosis (CF) may remain inconclusive despite comprehensive evaluation.

Objectives: Determine whether combined ion channel measurements (C-ICMs) obtained from different end-organ epithelia can help diagnose CF.

Methods: Prospective enrollment of (1) a training sample of 156 non-CF subjects and 107 patients with CF, and (2) a validation cohort of 202 patients with single-organ CF-like phenotypes.

Does extensive genotyping and nasal potential difference testing clarify the diagnosis of cystic fibrosis among patients with single-organ manifestations of cystic fibrosis?

Background: The phenotypic spectrum of cystic fibrosis (CF) has expanded to include patients affected by single-organ diseases. Extensive genotyping and nasal potential difference (NPD) testing have been proposed to assist in the diagnosis of CF when sweat testing is inconclusive. However, the diagnostic yield of extensive genotyping and NPD and the concordance between NPD and the sweat test have not been carefully evaluated.

Use of the University of Minnesota Biocatalysis/Biodegradation Database for study of microbial degradation.

Microorganisms are ubiquitous on earth and have diverse metabolic transformative capabilities important for environmental biodegradation of chemicals that helps maintain ecosystem and human health. Microbial biodegradative metabolism is the main focus of the University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD). UM-BBD data has also been used to develop a computational metabolic pathway prediction system that can be applied to chemicals for which biodegradation data is currently lacking.

Comparing the American and European diagnostic guidelines for cystic fibrosis: same disease, different language?

Background: The American and European cystic fibrosis (CF) guidelines recommend different diagnostic criteria. This study assessed diagnostic concordance between these recommendations.

Methods: Subjects with single organ manifestations suggestive of CF (chronic sinopulmonary disease (RESP), chronic/recurrent pancreatitis (PANC) or obstructive azoospermia (AZOOSP)) were prospectively evaluated by sweat test, nasal potential difference and genotyping.

Role of cystic fibrosis transmembrane conductance regulator in patients with chronic sinopulmonary disease.

Background: Previous studies report a high frequency of mutations in the cystic fibrosis (CF) transmembrane conductance regulator gene (CFTR) in patients with idiopathic bronchiectasis. However, most studies have based their findings on preselected patient groups or have performed limited testing for CF transmembrane conductance regulator (CFTR) dysfunction. The objective of our study was to evaluate the prevalence of CFTR gene mutations and/or CFTR-related ion channel abnormalities among subjects with idiopathic chronic sinopulmonary disease and the prevalence of CF or a CFTR-related disorder in this population.

The University of Minnesota Pathway Prediction System: multi-level prediction and visualization.

The University of Minnesota Pathway Prediction System (UM-PPS, http://umbbd.msi.umn.

Evidence of a generalized defect of acinar cell function in Shwachman-Diamond syndrome.

Background: : Because the acinar cells of the exocrine pancreas in patients with Shwachman-Diamond syndrome (SDS) are severely depleted, we hypothesized that a similar deficiency may be present in acinar cells of the parotid gland.

Patients And Methods: : We determined serum pancreatic isoamylase and parotid amylase activities in 16 patients with SDS, 13 healthy controls, and 13 disease controls (cystic fibrosis or fibrosing pancreatitis). Parotid amylase and electrolyte concentrations were measured in stimulated parotid gland secretions.

Predicting biodegradation products and pathways: a hybrid knowledge- and machine learning-based approach.

Motivation: Current methods for the prediction of biodegradation products and pathways of organic environmental pollutants either do not take into account domain knowledge or do not provide probability estimates. In this article, we propose a hybrid knowledge- and machine learning-based approach to overcome these limitations in the context of the University of Minnesota Pathway Prediction System (UM-PPS). The proposed solution performs relative reasoning in a machine learning framework, and obtains one probability estimate for each biotransformation rule of the system.

The behavioral phenotype of school-age children with shwachman diamond syndrome indicates neurocognitive dysfunction with loss of Shwachman-Bodian-Diamond syndrome gene function.

Objective: To investigate the cognitive, behavioral and adaptive functioning of children with Shwachman-Diamond syndrome (SDS).

Study Design: Thirty-two children with SDS (6-17 years) were evaluated by use of standardized neuropsychological tests. Results were compared with normative data, unaffected siblings (n = 13), and age-and sex-matched children with cystic fibrosis (CF; n = 20).

The University of Minnesota Biocatalysis/Biodegradation Database: improving public access.

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD, http://umbbd.msi.umn.

Improving infrastructure for pathway prediction.

The UM-BBD Pathway Prediction System (UM-PPS, http://umbbd.msi.umn.

Data-driven extraction of relative reasoning rules to limit combinatorial explosion in biodegradation pathway prediction.

Motivation: The University of Minnesota Pathway Prediction System (UM-PPS) is a rule-based expert system to predict plausible biodegradation pathways for organic compounds. However, iterative application of these rules to generate biodegradation pathways leads to combinatorial explosion. We use data from known biotransformation pathways to rationally determine biotransformation priorities (relative reasoning rules) to limit this explosion.

The University of Minnesota pathway prediction system: predicting metabolic logic.

The University of Minnesota pathway prediction system (UM-PPS, http://umbbd.msi.umn.

Meta-prediction of phosphorylation sites with weighted voting and restricted grid search parameter selection.

Meta-predictors make predictions by organizing and processing the predictions produced by several other predictors in a defined problem domain. A proficient meta-predictor not only offers better predicting performance than the individual predictors from which it is constructed, but it also relieves experimentally researchers from making difficult judgments when faced with conflicting results made by multiple prediction programs. As increasing numbers of predicting programs are being developed in a large number of fields of life sciences, there is an urgent need for effective meta-prediction strategies to be investigated.

A PATO-compliant zebrafish screening database (MODB): management of morpholino knockdown screen information.

Background: The zebrafish is a powerful model vertebrate amenable to high throughput in vivo genetic analyses. Examples include reverse genetic screens using morpholino knockdown, expression-based screening using enhancer trapping and forward genetic screening using transposon insertional mutagenesis. We have created a database to facilitate web-based distribution of data from such genetic studies.

Shwachman-Diamond syndrome is associated with low-turnover osteoporosis.

Introduction: Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency and bone marrow dysfunction. These result in malabsorption and hematological abnormalities. A skeletal dysplasia is also an integral feature of SDS.

Meta-prediction of protein subcellular localization with reduced voting.

Meta-prediction seeks to harness the combined strengths of multiple predicting programs with the hope of achieving predicting performance surpassing that of all existing predictors in a defined problem domain. We investigated meta-prediction for the four-compartment eukaryotic subcellular localization problem. We compiled an unbiased subcellular localization dataset of 1693 nuclear, cytoplasmic, mitochondrial and extracellular animal proteins from Swiss-Prot 50.

Amiloride-insensitive nasal potential difference varies with the menstrual cycle in cystic fibrosis.

Rationale: There is no adequate explanation for gender-based differences in rates of mortality and of deterioration in pulmonary function in cystic fibrosis (CF) patients. One potential explanation is that gender hormones (sex steroids) may modulate the severity of CF lung disease, the principal cause of mortality in CF, by altering respiratory transepithelial ion transport.

Objective: To determine whether respiratory epithelial ion transport varied during the menstrual cycle of CF females.

Genome-wide reverse genetics framework to identify novel functions of the vertebrate secretome.

Background: Understanding the functional role(s) of the more than 20,000 proteins of the vertebrate genome is a major next step in the post-genome era. The approximately 4,000 co-translationally translocated (CTT) proteins - representing the vertebrate secretome - are important for such vertebrate-critical processes as organogenesis. However, the role(s) for most of these genes is currently unknown.

Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials.

Aim: To examine the relationship between cystic fibrosis transmembrane regulator gene mutations (CFTR) and in vivo transepithelial potentials.

Methods: We prospectively evaluated 162 men including 31 healthy subjects, 21 obligate heterozygotes, 60 with congenital bilateral absence of the vas deferens (CBAVD) and 50 with CF by extensive CFTR genotyping, sweat chloride and nasal potential difference testing.

Results: Six (10%) men with CBAVD carried no CFTR mutations, 18 (30%) carried one mutation, including the 5T variant, and 36 (60%) carried mutations on both alleles, for a significantly higher rate carrying one or more mutations than healthy controls (90% versus 19%, p < 0.

Enteric-coated pancreatic enzyme with bicarbonate is equal to standard enteric-coated enzyme in treating malabsorption in cystic fibrosis.

Objectives: To compare the efficacy of an enteric-coated buffered pancreatic enzyme (EC buffered PE) containing 1.5 mEq of bicarbonate per capsule with a conventional enteric-coated enzyme (EC-PE) capsule in cystic fibrosis patients with signs or symptoms of moderate to severe malabsorption.

Methods: In a double-blind crossover study, subjects were randomly assigned to two consecutive, 2-week phases using an EC buffered PE product and conventional EC-PE product.

Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers.

Rationale: Cigarette smoke extract inhibits chloride secretion in human bronchial epithelial cells. Oxidants decrease gene expression, protein expression, and function of the cystic fibrosis transmembrane conductance regulator (CFTR).

Objectives: Because cigarette smoke is a rich source of oxidants, we verified the hypothesis that CFTR may be suppressed by exposure to cigarette smoke in vitro and in vivo.

Towards the ideal quantitative pancreatic function test: analysis of test variables that influence validity.

Background & Aims: Although pancreatic stimulation tests quantify acinar and ductal exocrine pancreatic function, no standard methodology exists. We evaluated the impact of several variables on test accuracy.

Methods: We performed a retrospective analysis of pancreatic stimulation tests, which involved continuous stimulation with cholecystokinin and secretin, 3 sampling periods (20-min each), and perfusion markers to correct for intestinal losses.