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Compliance with treatment and follow-up protocols in project MATCH: predictors and relationship to outcome.

Treatment and follow-up session attendance data from Project MATCH, a multisite clinical trial investigating patient-treatment matching, were analyzed to study compliance. High rates of compliance to both therapy and research protocols were achieved, enhancing treatment integrity and data quality. Strong baseline predictors of compliance did not emerge, and the small relationships found were consistent with reports from previous studies. Attendance at therapy sessions was moderately correlated with research follow-up participation. Treatment compliance predicted drinking outcome, underscoring the importance of retaining patients in treatment. Future studies should examine the associations between compliance and structural features of the treatment environment, treatment delivery, and context-features that are often under the control of the clinician/investigator.

Adult↗

ITTACA: a new database for integrated tumor transcriptome array and clinical data analysis.

Transcriptome microarrays have become one of the tools of choice for investigating the genes involved in tumorigenesis and tumor progression, as well as finding new biomarkers and gene expression signatures for the diagnosis and prognosis of cancer. Here, we describe a new database for Integrated Tumor Transcriptome Array and Clinical data Analysis (ITTACA). ITTACA centralizes public datasets containing both gene expression and clinical data. ITTACA currently focuses on the types of cancer that are of particular interest to research teams at Institut Curie: breast carcinoma, bladder carcinoma and uveal melanoma. A web interface allows users to carry out different class comparison analyses, including the comparison of expression distribution profiles, tests for differential expression and patient survival analyses. ITTACA is complementary to other databases, such as GEO and SMD, because it offers a better integration of clinical data and different functionalities. It also offers more options for class comparison analyses when compared with similar projects such as Oncomine. For example, users can define their own patient groups according to clinical data or gene expression levels. This added flexibility and the user-friendly web interface makes ITTACA especially useful for comparing personal results with the results in the existing literature. ITTACA is accessible online at http://bioinfo.curie.fr/ittaca.

Breast Neoplasms↗

Methodological considerations and approach to cross-technique comparisons using in vivo coronary plaque characterization based on intravascular ultrasound radiofrequency data analysis: insights from the Integrated Biomarker and Imaging Study (IBIS).

Grey scale intravascular ultrasound (IVUS) is a valuable clinical tool to assess the extent and severity of coronary atheroma. However, it cannot reliably identify plaques with a high-risk of future clinical events. Serial IVUS studies to assess the progression and/or regression of atherosclerotic plaques demonstrated only modest effects, of pharmacological intervention on plaque burden, even when clinical efficacy is documented. Spectral analysis of radiofrequency ultrasound data (IVUS-virtual histology (IVUS-VH), Volcano Therapeutics, Rancho Cordova, CA) has the potential to characterize accurately plaque composition. The Integrated Biomarker and Imaging Study (IBIS) evaluated both invasive and non-invasive imaging techniques along with the assessment of novel biomarkers to characterize sub-clinical atherosclerosis. IVUS-VH was not included at the start of the IBIS protocol. The purpose of this paper is to describe the methodology we used to obtain and analyse IVUS-VH images and the approach to cross-correlations with the other techniques.

Biomarkers↗

Growing evidence for diabetes susceptibility genes from genome scan data.

Genome-wide scans for linkage have provided one of the dominant approaches adopted by researchers in their efforts to identify genes responsible for the inherited component of type 2 diabetes susceptibility. Around 20 genome scans have now been completed, in a wide variety of populations. Integration of data from these diverse scans has proven far from trivial, but the contours of genome-wide linkage topography are steadily emerging from the fog of data. Identification of the calpain-10 gene as the probable basis for the chromosome 2q linkage seen in Mexican Americans has provided validation of this positional cloning approach. This report provides an update on recent type 2 diabetes genome scan data, focusing on several chromosomal regions where the evidence for linkage has considerably strengthened in the past year. The current and future value of genome-wide linkage information in the search for type 2 diabetes susceptibility effects is also discussed.

Diabetes Mellitus, Type 2↗

Thermodynamic database for protein-nucleic acid interactions (ProNIT).

MOTIVATION: Protein-nucleic acid interactions are fundamental to the regulation of gene expression. In order to elucidate the molecular mechanism of protein-nucleic acid recognition and analyze the gene regulation network, not only structural data but also quantitative binding data are necessary. Although there are structural databases for proteins and nucleic acids, there exists no database for their experimental binding data. Thus, we have developed a Thermodynamic Database for Protein-Nucleic Acid Interactions (ProNIT). RESULTS: We have collected experimentally observed binding data from the literature. ProNIT contains several important thermodynamic data for protein-nucleic acid binding, such as dissociation constant (K(d)), association constant (K(a)), Gibbs free energy change (DeltaG), enthalpy change (DeltaH), heat capacity change (DeltaC(p)), experimental conditions, structural information of proteins, nucleic acids and the complex, and literature information. These data are integrated into a relational database system together with structural and functional information to provide flexible searching facilities by using combinations of various terms and parameters. A www interface allows users to search for data based on various conditions, with different display and sorting options, and to visualize molecular structures and their interactions. AVAILABILITY: ProNIT is freely accessible at the URL http://www.rtc.riken.go.jp/jouhou/pronit/pronit.html.

Amino Acid Sequence↗

CSB.DB: a comprehensive systems-biology database.

SUMMARY: The open access comprehensive systems-biology database (CSB.DB) presents the results of bio-statistical analyses on gene expression data in association with additional biochemical and physiological knowledge. The main aim of this database platform is to provide tools that support insight into life's complexity pyramid with a special focus on the integration of data from transcript and metabolite profiling experiments. The central part of CSB.DB, which we describe in this applications note, is a set of co-response databases that currently focus on the three key model organisms, Escherichia coli, Saccharomyces cerevisiae and Arabidopsis thaliana. CSB.DB gives easy access to the results of large-scale co-response analyses, which are currently based exclusively on the publicly available compendia of transcript profiles. By scanning for the best co-responses among changing transcript levels, CSB.DB allows to infer hypotheses on the functional interaction of genes. These hypotheses are novel and not accessible through analysis of sequence homology. The database enables the search for pairs of genes and larger units of genes, which are under common transcriptional control. In addition, statistical tools are offered to the user, which allow validation and comparison of those co-responses that were discovered by gene queries performed on the currently available set of pre-selectable datasets. AVAILABILITY: All co-response databases can be accessed through the CSB.DB Web server (http://csbdb.mpimp-golm.mpg.de/).

Database Management Systems↗

Sexual networks: the integration of social and genetic data.

New methods for studying sexual networks are presented, drawing upon routine procedures followed in genitourinary medicine clinics in the UK for tracing partners and identifying strains of infection. The routine social procedures were developed to incorporate a structured interview. The routine microbiological diagnosis of gonorrhoea was augmented by phenotyping and the development of new genetic techniques for the fine discrimination of gonococcal strains (opa-typing). Selected results from a study in Sheffield, UK show that each method has limitations, when conducted separately, but these are minimised when the methods are combined. Moreover, the use of simple and routine methods of data collection resolve issues of scale and sample that have beset other network studies, as they provide a means of covering a larger and defined population. Popular concepts about these methods are discussed in the conclusion. The integrated approach employed in our research raises questions both about social methods, 'of people who lie, particularly when they talk about sex', and about microbiological methods, 'of genes that tell the truth' and bypass what people say and think altogether. We argue that these stereotypes are misleading insofar as they suggest that genetic techniques can substitute for the social, and we suggest that even the finest discrimination of organisms at the genetic level will never obviate the need for their interpretation in the light of social data.

Adult↗

Integrated displays and the perception of graphical data.

Three experiments are presented that apply a principle of compatibility of proximity to the perception of graphical data. These experiments demonstrate that the merits and costs of integral displays relative to separable displays depend in part on the task being performed. Experiment 1 employs a data extrapolation task in which information must be integrated. Here an integral display is found to be superior to a separable display. Experiment 2 employed a data perception task that requires focused attention. This reveals superior performance with separable displays. Experiment 3 employed a multiple cue judgement task in which information integration could be manipulated. Data from Experiment 3 were analysed using the Brunswick lens procedures, and indicated that knowledge of the task structure was influenced by the display type. When selective attention was required, knowledge of the task was superior with separable displays. The results are discussed with reference to the principle of compatibility of proximity, and the implications of the results for the perception of scientific data are noted.

Adult↗

Concerns of hospitalized care from patients perspectives.

Nurses constantly face the need to provide patient care, both physical and psychological, within the health care arena. Nursing staff must have an understanding of the concerns and experiences of hospitalization, and the sensitivity to elicit the patient s own private language of health care needs. The purpose of the study was to examine the concerns of health care needs from patients point of view. The specific objective was to understand the experiences of hospitalized patients. The grounded theory method was applied for this purpose with major assumptions from the symbolic interaction perspective. Twelve subjects were recruited from medical and surgical units at a teaching hospital using purposive sampling, and were interviewed. Data were in the form of transcripts from tapes, field notes, and analytic and process memos. The constant comparative technique was utilized to discover the core themes that would explain most of the variation and integrate the data, codes and memos. Three coding processes, open coding, axial coding, and selective coding, were employed. Six aspects were generated from the results of the study to describe patients concerns. The hospitalized experience was depicted as searching for certain aspects of health care needs including focus on the physical condition, promptness and effectiveness of nursing services, health professionals caring attitudes when giving service and their responsibility, food preparation, environment, and medical expenses.

Adult↗

Integration of multi-omics data uncovers novel germline susceptibility candidates in early-onset colorectal cancer.

Colorectal cancer (CRC) is increasingly diagnosed in individuals under 50 years of age, yet the underlying genetic predisposition remains largely unexplained, particularly in mismatch repair (MMR)-proficient cases. This study aimed to identify novel hereditary CRC susceptibility genes by integrating germline and tumour whole-exome sequencing (WES) with transcriptomic profiling across a cohort of early-onset CRC (EOCRC) patients. Tumours were categorised using Consensus Molecular Subtypes (CMS) classification and analysed for mutational signature and burden. We used a novel 'All vs One' multi-omic integration approach to identify loss-of-function rare germline variants with concordant gene expression alterations in tumour tissue. Five candidate genes (ADCY4, NOXO1, CDHR2, ARHGAP10, EEF2K) were prioritised based on this approach and potential biological relevance in CRC. These findings highlight the molecular heterogeneity of EOCRC and demonstrate the utility of multi-omic approaches in refining germline variant interpretation. Integrating tumour transcriptomics enhances gene discovery efforts and supports a more comprehensive understanding of CRC heritability in younger individuals.

Humans↗

Getting the data in: three year experience with a pediatric electronic medical record system.

The Clinician's Workstation (CWS) has provided the full-functionality of an on-line electronic patient record for outpatient pediatric clinics over the past 3 years. The implementation of the CWS built upon a substantial effort in integration of data from various sources. This paper addresses the subsequent design issues which had to be resolved in order to enable both physician and transcriptionist-driven data entry and retrieval, notably selecting a feasible mixture of controlled vocabulary and free text. Some of the consequences of these design decisions on clinical care, clinical education, clinical and basic research are reviewed with examples from the last three years.

Computer Systems↗

Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trials.

OBJECTIVE: To examine the safety and tolerability of the antidepressant duloxetine across multiple studies for major depressive disorder (MDD). METHOD: Safety data were integrated from the acute phases of eight double-blind, placebo-controlled trials in which patients were randomized to duloxetine (40-120 mg/d; n = 1139) or placebo (n = 777) for up to 9 weeks. This data set included all acute-phase clinical trials that formed the basis of the New Drug Application (United States) or European Union submission package for duloxetine in the treatment of MDD. Two studies included continuation phases in which acute treatment responders received duloxetine or placebo for an additional 26 weeks. Safety assessments included serious adverse event reports, rates of discontinuation, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory values, and electrocardiograms. RESULTS: The rates of serious adverse events for duloxetine- and placebo-treated patients were 0.3% and 0.6%, respectively (p = 0.282). Adverse events led to discontinuation in 9.7% of duloxetine-treated patients, compared with 4.2% of patients receiving placebo (p < 0.001). Treatment-emergent adverse events with an incidence for duloxetine > or = 5.0% and significantly greater than placebo were nausea, dry mouth, constipation, insomnia, dizziness, fatigue, somnolence, increased sweating and decreased appetite. Mean changes in blood pressure and heart rate were small, and the incidence of increases above normal ranges was low. Duloxetine-treated patients had a mean decrease in weight of 0.5 kg compared with an increase of 0.2 kg for patients receiving placebo (p < 0.001). No significant differences were found between duloxetine and placebo in the incidence of potentially clinically significant laboratory values at anytime while on treatment. CONCLUSION: These results are consistent with those obtained previously from smaller pooled data sets, and suggest that duloxetine is safe and well tolerated in patients with MDD.

Adolescent↗

Turning tapes into text: issues surrounding the transcription of interviews.

Transcription of interview data is a common practice in qualitative health research. However, there has been little discussion of the techniques of transcription and the issues inherent in the use of transcription as a strategy for managing qualitative data in nursing publications. The process of transcription may disclose or obscure certain information. Researchers need to question practices of transcription that have been taken for granted and make transparent the processes used to preserve the integrity of data. This paperfirst examines research reported in nursing and allied health journals employing interviews for data collection and the attention given to the transcription phase. It then deals with issues of concern regarding the transcription of interviews, and offers suggestions for promoting validity.

Ethics↗

Integrating electrophysiological and anatomical experimental data to create a large-scale model that simulates a delayed match-to-sample human brain imaging study.

We propose a model that draws together experimental evidence from anatomical, electrophysiological and imaging experiments in order to understand better the neural substrate of human imaging studies using positron electron tomography (PET) and functional magnetic resonance imaging (fMRI). First, we define a simple local circuit that reflects the major role that local connectivity plays in producing PET and fMRI data, which are thought to mainly reflect synaptic activity. Second, in order to account for the role of varying behaviors during the course of a typical imaging experiment, we propose a local circuit that can perform a delayed match-to-sample task. The elements of this circuit behave very much like neurons that have been found in the prefrontal cortex during similar tasks in monkeys. One subpopulation responds selectively only when stimuli are present. Two different populations show the two types of delay-period activity that have been identified, one with high activity both during the cue and the delay period, the other with a rise during the delay period only. Last, a subpopulation shows a brief response only if the second stimulus matches the first, thus mediating the decision about whether the stimuli match. We show that in addition to performing the task, the integrated summed synaptic activities of the model are similar to experimental PET data.

Behavior↗

SwinePan for pig graph-based pangenome and multiomics data mining.

Pigs are one of the most important livestock species worldwide. Although multiple high-quality reference genomes exist, reliance on a single linear reference limits the detection of structural variants (SVs) and the characterization of population-specific genetic diversity. To address this limitation, we developed SwinePan, a comprehensive and integrated multiomics database for pigs built on a graph-based pangenome framework. SwinePan incorporates a variome derived from the graph-based pangenome, covering 2,598 individuals across 35 breeds, including 185,759 SVs, 117 million SNPs, and 6.8 million indels. The database also integrates transcriptomic data from liver, loin muscle, abdominal fat, and backfat, along with over 150,000 phenotypic records. The online toolkit deployed in SwinePan enables genome-wide association studies (GWAS), expression quantitative trait locus (eQTL) mapping, and colocalization, while interactive modules visualize population structure and multiomics associations, streamlining candidate gene and variant exploration. Additionally, two proof-of-concept analyses demonstrate how SwinePan pinpoints trait-associated loci and deciphers their potential regulatory mechanisms.

Journal Article↗

The HELP system and its application to infection control.

The HELP system is a comprehensive hospital information system that is linked to an allied financial data base. The clinical data base integrates information from areas such as admitting, pharmacy, radiology, surgery, pathology, nursing, respiratory therapy, and the clinical laboratories, including microbiology. This allows for the creation of an electronic medical record that contains all the clinical and financial data for each patient. The HELP system combines both communication and advice features through the use of data- and time-driven algorithms. We have used the HELP system to automate the surveillance and analysis of hospital-acquired infections and to identify patients at high risk for nosocomial infection. The expert system features have also been used to suggest alternatives for patients receiving inappropriate antimicrobial therapy, to improve the timing of antibiotic prophylaxis in surgery, and to curtail unnecessarily prolonged prophylaxis. Automated hospital information systems such as HELP can facilitate the investigation of a broad range of infection control, quality improvement, and cost-containment issues.

Cross Infection↗

Defining home health care nursing: implications for continuing nursing education.

The purpose of this qualitative interpretivist study was to analyze and articulate the characteristics of nursing practice in the home health care context. Researchers sought to describe expert home health care nursing practice and how it developed. Twenty-one nurses, at various stages of practice development, were asked to write three clinical narratives describing their home health care practice. Data were analyzed to elicit themes and characteristics of nursing practice in the home health care context. Findings indicate that in the context of home health care, expert nursing practice develops along a continuum, until nurses can integrate physiological data with environmental and family data to provide seamless, intuitive, and highly complex nursing care. The results of this research can assist continuing education and staff development providers as they develop educational programs designed to facilitate professional development of new graduates and newly employed nurses in home health care.

Community Health Nursing↗

Protein interaction verification and functional annotation by integrated analysis of genome-scale data.

Assays capable of determining the properties of thousands of genes in parallel present challenges with regard to accurate data processing and functional annotation. Collections of microarray expression data are applied here to assess the quality of different high-throughput protein interaction data sets. Significant differences are found. Confidence in 973 out of 5342 putative two-hybrid interactions from S. cerevisiae is increased. Besides verification, integration of expression and interaction data is employed to provide functional annotation for over 300 previously uncharacterized genes. The robustness of these approaches is demonstrated by experiments that test the in silico predictions made. This study shows how integration improves the utility of different types of functional genomic data and how well this contributes to functional annotation.

Animals↗