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Evaluating integrated health care: a model for measurement.

PURPOSE: In the development of integrated care, there is an increasing need for knowledge about the actual degree of integration between different providers of health services. The purpose of this article is to describe the conceptualisation and validation of a practical model for measurement, which can be used by managers to implement and sustain integrated care. THEORY: The model is based on a continuum of integration, extending from full segregation through intermediate forms of linkage, coordination and cooperation to full integration. METHODS: The continuum was operationalised into a ratio scale of functional clinical integration. This scale was used in an explorative study of a local health authority in Sweden. Data on integration were collected in self-assessment forms together with estimated ranks of optimum integration between the different units of the health authority. The data were processed with statistical methods and the results were discussed with the managers concerned. RESULTS: Judging from this explorative study, it seems that the model of measurement collects reliable and valid data of functional clinical integration in local health care. The model was also regarded as a useful instrument for managers of integrated care. DISCUSSION: One of the main advantages with the model is that it includes optimum ranks of integration beside actual ranks. The optimum integration rank between two units is depending on the needs of both differentiation and integration.

Journal Article↗

ASTER: an integration of the AQUIRE data base and the QSAR system for use in ecological risk assessments.

Ecological risk assessments are used by the US Environmental Protection Agency (US EPA) and other governmental agencies to assist in determining the probability and magnitude of deleterious effects of hazardous chemicals on plants and animals. These assessments are important steps in formulating regulatory decisions. The completion of an ecological risk assessment requires the gathering of ecotoxicological hazard and environmental exposure information. This information is evaluated in the risk characterization section to assist in making the final risk assessment. ASTER (ASsessment Tools for the Evaluation of Risk) was designed by the US EPA Environmental Research Laboratory-Duluth (ERL-D) to assist regulators in producing assessments. ASTER is an integration of the ACQUIRE (AQUatic toxicity Information REtrieval system) and QSAR (Quantitative Structure Activity Relationships) systems. ACQUIRE is a data base of aquatic toxicity tests and QSAR is comprised of a data base of measured physicochemical properties, and various QSAR models that estimate physicochemical and ecotoxicological endpoints. ASTER will be available to international governmental agencies through the US EPA National Computing Center.

Animals↗

Extending traditional query-based integration approaches for functional characterization of post-genomic data.

MOTIVATION: To identify and characterize regions of functional interest in genomic sequence requires full, flexible query access to an integrated, up-to-date view of all related information, irrespective of where it is stored (within an organization or across the Internet) and its format (traditional database, flat file, web site, results of runtime analysis). Wide-ranging multi-source queries often return unmanageably large result sets, requiring non-traditional approaches to exclude extraneous data. RESULTS: Target Informatics Net (TINet) is a readily extensible data integration system developed at GlaxoSmith- Kline (GSK), based on the Object-Protocol Model (OPM) multidatabase middleware system of Gene Logic Inc. Data sources currently integrated include: the Mouse Genome Database (MGD) and Gene Expression Database (GXD), GenBank, SwissProt, PubMed, GeneCards, the results of runtime BLAST and PROSITE searches, and GSK proprietary relational databases. Special-purpose class methods used to filter and augment query results include regular expression pattern-matching over BLAST HSP alignments and retrieving partial sequences derived from primary structure annotations. All data sources and methods are accessible through an SQL-like query language or a GUI, so that when new investigations arise no additional programming beyond query specification is required. The power and flexibility of this approach are illustrated in such integrated queries as: (1) 'find homologs in genomic sequence to all novel genes cloned and reported in the scientific literature within the past three months that are linked to the MeSH term 'neoplasms"; (2) 'using a neuropeptide precursor query sequence, return only HSPs where the target genomic sequences conserve the G[KR][KR] motif at the appropriate points in the HSP alignment'; and (3) 'of the human genomic sequences annotated with exon boundaries in GenBank, return only those with valid putative donor/acceptor sites and start/stop codons'.

Animals↗

An integrated model for the analysis of pharmacokinetic data from microdialysis experiments.

PURPOSE: To develop an integrated model for microdialysis data that incorporates all data including the recovery measurements in one model, and to compare this model to a previous model and the results from a noncompartmental analysis. METHODS: The models were developed in NONMEM. The modes of analysis were compared with respect to parameter estimates, model structures, gained mechanistic insight, and practical aspects. RESULTS: Both modeling approaches resulted in similar model structures. The parameter estimates in blood and brain from the models and the results from the noncompartmental analysis were comparable. Using the integrated model all data, that is, the total arterial concentrations, the venous and brain dialysate concentrations, and the recovery measurements, were analyzed simultaneously. CONCLUSION: The theoretical benefits of the integrated model are related to the inclusion of the recovery in the model and the use of all collected data as it was observed. Thus, all data are described in a single model, corrections for the recovery and the protein binding are done within the model, and the dialysate observations are described by the integral over each collection interval. Thereby, the variability and the uncertainty in the model parameters are handled correctly to give more reliable parameter estimates.

Animals↗

Integrating medical and genomic data: a successful example for rare diseases.

The recent advances on genomics and proteomics research bring up a significant grow on the information that is publicly available. However, navigating through genetic and bioinformatics databases can be a too complex and unproductive task for a primary care physician. In this paper we present diseasecard, a web portal for rare disease that provides transparently to the user a virtually integration of distributed and heterogeneous information.

Computational Biology↗

Integrative analysis of genome-scale data by using pseudoinverse projection predicts novel correlation between DNA replication and RNA transcription.

We describe an integrative data-driven mathematical framework that formulates any number of genome-scale molecular biological data sets in terms of one chosen set of data samples, or of profiles extracted mathematically from data samples, designated the "basis" set. By using pseudoinverse projection, the molecular biological profiles of the data samples are least-squares-approximated as superpositions of the basis profiles. Reconstruction of the data in the basis simulates experimental observation of only the cellular states manifest in the data that correspond to those of the basis. Classification of the data samples according to their reconstruction in the basis, rather than their overall measured profiles, maps the cellular states of the data onto those of the basis and gives a global picture of the correlations and possibly also causal coordination of these two sets of states. We illustrate this framework with an integration of yeast genome-scale proteins' DNA-binding data with cell cycle mRNA expression time course data. Novel correlation between DNA replication initiation and RNA transcription during the yeast cell cycle, which might be due to a previously unknown mechanism of regulation, is predicted.

Cell Cycle↗

EXPANDER--an integrative program suite for microarray data analysis.

BACKGROUND: Gene expression microarrays are a prominent experimental tool in functional genomics which has opened the opportunity for gaining global, systems-level understanding of transcriptional networks. Experiments that apply this technology typically generate overwhelming volumes of data, unprecedented in biological research. Therefore the task of mining meaningful biological knowledge out of the raw data is a major challenge in bioinformatics. Of special need are integrative packages that provide biologist users with advanced but yet easy to use, set of algorithms, together covering the whole range of steps in microarray data analysis. RESULTS: Here we present the EXPANDER 2.0 (EXPression ANalyzer and DisplayER) software package. EXPANDER 2.0 is an integrative package for the analysis of gene expression data, designed as a 'one-stop shop' tool that implements various data analysis algorithms ranging from the initial steps of normalization and filtering, through clustering and biclustering, to high-level functional enrichment analysis that points to biological processes that are active in the examined conditions, and to promoter cis-regulatory elements analysis that elucidates transcription factors that control the observed transcriptional response. EXPANDER is available with pre-compiled functional Gene Ontology (GO) and promoter sequence-derived data files for yeast, worm, fly, rat, mouse and human, supporting high-level analysis applied to data obtained from these six organisms. CONCLUSION: EXPANDER integrated capabilities and its built-in support of multiple organisms make it a very powerful tool for analysis of microarray data. The package is freely available for academic users at http://www.cs.tau.ac.il/~rshamir/expander.

Algorithms↗

A review of positive conditioned reinforcement.

This review critically analyzes experimental data relevant to the concept of conditioned reinforcement. The review has five sections. Section I is a discussion of the relationship between primary and conditioned reinforcement in terms of chains of stimuli and responses. Section II is a detailed analysis of the conditions in which the component stimuli in chained schedules of reinforcement will become conditioned reinforcers; this section also analyzes studies of token reinforcement, observing responses, switching responses, implicit chained schedules, and higher-order conditioning. Section III analyzes experiments in which potential conditioned reinforcers are used either to prolong responding or to generate responding during experimental extinction. This section discusses hypotheses that have been offered as alternatives to the concept of conditioned reinforcement and hypotheses concerning the necessary and sufficient conditions for establishing a conditioned reinforcer. Section IV discusses other variables that act when a conditioned reinforcer is being established or that act when an established conditioned reinforcer is used to develop or maintain behavior. Section V is a general discussion of conditioned reinforcement. The evidence indicates that the conditioned reinforcing effectiveness of a stimulus is directly related to the frequency of primary reinforcement occurring in its presence, but is independent of the response rate or response pattern occurring in its presence. Results from chained schedules comprised of several components indicate that a stimulus can be established as a conditioned reinforcer by pairing it with an already established conditioned reinforcer rather than a primary reinforcer; however, this type of higher-order conditioning has not been clearly demonstrated with respondent conditioning procedures. Although discriminative stimuli are usually conditioned reinforcers, the available evidence indicates that establishing a stimulus as a discriminative stimulus is not necessary or sufficient for establishing it as a conditioned reinforcer. Discriminative stimuli in chained schedules with several components are not always conditioned reinforcers; stimuli that are simply paired with reinforcers can become conditioned reinforcers. The hypotheses that have been offered as alternatives to the concept of conditioned reinforcement are too limited to integrate the data that exist. The concepts of conditioned reinforcement and chained schedule, however, can be used to integrate the data obtained with diverse techniques. Recent experiments have revealed several techniques for the development of effective conditioned reinforcers. These techniques provide a powerful tool for advancing understanding of conditioned reinforcement and for extending control over behavior.

Conditioning, Classical↗

Gaze-evoked nystagmus and smooth pursuit deficits: their relationship studied in 52 patients.

Gaze-evoked nystagmus occurs with cerebellar and brainstem lesions and reflects a deficiency of the so-called common neural integrator. Experimental data show that loss of the neural integrator also abolishes slow conjugate eye movements, i.e. smooth pursuit eye movements and the vestibulo-ocular reflex (VOR). Since the smooth pursuit system has its own premotor circuits, a smooth pursuit deficit can be either the result of a premotor smooth pursuit lesion or the consequence of a gaze-holding deficit. To study this question DC eye movement recordings of 52 patients with horizontal gaze-evoked nystagmus and/or smooth pursuit deficits were studied in detail. It was found that the majority (71%) had a combined smooth pursuit and gaze-holding deficit. Thirteen patients (25%) had a smooth pursuit deficit only. Only 2 patients (4%) had an isolated gaze-evoked nystagmus, which was comparatively weak. Thus a major finding is that each substantial gaze-evoked nystagmus is combined with a smooth pursuit deficit; the two deficits are well correlated (coefficient r = 0.81). In all patients with a smooth pursuit deficit, visual suppression of the VOR was similarly impaired, when comparing the groups with and without gaze-evoked nystagmus. It is argued here that, although gaze-holding and smooth pursuit deficits are well correlated, the gaze-holding deficits seen in patients are not severe enough to explain the smooth pursuit deficit solely as a consequence of the gaze-holding deficit. Rather it probably reflects the close anatomical vicinity of gaze-holding and smooth pursuit mechanisms in the floccular region, the vestibular nuclei/nucleus prepositus complex and its connecting pathways.

Adult↗

Algorithm for the pharmacotherapy of anxiety disorders.

Since the introduction of distinct anxiety disorders in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, there has been a growing interest in these conditions, leading to a wealth of pharmacotherapy trials. Guidelines for the treatment of anxiety disorders have been developed on the basis of systematic reviews of the literature and expert consensus in areas where data are lacking. Algorithms provide scaffolding for integrating the data on pharmacotherapy and for pointing to gaps in current knowledge. Pharmacotherapy algorithms have the potential advantage of being concise, user-friendly, and evidence-based. However, such algorithms run the risk of oversimplifying complex clinical realities, and are only as good as the data on which they rest. In this article, an algorithm for the pharmacotherapy of anxiety disorders is presented.

Algorithms↗

A biophysical model of neuronal dendrites' integrative properties: relations to morphological data.

We used a biophysical model to probe the basic integrative properties of primate pallidal neurons in order to obtain a better understanding of Basal Ganglia physiology. The first results we present here deal mainly with the way dendritic morphology influences these properties. Neuronal morphology has been quantitatatively analyzed in 3D. Single fast excitatory synaptic inputs resulting in AMPA receptors activations have been simulated, without regenerative voltage dependent conductances. Dendrites of both pallidal segments (GPi and GPe) showed a strong dependence of the synaptic efficacy upon distance from soma, but even the most distal dendritic synaptic sites were able to substantially depolarize the cell body. The mean synaptic efficacy was the same in both populations, but the attenuation of propagated post-synaptic potentials was higher in GPi neurons. All these features were very dependent on the dendritic diameters which appear to constitute a key parameter in these neuronal populations both with respect to the integration of afferent information and to the differences between cells in performing this task.

Biophysical Phenomena↗

The biomechanical effects of angulated boxer's fractures.

Many clinical studies have demonstrated that in the conservative care of boxer's fractures (casting, with or without reduction), between 20 degrees and 70 degrees of dorsal angulation is acceptable. This biomechanical study characterized how boxer's fracture angulation affects the ability of the intrinsic muscles to initiate grip. The flexor digiti minimi and third volar interosseous were modeled in this study. Muscular excursion of the intrinsics were modeled with a cable and sheath device. Metacarpophalangeal joint flexion per unit excursion curves were collected when the metacarpal neck was at a fracture angle of 0 degree, 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 75 degrees . As fracture angles increased, the distance between the origin and insertion of the flexor digiti minimi decreased, creating shortening, or slack, of the modeled muscle. Slack was defined as excursion generating no joint flexion. Muscle shortening data were integrated with Jacobsen's muscle fiber length data and Elftmann's fiber length/tension relationship to estimate how the fracture angle affects the initiation of metacarpophalangeal joint flexion and the strength of grip. According to this model's data, fracture angles of up to 30 degrees are compatible with nearly normal mechanics. A 30 degrees angulation is associated with a flexor digiti minimi grip strength of 92% maximum and preserves 78% of the intact finger's range of motion. We therefore conclude that 30 degrees is the upper limit for acceptable final angulation.

Cadaver↗

Application of intake fraction to population exposure estimates in Hunan Province of China.

This article developed a new method, based on the concept of "intake fraction", to assess population exposure to primary and secondary fine particle matters from site-specific sources. This method was illustrated by a set of 17 power plants (totally 24 stacks) in Hunan Province of China. The CALPUFF long-range atmospheric dispersion model was used to simulate ambient concentrations of fine particles, and the GIS technology was used to generate a population distribution database from county-level population statistical data. An integrated computer program package was developed to carry out numerical integration of dispersion results over the population data, and produce intake fractions. The resulting average intake fractions within 500 km were 9.73 x 10(-6), 2.39 x 10(-6), and 2.47 x 10(-6) for primary fine particles, sulfate and nitrate respectively. Regression analyses were performed to explore the relationships between intake fractions and potential variables. Results showed that the stack height and aggregate populations could be used to predict intake fractions of fine particles. R2 of the regression equations were 0.83, 0.64, and 0.74 for primary fine particles, sulfate and nitrate respectively. Iso-intake fractions presenting geographical distributions of intake fractions in Hunan Province were mapped, showing a factor of about 2 between the highest values in the northeast and the lowest in the southwest of Hunan Province.

Air Pollutants↗

An approach to modelling in immunology.

Like most other fields in biology, immunology has been revolutionised by the techniques of molecular biology and the resulting explosion in available experimental data. It is argued that efforts to integrate the data to gain insight into how various subsystems in the immune system interact and function require mathematical modelling and computer simulation in close collaboration with experimentalists. This paper illustrates some of the techniques available for modelling immune systems, and highlights the issues that should be borne in mind by anyone starting down the modelling path.

Animals↗

AVA: visual analysis of gene expression microarray data.

SUMMARY: AVA (Array Visual Analyzer) is a Java program that provides a graphical environment for visualization and analysis of gene expression microarray data. Together with its interactive visualization tools and a variety of built-in data analysis and filtration methods, AVA effectively integrates microarray data normalization, quality assessment, and data mining into one application. AVAILABILITY: The software is freely available for academic users on request from the authors.

Algorithms↗

CDACHIE: chromatin domain annotation by integrating chromatin interaction and epigenomic data with contrastive learning.

MOTIVATION: Chromatin domain annotation identifies functional genomic regions, such as active and inactive zones, based on epigenomic features like histone modifications, DNA methylation, and chromatin accessibility. While recent methods have utilized both chromatin interaction data (e.g. Hi-C) and epigenomic data, they often overlook the direct relationship between these data types. RESULTS: In this study, we introduce Chromatin Domain Annotation using Contrastive Learning for Hi-C and Epigenomic Data (CDACHIE), a method for identifying chromatin domains from Hi-C and epigenomic data. Our approach leverages contrastive learning to generate aligned representative vectors for both data types at each genomic bin. The concatenated vectors are then clustered using K-means to classify distinct chromatin domain types. CDACHIE achieves superior performance in Variance Explained, evaluated across gene expression, replication timing, and ChIA-PET data. This highlights its robust ability to integrate semantic associations between Hi-C and epigenomic features within the embedding space. AVAILABILITY AND IMPLEMENTATION: The source code is available at GitHub: https://github.com/maruyama-lab-design/CDACHIE. An archival snapshot of the code used in this study is available on Zenodo: https://doi.org/10.5281/zenodo.15751780.

Chromatin↗

The ASAP II database: analysis and comparative genomics of alternative splicing in 15 animal species.

We have greatly expanded the Alternative Splicing Annotation Project (ASAP) database: (i) its human alternative splicing data are expanded approximately 3-fold over the previous ASAP database, to nearly 90,000 distinct alternative splicing events; (ii) it now provides genome-wide alternative splicing analyses for 15 vertebrate, insect and other animal species; (iii) it provides comprehensive comparative genomics information for comparing alternative splicing and splice site conservation across 17 aligned genomes, based on UCSC multigenome alignments; (iv) it provides an approximately 2- to 3-fold expansion in detection of tissue-specific alternative splicing events, and of cancer versus normal specific alternative splicing events. We have also constructed a novel database linking orthologous exons and orthologous introns between genomes, based on multigenome alignment of 17 animal species. It can be a valuable resource for studies of gene structure evolution. ASAP II provides a new web interface enabling more detailed exploration of the data, and integrating comparative genomics information with alternative splicing data. We provide a set of tools for advanced data-mining of ASAP II with Pygr (the Python Graph Database Framework for Bioinformatics) including powerful features such as graph query, multigenome alignment query, etc. ASAP II is available at http://www.bioinformatics.ucla.edu/ASAP2.

Alternative Splicing↗

Data-guided brain deformation modeling: evaluation of a 3-D adjoint inversion method in porcine studies.

Biomechanical models of brain deformation are useful tools for estimating parenchymal shift that results during open cranial procedures. Intraoperative data is likely to improve model estimates, but incorporation of such data into the model is not trivial. This study tests the adjoint equations method (AEM) for data assimilation as a viable approach for integrating displacement data into a brain deformation model. AEM was applied to two porcine experiments. AEM-based estimates were compared both to measured displacement data [from computed tomography (CT) scans] and to model solutions obtained without the guidance of sparse data, which we term the best prior estimate (BPE). Additionally, the sensitivity of the AEM solution to inverse parameter selection was investigated. The results suggest that it is most important to estimate the size of the variance in the measurement error correctly, make the correlation length long and estimate displacement (over stress) boundary conditions. Application of AEM shows an average 33% improvement over BPE. This paper represents the first evidence of successful use of the AEM technique in three dimensions with experimental data validation. The guidelines established for selection of model parameters are starting points for further optimization of the method under clinical conditions.

Algorithms↗