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Interactome: gateway into systems biology.

Protein-protein interactions are fundamental to all biological processes, and a comprehensive determination of all protein-protein interactions that can take place in an organism provides a framework for understanding biology as an integrated system. The availability of genome-scale sets of cloned open reading frames has facilitated systematic efforts at creating proteome-scale data sets of protein-protein interactions, which are represented as complex networks or 'interactome' maps. Protein-protein interaction mapping projects that follow stringent criteria, coupled with experimental validation in orthogonal systems, provide high-confidence data sets immanently useful for interrogating developmental and disease mechanisms at a system level as well as elucidating individual protein function and interactome network topology. Although far from complete, currently available maps provide insight into how biochemical properties of proteins and protein complexes are integrated into biological systems. Such maps are also a useful resource to predict the function(s) of thousands of genes.

Animals↗

Integrating a digital dictation system with a network data base for creating and managing radiologic teaching files.

RATIONALE AND OBJECTIVES: A method for facilitating the creation and management of radiologic teaching files is described. METHODS: A digital dictation system was integrated with a personal computer data base. The data base is maintained with user-friendly, graphically oriented software. Radiologists can dictate any examination for the teaching file from any dictation station in the department with minimal interruption of their clinical activities. The data base resides on a file server, thus providing department-wide access for radiologists and students. RESULTS: Attending radiologists and residents have responded favorably to the system. Maintenance and retrieval of teaching files are facilitated by using a computer for otherwise tedious aspects of information management. Data are stored in a well-organized manner, thus increasing the value of the teaching file while reducing redundant data entry. CONCLUSION: Computer technology can facilitate the maintenance of radiologic teaching files. Radiology departments that have a convenient, department-wide method for entering cases--such as a digital dictation system and existing computer network--are ideal for the technique that we describe.

Humans↗

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↗

Integrating multiple clinical information systems using the Java Message Service framework.

This article describes an application for capturing, delivering, and tracking urgent radiology exam results. Urgent exam findings are entered using a Web form embedded within the Picture archiving and communication system (PACS) display station. The findings are then accessible via soft copy using the PACS display stations, hospital information system (HIS) terminals, or wireless-enabled personal digital assistants (PDAs) or via hard copy printouts that are generated automatically or on demand. Additionally, quality control is performed on those findings entered by radiology residents and fellows, the results of which are used for both performance tracking and educational activities. The application was developed using Sun Microsystems' Java programming language. The Java Message Service (JMS) was used to manage the delivery of findings. JMS provides a robust, flexible framework for exchanging messages between disparate applications. The application is now used for all urgent exams; completely replacing the original paper-based system. The use of JMS provides the necessary level of reliability needed by this application.

Computer Communication Networks↗

Integrating multiple clinical information systems using the Java message service framework to enable the delivery of urgent exam results at the point of care.

The aim of this study is to determine if network-enabled personal digital assistants (PDAs) can be used to facilitate the timely delivery of urgent radiological exam results by reducing the interval from when the radiologist's initial interpretation is available to when it is first viewed by an emergency department (ED) physician. A web- and Java message service (JMS)-based application was built to replace the original fax-based wet-read procedure. The new system allows radiologists to enter wet-reads from the picture archiving and communication system (PACS) display station and to track discrepancies between the wet-read and final report. It also notifies the ED physicians when exam results are available via the PDAs and permits them to view the full text of the wet-read and final reports from the devices. The new system is compared to the original procedure with the results showing improvements with the wireless method. Furthermore, feedback from a qualitative survey of PDA users was positive, suggesting that PDAs may provide one means for accessing urgent clinical data at the point of care.

Computer Communication Networks↗

DNA-dependent PK inhibits adeno-associated virus DNA integration.

Recent studies have shown that recombinant adeno-associated virus (rAAV) can persist in episomal form; however, factors affecting rAAV persistence are poorly understood. DNA-dependent PK (DNA-PK) is a DNA repair enzyme, which we previously found played an important role in determining the molecular fate of the rAAV genome in mouse skeletal muscle. In the present study, we tested the effect of DNA-PK on AAV serotype 2 integration in vitro and in vivo in mouse liver. In an in vitro integration system, addition of DNA-PK decreased AAV integration, whereas antibody against DNA-PKcs increased integration. In vivo, matched doses of a recombinant AAV serotype 2 vector were injected into the portal vein of either C57BL/6 (DNA-PKcs(+/+)) or severe combined immunodeficient (DNA-PKcs(-/-)) mice. After partial hepatectomy to stimulate hepatocyte proliferation, retention of vector genomes and of transgene expression was substantially higher in severe combined immunodeficient mice, indicating that in the absence of DNA-PKcs, a greater proportion of genomes integrated into the cellular genome. In summary, we have provided evidence that DNA-PK inhibits AAV integration both in vitro and in vivo.

Animals↗

A critical change in a day in the life of intensive care nurses: rising to the e-challenge of an integrated clinical information system.

Critical care nurses in a large academic, tertiary care trauma center have adapted to a major system change since the implementation of a fully integrated Computerized Provider Order Entry (CPOE) system, an automated process of order entry. Working in a rapidly changing environment, clinicians are accustomed to viewing real-time discrete data and then using that data to provide safe, effective, and efficient intensive care to critically ill patients. This article describes how the implementation of the CPOE system from a major healthcare software vendor has changed the life of critical care nurses and the perceptions of the experience 1 year after the new technology was initiated. Through experience sharing, perhaps others may gain knowledge to ease their transition to CPOE.

Adult↗

Images for medical diagnoses.

Dr. Dietrich Meyer-Ebrecht provides a broad and helpful overview of the many techniques and latest trends in diagnostic imaging. Latest sensing technology is reviewed including: X-ray systems, ultrasound, thermography, radionuclide imaging, endoscopy, and optical methods. Approximate system cost ranges are indicated. This paper examines the technological trends in: sensors, imagers, hardcopy production, computer enhancement, storage, and communication of images. Dr. Meyer-Ebrecht describes three generations of computed tomographic scanners and alternative approaches to three-dimensional imaging. Image storage is presented as a major limitation of present technology. A view of future systems approaches envisions "picture bases" that will complement present data bases of hospital information systems. Integration of latest technology into diagnostic picture information systems will lead to advanced systems.

Computers↗

Neuroendocrine and immune system responses with spaceflights.

Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldosterone, and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flights data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T-lymphocytes and natural killer cells are decreased with post-flight conditions. Of the lymphokines, interleukin-2 production, lymphocyte responsiveness, and the activity of natural killer cells are consistently reduced post-flight. Limited head-down tilt (HDT) data suggest it is an effective simulation model for microgravity investigations. Neuroendocrine and pharmacological countermeasures are virtually nonexistent and should become high priority items for future research. Although exercise has the potential to be an effective countermeasure for various neuroendocrine-immune responses in microgravity, this concept must be tested before flights to Mars are scheduled.

Humans↗

Surge capacity for health care systems: early detection, methodologies, and process.

Excessive demand on hospital services from large-scale emergencies is something that every emergency department health care provider and hospital administrator knows could happen at any time. Nowhere in this country have we recently faced a disaster of the magnitude of concern we now face involving agents of mass destruction or social disruption, especially those in the area of infectious diseases and radiological materials. The war on terrorism is not a conventional war, and terrorists may use any means of convenience to carry out their objectives in an unpredictable time line. Have we adequately prepared for the potentially excessive surge in demand for medical services that a large-scale event could bring to our medical care system? Are our emergency departments ready for such events? Surveillance systems, such as BioWatch, BioSense, the National Biosurveillance Integration System, and the countermeasure program BioShield, offer hope that we will be able to meet these new challenges.

Delivery of Health Care↗

Resilience and sustainable development: building adaptive capacity in a world of transformations.

Emerging recognition of two fundamental errors underpinning past polices for natural resource issues heralds awareness of the need for a worldwide fundamental change in thinking and in practice of environmental management. The first error has been an implicit assumption that ecosystem responses to human use are linear, predictable and controllable. The second has been an assumption that human and natural systems can be treated independently. However, evidence that has been accumulating in diverse regions all over the world suggests that natural and social systems behave in nonlinear ways, exhibit marked thresholds in their dynamics, and that social-ecological systems act as strongly coupled, complex and evolving integrated systems. This article is a summary of a report prepared on behalf of the Environmental Advisory Council to the Swedish Government, as input to the process of the World Summit on Sustainable Development (WSSD) in Johannesburg, South Africa in 26 August 4 September 2002. We use the concept of resilience--the capacity to buffer change, learn and develop--as a framework for understanding how to sustain and enhance adaptive capacity in a complex world of rapid transformations. Two useful tools for resilience-building in social-ecological systems are structured scenarios and active adaptive management. These tools require and facilitate a social context with flexible and open institutions and multi-level governance systems that allow for learning and increase adaptive capacity without foreclosing future development options.

Agriculture↗

Influence of overtime work, sleep duration, and perceived job characteristics on the physical and mental status of software engineers.

To investigate the impact of overtime work, sleep duration, and perceived job characteristics on physical and mental status, a cross-sectional study was conducted on 377 workers (average age; 28 years old) in an information-technology (IT) company, engaged in consultation, system integration solution, and data management relevant to IT system. The psychophysical outcomes of overtime work were assessed using the Hamilton Depression Scale (HDS), Profile of Mood Status (POMS), major physical symptoms, and overtime work data for the preceding three-months. Sleep duration was directly asked by a physician. A job strain index was defined as the ratio of job-demands to job-control scores evaluated using the Job Content Questionnaire (JCQ). In a univariate analysis, overtime work was significantly related with HDS scores, POMS anger-hostility scores, and the total physical symptom count in both sexes (all p < 0.05), but not in multiple regression models, after controlling for sleep duration and the job strain index. Sleep duration was negatively related to the symptom count in men and to POMS tension-anxiety scores in women (both p < 0.05); the job strain index was positively related to POMS anger-hostility scores in both sexes and to HDS scores and POMS tension-anxiety scores in men (all p < 0.05). Although overtime work was associated with physical and mental complaints, sleep duration and the job strain index seemed to be better indicators for physical and mental distress in overloaded workers.

Adult↗

Introduction of managed care plans in a cardiac surgery unit.

Changes to output-based funding for health care as occurred recently in Victoria, and the goal of continuous improvement in quality of care, have provoked a rationalization of resource utilization and a greater focus on the process and outcomes of care in acute hospitals. The use of clinical management plans (CMPs) to monitor the efficiency of processes and the achievement of outcomes (managed care systems) is one approach to these challenges. A pilot study undertaken in the cardiac surgical unit at the Royal Melbourne Hospital is used to highlight the major considerations that need to be addressed when administering CMPs. These were the multidisciplinary, patient-focused approach of the managed care system, integration of the plans into the patient documentation system and the opportunities offered to research by variance analysis.

Cardiac Surgical Procedures↗