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First-episode psychosis: Part I. Editors' introduction.

Until recently, there has been a conspicuous lack of studies regarding the earliest phases of psychotic illness, with most research on schizophrenia and related disorders focusing on chronically ill patients. Currently, however, a number of investigators have turned their attention toward this topic, exploring the conceptual issues involved in defining the onset of psychosis, using case registers and population-based samples to do crucial epidemiologic studies on the course of schizophrenia, and developing mechanisms for identifying patients with first-episode psychosis and entering them into active research protocols. The issue of the Schizophrenia Bulletin is devoted to articles representing this full range of conceptual and empirical work on first-episode psychosis. The ultimate goal is for researchers working in this area to develop a network to enhance the sharing of concepts and data, with the eventual possibility of developing combined data bases and collaborative studies.

Female↗

Impact of clinical pathways for total hip replacement: a community-based analysis.

The implementation of clinical pathways for total hip replacement was carried out by five hospitals in the metropolitan area of Syracuse, New York. This process occurred under the leadership of clinical nurse specialists and nurse managers. It was supported by preadmission patient education programs and active physician involvement. The participating hospitals shared utilization quality assurance data and benchmarked with respect to the experience of Sacramento, California, and each others' progress. The effort produced substantial reductions in hospital stays without adverse impacts on quality of care.

Arthroplasty, Replacement, Hip↗

The case for interdepartmental research in primary care.

Research problems in human biology, clinical medicine, and health services delivery are complex, and increasingly require collaborative approaches. Despite the commitment of general internists, general pediatricians, and family physicians to comprehensive, coordinated, and longitudinal care, their substantial overlap in research topics, methods, and data sources, and their shared emphasis on research conducted in community-based settings, the three primary care disciplines rarely collaborate in research. The research enterprises of most primary care departments and divisions in the United States are small "cottage industries," while interdepartmental research units are rare. Interdepartmental research units can develop and maintain the critical mass of investigators, trainees, and staff that is necessary for an intellectually vibrant and financially sound primary care research enterprise. The University of Colorado Health Sciences Center School of Medicine has developed a successful interdepartmental research effort in primary care that includes joint fellowship training and faculty development programs and a Primary Care Research Unit that supports the analysis of secondary databases, practice-based research networks, and interdisciplinary research projects. Key elements of this collaboration include shared projects among faculty and trainees, proactive negotiation about resources, and shared research space, staff, and faculty. Such a collaboration provides the breadth of perspectives necessary to address complex health care problems, and the pragmatic infrastructure necessary to sustain research themes and careers.

Colorado↗

Correlates of hepatitis C virus infections among injection drug users.

Injection drug users are at high risk for hepatitis C virus (HCV) infection. In Baltimore, Maryland, the prevalence of anti-HCV is greater among injection drug users who are black, human immunodeficiency virus (HIV) infected, have injected longer, have injected more frequently, and have injected cocaine than among other injection drug users. HCV infection occurs quickly after the initiation of injecting illicit drugs, with 78% of study participants anti-HCV positive after 2 years of injecting. The prevalence of anti-HCV among injection drug users does not appear to be related to socioeconomic factors or sexual practices. Some injection drug users remain free of anti-HCV even after years of injecting and serologic evidence of other bloodborne pathogens. Some of these injection drug users have HCV infection, demonstrated by HCV RNA in their sera. However, the basis for viral persistence in the absence of anti-HCV and for the absence of HCV infection in long-term drug users is not known. Further studies are indicated to determine the mechanism or mechanisms for the absence of anti-HCV in persons exposed to the virus, because the biologic basis for this condition may elucidate the elements missing in the immune response of the majority of HCV-exposed persons who acquire persistent infection. In addition, interventions to prevent HCV infections should be applied in populations at risk for injection drug use early or before drug use begins.

Adolescent↗

Simultaneous detection of Dialister pneumosintes and Filifactor alocis in endodontic infections by 16S rDNA-directed multiplex PCR.

Dialister pneumosintes and Filifactor alocis have been recently considered as candidate endodontic pathogens. In this study, we devised a 16S rDNA-directed multiplex PCR protocol for simultaneous detection of these two bacterial species in endodontic infections. Samples were taken from infected root canals associated with asymptomatic periradicular lesions as well as from cases of acute periradicular abscesses. DNA extracted from the samples was used as template for simultaneous detection of D. pneumosintes and F. alocis through a multiplex PCR assay. Two fragments of the expected sizes, one specific for D. pneumosintes and the other for F. alocis, were simultaneously amplified from a mixture of reference genomic DNA containing DNA from both species. Clinical samples that were positive for the target species showed a single band of the predicted size for each species. D. pneumosintes was detected by multiplex PCR in 11 samples (7 asymptomatic and 4 abscesses) and F. alocis was identified in 9 cases (6 asymptomatic and 3 abscesses). Six samples (3 asymptomatic and 3 abscesses) shared the two species. Data from the present study confirmed that D. pneumosintes and F. alocis are common members of the microbiota present in primary endodontic infections and thereby may participate in the pathogenesis of periradicular lesions. The proposed multiplex PCR assay is a simple, rapid, and accurate method for the simultaneous detection of these two candidate endodontic pathogens.

Adult↗

Ambiguities in the scattering tomography for central potentials.

Invisibility devices exploit ambiguities in the inverse scattering problem of light in media. Scattering also serves as an important general tool to infer information about the structure of matter. We elucidate the nature of scattering ambiguities that arise in central potentials. We show that scattering is a tomographic projection: The integrated scattering angle is a projection of a scattering function onto the impact parameter. This function depends on the potential but may be multivalued, allowing for ambiguities where several potentials share the same scattering data. In addition, multivalued scattering angles also lead to ambiguities. We apply our theory to show that it is, in principle, possible to construct an invisibility device without infinite phase velocity of light.

Journal Article↗

CR2 complement receptor.

CR2, a membrane glycoprotein, is one of a number of cell-surface proteins which bind activation and processing fragments of the complement system. CR2, which is found on normal B lymphocytes, follicular dendritic cells in lymphoid organs, and epithelial cells, interacts preferentially with C3dg, the terminal activation/processing fragment of the third complement component. Attachment of C3dg to CR2 brings complement activators, bearing covalently bound C3dg, into direct membrane contact with CR2-bearing cells. Epstein-Barr virus, a human herpesvirus, also binds to CR2 on B lymphocytes. Attachment of EBV is followed by infection. CR2 has been purified and the binding properties of its ligands analyzed. Monoclonal antibodies have been developed and used to probe the structural correlates of CR2 functions. CR2 has been molecularly cloned and its primary amino acid sequence deduced. These data indicate that it shares characteristic structural features with a number of other complement and non-complement cell membrane and plasma proteins. Several of the complement-associated proteins in this family possess regulatory functions; they are encoded by linked genes which have been localized to band q32 on chromosome 1. CR2 has been expressed in primate and rodent cells by transfection of cDNA in antigenically and functionally intact form. It has also been expressed in soluble form and its structure, electron microscopic appearance and binding characteristics analyzed in detail. The present state of knowledge of the structure and genetics of CR2 and current understanding of its biologic functions are summarized here.

Animals↗

Comparative genome-wide profiling of post-transplant lymphoproliferative disorders and diffuse large B-cell lymphomas.

Post-transplant lymphoproliferative disorders (PTLD) are a major complication of solid organ transplantation, representing a cause of severe morbidity and mortality. Apart from Epstein-Barr virus infection, knowledge of the pathogenesis of monoclonal PTLD is limited. Powerful analysis techniques, such as whole genomic DNA profiling (array comparative genomic hybridisation), can improve our understanding of PTLD pathogenesis. Whole genome profiling using the Affymetrix GeneChip Human Mapping 10 k 2.0 was performed on 20 PTLD cases and 25 cases of diffuse large B-cell lymphoma (DLBCL) from immunocompetent patients as a control group. Recurrent lesions were detected among all the samples. Chromosome 18q, 7q, 3q and 12 were the most common gains in the control group. Chromosomes 5p and 11p were commonly gained in PTLD-DLBCL. The latter had frequent losses of 6q, 17p, 1p and 9p. Chromosome 12p was the most frequent target of deletions among PTLD-DLBCL cases. Loss of heterozygosity (LOH) did not always match DNA loss: chromosome 10 seemed to be targeted by uniparental disomy in PTLD. Small deletions and gains, involving both known (BCL2 and PAX5) and unknown genes (ZDHHC14), were identified. These data suggest that PTLD share, at a lower frequency, common genetic aberrations with DLBCL from immunocompetent patients. The demonstration of 9p13 amplification emphasises the importance of PAX5 in PTLD. The combination of DNA copy number and LOH assessment lead to the hypothesis that uniparental disomy may be a potential mechanism in B-cell lymphomagenesis.

Chromosome Aberrations↗

Fatigue in cancer: a phenomenological perspective.

Fatigue is a frequently encountered symptom in cancer populations. This study aimed to describe the experience of fatigue from the perspective of cancer patients who had recently completed a course of chemotherapy. A phenomenological method was used. The themes which emerged from the data indicated both a shared and individual experience of fatigue. These incorporated: the nature of fatigue; the causes, consequences, strategies for coping with fatigue; and the trajectory of the fatigue experience. Issues arising from the nature of phenomenological inquiry and the research were also elicited from this study. An understanding of the fatigue experience for this population and the use of phenomenology have implications for the nursing profession's knowledge base and for clinical practice.

Adaptation, Psychological↗

Stimulation of lymphocyte proliferation by non-lymphoid porcine tissue cells.

Cultured porcine non-lymphoid cells, characterized by biochemical and morphological criteria, were derived from different tissues of individuals typed by serological and mixed lymphocyte culture methods for gene products of the major histocompatibility complex. These cultured cells have been used as stimulators in mixed lymphocyte-tissue cell cultures in order to investigate (1) the magnitude, kinetics and dose-dependence of lymphocyte transformation caused by tissue cells compared with that caused by lymphocytes as stimulators; (2) the relationship between the expression of serologically detected Ia-like antigens by tissue cells and their ability to cause lymphocyte transformation; (3) the genetic control of stimulation by tissue cells and by lymphocytes and (4) the expression and genetic control of lymphocyte stimulatory properties restricted to tissue cells and absent from lymphocytes. It has been shown that some but not all kinds of tissue cells can stimulate allogeneic lymphocytes strongly and that the characteristics of such stimulation are similar to those observed in mixed lymphocyte cultures. Strong stimulation by tissue cells does not always correlate with the expression of serologically detectable Ia-like antigens, but appears to be controlled by the major histocompatibility complex. There is evidence that certain tissue cells possess lymphocyte stimulatory properties not shared by lymphocytes. Preliminary data suggest that such tissue cell specific stimulation is not controlled by the major histocompatibility complex, though more detailed genetic analysis is required.

Animals↗

Estimating genetic and non-genetic components of variance for fasting glucose levels in pedigrees ascertained through non-insulin dependent diabetes.

Fasting glucose levels measured on 337 individuals in 14 pedigrees ascertained through a proband with non-insulin dependent diabetes were used to estimate genetic and non-genetic components of variance under a multifactorial model of inheritance. In this sample genetic factors were important in controlling variation in basal carbohydrate metabolism, as represented by age-adjusted log-fasting glucose. There was no evidence that arbitrary sib common environments or arbitrary parent common environments accounted for significant portions of the variability in fasting glucose in these data. An arbitrary environment shared by parent and offspring, however, had a marginally significant impact on the likelihood. Parameter estimates obtained from multifactorial models analysed in this manner are sensitive to extreme phenotypic values, however, and caution must be exercised in estimating total genetic variation. While additive genetic factors did account for a significant proportion of the total variation in fasting glucose, a large proportion remained unexplained.

Adolescent↗

Correlations between physiology and lifespan--two widely ignored problems with comparative studies.

Comparative differences between species provide a powerful source of information that may inform our understanding of the aging process. However, two problems regularly attend such analyses. The co-variation of traits with body mass is frequently ignored, along with the lack of independence of the data due to a shared phylogenetic history. These problems undermine the use of simple correlations between various factors and maximum lifespan potential (MLSP) across different species as evidence that the factors in question have causal effects on aging. Both of these problems have been widely addressed by comparative biologists working in fields other than aging research, and statistical solutions to these issues are available. Using these statistical approaches, of making analyses of residual traits with the effects of body mass removed, and deriving phylogenetically independent contrasts, will allow analyses of the relationships between physiology and maximum lifespan potential to proceed unhindered by these difficulties, potentially leading to many useful insights into the aging process.

Animals↗

Migraine: a chronic sympathetic nervous system disorder.

OBJECTIVES: To determine the degree of diagnostic and clinical similarity between chronic sympathetic nervous system disorders and migraine. BACKGROUND: Migraine is an episodic syndrome consisting of a variety of clinical features that result from dysfunction of the sympathetic nervous system. During headache-free periods, migraineurs have a reduction in sympathetic function compared to nonmigraineurs. Sympathetic nervous system dysfunction is also the major feature of rare neurological disorders such as pure autonomic failure and multiple system atrophy. There are no known reports in the medical literature, however, comparing sympathetic nervous system function in individuals with migraine, pure autonomic failure, and multiple system atrophy. METHODS: A detailed review of the literature was performed to compare the results of a wide variety of diagnostic tests and clinical signs that have been described in these 3 heretofore unrelated disorders. RESULTS: The data indicate that migraine shares significant diagnostic and clinical features with both pure autonomic failure and multiple system atrophy, yet represents a distinct subtype of chronic sympathetic dysfunction. Migraine is most similar to pure autonomic failure in terms of reduced supine plasma norepinephrine levels, peripheral adrenergic receptor supersensitivity, and clinical symptomatology directly related to sympathetic nervous system dysfunction. The peripheral sympathetic nervous system dysfunction is much more severe in pure autonomic failure than in migraine. Migraine differs from both pure autonomic failure and multiple system atrophy in that migraineurs retain the ability, although suboptimal, to increase plasma norepinephrine levels following physiological stressors. CONCLUSIONS: The major finding of the present study is that migraine is a disorder of chronic sympathetic dysfunction, sharing many diagnostic and clinical characteristics with pure autonomic failure and multiple system atrophy. However, the sympathetic nervous system dysfunction in migraine differs from pure autonomic failure and multiple system atrophy in that occurs in an anatomically intact system. It is proposed that the sympathetic dysfunction in migraine relates to an imbalance of sympathetic co-transmitters. Specifically, it is suggested that a migraine attack is characterized by a relative depletion of sympathetic norepinephrine stores in conjunction with an increase in the release of other sympathetic cotransmitters such as dopamine, prostaglandins, adenosine triphosphate, and adenosine. An enhanced understanding of the sympathetic dysfunction in migraine may help to more effectively diagnose, prevent, and/or treat migraine and other types of headache.

Autonomic Nervous System Diseases↗

A continuous quality improvement approach to IL-372 documentation compliance in an academic emergency department, and its impact on dictation costs, billing practices, and average patient length of stay.

OBJECTIVE: To determine whether continuous quality improvement (CQI) methodology could improve and maintain IL-372 documentation compliance in an academic emergency department (ED). The impact on transcription costs, billing practices, and average patient length of stay was also analyzed. METHODS: Baseline IL-372 compliance data were collected and shared with staff during a multidisciplinary educational session. Faculty dictation became mandatory. Pocket-sized dictation templates were provided. A Documentation Improvement Committee monitored outcomes. Each month of the study period, a compliance officer reviewed approximately 100 records. The following indicators were monitored: IL-372 compliance rates, dictation rates, transcription costs, down-coding rates, percentage of billable records, and average patient length of stay. Individualized results were provided to faculty. RESULTS: During the ten-month study period, compliance rates increased from 60% to 100% (p-trend < 0.001), while dictation rates increased from 69% to 100% (p < 0.001). Rates of down-coding adjustments improved from 54% to 2% (p-trend < 0.001). The percentage of billable records increased from 65% to 100% (p-trend < 0.001). Transcription costs increased a modest 16%. The average patient length of stay remained unchanged. CONCLUSION: The application of CQI methodology, combined with the availability of dictation, resulted in sustained improvement in IL-372 compliance. This was associated with a parallel increase in dictation rates, although concurrent transcription costs increased only modestly. The percentage of billable records increased, while the number of charts requiring down-coding decreased, both beneficial outcomes. Average length of stay was not adversely impacted by this added documentation requirement.

Academic Medical Centers↗

Brucella group 3 outer membrane proteins contain a heat-modifiable protein.

Brucella melitensis and B. ovis outer membrane blebs contained a protein displaying a temperature-dependent molecular mass upshift from 25 kDa to 30 kDa. A fraction of the protein tightly bound to LPS did not show the molecular mass upshift which was also blocked by exposure of the protein to Zwittergent 314. The B. melitensis heat-modifiable protein and Escherichia coli OmpA shared antigenic determinants. These data indicate that the Brucella group 3 outer membrane proteins belonged to the OmpA family of proteins.

Bacterial Outer Membrane Proteins↗

What and how do we communicate?

The rapid, inexpensive transmission of words and data, brought about by the internet and cheap computers, is changing the world faster than anything mankind has ever experienced, reaching into nearly every aspect of our lives, public and private, commercial and governmental. We are in an Information Age with an essentially instantaneous availability of large volumes of information and data. Technological pressures have their own momentum. The changes and improvements in data handling and information sharing will take place, however much or little we do in veterinary medicine, whether at the international or national levels. In addition, there are new superpowers emerging in the world. These are the small and medium third world countries that are gradually gaining democracy through political restructuring and involving the civil society in decision making. There are also the marginal pressure groups, once too small and insignificant to be noticed. These are changing the rules by which the way the world is governed and they are doing it now by the internet and banding together to serve their common interests. The rapid provision of accurate information on animal diseases is desirable goal from a public health as well as an economic viewpoint.

Animal Diseases↗

Monitoring hemodialysis vascular access by digital phonoangiography.

We are intrigued by the possibility of using digital spectral analysis to detect hemodialysis vascular access stenosis. Such a monitor could be inexpensive, noninvasive, and portable enough to allow continuous monitoring. This report suggests how individuals wishing to conduct such research can use a simple but effective transducer design we have employed, how the data so obtained can be analyzed in the time and frequency domains using inexpensive digital signal processing software available via the Internet, and how data recordings might be shared via the Internet to facilitate collaboration.

Arteriovenous Shunt, Surgical↗

Salvicine functions as novel topoisomerase II poison by binding to ATP pocket.

Salvicine, a structurally modified diterpenoid quinone derived from Salvia prionitis, is a nonintercalative topoisomerase II (topo II) poison. The compound possesses potent in vitro and in vivo antitumor activity with a broad spectrum of anti-multidrug resistance activity and is currently in phase II clinical trials. To elucidate the distinct antitumor properties of salvicine and obtain valuable structural information of salvicine-topo II interactions, we characterized the effects of salvicine on human topo IIalpha (htopo IIalpha), including possible binding sites and molecular interactions. The enzymatic assays disclosed that salvicine mainly inhibits the catalytic activity with weak DNA cleavage action, in contrast to the classic topo II poison etoposide (VP16). Molecular modeling studies predicted that salvicine binds to the ATP pocket in the ATPase domain and superimposes on the phosphate and ribose groups. In a surface plasmon resonance binding assay, salvicine exhibited higher affinity for the ATPase domain of htopo IIalpha than ATP and ADP. Competitive inhibition tests demonstrated that ATP competitively and dose-dependently blocked the interactions between salvicine and ATPase domain of htopo IIalpha. The data illustrate that salvicine shares a common binding site with ATP and functions as an ATP competitor. To our knowledge, this is the first report to identify an ATP-binding pocket as the structural binding motif for a nonintercalative eukaryotic topo II poison. These findings collectively support the potential value of an ATP competitor of htopo IIalpha in tumor chemotherapy.

Adenosine Triphosphatases↗