Cognitive Differences in Chart Reading: A Comparison of Nurses and Physicians

This pilot study compares the mental models of a patient constructed by nurses and physicians while reading an electronic medical record. Preliminary results suggest that the participants' summaries were both quantitatively and qualitatively different. The physician made more inferences and focused on deeper relationships in the record, whereas the nurse focused on the descriptive surface structure of the record.

Imaging of pulmonary embolism and t-PA therapy effects using MDCT and liposomal iohexol blood pool agent – preliminary results in a rabbit model

Hypothesis and Objectives PEGylated liposomal blood pool contrast agents maintain contrast enhancement over several hours. This study aimed to evaluate (long-term) imaging of pulmonary arteries, comparing conventional iodinated contrast with a liposomal blood pool contrast agent. Secondly, visualization of the (real-time) therapeutic effects of tissue-Plasminogen Activator (t-PA) on pulmonary embolism (PE) was attempted. Materials and Methods Six rabbits (approximate 4 kg weight) had autologous blood clots injected through the superior vena cava. Imaging was performed using conventional contrast (iohexol, 350 mg I/ml, GE HealthCare, Princeton, NJ) at a dose of 1400 mgI per animal and after wash-out, animals were imaged using an iodinated liposomal blood pool agent (88 mg I/mL, dose 900 mgI/animal). Subsequently, five animals were injected with 2mg t-PA and imaging continued for up to 4 ½ hours. Results Both contrast agents identified PE in the pulmonary trunk and main pulmonary arteries in all rabbits. Liposomal blood pool agent yielded uniform enhancement, which remained relatively constant throughout the experiments. Conventional agents exhibited non uniform opacification and rapid clearance post injection. Three out of six rabbits had mistimed bolus injections, requiring repeat injections. Following t-PA, Pulmonary embolus volume (central to segmental) decreased in four of five treated rabbits (range 10–57%, mean 42%). One animal showed no response to t-PA. Conclusions Liposomal blood pool agents effectively identified acute PE without need for re-injection. PE resolution following t-PA was quantifiable over several hours. Blood pool agents offer the potential for repeated imaging procedures without need for repeated (nephrotoxic) contrast injections

Breast cancer on the world wide web: cross sectional survey of quality of information and popularity of websites.

OBJECTIVES: To determine the characteristics of popular breast cancer related websites and whether more popular sites are of higher quality. DESIGN: The search engine Google was used to generate a list of websites about breast cancer. Google ranks search results by measures of link popularity---the number of links to a site from other sites. The top 200 sites returned in response to the query "breast cancer" were divided into "more popular" and "less popular" subgroups by three different measures of link popularity: Google rank and number of links reported independently by Google and by AltaVista (another search engine). MAIN OUTCOME MEASURES: Type and quality of content. RESULTS: More popular sites according to Google rank were more likely than less popular ones to contain information on ongoing clinical trials (27% v 12%, P=0.01 ), results of trials (12% v 3%, P=0.02), and opportunities for psychosocial adjustment (48% v 23%, P<0.01). These characteristics were also associated with higher number of links as reported by Google and AltaVista. More popular sites by number of linking sites were also more likely to provide updates on other breast cancer research, information on legislation and advocacy, and a message board service. Measures of quality such as display of authorship, attribution or references, currency of information, and disclosure did not differ between groups. CONCLUSIONS: Popularity of websites is associated with type rather than quality of content. Sites that include content correlated with popularity may best meet the public's desire for information about breast cancer.

Encouraging adolescents toward mental health careers via website biographies.

This project designed, developed, implemented and is currently evaluating the effectiveness of an interactive, multi-media website designed to encourage adolescents to consider careers in mental health. This Web-based learning environment features biographies of mental health scientists. Evaluation is conducted in a systematic, structured way using cognitive achievement, usability (ease of use), and affective scales (e.g., fun to use) as outcome measures

Computer simulation of glioma growth and morphology.

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion.

The Houston Academy of Medicine--Texas Medical Center Library management information system.

A management information system (MIS) provides a means for collecting, reporting, and analyzing data from all segments of an organization. Such systems are common in business but rare in libraries. The Houston Academy of Medicine-Texas Medical Center Library developed an MIS that operates on a system of networked IBM PCs and Paradox, a commercial database software package. The data collected in the system include monthly reports, client profile information, and data collected at the time of service requests. The MIS assists with enforcement of library policies, ensures that correct information is recorded, and provides reports for library managers. It also can be used to help answer a variety of ad hoc questions. Future plans call for the development of an MIS that could be adapted to other libraries' needs, and a decision-support interface that would facilitate access to the data contained in the MIS databases.

Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

BACKGROUND: Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD), the most common cause of visual impairment in industrialized countries. METHODS/PRINCIPAL FINDINGS: We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75 x 10(-9); non-AMD controls and OR 2.79, p = 2.78 x 10(-19), blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls), respectively. Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression) model, a synergy index (departure-from-additivity model) and the mutual information method (MI), suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%. CONCLUSIONS/SIGNIFICANCE: Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI) index.

Quantitation of contacts among sensory, motor, and serotonergic neurons in the pedal ganglion of aplysia.

Present models of long-term sensitization in Aplysia californica indicate that the enhanced behavioral response is due, at least in part, to outgrowth of sensory neurons mediating defensive withdrawal reflexes. Presumably, this outgrowth strengthens pre-existing connections by formation of new synapses with follower neurons. However, the relationship between the number of sensorimotor contacts and the physiological strength of the connection has never been examined in intact ganglia. As a first step in addressing this issue, we used confocal microscopy to examine sites of contact between sensory and motor neurons in naive animals. Our results revealed relatively few contacts between physiologically connected cells. In addition, the number of contact sites was proportional to the amplitude of the EPSP elicited in the follower motor neuron by direct stimulation of the sensory neuron. This is the first time such a correlation has been observed in the central nervous system. Serotonin is the neurotransmitter most closely examined for its role in modulating synaptic strength at the sensorimotor synapse. However, the structural relationship of serotonergic processes and sensorimotor synapses has never been examined. Surprisingly, serotonergic processes usually made contact with sensory and motor neurons at sites located relatively distant from the sensorimotor synapse. This result implies that heterosynaptic regulation is due to nondirected release of serotonin into the neuropil.

Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis.

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA's mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects.

NEW TARGET GENES FOR TUMOR SUPPRESSORS p53 AND p73 IN REGENERATING LIVER

The p53-family of proteins regulates expression of target genes during tissue development and differentiation. Within the p53-family, p53 and p73 have hepatic-specific functions in development and tumor suppression. Despite a growing list of p53/p73 target genes, very few of these have been studied in vivo, and the knowledge regarding functions of p53 and p73 in normal tissues remains limited. p53+/-p73+/- mice develop hepatocellular carcinoma (HCC), whereas overexpression of p53 in human HCC leads to tumor regression. However, the mechanism of p53/p73 function in liver remains poorly characterized. Here, the model of mouse liver regeneration is used to identify new target genes for p53/p73 in normal quiescent vs. proliferating cells. In response to surgical removal of ~2/3 of liver mass (partial hepatectomy, PH), the remaining hepatocytes exit G0 of cell cycle and undergo proliferation to reestablish liver mass. The hypothesis tested in this work is that p53/p73 functions in cell cycle arrest, apoptosis and senescence are repressed during liver regeneration, and reactivated at the end of the regenerative response. Chromatin immunoprecipitation (ChIP), with a p73-antibody, was used to probe arrayed genomic sequences (ChIP-chip) and uncover 158 potential targets of p73-regulation in normal liver. Global microarray analysis of mRNA levels, at T=0-48h following PH, revealed sets of genes that change expression during regeneration. Eighteen p73-bound genes changed expression after PH. Four of these genes, Foxo3, Jak1, Pea15, and Tuba1 have p53 response elements (p53REs), identified in silico within the upstream regulatory region. Forkhead transcription factor Foxo3 is the most responsive gene among transcription factors with altered expression during regenerative, cellular proliferation. p53 and p73 bind a Foxo3 p53RE and maintain active expression in quiescent liver. During liver regeneration, binding of p53 and p73, recruitment of acetyltransferase p300, and an active chromatin structure of Foxo3 are disrupted, alongside loss of Foxo3 expression. These parameters of Foxo3 regulation are reestablished at completion of liver growth and regeneration, supporting a temporary suspension of p53 and p73 regulatory functions in normal cells during tissue regeneration.

Regulation of survivin gene expression in the human endometrium and endometrial cancer

In the United States, endometrial cancer is the leading cancer of the female reproductive tract. There are 40,100 new cases and 7,470 deaths from endometrial cancer estimated for 2008 (47). The average five year survival rate for endometrial cancer is 84% however, this figure is substantially lower in patients diagnosed with late stage, advanced disease and much higher for patients diagnosed in early stage disease (47). Endometrial cancer (EC) has been associated with several risk factors including obesity, diabetes, hypertension, previously documented occurrence of hereditary non-polyposis colorectal cancer (HNPCC), and heightened exposure to estrogen (25). As of yet, there has not been a dependable molecular predictor of endometrial cancer occurrence in women with these predisposing factors. The goal of our lab is to identify genes that are aberrantly expressed in EC and may serve as molecular biomarkers of EC progression. One candidate protein that we are exploring as a biomarker of EC progression is the cell survival protein survivin.

Randomized comparisons among health informatics students identify hypertutorial features as improving web-based instruction.

Hypertutorials optimize five features - presentation, learner control, practice, feedback, and elaborative learning resources. Previous research showed graduate students significantly and overwhelmingly preferred Web-based hypertutorials to conventional "Book-on-the-Web" statistics or research design lessons. The current report shows that the source of hypertutorials' superiority in student evaluations of instruction lies in their hypertutorial features. Randomized comparisons between the two methodologies were conducted in two successive iterations of a graduate level health informatics research design and evaluation course. The two versions contained the same text and graphics, but differed in the presence or absence of hypertutorial features: Elaborative learning resources, practice, feedback, and amount of learner control. Students gave high evaluations to both Web-based methodologies, but consistently rated the hypertutorial lessons as superior. Significant differences localized in the hypertutorial subscale that measured student responses to hypertutorial features.

Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.

TGF-beta1 in Aplysia: role in long-term changes in the excitability of sensory neurons and distribution of TbetaR-II-like immunoreactivity.

Exogenous recombinant human transforming growth factor beta-1 (TGF-beta1) induced long-term facilitation of Aplysia sensory-motor synapses. In addition, 5-HT-induced facilitation was blocked by application of a soluble fragment of the extracellular portion of the TGF-beta1 type II receptor (TbetaR-II), which presumably acted by scavenging an endogenous TGF-beta1-like molecule. Because TbetaR-II is essential for transmembrane signaling by TGF-beta, we sought to determine whether Aplysia tissues contained TbetaR-II and specifically, whether neurons expressed the receptor. Western blot analysis of Aplysia tissue extracts demonstrated the presence of a TbetaR-II-immunoreactive protein in several tissue types. The expression and distribution of TbetaR-II-immunoreactive proteins in the central nervous system was examined by immunohistochemistry to elucidate sites that may be responsive to TGF-beta1 and thus may play a role in synaptic plasticity. Sensory neurons in the ventral-caudal cluster of the pleural ganglion were immunoreactive for TbetaR-II, as well as many neurons in the pedal, abdominal, buccal, and cerebral ganglia. Sensory neurons cultured in isolation and cocultured sensory and motor neurons were also immunoreactive. TGF-beta1 affected the biophysical properties of cultured sensory neurons, inducing an increase of excitability that persisted for at least 48 hr. Furthermore, exposure to TGF-beta1 resulted in a reduction in the firing threshold of sensory neurons. These results provide further support for the hypothesis that TGF-beta1 plays a role in long-term synaptic plasticity in Aplysia.