Towards an Integrative Cognitive-Socio-Technical Approach in Health Informatics: Analyzing Technology-Induced Error Involving Health Information Systems to Improve Patient Safety

The purpose of this paper is to argue for an integration of cognitive and socio-technical approaches to assessing the impact of health information systems. Historically, health informatics research has examined the cognitive and socio-technical aspects of health information systems separately. In this paper we argue that evaluations of health information systems should consider aspects related to cognition as well as socio-technical aspects including impact on workflow (i.e. an integrated view). Using examples from the study of technology-induced error in healthcare, we argue for the use of simulations to evaluate the cognitive-socio-technical impacts of health information technology [36]. Implications of clinical simulations and analysis of cognitive-social-technical impacts are discussed within the context of the system development life cycle to improve health information system design, implementation and evaluation

Coordinate-Space Hartree-Fock-Bogoliubov Description of Superfluid Fermi Systems

Properties of strongly interacting, two-component finite Fermi systems are discussed within the recently developed coordinate-space Hartree-Fock-Bogoliubov (HFB) code {\hfbax}. Two illustrative examples are presented: (i) weakly bound deformed Mg isotopes, and (ii) spin-polarized atomic condensates in a strongly deformed harmonic trap.Comment: 4 pages, 2 figures, ENAM 2008 conference proceedings (EPJA

Linear Responses in Time-dependent Hartree-Fock-Bogoliubov Method with Gogny Interaction

A numerical method to integrate the time-dependent Hartree-Fock Bogoliubov (TDHFB) equations with Gogny interaction is proposed. The feasibility of the TDHFB code is illustrated by the conservation of the energy, particle numbers, and center-of-mass in the small amplitude vibrations of oxygen 20. The TDHFB code is applied to the isoscalar quadrupole and/or isovector dipole vibrations in the linear (small amplitude) region in oxygen isotopes (masses A = 18,20,22 and 24), titanium isotopes (A = 44,50,52 and 54), neon isotope (A = 26), and magnesium isotopes (A = 24 and 34). The isoscalar quadrupole and isovector dipole strength functions are calculated from the expectation values of the isoscalar quadrupole and isovector dipole moments.Comment: 10 pages, 13 figure

The role of chick Ebf genes in the mediolateral patterning of the somites

This study was conducted to check whether the three chick Early B-cell Factor (Ebf) genes, particularly cEbf1, would be targets for Shh and Bmp signals during somites mediolateral (ML) patterning. Tissue manipulations and gain and loss of function experiments for Shh and Bmp4 were performed and the results revealed that cEbf1 expression was initiated in the cranial presomitic mesoderm by low dose of Bmp4 from the lateral mesoderm and maintained in the ventromedial part of the epithelial somite and the medial sclerotome by Shh from the notochord; while cEbf2/3 expression was induced and maintained by Bmp4 and inhibited by high dose of Shh. To determine whether Ebf1 plays a role in somite patterning, transfection of a dominant-negative construct was carried out; this showed suppression of cPax1 expression in the medial sclerotome and upregulation and medial expansion of cEbf3 and cPax3 expression in sclerotome and dermomyotome, respectively, suggesting that Ebf1 is important for ML patterning. Thus, it is possible that low doses of Bmp4 set up Ebf1 expression which, together with Shh from the notochord, leads to establishment of the medial sclerotome and suppression of lateral identities. These data also conclude that Bmp4 is required in both the medial and lateral domain of the somitic mesoderm to keep the ML identity of the sclerotome through maintenance of cEbf gene expression. These striking findings are novel and give a new insight on the role of Bmp4 on mediolateral patterning of somites

Transcriptome analyses based on genetic screens for Pax3 myogenic targets in the mouse embryo

<p>Abstract</p> <p>Background</p> <p>Pax3 is a key upstream regulator of the onset of myogenesis, controlling progenitor cell survival and behaviour as well as entry into the myogenic programme. It functions in the dermomyotome of the somite from which skeletal muscle derives and in progenitor cell populations that migrate from the somite such as those of the limbs. Few Pax3 target genes have been identified. Identifying genes that lie genetically downstream of <it>Pax3 </it>is therefore an important endeavour in elucidating the myogenic gene regulatory network.</p> <p>Results</p> <p>We have undertaken a screen in the mouse embryo which employs a <it>Pax3^GFP</it>allele that permits isolation of Pax3 expressing cells by flow cytometry and a <it>Pax3^PAX3-FKHR</it>allele that encodes PAX3-FKHR in which the DNA binding domain of Pax3 is fused to the strong transcriptional activation domain of FKHR. This constitutes a gain of function allele that rescues the <it>Pax3 </it>mutant phenotype. Microarray comparisons were carried out between <it>Pax3^GFP/+</it>and <it>Pax3^{GFP/PAX3-FKHR}</it>preparations from the hypaxial dermomyotome of somites at E9.5 and forelimb buds at E10.5. A further transcriptome comparison between Pax3-GFP positive and negative cells identified sequences specific to myogenic progenitors in the forelimb buds. Potential Pax3 targets, based on changes in transcript levels on the gain of function genetic background, were validated by analysis on loss or partial loss of function <it>Pax3 </it>mutant backgrounds. Sequences that are up- or down-regulated in the presence of PAX3-FKHR are classified as somite only, somite and limb or limb only. The latter should not contain sequences from Pax3 positive neural crest cells which do not invade the limbs. Verification by whole mount <it>in situ </it>hybridisation distinguishes myogenic markers. Presentation of potential Pax3 target genes focuses on signalling pathways and on transcriptional regulation.</p> <p>Conclusions</p> <p>Pax3 orchestrates many of the signalling pathways implicated in the activation or repression of myogenesis by regulating effectors and also, notably, inhibitors of these pathways. Important transcriptional regulators of myogenesis are candidate Pax3 targets. Myogenic determination genes, such as <it>Myf5 </it>are controlled positively, whereas the effect of <it>Pax3 </it>on genes encoding inhibitors of myogenesis provides a potential brake on differentiation. In the progenitor cell population, <it>Pax7 </it>and also <it>Hdac5 </it>which is a potential repressor of <it>Foxc2</it>, are subject to positive control by <it>Pax3</it>.</p

An interdisciplinary team communication framework and its application to healthcare 'e-teams' systems design

<p>Abstract</p> <p>Background</p> <p>There are few studies that examine the processes that interdisciplinary teams engage in and how we can design health information systems (HIS) to support those team processes. This was an exploratory study with two purposes: (1) To develop a framework for interdisciplinary team communication based on structures, processes and outcomes that were identified as having occurred during weekly team meetings. (2) To use the framework to guide 'e-teams' HIS design to support interdisciplinary team meeting communication.</p> <p>Methods</p> <p>An ethnographic approach was used to collect data on two interdisciplinary teams. Qualitative content analysis was used to analyze the data according to structures, processes and outcomes.</p> <p>Results</p> <p>We present details for team meta-concepts of structures, processes and outcomes and the concepts and sub concepts within each meta-concept. We also provide an exploratory framework for interdisciplinary team communication and describe how the framework can guide HIS design to support 'e-teams'.</p> <p>Conclusion</p> <p>The structures, processes and outcomes that describe interdisciplinary teams are complex and often occur in a non-linear fashion. Electronic data support, process facilitation and team video conferencing are three HIS tools that can enhance team function.</p

The myogenic transcriptional network

Myogenesis has been a leading model for elucidating the molecular mechanisms that underlie tissue differentiation and development since the discovery of MyoD. During myogenesis, the fate of myogenic precursor cells is first determined by Pax3/Pax7. This is followed by regulation of the myogenic differentiation program by muscle regulatory factors (Myf5, MyoD, Myog, and Mrf4) to form muscle tissues. Recent studies have uncovered a detailed myogenic program that involves the RP58 (Zfp238)-dependent regulatory network, which is critical for repressing the expression of inhibitor of DNA binding (Id) proteins. These novel findings contribute to a comprehensive understanding of the muscle differentiation transcriptional program

PAX3 Expression in Normal Skin Melanocytes and Melanocytic Lesions (Naevi and Melanomas)

Background Cutaneous Malignant Melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 regulates melanocyte specification from neural crest cells during development but expression in differentiated melanocytes is uncertain. By contrast it is frequently found in melanomas and naevi and is a marker for melanoma staging and detection. In this study we analysed the expression of PAX3 across the spectrum of melanocytic cells, from normal melanocytes to cells of benign and malignant lesions to better assess its function in these various tissues. Pax3 and PAX3 (italicized) refer to the mouse and human gene, respectively; whereas Pax3 and PAX3 (non-italicized) refer to the corresponding mouse and human protein. Methodology and Principal Findings PAX3 expression was analysed by immunohistochemistry and qRT-PCR. Immunofluorescence was used for co-expression with differentiation, migration and survival markers. As expected PAX3 expression was observed in naevi and melanoma cells. It was also found in melanocytes of normal skin where it co-expressed with melanocyte markers, MITF and MLANA. Co-expression with its downstream target, antiapoptotic factor BCL2L1 confirms PAX3 as a cell survival regulator. PAX3 was also co-expressed with melanoma cell migration marker MCAM in dermal naevi and melanoma cell nests, but this downstream target of PAX3 was not present in normal epidermal melanocytes, suggesting differential roles for PAX3 in normal epidermal melanocytes and melanoma cells. Most interestingly, a proportion of PAX3-positive epidermal melanocytes in normal skin show HES1 and Ki67 co-expression, indicating their less differentiated proliferative phenotype. Conclusions and Significance Our results suggest that a previously identified role for PAX3, that of regulator of an undifferentiated plastic state, may operate in melanocytes of normal skin. This role, possibly required for cellular response to environmental stimuli, may contribute to formation and development of melanocytic lesions in which PAX3 expression is prominent

In the Absence of Sonic Hedgehog, p53 Induces Apoptosis and Inhibits Retinal Cell Proliferation, Cell-Cycle Exit and Differentiation in Zebrafish

Background: Sonic hedgehog (Shh) signaling regulates cell proliferation during vertebrate development via induction of cell-cycle regulator gene expression or activation of other signalling pathways, prevents cell death by an as yet unclear mechanism and is required for differentiation of retinal cell types. Thus, an unsolved question is how the same signalling molecule can regulate such distinct cell processes as proliferation, cell survival and differentiation. Methodology/Principal Findings: Analysis of the zebrafish shh 2/2 mutant revealed that in this context p53 mediates elevated apoptosis during nervous system and retina development and interferes with retinal proliferation and differentiation. While in shh 2/2 mutants there is activation of p53 target genes and p53-mediated apoptosis, an increase in Hedgehog (Hh) signalling by over-expression of dominant-negative Protein Kinase A strongly decreased p53 target gene expression and apoptosis levels in shh 2/2 mutants. Using a novel p53 reporter transgene, I confirm that p53 is active in tissues that require Shh for cell survival. Proliferation assays revealed that loss of p53 can rescue normal cell-cycle exit and the mitotic indices in the shh 2/2 mutant retina at 24, 36 and 48 hpf. Moreover, generation of amacrine cells and photoreceptors was strongly enhanced in the double p53 2/2 shh 2/2 mutant retina suggesting the effect of p53 on retinal differentiation. Conclusions: Loss of Shh signalling leads to the p53-dependent apoptosis in the developing nervous system and retina