Clinical decision support system for point of care use: ontology driven design and software implementation

OBJECTIVES: The objective of this research was to design a clinical decision support system (CDSS) that supports heterogeneous clinical decision problems and runs on multiple computing platforms. Meeting this objective required a novel design to create an extendable and easy to maintain clinical CDSS for point of care support. The proposed solution was evaluated in a proof of concept implementation. METHODS: Based on our earlier research with the design of a mobile CDSS for emergency triage we used ontology-driven design to represent essential components of a CDSS. Models of clinical decision problems were derived from the ontology and they were processed into executable applications during runtime. This allowed scaling applications' functionality to the capabilities of computing platforms. A prototype of the system was implemented using the extended client-server architecture and Web services to distribute the functions of the system and to make it operational in limited connectivity conditions. RESULTS: The proposed design provided a common framework that facilitated development of diversified clinical applications running seamlessly on a variety of computing platforms. It was prototyped for two clinical decision problems and settings (triage of acute pain in the emergency department and postoperative management of radical prostatectomy on the hospital ward) and implemented on two computing platforms-desktop and handheld computers. CONCLUSIONS: The requirement of the CDSS heterogeneity was satisfied with ontology-driven design. Processing of application models described with the help of ontological models allowed having a complex system running on multiple computing platforms with different capabilities. Finally, separation of models and runtime components contributed to improved extensibility and maintainability of the system.

Asymmetric epoxidation of alkenes by a chiral manganese(III) salen complex anchored onto a functionalised hexagonal mesoporous silica

A Jacobsen-type catalyst was anchored onto an amine functionalised hexagonal mesoporous silica (HMS) through the diimine bridge fragment of the complex. The new heterogeneous catalyst, as well as the precedent materials, were characterised by elemental analyses, FTIR-DRIFT, UV-vis, porosimetry and XPS which showed that the complex was successfully anchored. This material was active in the epoxidation of styrene and α-methylstyrene in dichloromethane at 0°C using, respectively, m-CPBA/NMO and NaOCl. With the former substrate no asymmetric induction was found in the epoxide, whereas with the latter substrate higher %ee was found than in homogeneous phase. Using the latter experimental conditions, catalyst reuse led to no significant loss of catalytic activity and enantioselectivity. © 2005 Elsevier B.V. All rights reserved.

Visualisation of bioinformatics datasets

Analysing the molecular polymorphism and interactions of DNA, RNA and proteins is of fundamental importance in biology. Predicting functions of polymorphic molecules is important in order to design more effective medicines. Analysing major histocompatibility complex (MHC) polymorphism is important for mate choice, epitope-based vaccine design and transplantation rejection etc. Most of the existing exploratory approaches cannot analyse these datasets because of the large number of molecules with a high number of descriptors per molecule. This thesis develops novel methods for data projection in order to explore high dimensional biological dataset by visualising them in a low-dimensional space. With increasing dimensionality, some existing data visualisation methods such as generative topographic mapping (GTM) become computationally intractable. We propose variants of these methods, where we use log-transformations at certain steps of expectation maximisation (EM) based parameter learning process, to make them tractable for high-dimensional datasets. We demonstrate these proposed variants both for synthetic and electrostatic potential dataset of MHC class-I. We also propose to extend a latent trait model (LTM), suitable for visualising high dimensional discrete data, to simultaneously estimate feature saliency as an integrated part of the parameter learning process of a visualisation model. This LTM variant not only gives better visualisation by modifying the project map based on feature relevance, but also helps users to assess the significance of each feature. Another problem which is not addressed much in the literature is the visualisation of mixed-type data. We propose to combine GTM and LTM in a principled way where appropriate noise models are used for each type of data in order to visualise mixed-type data in a single plot. We call this model a generalised GTM (GGTM). We also propose to extend GGTM model to estimate feature saliencies while training a visualisation model and this is called GGTM with feature saliency (GGTM-FS). We demonstrate effectiveness of these proposed models both for synthetic and real datasets. We evaluate visualisation quality using quality metrics such as distance distortion measure and rank based measures: trustworthiness, continuity, mean relative rank errors with respect to data space and latent space. In cases where the labels are known we also use quality metrics of KL divergence and nearest neighbour classifications error in order to determine the separation between classes. We demonstrate the efficacy of these proposed models both for synthetic and real biological datasets with a main focus on the MHC class-I dataset.

Alternative Characterization of the Class k-UCV and Related Classes of Univalent Functions

In this paper an alternative characterization of the class of functions called k -uniformly convex is found. Various relations concerning connections with other classes of univalent functions are given. Moreover a new class of univalent functions, analogous to the ’Mocanu class’ of functions, is introduced. Some results concerning this class are derived.

Algorithms for Evaluation of the Wright Function for the Real Arguments’ Values

2000 Math. Subject Classification: 33E12, 65D20, 33F05, 30E15

A Note on Univalent Functions with Finitely many Coefficients

MSC 2010: 30C45

On Root Arrangements of Polynomial-Like Functions and their Derivatives

2000 Mathematics Subject Classification: 12D10.

A knowledge based system of principled negotiation for complex business contract

Automated negotiation systems can do better than human being in many aspects, and thus are applied into many domains ranging from business to computer science. However, little work about automating negotiation of complex business contract has been done so far although it is a kind of the most important negotiation in business. In order to address this issue, in this paper we developed an automated system for this kind of negotiation. This system is based on the principled negotiation theory, which is the most effective method of negotiation in the domain of business. The system is developed as a knowledge-based one because a negotiating agent in business has to be economically intelligent and capable of making effective decisions based on business experiences and knowledge. Finally, the validity of the developed system is shown in a real negotiation scenario where on behalf of human users, the system successfully performed a negotiation of a complex business contract between a wholesaler and a retailer. © 2013 Springer-Verlag Berlin Heidelberg.

Complex Analogues of the Rolle's Theorem

2000 Mathematics Subject Classification: 30C10.

Inequalities and Asymptotic Formulae for the Three Parametric Mittag-Leffler Functions

MSC 2010: 33E12, 30A10, 30D15, 30E15

Regulating the expression of eEF1A to decipher its non canonical functions in eukaryotic cells

The canonical function of eEF1A is delivery of the aminoacylated tRNA to the A site of the ribosome during protein translation, however, it is also known to be an actin binding protein. As well as this actin binding function, eEF1A has been shown to be involved in other cellular processes such as cell proliferation and apoptosis. It has long been thought that the actin cytoskeleton and protein synthesis are linked and eEF1A has been suggested to be a candidate protein to form this link, though very little is understood about the relationship between its two functions. Overexpression of eEF1A has also been shown to be implicated in many different types of cancers, especially cancers that are metastatic, therefore it is important to further understand how eEF1A can affect both translation and the organisation of the actin cytoskeleton. To this end, we aimed to determine the effects of reduced expression of eEF1A on both translation and its non canonical functions in CHO cells. We have shown that reduced expression of eEF1A in this cell system results in no change in protein synthesis, however results in an increased number of actin stress fibres and other proteins associated with these fibres such as myosin IIA, paxillin and vinculin. Cell motility and attachment are also affected by this reduction in eEF1A protein expression. The organisational and motility phenotypes were found to be specific to eEF1A by transforming the cells with plasmids containing either human eEF1A1 or eEF1A2. Though the mechanisms by which these effects are regulated have not yet been established, this data provides evidence to show that the translation and actin binding functions of eEF1A are independent of each other as well as being suggestive of a role for eEF1A in cell motility as supported by the observation that overexpression of eEF1A protein tends to be associated with the cancer cells that are metastatic.

A marketing, a termelés és a logisztika hozzájárulása a vállalati eredményességhez (The Contribution of Marketing, Production and Logistics to Business Performance)

A Budapesti Corvinus Egyetem Versenyképességkutató Központjának 2004-ben lekérdezett kérdőíve alapján, ami 154 feldolgozóipari vállalat adatait tartalmazza, azt vizsgáljuk, hogy az ellátási lánc három lényeges vállalati funkciója, a marketing, a termelés és a logisztika milyen mértékben járul hozzá az üzleti eredményességhez. Az eredmények szerint a marketingnek és a termelésnek erősebb hatása van a vállalati teljesítményre, mint a logisztikának. A három funkció együttesen csekély, bár statisztikai értelemben szignifikáns szerepet játszik az üzleti sikerben. _____ Companies are complex organizations where a lot of activities and processes have to work properly in order to reach success. Depending on several factors, sometimes some activities get more emphasis while others work in the background. Since organizational functions have separate literature and practical knowledge, and transit between them is rare, we do have very little knowledge on how the various functions together contribute to company success. Based on a wide-scale empirical study on Hungarian competitiveness, which includes data on 154 companies from the process industry, we examine to what extent three functions of the supply chain, marketing, manufacturing and logistics, can contribute to business success. Results show that marketing and manufacturing have larger effect on company performance than logistics. However, the three functions together play a minor, although significant role in company success.

Characterization of the amp genes involved in the regulation of beta-lactamase expression in Pseudomonas aeruginosa

Antibiotic resistance, production of alginate and virulence factors, and altered host immune responses are the hallmarks of chronic Pseudomonas aeruginosa infection. Failure of antibiotic therapy has been attributed to the emergence of P. aeruginosa strains that produce β-lactamase constitutively. In Enterobacteriaceae, β-lactamase induction involves four genes with known functions: ampC, ampR, ampD, and ampG, encoding the enzyme, transcriptional regulator, amidase and permease, respectively. In addition to all these amp genes, P. aeruginosa possesses two ampG paralogs, designated ampG and ampP. In this study, P. aeruginosa ampC, ampR, ampG and ampP were analyzed. Inactivation of ampC in the prototypic PAO1 failed to abolish the β-lactamase activity leading to the discovery of P. aeruginosa oxacillinase PoxB. Cloning and expression of poxB in Escherichia coli confers β-lactam resistance. Both AmpC and PoxB contribute to P. aeruginosa resistance against a wide spectrum of β-lactam antibiotics. The expression of PoxB and AmpC is regulated by a LysR-type transcriptional regulator AmpR that up-regulates AmpC but down-regulates PoxB activities. Analyses of P. aeruginosa ampR mutant demonstrate that AmpR is a global regulator that modulates the expressions of Las and Rhl quorum sensing (QS) systems, and the production of pyocyanin, LasA protease and LasB elastase. Introduction of the ampR mutation into an alginate-producing strain reveals the presence of a complex co-regulatory network between antibiotic resistance, QS alginate and other virulence factor production. Using phoA and lacZ protein fusion analyses, AmpR, AmpG and AmpP were localized to the inner membrane with one, 16 and 10 transmembrane helices, respectively. AmpR has a cytoplasmic DNA-binding and a periplasmic substrate binding domains. AmpG and AmpP are essential for the maximal expression of β-lactamase. Analysis of the murein breakdown products suggests that AmpG exports UDP-N-acetylmuramyl-L-alanine-γ-D-glutamate-meso-diaminopimelic acid-D-alanine-D-alanine (UDP-MurNAc-pentapeptide), the corepressor of AmpR, whereas AmpP imports N-acetylglucosaminyl-beta-1,4-anhydro-N-acetylmuramic acid-Ala-γ-D-Glu-meso-diaminopimelic acid (GlcNAc-anhMurNAc-tripeptide) and GlcNAc-anhMurNAc-pentapeptide, the co-inducers of AmpR. This study reveals a complex interaction between the Amp proteins and murein breakdown products involved in P. aeruginosa β-lactamase induction. In summary, this dissertation takes us a little closer to understanding the P. aeruginosa complex co-regulatory mechanism in the development of β-lactam resistance and establishment of chronic infection. ^

Efficient numerical methods for the random-field Ising model: Finite-size scaling, reweighting extrapolation, and computation of response functions

It was recently shown [Phys. Rev. Lett. 110, 227201 (2013)] that the critical behavior of the random-field Ising model in three dimensions is ruled by a single universality class. This conclusion was reached only after a proper taming of the large scaling corrections of the model by applying a combined approach of various techniques, coming from the zero-and positive-temperature toolboxes of statistical physics. In the present contribution we provide a detailed description of this combined scheme, explaining in detail the zero-temperature numerical scheme and developing the generalized fluctuation-dissipation formula that allowed us to compute connected and disconnected correlation functions of the model. We discuss the error evolution of our method and we illustrate the infinite limit-size extrapolation of several observables within phenomenological renormalization. We present an extension of the quotients method that allows us to obtain estimates of the critical exponent a of the specific heat of the model via the scaling of the bond energy and we discuss the self-averaging properties of the system and the algorithmic aspects of the maximum-flow algorithm used.

The effect of complex workplace dietary interventions on employees dietary behaviours, nutrition knowledge and health status

Background The growing prevalence and associated burden of diet-related non-communicable diseases is a global public health concern. The environments in which people live and work influences their dietary behaviours. Aim The focus of this thesis was on the effectiveness of complex workplace dietary interventions. The comparative effectiveness of a complex workplace environmental dietary modification intervention and an educational intervention were assessed both alone and in combination relative to a control workplace setting. Methods The systematic review was guided by the PRISMA statement. In a cluster controlled trial, four workplaces were purposively allocated to control, nutrition education alone (Education), environmental dietary modification alone (Environment) and nutrition education and environmental dietary modification (Combined intervention). The interventions were guided by the MRC framework. In the control workplace, data were collected at baseline and follow-up. In the intervention related sub-study, the relationships between nutrition knowledge, diet quality and hypertension were examined. Results The systematic review provided limited evidence. In the FCW study, 850 employees aged 18-64 years were recruited at baseline with N(response rate %) in each workplace as follows: Control: 111(72%), Education: 226(71%), Environment: 113(91%), Combined intervention: 400(61%). Complete follow-up data was obtained for 517 employees (61%). There were significant positive changes in dietary intakes of saturated fat(p=0.013), salt(p=0.010) and nutrition knowledge(p=0.034) between baseline and follow-up at 7-9 months in the combined intervention versus the control workplace in the fully adjusted multivariate analysis. Small but significant changes in BMI(-1.2kg/m2 (p=0.047) were also observed in the combined intervention. In the sub-study, nutrition knowledge was positively significantly associated with diet quality and blood pressure but no evidence of a mediation effect of the DASH score was detected between nutrition knowledge and blood pressure. Conclusion This thesis provides critical evidence on the effectiveness of complex workplace dietary interventions in a manufacturing working population.