Hospital electronic prescribing and medicines administration (HEPMA) system implementation is advocated by national e-health strategies to produce patient safety benefits. No previous study has evaluated HEPMA implementation impacting discharge information communication or assessed discharge prescribing errors. The aims were to assess HEPMA system implementation impact on medicines related discharge communication and prescribing errors, and to gain the perspective of hospital staff involved in the communication process. Following a narrative literature review, a convergent parallel mixed methods was selected, consisting of interpretative phenomenology and experimental before and after study design. Face-to-face semi-structured interviews of a purposive sample of hospital staff involved in discharge information communication were undertaken using the Theoretical Domains Framework (TDF) as a theoretical lens. In addition a quasi experimental retrospective case notes review, both before and after implementation was completed. Pre-implementation, staff described patient safety concerns with traditional discharge communication processes. They cited frequent prescribing errors, and associated adverse events and hospital readmissions. HEPMA implementation was anticipated to improve patient safety and create more efficient discharge communication. Post-implementation staff articulated improved information quality highlighting fewer omitted medicines and improved patient safety. TDF findings of behaviour change highlighted behavioural alteration including adaption of processes to improve discharge quality. Quantitative data collection (n=159 before and after) confirmed qualitative findings; increased compliance with discharge documentation, for example staff grade recorded increased from 40% to 100% (p<0.001). Prescribing error quantity and severity were reduced; errors reduced from 99% to 23% of patients (p<0.001); only 22% of identified errors likely to cause harm. Omitted medicines decreased from 42% to 11% of patients (p<0.001). The findings contribute original knowledge concerning HEPMA implementation impacting discharge information communication and prescribing errors. The study demonstrated reduced prescribing errors and improved patient safety which potentially impacted health and wellbeing. Qualitative findings and quantitative results are transferable and applicable to other NHS organisations or similar healthcare settings.

Embedded systems have been present in our daily lives for some time, but trends clearly show a rise in inter-connectivity in such devices. This presents promising new applications and possibilities, but also opens up a lot attack surface. Our goal in this thesis is to find out how you can develop such interconnected embedded systems in a way that guarantees the three major components of information security: Confidentialy, Integrity and Availability. The main focus of security is networked security. In this thesis, a dual approach is taken: investigate the development process of building secure systems, and perform such an implementation. The artifacts produced as byproducts, the software itself, deployment instructions and lessons learned are all presented. It is shown that the process used helps businesses find a somewhat deterministic approach to security, have a higher level of confidence, helps justify the costs that security work entails and helps in seeing security as a business decision. Embedded systems were also shown to present unforeseen obstacles, such as how the lack of a motherboard battery clashes with X.509. In the end, a discussion is made about how far the system can guarantee information security, what problems still exist and what could be done to mitigate them.

Modular domains of proteins are important in cellular signaling processes. Eukaryotic cells are constantly undergoing DNA damage due to exogenous and endogenous sources of damage. The DNA damage response (DDR) involves a complex network of signaling events mediated by modular domains such as the BRCT (BRCA1 C-terminal) domains. Therefore, proteins containing BRCT domains are important for DNA damage detection and signaling. In this dissertation, we focus on two BRCT-containing proteins BRCA1 and PAXIP1. BRCA1 is a gene that is known to be associated with increased risk of hereditary breast and ovarian cancer. Germline variants of BRCA1 are assessed to determine lifetime risk of developing breast and ovarian cancer. This is performed by genetic testing of the BRCA1 sequence and the variants can be classified as pathogenic, non-pathogenic or variants of unknown significance (VUS). Using family history, segregation analysis, co-occurrence and tumor pathology, certain variants have been classified as either pathogenic or non-pathogenic. However, a large majority of the variants are classified as VUS. Functional assays are critical in providing insight in the case of VUS results. We have a developed a visualization resource to aid in functional analysis of BRCA1 missense variants that occur due to single amino acid changes. This tool is known as BRCA1 Circos (http://research.nhgri.nih.gov/bic/circos/) and it aggregates, harmonizes and allows interpretation of data from all published studies on functional analysis of BRCA1 missense variants. Therefore, this is an important tool that will aid in the meta-analysis of functional data needed to better assess VUS. Functional studies of BRCA1 also demonstrate that majority of the variants that have a functional impact on the protein lie in the BRCT region of the protein. This indicates that the BRCT region is important in cancer development. To further analyze the function of BRCT-containing proteins, a study was previously undertaken to evaluate the role of BRCT-containing proteins and their interaction partners in the DNA damage response and consequently, cancer. BRCT domains of seven BRCT-containing proteins were used as baits and their binding partners were demonstrated to be highly enriched in the DDR process. We hypothesized that members of this BRCT-centric protein-protein interaction network could constitute targets for sensitization to DNA damaging chemotherapy agents in lung cancer. Therefore, we probed this established dataset containing the protein-protein interaction network (PPIN) of seven BRCT-containing proteins to identify seventeen kinases. A systematic pharmacological screen was performed to evaluate these kinases as targets to enhance platinum-based chemotherapy in lung cancer and this revealed WEE1, a mitotic kinase, as a potential target. Of the seventeen kinases, inhibition of mitotic kinase, WEE1, was found to have the most effective response in combination with platinum-based compounds in lung cancer cell lines. In the PPIN, WEE1 was shown to interact with PAXIP1 (PTIP), a BRCT-containing protein involved in transcription and in the cellular response to DNA damage. PAXIP1 has been shown to bind DDR proteins, such as 53BP1 and γH2AX, and also shown to be an important part of immune development. In this dissertation, we observe that WEE1 binds to PAXIP1 and PAXIP1 regulates the WEE1-mediated phosphorylation of its main substrate, CDK1. We also demonstrate that ectopic expression of PAXIP1 combined with WEE1 inhibitor, AZD1775, leads to an increase in the mitotic index at the G2/M checkpoint. Overexpression of PAXIP1 combined with AZD1775 treatment in cells with prior DNA damage causes high levels of caspase-3 mediated apoptosis as compared to AZD1775 treatment alone. In summary, we identify the role of PAXIP1 in sensitizing lung cancer cells to the WEE1 inhibitor, AZD1775, in combination with platinum-based therapy and propose the use of WEE1 and PAXIP1 levels as mechanism-based biomarkers. Overall, these studies indicate that BRCT-containing proteins through their role in the DDR and the cell cycle are crucial for both cancer prevention and therapy.

Diplomová práca sa zameriava na vývoj marketingovej stratégie firmy Mediahost.sk na slovenskom trhu. Analyzuje makro a mikro prostredie v IT priemysle, a to najmä so zameraním na webhosting. Aktuálna marketingová stratégia spoločnosti je popísaná a hlavné ovplyvňujúce faktory sú rozpoznané. Diplomová práca obsahuje návrhy zmien a odporúčania zahrnuté v novej marketingovej stratégii spoločnosti. Navyše, je navrhnutý plán a rozpočet realizácie.

Gram-positive pathogenic bacteria utilize cell-surface anchored proteins to bind and transport heme into the cell. These bacteria acquire iron from host proteins containing heme e.g., hemoglobin. Proteins like HmuT from Corynebacterium diphtheriae bind and help transport heme into the cell. Residues His136 and Tyr235 are utilized as the axial ligands, with a conserved Arg237 residue acting as the hydrogen bonding partner to the axial Tyr235. Similarly, Streptococcus pyogenes utilizes the cell anchored protein Shr to transfer heme into the cell. Shr-NEAT2 is hexacoordinated by two axial methionines and is prone to autoreduction where lysines are the most likely source of electrons. Lastly, PefR of Group A Streptococcus is a DNA transcription factor which regulates protein expression. Preliminary studies indicate a cysteine may coordinate the heme. A combination of UV-visible, resonance Raman, and magnetic circular dichroism spectroscopies shows these proteins play a crucial role heme transport and regulation.

In developed regions, the body of knowledge of general entrepreneurship in the sales, services and technology-based business domains, is well researched and established. This is not the case with technological entrepreneurship in developing regions. Little is known about the entrepreneur, new venture creation and growth processes of technology-based enterprises in emerging regions. This research project studied a sample frame of practising technological entrepreneurs in a multi-cultural province within an emerging economic region. Data was collected from 210 entrepreneurs who have founded and still manage a technology-based enterprise in the province of KwaZulu-Natal, South Africa. Over 25,000 data points were collected through questionnaires and were statistically analysed, using multiple regression and model building analysis techniques. A control study of 167 post-graduate students at the University of Pretoria was also done. A representative profile was developed from a frequency distribution analysis of the survey sample. This profile was compared with that of a similar survey sample of entrepreneurs in high-technology spin-off companies in a developed region. The results culminated in a three-part model that identifies the most prominent external influences on the technological entrepreneur, the new venture creation process and the mature enterprise. Inferences of hypotheses, as well as several conclusions, were made from the results on the following contemporary issues: 1) cultural heritage; 2) the first-born debate; 3) the self-employed status of parents; 4) financing of the new technological enterprise and 5) training in entrepreneurship. Policy makers could use these results to develop technological entrepreneurship in emerging regions. / Thesis (PhD (Engineering Management))--University of Pretoria, 2006. / Graduate School of Technology Management (GSTM) / unrestricted

HTTP botnets are currently the most popular form of botnets compared to IRC and P2P botnets. This is because, they are not only easier to implement, operate, and maintain, but they can easily evade detection. Likewise, HTTP botnets flows can easily be buried in the huge volume of legitimate HTTP traffic occurring in many organizations, which makes the detection harder. In this thesis, a new detection framework involving three detection models is proposed, which can run independently or in tandem. The first detector profiles the individual applications based on their interactions, and isolates accordingly the malicious ones. The second detector tracks the regularity in the timing of the bot DNS queries, and uses this as basis for detection. The third detector analyzes the characteristics of the domain names involved in the DNS, and identifies the algorithmically generated and fast flux domains, which are staples of typical HTTP botnets. Several machine learning classifiers are investigated for each of the detectors. Experimental evaluation using public datasets and datasets collected in our testbed yield very encouraging performance results. / Graduate

We wish to study those domains in Cn,for n ≥ 2, the so-called domains of holomorphy, which are in some sense the maximal domains of existence of the holomorphic functions defined on them. We demonstrate that this study is radically different from that of domains in C by discussing some examples of special types of domains in Cn , n ≥2, such that every function holomorphic on them extends to strictly larger domains. Given a domain in Cn , n ≥ 2, we wish to construct the maximal domain of existence for the holomorphic functions defined on the given domain. This leads to Thullen’s construction of a domain (not necessarily in Cn)spread overCn, the so-called envelope of holomorphy, which fulfills our criteria. Unfortunately this turns out to beavery abstract space, far from giving us sense in general howa domain sitting in Cn can be constructed which is strictly larger than the given domain and such that all the holomorphic functions defined on the given domain extend to it. But with the help of this abstract approach we can give a characterization of the domains of holomorphyin Cn , n ≥ 2. The aforementioned characterization is as follows: adomain in Cn is a domain of holomorphy if and only if it is holomorphically convex. However, holomorphic convexity is a very difficult property to check. This calls for other (equivalent) criteria for a domain in Cn , n ≥ 2, to be a domain of holomorphy. We survey these criteria. The proof of the equivalence of several of these criteria are very technical – requiring methods coming from partial differential equations. We provide those proofs that rely on the first part of our survey: namely, on analytic continuation theorems. If a domain Ω Cn , n ≥ 2, is not a domain of holomorphy, we would still like to explicitly describe a domain strictly larger than Ω to which all functions holomorphic on Ω continue analytically. Aspects of Thullen’s approach are also useful in the quest to construct an explicit strictly larger domain in Cn with the property stated above. The tool used most often in such constructions s called “Kontinuitatssatz”. It has been invoked, without a clear statement, in many works on analytic continuation. The basic (unstated) principle that seems to be in use in these works appears to be a folk theorem. We provide a precise statement of this folk Kontinuitatssatz and give a proof of it.

Abstract: Family history (FH) is a risk factor for many conditions that can affect pediatric patients. While there is no evidence of the clinical utility of FH taking in pediatrics and there is no standard of care as to FH taking, many suggestions were made as to what conditions should be covered in a pediatric FH assessment. There is also no evidence of the current practice. In this study the Theoretical Domains Framework was applied to FH taking and used to conduct semi-structured interviews with pediatricians to explore their FH taking practice. The pediatricians reported similar FH taking habits. Their FH taking was reported to include a wide range of conditions and determinants of health, and they used this information for a broad range of clinical tasks. FH taking in pediatric practice was reported to be complex and embedded with other aspects of practice. Résumé: Les antécédents familiaux (AF) sont des facteurs de risque pour plusieurs maladies affectant les patients pédiatriques. Alors qu'il n'y a ni données probantes concernant l'utilité des AF en pédiatrie ni normes pour la prise d'AF, plusieurs ont fait des suggestions quant à ce qui devrait être couvert par la prise d'AF. Il n'y a pas de données probantes décrivant la pratique actuelle de prise d'AF en pédiatrie. Dans cette étude, le Theoretical Domains Framework a été appliqué à la prise d'AF et utilisé afin de diriger des entrevues semi-structurées avec des pédiatres, dans le but de décrire leur pratique actuelle. Les pédiatres ont dit avoir des habitudes semblables quant à la prise d'AF. Cette dernière inclut plusieurs maladies et déterminants de la santé, et ils utilisent cette information pour plusieurs tâches. La prise d'AF en pédiatrie a été décrite comme étant complexe et très intégrée à leur pratique entière.

Dans ce travail de thèse, une méthode de pénalisation en volume pour la simulation d'écoulements magnétohydrodynamiques (MHD) en domaines confinés est présentée. Les équations incompressibles de la MHD résistives sont résolues par le truchement d'un solveur pseudo-spectral parallèlisé. La pénalisation en volume est une méthode de frontières immergées, caractérisée par une grande flexibilité dans le choix de la géométrie de l'écoulement. Dans le cas présent, elle permet d'utiliser des conditions aux limites non-périodiques dans un schéma pseudo-spectral Fourier. La méthode numérique est validée et sa convergence est quantifiée pour des écoulements hydrodynamiques et MHD, en deux et trois dimensions, en comparant les résultats numériques à ceux de la littérature et à des solutions analytiques. Dans un second temps, la génération spontanée de moment cinétique et magnétique est étudiée pour des écoulements MHD confinés 2D et 3D. L'influence du nombre de Reynolds et du rapport des énergies cinétique/magnétique est explorée, ainsi que les différences induites par les conditions aux limites. Le fait que l'axisymétrie des frontières résulte en un terme de pression non-nul est primordial pour engendrer de grandes valeurs du moment cinétique. L'exclusivité de cette auto-organisation aux écoulements 2D est étudiée en considérant la MHD 3D en présence d'un fort champ magnétique axial. La suite est consacrée à la simulation d'un fluide conducteur dans un cylindre avec un forçage magnétique axial et poloidal. En faisant varier l'amplitude du forçage poloidal, différents états dynamiques sont atteints. Enfin, l'effet du nombre de Prandtl sur le seuil des instabilitées est étudié. / A volume penalization method for the simulation of magnetohydrodynamic (MHD) flows in confined domains is presented. Incompressible resistive MHD equations are solved in 3D by means of a parallelized pseudo-spectral solver. The volume penalization technique is an immersed boundary method, characterized by a high flexibility in the choice of the geometry of the considered flow. In the present case, it allows the use of conditions different from periodic boundaries in a Fourier pseudo-spectral scheme. The numerical method is validated and its convergence is assessed for two- and three-dimensional hydrodynamical and MHD flows by comparing the numerical results with those of the literature or analytical solutions. Then, the spontaneous generation of kinetic and magnetic angular momentum is studied for confined 2D and 3D MHD flows. The influence of the Reynolds number and of the ratio of kinetic/magnetic energies is explored, as well as the differences induced by the boundary conditions. The fact that axisymmetric borders introduce a non-zero pressure term in the evolution equation of the angular momentum is essential to generate large values of the angular momentum. It is investigated whether this self-organization is exclusively observed in 2D flows by considering 3D MHD in the presence of a strong axial magnetic field. The last part is devoted to the simulation of a conducting fluid in a periodic cylinder with imposed axial and poloidal magnetic forcing, implying a resulting magnetic field. By varying the amplitude of the poloidal forcing, different dynamical states can be achieved. The effect of the Prandtl number on the threshold of the instabilities is then studied.