Care: an integrated framework to support continuous, adaptable, reflective evaluation of eGovernment systems: A research note

CARE: an Integrated Framework to Support Continuous, Adaptable, Reflective Evaluation of Egovernment SystemsThis is an eGISE network paper. It is motivated by a concern to develop a better approach to learning from the experience of an eGovernment project and applying that knowledge in future projects. The proposed project is based on previous work in the construction industry that developed COLA, a Cross Organisational Learning Approach. Developing a similar strategy for Knowledge Management is likely to be effective because the ‘silo’ culture of local government organisations has parallels with the segmented organisational structures within the construction industry.Engineering and Physical Sciences Research Council (EPSRC) UK (grant GR/T27020/01

Performance of AAV8 vectors expressing human factor IX from a hepatic-selective promoter following intravenous injection into rats

Background: Vectors based on adeno-associated virus-8 (AAV8) have shown efficiency and efficacy for liver-directed gene therapy protocols following intravascular injection, particularly in relation to haemophilia gene therapy. AAV8 has also been proposed for gene therapy targeted at skeletal and cardiac muscle, again via intravascular injection. It is important to assess vector targeting at the level of virion accumulation and transgene expression in multiple species to ascertain potential issues relating to species variation in infectivity profiles. Methods: We used AAV8 vectors expressing human factor IX (FIX) from the liver-specific LP-1 promoter and administered this virus via the intravascular route of injection into 12 week old Wistar Kyoto rats. We assessed FIX levels in serum by ELISA and transgene expression at sacrifice by immunohistochemistry using anti-FIX antibodies. Vector DNA levels in organs we determined by real time PCR. Results: Administration of 1 × 1011 or 5 × 1011 scAAV8-LP1-hFIX vector particles/rat resulted in efficient production of physiological hFIX levels, respectively in blood assessed 4 weeks post-injection. This was maintained for the 4 month duration of the study. At 4 months we observed liver persistence of vector with minimal non-hepatic distribution. Conclusion: Our results demonstrate that AAV8 is a robust vector for delivering therapeutic genes into rat liver following intravascular injection

Orthologues of Bacillus subtilis Spore Crust Proteins Have a Structural Role in the Bacillus megaterium QM B1551 Spore Exosporium.

The exosporium of Bacillus megaterium QM B1551 spores is morphologically distinct from exosporia observed for the spores of many other species. Previous work has demonstrated that unidentified genes carried on one of the large indigenous plasmids are required for the assembly of the Bacillus megaterium exosporium. Here, we provide evidence that pBM600-encoded orthologues of the Bacillus subtilis CotW and CotX proteins, which form the crust layer in spores of that species, are structural components of the Bacillus megaterium QM B1551 spore exosporium. The introduction of plasmid-borne cotW and orthologous cotX genes to the PV361 strain, which lacks all indigenous plasmids and produces spores that are devoid of an exosporium, results in the development of spores with a rudimentary exosporium-type structure. Additionally, purified recombinant CotW protein is shown to assemble at the air-water interface to form thin sheets of material, which is consistent with the idea that this protein may form a basal layer in the Bacillus megaterium QM B1551 exosporium.IMPORTANCE When starved of nutrients, some bacterial species develop metabolically dormant spores that can persist in a viable state in the environment for several years. The outermost layers of spores are of particular interest since (i) these represent the primary site for interaction with the environment and (ii) the protein constituents may have biotechnological applications. The outermost layer, or exosporium, in Bacillus megaterium QM B1551 spores is of interest, as it is morphologically distinct from the exosporia of spores of the pathogenic Bacillus cereus family. In this work, we provide evidence that structurally important protein constituents of the Bacillus megaterium exosporium are different from those in the Bacillus cereus family. We also show that one of these proteins, when purified, can assemble to form sheets of exosporium-like material. This is significant, as it indicates that spore-forming bacteria employ different proteins and mechanisms of assembly to construct their external layers.Julia Manetsberger was the recipient of an EPSRC studentship, awarded from the departmental block DTG

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels

A comparative study between motivated learning and reinforcement learning

This paper analyzes advanced reinforcement learning techniques and compares some of them to motivated learning. Motivated learning is briefly discussed indicating its relation to reinforcement learning. A black box scenario for comparative analysis of learning efficiency in autonomous agents is developed and described. This is used to analyze selected algorithms. Reported results demonstrate that in the selected category of problems, motivated learning outperformed all reinforcement learning algorithms we compared with

A prospective key informant surveillance system to measure maternal mortality – findings from indigenous populations in Jharkhand and Orissa, India

<p>Abstract</p> <p>Background</p> <p>In places with poor vital registration, measurement of maternal mortality and monitoring the impact of interventions on maternal mortality is difficult and seldom undertaken. Mortality ratios are often estimated and policy decisions made without robust evidence. This paper presents a prospective key informant system to measure maternal mortality and the initial findings from the system.</p> <p>Methods</p> <p>In a population of 228 186, key informants identified all births and deaths to women of reproductive age, prospectively, over a period of 110 weeks. After birth verification, interviewers visited households six to eight weeks after delivery to collect information on the ante-partum, intra-partum and post-partum periods, as well as birth outcomes. For all deaths to women of reproductive age they ascertained whether they could be classified as maternal, pregnancy related or late maternal and if so, verbal autopsies were conducted.</p> <p>Results</p> <p>13 602 births were identified, with a crude birth rate of 28.2 per 1000 population (C.I. 27.7–28.6) and a maternal mortality ratio of 722 per 100 000 live births (C.I. 591–882) recorded. Maternal deaths comprised 29% of all deaths to women aged 15–49. Approximately a quarter of maternal deaths occurred ante-partum, a half intra-partum and a quarter post-partum. Haemorrhage was the commonest cause of all maternal deaths (25%), but causation varied between the ante-partum, intra-partum and post-partum periods. The cost of operating the surveillance system was US$386 a month, or US$0.02 per capita per year.</p> <p>Conclusion</p> <p>This low cost key informant surveillance system produced high, but plausible birth and death rates in this remote population in India. This method could be used to monitor trends in maternal mortality and to test the impact of interventions in large populations with poor vital registration and thus assist policy makers in making evidence-based decisions.</p

Towards an Efficient Finite Element Method for the Integral Fractional Laplacian on Polygonal Domains

We explore the connection between fractional order partial differential equations in two or more spatial dimensions with boundary integral operators to develop techniques that enable one to efficiently tackle the integral fractional Laplacian. In particular, we develop techniques for the treatment of the dense stiffness matrix including the computation of the entries, the efficient assembly and storage of a sparse approximation and the efficient solution of the resulting equations. The main idea consists of generalising proven techniques for the treatment of boundary integral equations to general fractional orders. Importantly, the approximation does not make any strong assumptions on the shape of the underlying domain and does not rely on any special structure of the matrix that could be exploited by fast transforms. We demonstrate the flexibility and performance of this approach in a couple of two-dimensional numerical examples

A prospective key informant surveillance system to measure maternal mortality – findings from indigenous populations in Jharkhand and Orissa, India

In places with poor vital registration, measurement of maternal mortality and monitoring the impact of interventions on maternal mortality is difficult and seldom undertaken. Mortality ratios are often estimated and policy decisions made without robust evidence. This paper presents a prospective key informant system to measure maternal mortality and the initial findings from the system

Optically trapped bacteria pairs reveal discrete motile response to control aggregation upon cell–cell approach

Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell–cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 μm. Moreover, the motile response displays spatial sensitivity with greater cell–cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation