148 research outputs found

    The Erythrocyte Sedimentation Rate: Choice of Technique for Sanatorium Use

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    The development and promotion of electronic theses and dissertations (ETDs) within the UK.

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    An increasing number of universities are accepting and encouraging the submission of theses and dissertations in electronic format. Two hundred and three institutions are now members of the international 'Networked Digital Library of Theses and Dissertations' (NDLTD), and in May 2003 over 200 individuals travelled to Berlin to participate in the ETD symposium ('Next Steps - Electronic Theses and Dissertations Worldwide'). The support of UNESCO and the work undertaken by key institutions such as Virginia Tech. has led to wide-scale developments at national and individual level. Within the UK, funding from the Joint Information Systems Committee (JISC) has enabled three project teams to engage in research and development associated with the creation, management, and use of electronic theses and dissertations (ETDs). This paper considers recent ETD-related activity in the UK within the broader international context. It concentrates, in particular, on the work of the Electronic Theses project consortium that is led by The Robert Gordon University. The benefits of ETDs, issues of concern, the selection of software, and advocacy requirements are amongst the topics addressed. The authors welcome comments on both the project and the information available on the Electronic Theses project Web pages

    Adaptive monitoring using the endangered northern corroboree frog (Pseudophryne pengilleyi) as a case study

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    Abstract Monitoring programs are most successful when they undertake regular evaluation of their data to determine if the goals of the programs are achievable and allow changes to achieve this as necessary -so called adaptive monitoring. We use data from a monitoring program for the northern corroboree frog (Pseudophryne pengilleyi), a declining species in south-eastern Australia, to determine the inter-annual variability in the counts and assess what levels of population change would be detectable using different statistical and monitoring approaches. The existing monitoring program would only successfully statistically detect a 3% annual decline (34% total decline) in population size over a ten year period. Monitoring 40 sites would allow an 80% or greater chance of detecting a 2% or greater annual increase over a ten year period (22% increase). Detecting population decreases is more difficult as monitoring 40 sites with a 2% annual decline (19% total decline) will have a less than 40% chance of being detected after 10 years. A larger monitoring program is required to detect smaller annual changes in the population of this species. These findings have implications for the likely effectiveness of other anuran monitoring programs as the northern corroboree frog appears to be far more consistent in detectable call effort compared to most species

    Electronic theses: the turning point.

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    Purpose: To describe the key findings of the UK JISC-funded Electronic Theses project that was led by The Robert Gordon University, as well as the results of associated projects that formed part of the JISC-funded “FAIR” programme, and the way in which the recommendations will be taken forward. Design/methodology/approach: The research involved: an assessment of existing best practice relating to the production, management and use of e-theses; the use of questionnaires to obtain feedback from potential users; the identification and testing of potentially useful software; consideration of the elements required in a metadata core set, and discussions with representative bodies to ensure that the model recommended for use in the UK had support from the key stakeholders. Findings: Information is provided about the value of the NDLTD web site, the suitability of DSpace and EPrints software for institutional e-theses repositories, and the recommended infrastructure for the operation of an e-theses service at national level. Details are included about the agreed metadata core set for UK e-theses, and advice is provided about administrative, legal and cultural issues. Practical implications: The JISC-funded EThOS project is taking forward many of the recommendations from the Electronic Theses project. Originality/value: The research results described in this paper will be of use to institutions, which are aiming to establish their own e-theses collections. The details provided about the UK approach towards the management of e-theses may be of use in countries, which have not yet made their theses available in electronic format

    Discovery of Bisamide-heterocycles as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake

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    A new series of potent inhibitors of cellular lipid uptake from HDL particles mediated by scavenger receptor, class B, type I (SR-BI) was identified. The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) that measured the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is characterized by a linear peptidomimetic scaffold with two adjacent amide groups, as well as an aryl-substituted heterocycle. Analogs of the initial hit were rapidly prepared via Ugi 4-component reaction, and select enantiopure compounds were prepared via a stepwise sequence. Structure–activity relationship (SAR) studies suggest an oxygenated arene is preferred at the western end of the molecule, as well as highly lipophilic substituents on the central and eastern nitrogens. Compound 5e, with (R)-stereochemistry at the central carbon, was designated as probe ML279. Mechanistic studies indicate that ML279 stabilizes the interaction of HDL particles with SR-BI, and its effect is reversible. It shows good potency (IC50 = 17 nM), is non-toxic, plasma stable, and has improved solubility over our alternative probe ML278

    Using a population-based approach to prevent hepatocellular cancer in New South Wales, Australia: effects on health services utilisation

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    <p>Abstract</p> <p>Background</p> <p>Australians born in countries where hepatitis B infection is endemic are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. However, a program of screening, surveillance and treatment of chronic hepatitis B (CHB) in high risk populations could significantly reduce disease progression and death related to end-stage liver disease and HCC. Consequently we are implementing the <it>B Positive </it>pilot project, aiming to optimise the management of CHB in at-risk populations in south-west Sydney. Program participants receive routine care, enhanced disease surveillance or specialist referral, according to their stage of CHB infection, level of viral load and extent of liver injury. In this paper we examine the program's potential impact on health services utilisation in the study area.</p> <p>Methods</p> <p>Estimated numbers of CHB infections were derived from Australian Bureau of Statistics data and applying estimates of HBV prevalence rates from migrants' countries of birth. These figures were entered into a Markov model of disease progression, constructing a hypothetical cohort of Asian-born adults with CHB infection. We calculated the number of participants in different CHB disease states and estimated the numbers of GP and specialist consultations and liver ultrasound examinations the cohort would require annually over the life of the program.</p> <p>Results</p> <p>Assuming a 25% participation rate among the 5,800 local residents estimated to have chronic hepatitis B infection, approximately 750 people would require routine follow up, 260 enhanced disease surveillance and 210 specialist care during the first year after recruitment is completed. This translates into 5 additional appointments per year for each local GP, 25 for each specialist and 420 additional liver ultrasound examinations.</p> <p>Conclusions</p> <p>While the program will not greatly affect the volume of local GP consultations, it will lead to a significant increase in demand for specialist services. New models of CHB care may be required to aid program implementation and up scaling the program will need to factor in additional demands on health care utilisation in areas of high hepatitis B sero-prevalence.</p

    Mapping the sex determination locus in the Atlantic halibut (Hippoglossus hippoglossus) using RAD sequencing

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    Background:Atlantic halibut (Hippoglossus hippoglossus) is a high-value, niche market species for cold-water marine aquaculture. Production of monosex female stocks is desirable in commercial production since females grow faster and mature later than males. Understanding the sex determination mechanism and developing sex-associated markers will shorten the time for the development of monosex female production, thus decreasing the costs of farming.Results:Halibut juveniles were masculinised with 17 &alpha;-methyldihydrotestosterone (MDHT) and grown to maturity. Progeny groups from four treated males were reared and sexed. Two of these groups (n = 26 and 70) consisted of only females, while the other two (n = 30 and 71) contained balanced sex ratios (50% and 48% females respectively). DNA from parents and offspring from the two mixed-sex families were used as a template for Restriction-site Associated DNA (RAD) sequencing. The 648 million raw reads produced 90,105 unique RAD-tags. A linkage map was constructed based on 5703 Single Nucleotide Polymorphism (SNP) markers and 7 microsatellites consisting of 24 linkage groups, which corresponds to the number of chromosome pairs in this species. A major sex determining locus was mapped to linkage group 13 in both families. Assays for 10 SNPs with significant association with phenotypic sex were tested in both population data and in 3 additional families. Using a variety of machine-learning algorithms 97% correct classification could be obtained with the 3% of errors being phenotypic males predicted to be females.Conclusion:Altogether our findings support the hypothesis that the Atlantic halibut has an XX/XY sex determination system. Assays are described for sex-associated DNA markers developed from the RAD sequencing analysis to fast track progeny testing and implement monosex female halibut production for an immediate improvement in productivity. These should also help to speed up the inclusion of neomales derived from many families to maintain a larger effective population size and ensure long-term improvement through selective breeding

    Reverse immunodynamics : a new method for identifying targets of protective immunity

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    Despite a dramatic increase in our ability to catalogue variation among pathogen genomes, we have made far fewer advances in using this information to identify targets of protective immunity. Epidemiological models predict that strong immune selection can cause antigenic variants to structure into genetically discordant sets of antigenic types (e.g. serotypes). A corollary of this theory is that targets of immunity may be identified by searching for non-overlapping associations of amino acids among co-circulating antigenic variants. We propose a novel population genetics methodology that combines such predictions with phylogenetic analyses to identify genetic loci (epitopes) under strong immune selection. We apply this concept to the AMA-1 protein of the malaria parasite Plasmodium falciparum and find evidence of epitopes among certain regions of low variability which could render them ideal vaccine candidates. The proposed method can be applied to a myriad of multi-strain pathogens for which vast amounts of genetic data has been collected in recent years

    PET Imaging a MPTP-Induced Mouse Model of Parkinson’s Disease Using the Fluoropropyl-Dihydrotetrabenazine Analog [18F]-DTBZ (AV-133)

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    Parkinson’s disease (PD) is characterized by the loss of dopamine-producing neurons in the nigrostriatal system. Numerous researchers in the past have attempted to track the progression of dopaminergic depletion in PD. We applied a quantitative non-invasive PET imaging technique to follow this degeneration process in an MPTP-induced mouse model of PD. The VMAT2 ligand 18F-DTBZ (AV-133) was used as a radioactive tracer in our imaging experiments to monitor the changes of the dopaminergic system. Intraperitoneal administrations of MPTP (a neurotoxin) were delivered to mice at regular intervals to induce lesions consistent with PD. Our results indicate a significant decline in the levels of striatal dopamine and its metabolites (DOPAC and HVA) following MPTP treatment as determined by HPLC method. Images obtained by positron emission tomography revealed uptake of 18F-DTBZ analog in the mouse striatum. However, reduction in radioligand binding was evident in the striatum of MPTP lesioned animals as compared with the control group. Immunohistochemical analysis further confirmed PET imaging results and indicated the progressive loss of dopaminergic neurons in treated animals compared with the control counterparts. In conclusion, our findings suggest that MPTP induced PD in mouse model is appropriate to follow the degeneration of dopaminergic system and that 18F-DTBZ analog is a potentially sensitive radiotracer that can used to diagnose changes associated with PD by PET imaging modality
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