392 research outputs found
MOARF, an Integrated Workflow for Multiobjective Optimization: Implementation, Synthesis, and Biological Evaluation
No full textWe
describe the development and application of an integrated, multiobjective
optimization workflow (MOARF) for directed medicinal chemistry design.
This workflow couples a rule-based molecular fragmentation scheme
(SynDiR) with a pharmacophore fingerprint-based fragment replacement
algorithm (RATS) to broaden the scope of reconnection options considered
in the generation of potential solution structures. Solutions are
ranked by a multiobjective scoring algorithm comprising ligand-based
(shape similarity) biochemical activity predictions as well as physicochemical
property calculations. Application of this iterative workflow to optimization
of the CDK2 inhibitor Seliciclib (CYC202, R-roscovitine) generated
solution molecules in desired physicochemical property space. Synthesis
and experimental evaluation of optimal solution molecules demonstrates
CDK2 biochemical activity and improved human metabolic stability
Opportunities and Barriers for Adoption of a Decision-Support Tool for Alzheimer's Disease
No full textClinical
decision-support tools (DSTs)
represent a valuable resource in healthcare. However, lack of Human Factors considerations and early design research has often limited their successful adoption. To complement previous technically focused work, we studied adoption opportunities of a future DST built on a predictive model of
Alzheimer’s Disease (AD)
progression. Our aim is two-fold: exploring adoption opportunities for DSTs in AD clinical care, and testing a novel combination of methods to support this process. We focused on understanding current clinical needs and practices, and the potential for such a tool to be integrated into the setting, prior to its development. Our user-centred approach was based on field observations and semi-structured interviews, analysed through workflow analysis, user profiles, and a design-reality gap model. The first two are common practice, whilst the latter provided added value in highlighting specific adoption needs. We identified the likely early adopters of the tool as being both psychiatrists and neurologists based in research-oriented clinical settings. We defined ten key requirements for the translation and adoption of DSTs for AD around IT, user, and contextual factors. Future works can use and build on these requirements to stand a greater chance to get adopted in the clinical setting
Morphology and significance of transverse ridges (De Geer moraines) adjacent to the Moray Firth, NE Scotland
No full textHigh-resolution NEXTMap digital surface models and aerial photographs are used to map suites of transverse ridges at Tarbat Ness and to the west of Elgin, along the margins of the Moray Firth in northeast Scotland. Based on their morphology, configuration and location, interpret these landforms as De Geer moraines which formed at or near former grounding line positions of the Moray Firth palaeo-ice stream. The Tarbat Ness De Geer moraines almost certainly formed at a marine margin. Reaching altitudes of 55 m above present OD, these landforms may provide one of the highest geomorphological indicators for former relative sea level in mainland Britain. Evidence from surrounding landforms and sediments suggest that the ridges formed between c. 15 000-18 000 cal yrs BP, indicating that a significant fall in relative sea level may have taken place prior to an ice margin re-advance in the Moray Firth, known as the Ardersier Oscillation
Dynamics and disintegration of the Moray Firth palaeo-ice stream
No full textWe combine the Olex echosounder dataset and high resolution NEXTMap digital surface models with aerial photographs and field observations to build on existing models of Late Devensian ice-sheet deglaciation in the Moray Firth area of northern Scotland. Morphological mapping of the offshore area, coupled with onshore sedimentological investigations suggest that following separation of British and Fennoscandian ice, the dynamics of the north-east sector of the British Ice Sheet was dominated by the Moray Firth ice stream. Onshore, a strongly convergent pattern of highly elongate, mega-scale rock drumlins, glacial grooves and till ridges documents ice flow at that time. Offshore, well-preserved, west-east trending tunnel valley networks indicate a period of significant subglacial drainage. A coherent suite of arcuate ridges preserved on the sea bed in the outer Moray Firth provide evidence for a major glacial advance, which probably took place c. 18 – 22 ka BP. Onshore, geomorphological, lithostratigraphical and sedimentological investigations indicate that at least two significant oscillations of the ice margin took place during retreat, leaving recessional moraines at Elgin and Ardersier. Between these two positions, suites of well-preserved De Geer moraines at Tarbat Ness suggest that relative sea level at the grounding line stood at least 55 metres above present OD. Towards the ice divide around Loch Shin, several fields of Rogen moraine may reflect a local change in thermal regime from cold-based to warm-based conditions, possibly associated with continued late-stage ice stream activity in NE Scotland
Effectiveness of participative community singing intervention program on promoting resilience and mental health of Aboriginal and Torres Strait Islander people in Australia
No full textThis book chapter reports on a study that sought to investigate the efficacy of community participative singing on the mental health and wellbeing of Aboriginal and Torres Strait Islander people from several South East Queensland communities. Five groups of participants took part in the singing program over two, three month blocks. The sessions lasted for two hours and included relaxation, posture, breathing, and vocal exercises, as well as singing and socialisation. Using measures of resilience, depression, and quality of life, the results showed participants reported decreases in symptoms of depression and medication use, and improvements in quality of life and resilience over a six month period, thus demonstrating the effectiveness of participative community singing in enhancing the mental health and wellbeing of Aboriginal and Torres Strait Islander people. The chapter is from the book: Olisah V, ed. Essential notes in psychiatry published by InTech, pages 245-252
Exit polling in a cold climate : the BBC-ITV experience in Britain in 2005
No full textConducting an exit poll to forecast the outcome of a national election in terms of both votes and seats is particularly difficult in Britain. No official information is available on how individual polling stations voted in the past, use of single-member plurality means that there is no consistent relationship between votes and seats, electors can choose to vote by post and most of those who vote in person do so late in the day. In addition, around one in every six intended exit poll respondents refuses to participate. Methods that were developed to overcome these problems, and their use in the successful 2005 British Broadcasting Corporation-Independent Television exit poll, are described and evaluated. The methodology included a panel design to allow the estimation of electoral change at local level, coherent multiple-regression modelling of multiparty electoral change to capture systematic patterns of variation, probabilistic prediction of constituency winners to account for uncertainty in projected constituency level shares, collection of information about the voting intentions of postal voters before polling day and access to interviewer guesses on the voting behaviour of refusals. The coverage and accuracy of the exit poll data are critically examined, the effect of key aspects of the statistical modelling of the data is assessed and some general lessons are drawn for the design and analysis of electoral exit polls
[IC‐P‐141]: ANALYSIS OF THE HETEROGENEITY OF POSTERIOR CORTICAL ATROPHY: DATA‐DRIVEN MODEL PREDICTS DISTINCT ATROPHY PATTERNS FOR THREE DIFFERENT COGNITIVE SUBGROUPS
No full textSpatial variation in foraging behaviour of a marine top predator (Phoca vitulina) determined by a large-scale satellite tagging program
No full textThe work was supported by the United Kingdom Department of Trade and industry, now the Department of Energy and Climate Change (http://www. decc.gov.uk/) through its Strategic Environmental Assessment programme (http://www.offshore-sea. .uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The harbour seal (Phoca vitulina) is a widespread marine predator in Northern Hemisphere waters. British populations have been subject to rapid declines in recent years. Food supply or inter-specific competition may be implicated but basic ecological data are lacking and there are few studies of harbour seal foraging distribution and habits. In this study, satellite tagging conducted at the major seal haul outs around the British Isles showed both that seal movements were highly variable among individuals and that foraging strategy appears to be specialized within particular regions. We investigated whether these apparent differences could be explained by individual level factors: by modelling measures of trip duration and distance travelled as a function of size, sex and body condition. However, these were not found to be good predictors of foraging trip duration or distance, which instead was best predicted by tagging region, time of year and inter-trip duration. Therefore, we propose that local habitat conditions and the constraints they impose are the major determinants of foraging movements. Specifically the distance to profitable feeding grounds from suitable haul-out locations may dictate foraging strategy and behaviour. Accounting for proximity to productive foraging resources is likely to be an important component of understanding population processes. Despite more extensive offshore movements than expected, there was also marked fidelity to the local haul-out region with limited connectivity between study regions. These empirical observations of regional exchange at short time scales demonstrates the value of large scale electronic tagging programs for robust characterization of at-sea foraging behaviour at a wide spatial scale.Peer reviewe
Intensive Interaction: a Research Review
No full textIntensive Interaction is a socially interactive approach to supporting and developing the pre verbal communication and sociability of people with severe or profound learning disabilities, or severe autism. Developed in the 1980’s from the psychological model of ‘augmented mothering’ the approach currently has an increasing number of proponents who make claims for increased social responsiveness due to the use of the approach. This short paper aims to evaluate some of the evidential claims of consequential increased social responses from people with severe and profound and multiple learning disabilities due to the use of Intensive Interaction techniques. Thus the paper presents a review of findings presented in relevant research papers which have been published in generally recognised academic journals.
From this review the author concludes that although expanding, the current body of research has been limited in scope and scale, and has generally been conducted by a small number of Intensive Interaction practitioners and advocates. However, increased client social responsiveness was consistently reported across the research projects reviewed.
In conclusion, this paper advocates for further systematic research into the approach by the wider research community to further develop the evidential base of the approach
The effect of injectable barium selenate on the selenium status of horses on pasture
No full textAIM: To examine the effect of intramuscular barium selenate on the blood selenium concentration of horses with marginal selenium status. METHODS: Eighteen mares were assigned to one of six groups. The mares in groups 1-4 received barium selenate at 0.5, 0.75, 1.0 and 1.5 mg Se/kg, respectively, injected into the right pectoral muscle mass. The mares in group 5 received sodium selenate at 0.05 mg Se/kg orally at 8-week intervals. The mares in group 6 were left untreated. Blood samples were collected at 0, 1, 2, 5, 10, 30, 60, 90, 120, 180, 240, 300 and 360 days after the initial treatment for assay of whole blood and plasma selenium. Injection site reactions were recorded on each sampling date. RESULTS: Treatment with barium selenate at each dose rate significantly increased whole blood, plasma and blood cell selenium concentrations when compared to no treatment or oral treatment with sodium selenate, and maintained group mean whole blood selenium concentrations in the adequate range (>1600 nmol/l) until the end of the experimental period of 1 year. The severity of injection site reactions increased with dose rate but was considered acceptable alt the lower dose rates used. CONCLUSION: The injection of barium selenate placed aseptically at a deep intramuscular site was efficacious in correcting the selenium status of mares grazing pasture with a selenium content of 0.01-0.07 mg/kg DM. However, some swelling and fibrosis at the injection site was apparent at all dose rates used. CLINICAL RELEVANCE: There is currently no long-acting selenium supplementation product licensed in New Zealand for use in horses. Barium selenate promises to provide a useful method for selenium supplementation for horses, with an effective duration of at least 1 year following a single injection.PUBM: Print; JID: 0021406; ppublishSource type: Electronic(1
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