Randomised controlled trial and health economic evaluation of the impact of diagnostic testing for influenza, respiratory syncytial virus and Streptococcus pneumoniae infection on the management of acute admissions in the elderly and high-risk 18- to 64-year-olds

Please cite the published version which is available via the DOI link in this record.Western industrialised nations face a large increase in the number of older people. People over the age of 60 years account for almost half of the 16.8 million hospital admissions in England from 2009 to 2010. During 2009-10, respiratory infections accounted for approximately 1 in 30 hospital admissions and 1 in 20 of the 51.5 million bed-days.HTA ProgrammeNational Institute for Health Research (NIHR

The Influence of the effect of solute on the thermodynamic driving force on grain refinement of Al alloys

Grain refinement is known to be strongly affected by the solute in cast alloys. Addition of some solute can reduce grain size considerably while others have a limited effect. This is usually attributed to the constitutional supercooling which is quantified by the growth restriction factor, Q. However, one factor that has not been considered is whether different solutes have differing effects on the thermodynamic driving force for solidification. This paper reveals that addition of solute reduces the driving force for solidification for a given undercooling, and that for a particular Q value, it is reduced more substantially when adding eutectic-forming solutes than peritectic-forming elements. Therefore, compared with the eutectic-forming solutes, addition of peritectic-forming solutes into Al alloys not only possesses a higher initial nucleation rate resulted from the larger thermodynamic driving force for solidification, but also promotes nucleation within the constitutionally supercooled zone during growth. As subsequent nucleation can occur at smaller constitutional supercoolings for peritectic-forming elements, a smaller grain size is thus produced. The very small constitutional supercooling required to trigger subsequent nucleation in alloys containing Ti is considered as a major contributor to its extraordinary grain refining efficiency in cast Al alloys even without the deliberate addition of inoculants.The Australian Research Council (ARC DP10955737)

Intestinal stem cells lacking the Math1 tumour suppressor are refractory to Notch inhibitors

Intestinal cells are constantly produced from a stem cell reservoir that gives rise to proliferating transient amplifying cells, which subsequently differentiate into one of the four principal cell types. Signalling pathways, including the Notch signalling pathway, coordinate these differentiation processes and their deregulation may cause cancer. Pharmacological inhibition through γ-secretase inhibitors or genetic inactivation of the Notch signalling pathway results in the complete loss of proliferating crypt progenitors due to their conversion into post-mitotic goblet cells. The basic helix–loop–helix transcription factor Math1 is essential for intestinal secretory cell differentiation. Because of the critical roles of both Math1 and Notch signalling in intestinal homeostasis and neoplastic transformation, we sought to determine the genetic hierarchy regulating the differentiation of intestinal stem cells into secretory cells. In this paper, we demonstrate that the conversion of intestinal stem cells into goblet cells upon inhibition of the Notch signalling pathway requires Math1

A preliminary study of genetic factors that influence susceptibility to bovine tuberculosis in the British cattle herd

Associations between specific host genes and susceptibility to Mycobacterial infections such as tuberculosis have been reported in several species. Bovine tuberculosis (bTB) impacts greatly the UK cattle industry, yet genetic predispositions have yet to be identified. We therefore used a candidate gene approach to study 384 cattle of which 160 had reacted positively to an antigenic skin test (‘reactors’). Our approach was unusual in that it used microsatellite markers, embraced high breed diversity and focused particularly on detecting genes showing heterozygote advantage, a mode of action often overlooked in SNP-based studies. A panel of neutral markers was used to control for population substructure and using a general linear model-based approach we were also able to control for age. We found that substructure was surprisingly weak and identified two genomic regions that were strongly associated with reactor status, identified by markers INRA111 and BMS2753. In general the strength of association detected tended to vary depending on whether age was included in the model. At INRA111 a single genotype appears strongly protective with an overall odds ratio of 2.2, the effect being consistent across nine diverse breeds. Our results suggest that breeding strategies could be devised that would appreciably increase genetic resistance of cattle to bTB (strictly, reduce the frequency of incidence of reactors) with implications for the current debate concerning badger-culling

Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012

Coronaviruses have the potential to cause severe transmissible human disease, as demonstrated by the severe acute respiratory syndrome (SARS) outbreak of 2003. We describe here the clinical and virological features of a novel coronavirus infection causing severe respiratory illness in a patient transferred to London, United Kingdom, from the Gulf region of the Middle East

Hes5 Expression in the Postnatal and Adult Mouse Inner Ear and the Drug-Damaged Cochlea

The Notch signaling pathway is known to have multiple roles during development of the inner ear. Notch signaling activates transcription of Hes5, a homologue of Drosophila hairy and enhancer of split, which encodes a basic helix-loop-helix transcriptional repressor. Previous studies have shown that Hes5 is expressed in the cochlea during embryonic development, and loss of Hes5 leads to overproduction of auditory and vestibular hair cells. However, due to technical limitations and inconsistency between previous reports, the precise spatial and temporal pattern of Hes5 expression in the postnatal and adult inner ear has remained unclear. In this study, we use Hes5-GFP transgenic mice and in situ hybridization to report the expression pattern of Hes5 in the inner ear. We find that Hes5 is expressed in the developing auditory epithelium of the cochlea beginning at embryonic day 14.5 (E14.5), becomes restricted to a particular subset of cochlear supporting cells, is downregulated in the postnatal cochlea, and is not present in adults. In the vestibular system, we detect Hes5 in developing supporting cells as early as E12.5 and find that Hes5 expression is maintained in some adult vestibular supporting cells. In order to determine the effect of hair cell damage on Notch signaling in the cochlea, we damaged cochlear hair cells of adult Hes5-GFP mice in vivo using injection of kanamycin and furosemide. Although outer hair cells were killed in treated animals and supporting cells were still present after damage, supporting cells did not upregulate Hes5-GFP in the damaged cochlea. Therefore, absence of Notch-Hes5 signaling in the normal and damaged adult cochlea is correlated with lack of regeneration potential, while its presence in the neonatal cochlea and adult vestibular epithelia is associated with greater capacity for plasticity or regeneration in these tissues; which suggests that this pathway may be involved in regulating regenerative potential

Sheep Updates 2005 - Part 4

This session covers twelve papers from different authors: REPRODUCTION 1. Is it worth increasing investment to increase lambing percentages? Lucy Anderton Department of Agriculture Western Australia. 2. What value is a lamb? John Young, Farming Systems Analysis Service, Kojonup, WA 3. Providing twin-bearing ewes with extra energy at lambing produces heavier lambs at marking. Rob Davidson WAMMCO International,, formerly University of Western Australia; Keith Croker, Ken Hart, Department of Agriculture Western Australia, Tim Wiese, Chuckem , Highbury, Western Australia. GENETICS 4. Underlying biological cause of trade-off between meat and wool. Part 1. Wool and muscle glycogen, BM Thomson, I Williams, University of WA, Crawley, JRBriegel, CSIRO Livestock Industries, Floreat Park WA &CRC for the Australian Sheep Industry, JC Greeff, Department of Agriculture Western Australia &CRC for the Australian Sheep Industry. 5. Underlying biological cause of trade-off between meat and wool. Part 2. Wool and fatness, NR Adams1,3, EN Bermingham1,3, JR Briegel1,3, JC Greeff2,3 1CSIRO Livestock Industries, Floreat Park WA 2Department of Agriculture Western Australia, 3CRC for the Australian Sheep Industry 6. Genetic trade-offs between lamb and wool production in Merino breeding programs, Johan Greeff, Department of Agriculture, Western Australia. 7. Clean fleece weight is no phenotypically independent of other traits. Sue Hatcherac and Gordon Refshaugebc aNSWDPI Orange Agricultural Institute, Orange NSW 2800 bUNE c/- NSWDPI Cowra AR&AS Cowra NSW 2794 cAustralian Sheep Industry CRC. 8. When you\u27re on a good thing, do it better: An economic analysis of sheep breed profitability. Emma Kopke, Ross Kingwell, Department of Agriculture, Western Australia, John Young, Farming Systems Analysis Service, Kojonup, WA. 9. Selection Demonstration Flocks: Demonstrating improvementsin productivity of merinos, K.E. Kemper, M.L. Hebart, F.D. Brien, K.S. Jaensch, R.J. Grimson, D.H. Smith South Australian Research and Development Institute 10. You are compromising yield by using Dust Penetration and GFW in breeding programs, Melanie Dowling, Department of Agriculture, Western Australia, A. (Tony) Schlink, CSIRO Livestock Industries, Wembley, Johan Greeff, Department of Agriculture Western Australia. 11. Merino Sheep can be bred for resistance to breech strike. Johan Greeff , John Karlsson, Department of Agriculture Western Australia 12. Parasite resistant sheep and hypersensitivity diarrhoea, L.J.E. Karlsson & J.C. Greeff, Department of Agriculture Western Australi

Transferring research from a university to the United Kingdom National Health Service : The implications for impact

This is an Open Access article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.The aim of this article is to inform readers of the author's reflections on the experience of transferring universitybased research into the commercial sector, and of the processes and strategies employed when preparing for impact in so doing. Concepts for the transfer are illustrated by the author's reflection on aspects that arose during the birthing and subsequent start-up of a university spin-off, Pathways2Wellbeing, a form of reflection-on-action. This is the vehicle for the adaption required to transfer research into the delivery of a specialised clinic in the United Kingdom National Health Service for people with medically unexplained, persistent, bodily symptoms such as fibromyalgia, chronic fatigue and chronic pain. It is hoped that the article will provide readers with an insight into how knowledge transfer can take place through engagement with stakeholders to create an exchange of knowledges to result in impact on health service policy for service users, despite the challenges, and the enablers that facilitated this process. The reflections on the process of knowledge transfer and the implications for impact are underpinned by relevant theory.Peer reviewedFinal Published versio

HIV-related discrimination reported by people living with HIV in London, UK

The objective was to examine the extent to which people living with HIV in London reported being discriminated against because of their infection. In 2004–2005, people living with HIV attending NHS outpatient HIV clinics in north east London were asked: “Have you ever been treated unfairly or differently because of your HIV status—in other words discriminated against?”. Of the 1,687 people who returned a questionnaire (73% response rate), data from 1,385 respondents were included in this analysis; 448 heterosexual women and 210 heterosexual men of black African origin, 727 gay/bisexual men (621 white, 106 ethnic minority). Overall, nearly one-third of respondents (29.9%, 414/1,385) said they had been discriminated against because of their HIV infection. Of those who reported experiencing HIV-related discrimination, almost a half (49.6%, 200/403) said this had involved a health care worker including their dentist (n = 102, 25.3%) or primary care physician (n = 70, 17.4%)