Investigation of shock waves in explosive blasts using fibre optic pressure sensors

The published version of this article may be accessed at the link below. Copyright @ IOP Publishing, 2006.We describe miniature all-optical pressure sensors, fabricated by wafer etching techniques, less than 1 mm(2) in overall cross-section with rise times in the mu s regime and pressure ranges typically 900 kPa (9 bar). Their performance is suitable for experimental studies of the pressure-time history for test models exposed to shocks initiated by an explosive charge. The small size and fast response of the sensors promises higher quality data than has been previously available from conventional electrical sensors, with potential improvements to numerical models of blast effects. Results from blast tests are presented in which up to six sensors were multiplexed, embedded within test models in a range of orientations relative to the shock front.Support from the UK Engineering&Physical Sciences Research Council and Dstl Fort Halstead through the MoD Joint Grants Scheme are acknowledged. WN MacPherson is supported by an EPSRC Advanced Research Fellowship

Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders

Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD

Circadian clock mechanism driving mammalian photoperiodism

From Springer Nature via Jisc Publications RouterHistory: received 2020-01-16, accepted 2020-07-27, registration 2020-08-04, pub-electronic 2020-08-27, online 2020-08-27, collection 2020-12Publication status: PublishedAbstract: The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-based coincidence timer for photoperiodic synchronization in plants. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that long photoperiods induce the circadian transcription factor BMAL2, in the pars tuberalis of the pituitary, and triggers summer biology through the eyes absent/thyrotrophin (EYA3/TSH) pathway. Conversely, long-duration melatonin signals on short photoperiods induce circadian repressors including DEC1, suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock-pituitary epigenetic pathway interactions form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates

Development of a measure of model fidelity for mental health Crisis Resolution Teams

Background Crisis Resolution Teams (CRTs) provide short-term intensive home treatment to people experiencing mental health crisis. Trial evidence suggests CRTs can be effective at reducing hospital admissions and increasing satisfaction with acute care. When scaled up to national level however, CRT implementation and outcomes have been variable. We aimed to develop and test a fidelity scale to assess adherence to a model of best practice for CRTs, based on best available evidence. Methods A concept mapping process was used to develop a CRT fidelity scale. Participants (n = 68) from a range of stakeholder groups prioritised and grouped statements (n = 72) about important components of the CRT model, generated from a literature review, national survey and qualitative interviews. These data were analysed using Ariadne software and the resultant cluster solution informed item selection for a CRT fidelity scale. Operational criteria and scoring anchor points were developed for each item. The CORE CRT fidelity scale was then piloted in 75 CRTs in the UK to assess the range of scores achieved and feasibility for use in a 1-day fidelity review process. Trained reviewers (n = 16) rated CRT service fidelity in a vignette exercise to test the scale’s inter-rater reliability. Results There were high levels of agreement within and between stakeholder groups regarding the most important components of the CRT model. A 39-item measure of CRT model fidelity was developed. Piloting indicated that the scale was feasible for use to assess CRT model fidelity and had good face validity. The wide range of item scores and total scores across CRT services in the pilot demonstrate the measure can distinguish lower and higher fidelity services. Moderately good inter-rater reliability was found, with an estimated correlation between individual ratings of 0.65 (95% CI: 0.54 to 0.76). Conclusions The CORE CRT Fidelity Scale has been developed through a rigorous and systematic process. Promising initial testing indicates its value in assessing adherence to a model of CRT best practice and to support service improvement monitoring and planning. Further research is required to establish its psychometric properties and international applicability

Exploring the relationship between media coverage and participation in entrepreneurship : initial global evidence and research implications

Using a set of variables measured in the Global Entrepreneurship Monitor (GEM) study, our empirical investigation explored the influence of mass media through national culture on national entrepreneurial participation rates in 37 countries over 4 years (2000 to 2003). We found that stories about successful entrepreneurs, conveyed in mass media, were not significantly associated with the rate of nascent (opportunity searching) or the rate of actual (business activities commenced up to 3 months old) start-up activity, but that there was a significant positive association between the volume of entrepreneurship media stories and a nation&rsquo;s volume of people running a young business (that is in GEM terminology, a business aged greater than 3 but less than 42 months old). More particularly, such stories had strong positive association with opportunity oriented operators of young businesses. Together, these findings are compatible with what in the mass communications theory literature may be called the &lsquo;reinforcement model&rsquo;. This argues that mass media are only capable of reinforcing their audience&rsquo;s existing values and choice propensities but are not capable of shaping or changing those values and choices. In the area covered by this paper, policy-makers are committing public resources to media campaigns of doubtful utility in the absence of an evidence base. A main implication drawn from this study is the need for further and more sophisticated investigation into the relationship between media coverage of entrepreneurship, national culture and the rates and nature of people&rsquo;s participation in the various stages of the entrepreneurial process.<br /

Working up a debt: Students as vulnerable consumers

Students are recognised as vulnerable consumers where financial matters are concerned, particularly with reference to indebtedness. This study examines student indebtedness in order to initiate wider debate about student vulnerability. We consider vulnerability as dynamic and temporal, linked to an event that renders the consumer susceptible to becoming vulnerable. Using data collected from a relatively small-scale survey of UK university students, the key findings are: reasons for debt are many and varied, typically linked to changes associated with study year; the placement year is a critical time for student debt in response to changes in circumstances and specifically lifestyle expectations; students are not accessing the best sources of advice to help them with financial decisions; and the findings suggest student insouciance towards debt with potential long term consequences. This study extends existing knowledge of consumer vulnerability and calls for greater efforts to be made to raise awareness about student indebtedness

Failure to report as a breach of moral and professional expectation

Cases of poor care have been documented across the world. Contrary to professional requirements, evidence indicates that these sometimes go unaddressed. For patients the outcomes of this inaction are invariably negative. Previous work has either focused on why poor care occurs and what might be done to prevent it, or on the reasons why those who are witness to it find it difficult to raise their concerns. Here we build on this work but specifically foreground the responsibilities of registrants and students who witness poor care. Acknowledging the challenges associated with raising concerns, we make the case that failure to address poor care is a breach of moral expectation, professional requirement and sometimes, legal frameworks. We argue that reporting will be more likely to take place if those who wish to enter the profession have a realistic view of the challenges they may encounter. When nurses are provided with robust and applied education on ethics, when ‘real-world’ cases and exemplars are used in practice and when steps are taken to develop and encourage individual moral courage, we may begin to see positive change. Ultimately however, significant change is only likely to take place where practice cultures invite and welcome feedback, promote critical reflection, and where strong, clear leadership support is shown by those in positions of influence across organisations

Nanostructures Technology, Research, and Applications

Contains reports on twenty-four research projects and a list of publications.Joint Services Electronics Program Grant DAAHO4-95-1-0038Defense Advanced Research Projects Agency/Semiconductor Research Corporation SA1645-25508PGU.S. Army Research Office Grant DAAHO4-95-1-0564Defense Advanced Research Projects Agency/U.S. Navy - Naval Air Systems Command Contract N00019-95-K-0131Suss Advanced Lithography P. O. 51668National Aeronautics and Space Administration Contract NAS8-38249National Aeronautics and Space Administration Grant NAGW-2003Defense Advanced Research Projects Agency/U.S. Army Research Office Grant DAAHO4-951-05643M CorporationDefense Advanced Research Projects Agency/U.S. Navy - Office of Naval Research Contract N66001-97-1-8909National Science Foundation Graduate FellowshipU.S. Army Research Office Contract DAAHO4-94-G-0377National Science Foundation Contract DMR-940034National Science Foundation Grant DMR 94-00334Defense Advanced Research Projects Agency/U.S. Air Force - Office of Scientific Research Contract F49620-96-1-0126Harvard-Smithsonian Astrophysical Observatory Contract SV630304National Aeronautics and Space Administration Grant NAG5-5105Los Alamos National Laboratory Contract E57800017-9GSouthwest Research Institute Contract 83832MIT Lincoln Laboratory Advanced Concepts ProgramMIT Lincoln Laboratory Contract BX-655

NRF2 Activation Restores Disease Related Metabolic Deficiencies in Olfactory Neurosphere-Derived Cells from Patients with Sporadic Parkinson's Disease

Extent: 14p.Background: Without appropriate cellular models the etiology of idiopathic Parkinson’s disease remains unknown. We recently reported a novel patient-derived cellular model generated from biopsies of the olfactory mucosa (termed olfactory neurosphere-derived (hONS) cells) which express functional and genetic differences in a disease-specific manner. Transcriptomic analysis of Patient and Control hONS cells identified the NRF2 transcription factor signalling pathway as the most differentially expressed in Parkinson’s disease. Results: We tested the robustness of our initial findings by including additional cell lines and confirmed that hONS cells from Patients had 20% reductions in reduced glutathione levels and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium, inner salt] metabolism compared to cultures from healthy Control donors. We also confirmed that Patient hONS cells are in a state of oxidative stress due to higher production of H2O2 than Control cultures. siRNA-mediated ablation of NRF2 in Control donor cells decreased both total glutathione content and MTS metabolism to levels detected in cells from Parkinson’s Disease patients. Conversely, and more importantly, we showed that activation of the NRF2 pathway in Parkinson’s disease hONS cultures restored glutathione levels and MTS metabolism to Control levels. Paradoxically, transcriptomic analysis after NRF2 pathway activation revealed an increased number of differentially expressed mRNAs within the NRF2 pathway in L-SUL treated Patient-derived hONS cells compared to L-SUL treated Controls, even though their metabolism was restored to normal. We also identified differential expression of the PI3K/AKT signalling pathway, but only post-treatment. Conclusions: Our results confirmed NRF2 as a potential therapeutic target for Parkinson’s disease and provided the first demonstration that NRF2 function was inducible in Patient-derived cells from donors with uniquely varied genetic backgrounds. However, our results also demonstrated that the response of PD patient-derived cells was not co-ordinated in the same way as in Control cells. This may be an important factor when developing new therapeutics.Anthony L. Cook, Alejandra M. Vitale, Sugandha Ravishankar, Nicholas Matigian, Greg T. Sutherland, Jiangou Shan, Ratneswary Sutharsan, Chris Perry, Peter A. Silburn, George D. Mellick, Murray L. Whitelaw, Christine A. Wells, Alan Mackay-Sim and Stephen A. Woo