X-Ray Measurement of Material Properties in Composites

Advanced materials for use in the aerospace industry are presently being developed and applied at an astonishing rate. This pace is driven by the need for materials that can withstand higher operating temperatures and loads, yet remain cost competitive. As the performance demands of aerospace materials push nearer and nearer the theoretical limit for strength, the allowed flaw size in traditional materials is driven smaller, making quality control more stringent. This demand for improved performance characteristics is also generating strong interest in other materials such as: exotic alloys, ceramics and reinforced composites. A need exists for characterizing these advanced materials for composition variations, flaw content, inclusions and porosity using nondestructive techniques at all stages of the materials life cycle. These stages include initial characterization of a new material, process control during the manufacturing of the material, quality control of incoming material, and the in service inspection of the final part

A comparison of microsatellite instability in early onset gastric carcinomas from relatively low and high incidence European populations.

We have investigated the genetic basis of gastric carcinomas occurring in patients aged under 40 years from a Portuguese population with a relatively high incidence of gastric cancer. We analysed a panel of 12 microsatellite loci in DNA extracted from gastric carcinomas arising in 16 patients aged 24-39 years from Braga, Portugal. Overall, microsatellite instability (MI) in at least 1 locus was detected in 44% (7 of 16) of carcinomas. A single patient demonstrated a mutator phenotype suggestive of the hereditary nonpolyposis colorectal cancer syndrome with instability in 82% of loci. This carcinoma showed loss of expression of the hMLH1 mismatch repair protein. In a previous study, we found no evidence of MI among 10 cases of early onset gastric carcinomas from an English population, which has a relatively low incidence of gastric cancer. Comparing the 2 series, we found that there was a significant difference (p = 0.04) in the prevalence of MI (at least 1 marker affected). This geographical difference in low-level MI may be related to a significantly higher prevalence of background chronic atrophic gastritis (8 of 16 vs. 0 of 8) and Helicobacter pylori infection (15 of 16 vs. 2 of 8) in Portuguese carcinomas compared with English cases. Genetic mechanisms underlying the hereditary non-polyposis colorectal cancer syndrome may play a role in a small number of early onset gastric carcinomas. The difference in prevalence of low-level MI between these relatively high and low incidence European populations requires further investigation

Cross-sectional evaluation of a longitudinal consultation skills course at a new UK medical school

Background: Good communication is a crucial element of good clinical care, and it is important to provide appropriate consultation skills teaching in undergraduate medical training to ensure that doctors have the necessary skills to communicate effectively with patients and other key stakeholders. This article aims to provide research evidence of the acceptability of a longitudinal consultation skills strand in an undergraduate medical course, as assessed by a cross-sectional evaluation of students' perceptions of their teaching and learning experiences. Methods: A structured questionnaire was used to collect student views. The questionnaire comprised two parts: 16 closed questions to evaluate content and process of teaching and 5 open-ended questions. Questionnaires were completed at the end of each consultation skills session across all year groups during the 2006-7 academic year (5 sessions in Year 1, 3 in Year 2, 3 in Year 3, 10 in Year 4 and 10 in Year 5). 2519 questionnaires were returned in total. Results: Students rated Tutor Facilitation most favourably, followed by Teaching, then Practice & Feedback, with suitability of the Rooms being most poorly rated. All years listed the following as important aspects they had learnt during the session: • how to structure the consultation • importance of patient-centredness • aspects of professionalism (including recognising own limits, being prepared, generally acting professionally). All years also noted that the sessions had increased their confidence, particularly through practice. Conclusions: Our results suggest that a longitudinal and integrated approach to teaching consultation skills using a well structured model such as Calgary-Cambridge, facilitates and consolidates learning of desired process skills, increases student confidence, encourages integration of process and content, and reinforces appreciation of patient-centredness and professionalism

Variation in quality of acute stroke care by day and time of admission: prospective cohort study of weekday and weekend centralised hyperacute stroke unit care and non-centralised services.

OBJECTIVE: To investigate variations in quality of acute stroke care and outcomes by day and time of admission in London hyperacute stroke units compared with the rest of England. DESIGN: Prospective cohort study using anonymised patient-level data from the Sentinel Stroke National Audit Programme. SETTING: Acute stroke services in London hyperacute stroke units and the rest of England. PARTICIPANTS: 68 239 patients with a primary diagnosis of stroke admitted between January and December 2014. INTERVENTIONS: Hub-and-spoke model for care of suspected acute stroke patients in London with performance standards designed to deliver uniform access to high-quality hyperacute stroke unit care across the week. MAIN OUTCOME MEASURES: 16 indicators of quality of acute stroke care, mortality at 3 days after admission to the hospital, disability at the end of the inpatient spell, length of stay. RESULTS: There was no variation in quality of care by day and time of admission to the hospital across the week in terms of stroke nursing assessment, brain scanning and thrombolysis in London hyperacute stroke units, nor was there variation in 3-day mortality or disability at hospital discharge (all p values>0.05). Other quality of care measures significantly varied by day and time of admission across the week in London (all p values0.05). CONCLUSIONS: The London hyperacute stroke unit model achieved performance standards for 'front door' stroke care across the week. The same benefits were not achieved by other models of care in the rest of England. There was no weekend effect for mortality in London or the rest of the England. Other aspects of care were not constant across the week in London hyperacute stroke units, indicating some performance standards were perceived to be more important than others

Treatment delays in paediatric dento-alveolar trauma at a tertiary referral hospital

Background: Paediatric dento-alveolar trauma is a common event. Delays in treatment can have adverse effects on long term outcomes and the aim of this study was to quantify the treatment delays in paediatric dento-alveolar trauma in a tertiary referral hospital. Methods: All cases of paediatric dento-alveolar trauma over a two-year period from July 2000 to June 2002 were identified and the charts were reviewed retrospectively. All children presenting the emergency department with dento-alveolar trauma within 48 hours of injury during the time period were included. Results: Forty-three patients were identified. The average age was 5.51 years, though there was a bias towards one and two year olds. Males were injured 1.5 times more frequently than females. There was an average delay of 9.6 hours between injury and treatment for all patients. Transit time from outside practitioners to hospital and waiting times in hospital made up the greatest delays. Children injured an average of 2.37 teeth and only 14 per cent were uncomplicated crown fractures. Conclusions: Children who present to children's hospitals for treatment of dento-alveolar trauma have more severe injuries than those treated elsewhere. They have large but potentially reducible delays between injury and treatment

What does it take to provide clinical interventions with temporal consistency? A qualitative study of London hyperacute stroke units.

OBJECTIVES: Seven-day working in hospitals is a current priority of international health research and policy. Previous research has shown variability in delivering evidence-based clinical interventions across different times of day and week. We aimed to identify factors influencing such variations in London hyperacute stroke units (HASUs). DESIGN: Interview and observation study to explain patterns of variation in delivery and outcomes of care described in a quantitative partner paper (Melnychuk et al). SETTING: Eight HASUs in London. PARTICIPANTS: We interviewed HASU staff (n=76), including doctors, nurses, therapists and administrators. We also conducted non-participant observations of delivery of care at different times of the day and week (n=45; ~102 hours). We analysed the data for thematic content relating to the ability of staff to provide evidence-based interventions consistently at different times of the day and week. RESULTS: Staff were able to deliver 'front door' interventions consistently by taking on additional responsibilities out of hours (eg, deciding eligibility for thrombolysis); creating continuities between day and night (through, eg, governance processes and staggering rotas); building trusting relationships with, eg, Radiology and Emergency Departments and staff prioritisation of 'front door' interventions. Variations by time of day resulted from reduced staffing in HASUs and elsewhere in hospitals in the evenings and at the weekend. Variations by day of week (eg, weekend effect) resulted from lack of therapy input and difficulties repatriating patients at weekends, and associated increases in pressure on Fridays and Mondays. CONCLUSIONS: Evidence-based service standards can facilitate 7-day working in acute stroke services. Standards should ensure that the capacity and capabilities required for 'front door' interventions are available 24/7, while other services, for example, therapies are available every day of the week. The impact of standards is influenced by interdependencies between HASUs, other hospital services and social services

TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

<p>Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.</p> <p>Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.</p> <p>Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.</p&gt