239 research outputs found
A Novel Run-Time Monitoring Architecture for Safe and Efficient Inline Monitoring
20th International Conference on Reliable Software Technologies - Ada-Europe 2015 (Ada-Europe 2015), Madrid, Spain.Verification and testing are two of the most costly and time consuming steps during the development of safety critical systems. The advent of complex and sometimes partially unpredictable computing architectures such as multicore commercial-of-the-shelf platforms, together with the composable development approach adopted in multiple industrial domains such as avionics and automotive, rendered the exhaustive testing of all situations that could potentially be encountered by the system once deployed on the field nearly impossible. Run-time verification (RV) is a promising solution to help accelerate the development of safety critical applications whilst maintaining the high degree of reliability required by such systems. RV adds monitors in the application, which check at run-time if the system is behaving according to predefined specifications. In case of deviations from the specifications during the runtime, safeguarding measures can be triggered in order to keep the system and its environment in a safe state, as well as potentially attempting to recover from the fault that caused the misbehaviour. Most of the state-of-the-art on RV essentially focused on the monitor generation, concentrating on the expressiveness of the specification language and its translation in correct-by-construction monitors. Few of them addressed the problem of designing an efficient and safe run-time monitoring (RM) architecture. Yet, RM is a key component for RV. The RM layer gathers information from the monitored application and transmits it to the monitors. Therefore, without an efficient and safe RM architecture, the whole RV system becomes useless, as its inputs and hence by extension its outputs cannot be trusted. In this paper, we discuss the design of a novel RM architecture suited to safety critical applications
Researching the use of force: The background to the international project
This article provides the background to an international project on use of force by the police that was carried out in eight countries. Force is often considered to be the defining characteristic of policing and much research has been conducted on the determinants, prevalence and control of the use of force, particularly in the United States. However, little work has looked at police officers’ own views on the use of force, in particular the way in which they justify it. Using a hypothetical encounter developed for this project, researchers in each country conducted focus groups with police officers in which they were encouraged to talk about the use of force. The results show interesting similarities and differences across countries and demonstrate the value of using this kind of research focus and methodology
Ethnicity and prediction of cardiovascular disease: performance of QRISK2 and Framingham scores in a U.K. tri-ethnic prospective cohort study (SABRE--Southall And Brent REvisited).
OBJECTIVE: To evaluate QRISK2 and Framingham cardiovascular disease (CVD) risk scores in a tri-ethnic U.K. population. DESIGN: Cohort study. SETTING: West London. PARTICIPANTS: Randomly selected from primary care lists. Follow-up data were available for 87% of traced participants, comprising 1866 white Europeans, 1377 South Asians, and 578 African Caribbeans, aged 40-69 years at baseline (1998-1991). MAIN OUTCOME MEASURES: First CVD events: myocardial infarction, coronary revascularisation, angina, transient ischaemic attack or stroke reported by participant, primary care or hospital records or death certificate. RESULTS: During follow-up, 387 CVD events occurred in men (14%) and 78 in women (8%). Both scores underestimated risk in European and South Asian women (ratio of predicted to observed risk: European women: QRISK2: 0.73, Framingham: 0.73; South Asian women: QRISK2: 0.52, Framingham: 0.43). In African Caribbeans, Framingham over-predicted in men and women and QRISK2 over-predicted in women. Framingham classified 28% of participants as high risk, predicting 54% of all such events. QRISK2 classified 19% as high risk, predicting 42% of all such events. Both scores performed poorly in identifying high risk African Caribbeans; QRISK2 and Framingham identified as high risk only 10% and 24% of those who experienced events. CONCLUSIONS: Neither score performed consistently well in all ethnic groups. Further validation of QRISK2 in other multi-ethnic datasets, and better methods for identifying high risk African Caribbeans and South Asian women, are required
Care(ful) relationships: supporting children in secure care
Secure children's homes are used to accommodate children aged 10–16 under two main categories; while half are sentenced after committing a serious offence, the other half are placed because there are serious concerns around their safety in the community. Secure children's homes are prized within the secure estate, and they administer complex therapeutic support to ‘the most vulnerable’ young people, however little is known about the experiences of those employed to work in such spaces. This paper shares findings from PhD research conducted in one secure children's home over 1 year. Data presented are drawn from sensitive ethnographic fieldwork and in‐depth interviews with residential staff and residents in the home. Although young people's views are important, we concentrate here on the perspectives of residential staff to share their reflections of delivering ‘care’ and the strategies used to manage successful relationships within a secure setting. We conclude that residential staff tread a fine line between creating emotional closeness while maintaining physical distance and that they are sometimes unable to return the intensity of feeling that residents' direct towards them. We recommend that all residential staff receive regular and detailed supervision to provide opportunity to request support when necessary
Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid
The transport of monocarboxylates, such as lactate and pyruvate, is mediated by the SLC16A family of proton-linked membrane transport proteins known as monocarboxylate transporters (MCTs). Fourteen MCT-related genes have been identified in mammals and of these seven MCTs have been functionally characterized. Despite their sequence homology, only MCT1–4 have been demonstrated to be proton-dependent transporters of monocarboxylic acids. MCT6, MCT8 and MCT10 have been demonstrated to transport diuretics, thyroid hormones and aromatic amino acids, respectively. MCT1–4 vary in their regulation, tissue distribution and substrate/inhibitor specificity with MCT1 being the most extensively characterized isoform. Emerging evidence suggests that in addition to endogenous substrates, MCTs are involved in the transport of pharmaceutical agents, including γ-hydroxybuytrate (GHB), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), salicylic acid, and bumetanide. MCTs are expressed in a wide range of tissues including the liver, intestine, kidney and brain, and as such they have the potential to impact a number of processes contributing to the disposition of xenobiotic substrates. GHB has been extensively studied as a pharmaceutical substrate of MCTs; the renal clearance of GHB is dose-dependent with saturation of MCT-mediated reabsorption at high doses. Concomitant administration of GHB and l-lactate to rats results in an approximately two-fold increase in GHB renal clearance suggesting that inhibition of MCT1-mediated reabsorption of GHB may be an effective strategy for increasing renal and total GHB elimination in overdose situations. Further studies are required to more clearly define the role of MCTs on drug disposition and the potential for MCT-mediated detoxification strategies in GHB overdose
Sodium-coupled Monocarboxylate Transporters in Normal Tissues and in Cancer
SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na+-coupled manner. They are expressed in the gastrointestinal tract, kidney, thyroid, brain, and retina. SLC5A8 is localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to neurons and the retinal pigment epithelium. The physiologic functions of SLC5A8 include absorption of short-chain fatty acids in the colon and small intestine, reabsorption of lactate and pyruvate in the kidney, and cellular uptake of lactate and ketone bodies in neurons. It also transports the B-complex vitamin nicotinate. SLC5A12 is also localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to astrocytes and Müller cells. SLC5A8 also functions as a tumor suppressor; its expression is silenced in tumors of colon, thyroid, stomach, kidney, and brain. The tumor-suppressive function is related to its ability to mediate concentrative uptake of butyrate, propionate, and pyruvate, all of which are inhibitors of histone deacetylases. SLC5A8 can also transport a variety of pharmacologically relevant monocarboxylates, including salicylates, benzoate, and γ-hydroxybutyrate. Non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen, also interact with SLC5A8. These drugs are not transportable substrates for SLC5A8, but instead function as blockers of the transporter. Relatively less is known on the role of SLC5A12 in drug transport
Physical activity but not sedentary activity is reduced in primary Sjögren’s syndrome
The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren’s syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594–3158) versus 3708 (1732–8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135–375) versus 343 (223–433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0–480) versus 1560 (570–3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0–480) versus 480 (0–1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS
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