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Introduction Chronic stable angina is common and disabling. Cardiac rehabilitation is routinely offered to people following myocardial infarction or revascularisation procedures and has the potential to help people with chronic stable angina. However, there is insufficient evidence of effectiveness and cost-effectiveness for its routine use in this patient group. The objectives of this study are to compare the effectiveness and cost-effectiveness of the ‘Activate Your Heart’ cardiac rehabilitation programme for people with chronic stable angina compared with usual care.Methods and analysis ACTIVATE is a multicentre, parallel-group, two-arm, superiority, pragmatic randomised controlled trial, with recruitment from primary and secondary care centres in England and Wales and a target sample size of 518 (1:1 allocation; allocation sequence by minimisation programme with built-in random element). The study uses secure web-based allocation concealment. The two treatments will be optimal usual care (control) and optimal usual care plus the ‘Activate Your Heart’ web-based cardiac rehabilitation programme (intervention). Outcome assessment and statistical analysis will be performed blinded; participants will be unblinded. Outcomes will be measured at baseline and at 6 and 12 months’ follow-up. Primary outcome will be the UK version of Seattle Angina Questionnaire (SAQ-UK), physical limitations domain at 12 months’ follow-up. Secondary outcomes will be the remaining two domains of SAQ-UK, dyspnoea, anxiety and depression, health utility, self-efficacy, physical activity and the incremental shuttle walk test. All safety events will be recorded, and serious adverse events assessed to determine whether they are related to the intervention and expected. Concurrent economic evaluation will be cost–utility analysis from health service perspective. An embedded process evaluation will determine the mechanisms and processes that explain the implementation and impacts of the cardiac rehabilitation programme.Ethics and dissemination North of Scotland National Health Service Research Ethics Committee approval, reference 21/NS/0115. Participants will provide written informed consent. Results will be disseminated by peer-reviewed publication.Trial registration number ISRCTN10054455.

Objective The perioperative management of patients on antiplatelet drugs is a rising challenge in orthopedic trauma because antiplatelet drugs are frequently encountered and carry an increased risk of hemorrhagic consequences. The study objective was to examine the effect of aspirin on bleeding outcomes for patients with lower extremity fractures.Methods This retrospective study included patients requiring surgical fixation of traumatic hip, femur, and tibia fractures from January 1, 2018, to March 1, 2020. Patients were excluded if they had a significant head injury, were on chronic anticoagulant therapy, or they did not receive venous thromboembolism chemoprophylaxis. Comparisons between aspirin users (patients on aspirin therapy preinjury) and non-aspirin users were examined using χ2 tests, Cochran-Mantel-Haenszel tests, and multivariate logistic regression. The primary outcome was an overt, actionable bleed (eg, blood transfusion for surgical site hemorrhage) within 24 hours postoperative.Results There were 864 patients with lower extremity long bone fractures and 24% were aspirin users. The incidence of postoperative bleeding was 8.8% and significantly differed for patients taking aspirin versus not (13.6% vs 7.3%, p=0.01). However, biological sex at birth (M/F) was a significant effect modifier (interaction p=0.04). Among women, there were significantly more postoperative bleeds for aspirin users (17.8% aspirin vs 7.4% no aspirin, adjusted OR (AOR): 2.48 (1.28–4.81), p=0.01). Among men, there were similar postoperative bleeding events by aspirin use (5.6% aspirin vs 7.2% no aspirin, AOR: 0.50 (0.14–1.82), p=0.30). Postoperative hemoglobin values

Entomological research studies on mosquito vector biology, vector competence, insecticide resistance, dispersal, and survival (using mark-release-recapture techniques) often rely on laboratory-reared mosquito colonies to produce large numbers of consistently reared, aged, and sized mosquitoes. We developed a low-cost blood feeding apparatus that supports temperatures consistent with warm blooded animals, using commonly available materials found in low resource environments. We compare our system ("Caserotek") to Hemotek and glass/membrane feeding methods. Two experiments were conducted with Aedes aegypti (Linnaeus 1762) and one with Anopheles darlingi (Root 1926) (Diptera: Culicidae); 3 replicates were conducted for each experiment. Aedes aegypti female mosquitoes were provided chicken blood once per week for 30 min (Experiment #1) for 14 days or 1 hour (Experiment #2) for 21 days. Anopheles darlingi were fed once for 1 hour (Experiment #3). Blood-feeding rates, survival rates, and egg production were calculated across replicates. Caserotek had a significantly higher 30-min engorgement rate (91.1%) than Hemotek (47.7%), and the glass feeder (29.3%) whereas for 1-hour feeding, Hemotek had a significantly lower engorgement rate than either of the other two devices (78% versus 91%). Thirty-day survival was similar among the feeding devices, ranging from 86% to 99%. Mean egg production was highest for the Caserotek feeder (32 eggs per female) compared to the glass feeder and Hemotek device (21-22 eggs per female). Our new artificial feeding system had significantly higher blood feeding rates than for more expensive artificial systems and was equivalent to other fitness parameters. Caserotek only requires the ability to boil water to maintain blood temperatures using a Styrofoam liner. It can be easily scaled up to large production facilities and used under austere conditions.

This study addresses the paucity of research concerning the subjective experiences of those affected by anosmia. In the study, we interviewed individuals(n = 11) recruited via the charity (Fifth Sense) and used Interpretative Phenomenological Analysis (IPA) to analyse the data. Findings revealed three main themes and seven sub themes. The main themes are Living with Anosmia; Remembrance of things old and new and Resilience. The study reveals the process of becoming aware of being anosmic and the relationships with others in this process including potentially unhelpful minimisations of the impact by professionals. In addition to a sense of isolation and insecurity, living with anosmia for some participants brought with it an identification of being 'anosmic' and feeling part of a community. This was in contrast to a general lack of public knowledge and understanding of anosmia. The findings of the study demonstrated the importance of smell to time, place and relationship and the recalling of smells as bringing a sense of connectivity to loved ones, of times past and also a sense of loss of ability. Participants also described the ways in which they coped and adapted to a life with anosmia and focused on positive aspects of life. These findings provide a rich qualitative account of the experience of anosmia. The findings point towards future research which could inform us about the lives of those who are anosmic and currently unaware and of those recently diagnosed, which will create a richer understanding of the experiences of anosmia.

Abstract This study describes the evolution of knockdown resistance (kdr) haplotypes in Aedes aegypti in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (~10,000 samples), this is the most thorough study of kdr population genetics in Ae. aegypti to date within a city. We provide evidence for the direct connection between programmatic citywide pyrethroid spraying and the increase in frequency of specific kdr haplotypes by identifying two evolutionary events in the population. The relatively high selection coefficients, even under infrequent insecticide pressure, emphasize how quickly Ae. aegypti populations can evolve. In our examination of the literature on mosquitoes and other insect pests, we could find no cases where a pest evolved so quickly to so few exposures to low or nonresidual insecticide applications. The observed rapid increase in frequency of resistance alleles might have been aided by the incomplete dominance of resistance‐conferring alleles over corresponding susceptibility alleles. In addition to dramatic temporal shifts, spatial suppression experiments reveal that genetic heterogeneity existed not only at the citywide scale, but also on a very fine scale within the city.

Abstract In sub-Saharan Africa, over half of the population is exposed to contaminated drinking water. The WHO recommends both sanitary inspection and water quality analysis to assess the risk of water source contamination, but the relationship between these tools is poorly understood. We explore the relationship between sanitary inspection and water quality analysis using data from 1028 boreholes with handpumps in 12 countries in sub-Saharan Africa. Sanitary inspection scores and E. coli occurrence were compared using the models described in published literature, and an alternative model that better reflects causal pathways of contamination. In the alternative model, sanitary risk factors were categorized as contamination sources, carriers, or barrier breakdowns, and the relationships between risk factor combinations and E. coli occurrence were assessed. We found no associations between sanitary risk score and E. coli occurrence using either the established or alternative model. These results confirm that sanitary inspections and microbial analyses convey distinct information, and perfect correlation is neither expected nor desired. The alternative model demonstrated a slightly better model fit than most established models, and the model fit further improved when the occurrence of rainfall in the past two days was added as a carrier. We recommend that: implementers train water system operators to conduct sanitary inspection; and researchers work to improve our understanding of the effect of individual sanitary risk factors, as well as incorporate contextual data into their assessments of sanitary inspection and water quality.

Abstract Background Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD. Methods From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale. Results Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p

Background Major bleeding after acute coronary syndrome predicts a poor outcome but is challenging to define. The choice of antiplatelet influences bleeding risk. Methods and Results Major bleeding, subsequent myocardial infarction (MI), and all‐cause mortality to 1 year were compared in consecutive patients with acute coronary syndrome treated with clopidogrel (n=2491 between 2011 and 2013) and ticagrelor (n=2625 between 2012 and 2015) in 5 English hospitals. Clinical outcomes were identified from national hospital episode statistics. Bleeding and MI events were independently adjudicated by 2 experienced clinicians, blinded to drug, sequence, and year. Bleeding events were categorized using Bleeding Academic Research Consortium 3 to 5 and PLATO (Platelet Inhibition and Patient Outcomes) criteria and MI by the Third Universal Definition. Multivariable regression analysis was used to adjust outcomes for case mix. The median age was 68 years and 34% were women. 39% underwent percutaneous coronary intervention and 13% coronary artery bypass graft surgery. Clinical outcome data were 100% complete for bleeding and 99.7% for MI. No statistically significant difference was seen in crude or adjusted major bleeding for ticagrelor compared with clopidogrel (Bleeding Academic Research Consortium 3–5, hazard ratio [HR], 1.23; 95% CI, 0.90–1.68; P=0.2, PLATO major adjusted HR, 1.30; 95% CI, 0.98–1.74; P=0.07) except in the non‐coronary artery bypass graft cohort (n=4464), where bleeding was more frequent with ticagrelor (Bleeding Academic Research Consortium 3–5, adjusted HR, 1.58; 95% CI, 1.09–2.31; P=0.017; and PLATO major HR, 1.67; 95% CI, 1.18–2.37; P=0.004). There was no difference in crude or adjusted subsequent MI (adjusted HR, 1.20; 95% CI, 0.87–1.64; P=0.27). Crude mortality was higher in the clopidogrel group but not after adjustment, using either Cox proportional hazards or propensity matched population (HR, 0.90; 95% CI, 0.76–1.10; P=0.21) as was the case for stroke (HR, 0.82; 95% CI, 0.52–1.32; P=0.42). Conclusions This observational study indicates that the apparent benefit of ticagrelor demonstrated in a clinical trial population may not be observed in the broader population encountered in clinical practice. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02484924.

We aimed to investigate if major vascular surgery induces LDL oxidation, and whether circulating antibodies against malondialdehyde-modified LDL (MDA-LDL) alter dynamically in this setting. We also questioned relationships between these biomarkers and post-operative cardiovascular events. Major surgery can induce an oxidative stress response. However, the role of the humoral immune system in clearance of oxidized LDL following such an insult is unknown. Plasma samples were obtained from a prospective cohort of 131 patients undergoing major non-cardiac vascular surgery, with samples obtained preoperatively and at 24- and 72 h postoperatively. Enzyme-linked immunoassays were developed to assess MDA-LDL-related antibodies and complexes. Adverse events were myocardial infarction (primary outcome), and a composite of unstable angina, stroke and all-cause mortality (secondary outcome). MDA-LDL significantly increased at 24 h post-operatively (p < 0.0001). Conversely, levels of IgG and IgM anti-MDA-LDL, as well as IgG/IgM-MDA-LDL complexes and total IgG/IgM, were significantly lower at 24 h (each p < 0.0001). A smaller decrease in IgG anti-MDA-LDL related to combined clinical adverse events in a post hoc analysis, withstanding adjustment for age, sex, and total IgG (OR 0.13, 95% CI [0.03–0.5], p < 0.001; p value for trend

Objectives Early access to invasive coronary angiography and revascularisation for high-risk non-ST elevation myocardial infarction (NSTEMI) improves outcomes and is supported by current guidelines. We sought to determine the most effective criteria at presentation to emergency department (ED) to identify high-risk NSTEMI.Setting Secondary care centre northwest England with national follow-up.Participants 1642 consecutive patients (median age 59, 52% male) presenting to ED with a primary symptom of chest pain in whom there is suspicion of NSTEMI.Primary and secondary measures Multivariate logistic regression analysis for the prediction of all-cause death (primary) and major adverse cardiac event (MACE defined as all-cause death, unplanned coronary revascularisation and adjudicated NSTEMI (third universal definition)) (secondary measure) at 1 year.Results The incidence of adjudicated NSTEMI was 10.7%, and 1-year mortality was 6.3%. Independent predictors for all-cause death at 1 year were Global Registry of Acute Coronary Events (GRACE) >140, age (per decade increase) and high-sensitive cardiac troponin T (hs-cTnT) >50 ng/L. hs-cTnT >50 ng/L was associated with adjudicated index presentation NSTEMI in the greatest proportion of patients (61.7%). When using MACE at 12 months, as opposed to all-cause death, as an end point History, ECG, Age, Risk factors and Troponin (HEART) score ≥7 was included in the multivariate model and had better prediction of index NSTEMI than GRACE>140. Combining hs-cTnT >50 ng/L and a second independent predictor identified both a high proportion of index NSTEMI and elevated risk of all-cause death at 1 year.Conclusions hs-cTnT >50 ng/L or HEART score ≥7 appear effective strategies to identify high-risk NSTEMI at presentation to emergency room with chest pain. Multicentre prospective studies enriched with early presenters, and with competitor high-sensitive and point-of-care troponins, are required to validate and extend these findings.Trial registration number NCT02581540.

Recent rapid technological advancements in cardiac CT have improved image quality and reduced radiation exposure to patients. Furthermore, key insights from large cohort trials have helped delineate cardiovascular disease risk as a function of overall coronary plaque burden and the morphological appearance of individual plaques. The advent of CT-derived fractional flow reserve promises to establish an anatomical and functional test within one modality. Recent data examining the short-term impact of CT-derived fractional flow reserve on downstream care and clinical outcomes have been published. In addition, machine learning is a concept that is being increasingly applied to diagnostic medicine. Over the coming decade, machine learning will begin to be integrated into cardiac CT, and will potentially make a tangible difference to how this modality evolves. The authors have performed an extensive literature review and comprehensive analysis of the recent advances in cardiac CT. They review how recent advances currently impact on clinical care and potential future directions for this imaging modality.

A drive to reduce costs, carbon emissions, and the number of required personnel in the offshore energy industry has led to proposals for the increased use of autonomous/robotic systems for many maintenance tasks. There are questions over how such missions can be shown to be safe. A corollary exists in the manned aviation world for helicopter–ship operations where a test pilot attempts to operate from a ship under a range of wind conditions and provides subjective feedback on the level of difficulty encountered. This defines the ship–helicopter operating limit envelope (SHOL). Due to the cost of creating a SHOL there has been considerable research activity to demonstrate that much of this process can be performed virtually. Unmanned vehicles, however, have no test pilot to provide feedback. This paper therefore explores the possibility of adapting manned simulation techniques to the unmanned world to demonstrate that a mission is safe. Through flight modelling and simulation techniques it is shown that operating envelopes can be created for an oil rig inspection task and that, by using variable performance specifications, these can be tailored to suit the level of acceptable risk. The operating envelopes produced provide condensed and intelligible information regarding the environmental conditions under which the UAS can perform the task.

Usually, the design of an Autonomous Vehicle (AV) does not take into account traffic rules and so the adoption of these rules can bring some challenges, e.g., how to come up with a Digital Highway Code which captures the proper behaviour of an AV against the traffic rules and at the same time minimises changes to the existing Highway Code? Here, we formally model and implement three Road Junction rules (from the UK Highway Code). We use timed automata to model the system and the MCAPL (Model Checking Agent Programming Language) framework to implement an agent and its environment. We also assess the behaviour of our agent according to the Road Junction rules using a double-level Model Checking technique, i.e., UPPAAL at the design level and AJPF (Agent Java PathFinder) at the development level. We have formally verified 30 properties (18 with UPPAAL and 12 with AJPF), where these properties describe the agent’s behaviour against the three Road Junction rules using a simulated traffic scenario, including artefacts like traffic signs and road users. In addition, our approach aims to extract the best from the double-level verification, i.e., using time constraints in UPPAAL timed automata to determine thresholds for the AVs actions and tracing the agent’s behaviour by using MCAPL, in a way that one can tell when and how a given Road Junction rule was selected by the agent. This work provides a proof-of-concept for the formal verification of AV behaviour with respect to traffic rules.

The advent of sophisticated robotics and AI technology makes sending humans into hazardous and distant environments to carry out inspections increasingly avoidable. Being able to send a robot, rather than a human, into a nuclear facility or deep space is very appealing. However, building these robotic systems is just the start and we still need to carry out a range of verification and validation tasks to ensure that the systems to be deployed are as safe and reliable as possible. Based on our experience across three research and innovation hubs within the UK’s “Robots for a Safer World” programme, we present an overview of the relevant techniques and challenges in this area. As the hubs are active across nuclear, offshore, and space environments, this gives a breadth of issues common to many inspection robots.

The development and deployment of Autonomous Vehicles (AVs) on our roads is not only realistic in the near future but can also bring significant benefits. In particular, it can potentially solve several problems relating to vehicles and traffic, for instance: (i) possible reduction of traffic congestion, with the consequence of improved fuel economy and reduced driver inactivity; (ii) possible reduction in the number of accidents, assuming that an AV can minimise the human errors that often cause traffic accidents; and (iii) increased ease of parking, especially when one considers the potential for shared AVs. In order to deploy an AV there are significant steps that must be completed in terms of hardware and software. As expected, software components play a key role in the complex AV system and so, at least for safety, we should assess the correctness of these components. In this paper, we are concerned with the high-level software component(s) responsible for the decisions in an AV. We intend to model an AV capable of navigation; obstacle avoidance; obstacle selection (when a crash is unavoidable) and vehicle recovery, etc, using a rational agent. To achieve this, we have established the following stages. First, the agent plans and actions have been implemented within the Gwendolen agent programming language. Second, we have built a simulated automotive environment in the Java language. Third, we have formally specified some of the required agent properties through LTL formulae, which are then formally verified with the AJPF verification tool. Finally, within the MCAPL framework (which comprises all the tools used in previous stages) we have obtained formal verification of our AV agent in terms of its specific behaviours. For example, the agent plans responsible for selecting an obstacle with low potential damage, instead of a higher damage obstacle (when possible) can be formally verified within MCAPL. We must emphasise that the major goal (of our present approach) lies in the formal verification of agent plans, rather than evaluating real-world applications. For this reason we utilised a simple matrix representation concerning the environment used by our agent.

An amendment to this paper has been published and can be accessed via the original article.

Rotator cuff tears are increasing in frequency in the aging population and are a common issue seen by orthopaedic surgeons. In patients with large, multi-tendon rotator cuff tears or retears, treatment can be challenging. Failure rates of up to 90% have been reported for rotator cuff repair (RCR) of large, multi-tendon tears. Biological augmentation has been an area of interest because of the distinctly different biology of the repaired tendon compared with the native tendon. These biological differences affect the ultimate tensile properties of the repair and may contribute to gap formation and the high failure rate of repairs. RCR with allograft augmentation is a technique that shows potential benefit to healing and preventing retears. Arthroscopic augmentation of RCRs can be challenging. The technique described in this Technical Note illustrates a simple and easily reproducible method for augmenting RCRs with human acellular dermal allograft.

As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer’s disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia.

Sensor-driven systems provide data and information that facilitate real-time decision-making and autonomous actuation, as well as enable informed policy choices. However, can we be sure that these systems work as expected? Can we model them in a way that captures all the key issues? We define two concepts: frames of reference and frames of function that help us organise models of sensor-based systems and their purpose. Examples from a smart water distribution network illustrate how frames offer a lens through which to organise and balance multiple views of the system. Frames aid communication between modellers, analysts and stakeholders, and distinguish the purpose of each model, which contributes towards our trust that the system fulfils its purpose.

Current approaches to the engineering of space software such as satellite control systems are based around the development of feedback controllers using packages such as MatLab's Simulink toolbox. These provide powerful tools for engineering real time systems that adapt to changes in the environment but are limited when the controller itself needs to be adapted. We are investigating ways in which ideas from temporal logics and agent programming can be integrated with the use of such control systems to provide a more powerful layer of autonomous decision making. This paper will discuss our initial approaches to the engineering of such systems.

Background: Acute coronary syndromes (ACSs) are life-threatening conditions associated with acute myocardial ischaemia. There are three main types of ACS: ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA). One treatment for ACS is percutaneous coronary intervention (PCI) plus adjunctive treatment with antiplatelet drugs. Dual therapy antiplatelet treatment [aspirin plus either prasugrel (Efient®, Daiichi Sankyo Company Ltd UK/Eli Lilly and Company Ltd), clopidogrel or ticagrelor (Brilique®, AstraZeneca)] is standard in UK clinical practice. Prasugrel is the focus of this review. Objectives: The remit is to appraise the clinical effectiveness and cost-effectiveness of prasugrel within its licensed indication for the treatment of ACS with PCI and is a review of National Institute for Health and Care Excellence technology appraisal TA182. Data sources: Four electronic databases (MEDLINE, EMBASE, The Cochrane Library, PubMed) were searched from database inception to June 2013 for randomised controlled trials (RCTs) and to August 2013 for economic evaluations comparing prasugrel with clopidogrel or ticagrelor in ACS patients undergoing PCI. Methods: Clinical outcomes included non-fatal and fatal cardiovascular (CV) events, adverse effects of treatment and health-related quality of life (HRQoL). Cost-effectiveness outcomes included incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. An independent economic model assessed four mutually exclusive subgroups: ACS patients treated with PCI for STEMI and with and without diabetes mellitus and ACS patients treated with PCI for UA or NSTEMI and with and without diabetes mellitus. Results: No new RCTs were identified beyond that reported in TA182. TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction 38) compared prasugrel with clopidogrel in ACS patients scheduled for PCI. No relevant economic evaluations were identified. Our analyses focused on a key subgroup of patients: those aged 60 kg (no previous stroke or transient ischaemic attack). For the primary composite end point (death from CV causes, non-fatal myocardial infarction or non-fatal stroke) statistically significantly fewer events occurred in the prasugrel arm (8.3%) than in the clopidogrel arm (11%). No statistically significant difference in major bleeding events was noted. However, there was a significant difference in favour of clopidogrel when major and minor bleeding events were combined (3.0 vs. 3.9%). No conclusions could be drawn regarding HRQoL. The results of sensitivity analyses confirmed that it is likely that, for all four ACS subgroups, within 5–10 years prasugrel is a cost-effective treatment option compared with clopidogrel at a willingness-to-pay threshold of £20,000 to £30,000 per QALY gained. At the full 40-year time horizon, all estimates are

DNA and RNA micro- and nanoparticles are increasingly being used for gene and siRNA drug delivery and a variety of other applications in bionanotechnology. On the nanoscale, these entities represent unique challenges from a physicochemical characterization perspective. Here, nucleic acid conjugates with protamine and gold nanoparticles (GNP) were characterized comparatively in the nanorange of concentration by UV/Vis NanoDrop spectroscopy, fluorimetry, and gel electrophoresis. Given the intense interest in splice-site switching oligomers (SSOs), we utilized a human tumor cell culture system (HeLa pLuc-705), in which SSO-directed splicing repair upregulates luciferase expression, in order to investigate bioactivity of the bionanoconjugates. Process parameters important for bioactivity were investigated, and the bimolecular nanoconjugates were confirmed by shifts in the dynamic laser light scatter (DLLS), UV/Vis spectrum, gel electrophoresis, or sedimentation pattern. The data presented herein may be useful in the future development of pharmaceutical and biotechnology formulations, processes, and analyses concerning protein, DNA, or RNA bionanoconjugates.

It is a characteristic of swarm robotics that specifying overall emergent swarm behaviours in terms of the low-level behaviours of individual robots is very difficult. Yet if swarm robotics is to make the transition from the laboratory to real-world engineering realisation we need such specifications. This paper explores the use of temporal logic to formally specify, and possibly also prove, the emergent behaviours of a robotic swarm. The paper makes use of a simplified wireless connected swarm as a case study with which to illustrate the approach. Such a formal approach could be an important step toward a disciplined design methodology for swarm robotics.

Cellular molecules possess various mechanisms in responding to oxidant stress. In terms of protein responses, protein S-glutathionylation is a unique post-translational modification of protein reactive cysteines forming disulfides with glutathione molecules. This modification has been proposed to play roles in antioxidant, regulatory and signaling in cells under oxidant stress. Recently, the increased level of protein S-glutathionylation has been linked with the development of diseases. In this report, specific S-glutathionylated proteins were demonstrated in human embryonic kidney 293 cells treated with two different oxidative reagents: diamide and hydrogen peroxide. Diamide is a chemical oxidizing agent whereas hydrogen peroxide is a physiological oxidant. Under the experimental conditions, these two oxidants decreased glutathione concentration without toxicity. S-glutathionylated proteins were detected by immunoblotting and glutathione concentrations were determined by high performance liquid chromatography. We further show the effect of alteration of the cellular thiol pool on the amount of protein S-glutathionylation in oxidant-treated cells. Cellular thiol concentrations were altered either by a specific way using buthionine sulfoximine, a specific inhibitor of glutathione biosynthesis or by a non-specific way, incubating cells in cystine-methionine deficient media. Cells only treated with either buthionine sulfoximine or cystine-methionine deficient media did not induce protein S-glutathionylation, even though both conditions decreased 65% of cellular glutathione. Moreover, the amount of protein S-glutathionylation under both conditions in the presence of oxidants was not altered when compared to the amount observed in regular media with oxidants present. Protein S-glutathionylation is a dynamic reaction which depends on the rate of adding and removing glutathione. Phenylarsine oxide, which specifically forms a covalent adduct with vicinal thiols, was used to determine the possible role of vicinal thiols in the amount of glutathionylation. Our data shows phenylarsine oxide did not change glutathione concentrations, but it did enhance the amount of glutathionylation in oxidant-treated cells.

It is a characteristic of swarm robotics that specifying overall emergent swarm behaviours in terms of the low-level behaviours of individual robots is very difficult. Yet if swarm robotics is to make the transition from the laboratory to real-world engineering realisation we need such specifications. This paper explores the use of temporal logic to formally specify, and possibly also prove, the emergent behaviours of a robotic swarm. The paper makes use of a simplified wireless connected swarm as a case study with which to illustrate the approach. Such a formal approach could be an important step toward a disciplined design methodology for swarm robotics.