Economic costs of congestion in the East Midlands

This report estimates levels of congestion in the East Midlands and quantifies the economic costs associated with this congestion. Analyses for both the strategic road network (motorways and trunk roads) and the region's main urban areas are provided

Economic impacts of climate change adaptation/mitigation in the east midlands stage 2 report

This study builds intelligence regarding the impacts of climate change on the region and creates insights as to how the likely economic, environmental and social impacts can be mitigated, adaptive actions undertaken and market opportunities exploited by businesses in the region. This stage 2 report presents a number of detailed sector case studies

Improving public services through open data: public toilets

Bichard’s work for the TACT3 project (Bichard REF Output 3) found that UK toilet provision is not centrally collated and no national map or database of toilets exists. In contrast, the UK government’s white paper Open Public Services (2011) emphasised its commitment to incorporating the use of Open Data in public services provision that could be tailored to community preferences, and therefore be more sustainable. Incorporating Open Data on public toilet provision, Bichard and Knight (RCA) developed The Great British Public Toilet Map (GBPTM). Whilst a number of other websites and applications map toilets by ‘crowd surfing’, GBPTM is entirely populated by Open Data, and not only uses the data as information for users, but informs members of the public that such information is available and accessible for their use. This paper presents the development of the GBPTM, including inclusive design research and studies that compare accuracy of information directly provided by users with Open Data collected by local authorities. It suggests that, to meet the health and well-being of an ageing population, a sustainable and cost-effective solution must be found for ‘publicly accessible’ toilet provision, including opening up provision beyond that ‘for customers only’ and providing accurate information on current public provision. The paper highlights the barriers encountered in the production of Open Data by local authorities. A review of the paper in the journal Civil Engineering (May 2013) described the design of the GBPTM as a ‘simple and elegant solution’. The development of a digital output and an understanding of digitally based research led to Bichard’s successful submission to an EPSRC Digital Economy sandpit, in which she developed an interdisciplinary project with the Universities of Newcastle, Bournemouth and the West of England. The project, Family Rituals 2.0, secured £750,000 in research funding with Bichard as co-investigator (2013–15)

Is there evidence for accelerated polyethylene wear in uncemented compared to cemented acetabular components? A systematic review of the literature

Joint arthroplasty registries show an increased rate of aseptic loosening in uncemented acetabular components as compared to cemented acetabular components. Since loosening is associated with particulate wear debris, we postulated that uncemented acetabular components demonstrate a higher polyethylene wear rate than cemented acetabular components in total hip arthroplasty. We performed a systematic review of the peer-reviewed literature, comparing the wear rate in uncemented and cemented acetabular components in total hip arthroplasty. Studies were identified using MEDLINE (PubMed), EMBASE and the Cochrane Central Register of Controlled Trials. Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search resulted in 425 papers. After excluding duplicates and selection based on title and abstracts, nine studies were found eligible for further analysis: two randomised controlled trials, and seven observational studies. One randomised controlled trial found a higher polyethylene wear rate in uncemented acetabular components, while the other found no differences. Three out of seven observational studies showed a higher polyethylene wear in uncemented acetabular component fixation; the other four studies did not show any differences in wear rates. The available evidence suggests that a higher annual wear rate may be encountered in uncemented acetabular components as compared to cemented components

Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza

Pandemic influenza A virus (IAV) remains a significant threat to global health. Preparedness relies primarily upon a single class of neuraminidase (NA) targeted antivirals, against which resistance is steadily growing. The M2 proton channel is an alternative clinically proven antiviral target, yet a near-ubiquitous S31N polymorphism in M2 evokes resistance to licensed adamantane drugs. Hence, inhibitors capable of targeting N31 containing M2 (M2-N31) are highly desirable. Rational in silico design and in vitro screens delineated compounds favouring either lumenal or peripheral M2 binding, yielding effective M2-N31 inhibitors in both cases. Hits included adamantanes as well as novel compounds, with some showing low micromolar potency versus pandemic “swine” H1N1 influenza (Eng195) in culture. Interestingly, a published adamantane-based M2-N31 inhibitor rapidly selected a resistant V27A polymorphism (M2-A27/N31), whereas this was not the case for non-adamantane compounds. Nevertheless, combinations of adamantanes and novel compounds achieved synergistic antiviral effects, and the latter synergised with the neuraminidase inhibitor (NAi), Zanamivir. Thus, site-directed drug combinations show potential to rejuvenate M2 as an antiviral target whilst reducing the risk of drug resistance

IACT observations of gamma-ray bursts: prospects for the Cherenkov Telescope Array

Gamma rays at rest frame energies as high as 90 GeV have been reported from gamma-ray bursts (GRBs) by the Fermi Large Area Telescope (LAT). There is considerable hope that a confirmed GRB detection will be possible with the upcoming Cherenkov Telescope Array (CTA), which will have a larger effective area and better low-energy sensitivity than current-generation imaging atmospheric Cherenkov telescopes (IACTs). To estimate the likelihood of such a detection, we have developed a phenomenological model for GRB emission between 1 GeV and 1 TeV that is motivated by the high-energy GRB detections of Fermi-LAT, and allows us to extrapolate the statistics of GRBs seen by lower energy instruments such as the Swift-BAT and BATSE on the Compton Gamma-ray Observatory. We show a number of statistics for detected GRBs, and describe how the detectability of GRBs with CTA could vary based on a number of parameters, such as the typical observation delay between the burst onset and the start of ground observations. We also consider the possibility of using GBM on Fermi as a finder of GRBs for rapid ground follow-up. While the uncertainty of GBM localization is problematic, the small field-of-view for IACTs can potentially be overcome by scanning over the GBM error region. Overall, our results indicate that CTA should be able to detect one GRB every 20 to 30 months with our baseline instrument model, assuming consistently rapid pursuit of GRB alerts, and provided that spectral breaks below 100 GeV are not a common feature of the bright GRB population. With a more optimistic instrument model, the detection rate can be as high as 1 to 2 GRBs per year.Comment: 28 pages, 24 figures, 4 tables, submitted to Experimental Astronom

Safety of low-carbohydrate diets

Low-carbohydrate diets have re-emerged into the public spotlight and are enjoying a high degree of popularity as people search for a solution to the population\u27s ever-expanding waistline. The current evidence though indicates that low-carbohydrate diets present no significant advantage over more traditional energy-restricted diets on long-term weight loss and maintenance. Furthermore, a higher rate of adverse side-effects can be attributed to low-carbohydrate dieting approaches. Short-term efficacy of low-carbohydrate diets has been demonstrated for some lipid parameters of cardiovascular risk and measures of glucose control and insulin sensitivity, but no studies have ascertained if these effects represent a change in primary outcome measures. Low-carbohydrate diets are likely effective and not harmful in the short term and may have therapeutic benefits for weight-related chronic diseases although weight loss on such a program should be undertaken under medical supervision. While new commercial incarnations of the low-carbohydrate diet are now addressing overall dietary adequacy by encouraging plenty of high-fibre vegetables, fruit, low-glycaemic-index carbohydrates and healthier fat sources, this is not the message that reaches the entire public nor is it the type of diet adopted by many people outside of the world of a well-designed clinical trial. Health effects of long-term ad hoc restriction of inherently beneficial food groups without a concomitant reduction in body weight remains unanswered.<br /

ALC: automated reduction of rule-based models

<p>Abstract</p> <p>Background</p> <p>Combinatorial complexity is a challenging problem for the modeling of cellular signal transduction since the association of a few proteins can give rise to an enormous amount of feasible protein complexes. The layer-based approach is an approximative, but accurate method for the mathematical modeling of signaling systems with inherent combinatorial complexity. The number of variables in the simulation equations is highly reduced and the resulting dynamic models show a pronounced modularity. Layer-based modeling allows for the modeling of systems not accessible previously.</p> <p>Results</p> <p>ALC (Automated Layer Construction) is a computer program that highly simplifies the building of reduced modular models, according to the layer-based approach. The model is defined using a simple but powerful rule-based syntax that supports the concepts of modularity and macrostates. ALC performs consistency checks on the model definition and provides the model output in different formats (C MEX, MATLAB, <it>Mathematica </it>and SBML) as ready-to-run simulation files. ALC also provides additional documentation files that simplify the publication or presentation of the models. The tool can be used offline or via a form on the ALC website.</p> <p>Conclusion</p> <p>ALC allows for a simple rule-based generation of layer-based reduced models. The model files are given in different formats as ready-to-run simulation files.</p

Injection therapy and denervation procedures for chronic low-back pain: a systematic review

Injection therapy and denervation procedures are commonly used in the management of chronic low-back pain (LBP) despite uncertainty regarding their effectiveness and safety. To provide an evaluation of the current evidence associated with the use of these procedures, a systematic review was performed. Existing systematic reviews were screened, and the Cochrane Back Review Group trial register was searched for randomized controlled trials (RCTs) fulfilling the inclusion criteria. Studies were included if they recruited adults with chronic LBP, evaluated the use of injection therapy or denervation procedures and measured at least one clinically relevant outcome (such as pain or functional status). Two review authors independently assessed studies for eligibility and risk of bias (RoB). A meta-analysis was performed with clinically homogeneous studies, and the GRADE approach was used to determine the quality of evidence. In total, 27 RCTs were included, 14 on injection therapy and 13 on denervation procedures. 18 (66%) of the studies were determined to have a low RoB. Because of clinical heterogeneity, only two comparisons could be pooled. Overall, there is only low to very low quality evidence to support the use of injection therapy and denervation procedures over placebo or other treatments for patients with chronic LBP. However, it cannot be ruled out that in carefully selected patients, some injection therapy or denervation procedures may be of benefit