The accuracy of ADC measurements in liver is improved by a tailored and computationally efficient local-rigid registration algorithm

This study describes post-processing methodologies to reduce the effects of physiological motion in measurements of apparent diffusion coefficient (ADC) in the liver. The aims of the study are to improve the accuracy of ADC measurements in liver disease to support quantitative clinical characterisation and reduce the number of patients required for sequential studies of disease progression and therapeutic effects. Two motion correction methods are compared, one based on non-rigid registration (NRA) using freely available open source algorithms and the other a local-rigid registration (LRA) specifically designed for use with diffusion weighted magnetic resonance (DW-MR) data. Performance of these methods is evaluated using metrics computed from regional ADC histograms on abdominal image slices from healthy volunteers. While the non-rigid registration method has the advantages of being applicable on the whole volume and in a fully automatic fashion, the local-rigid registration method is faster while maintaining the integrity of the biological structures essential for analysis of tissue heterogeneity. Our findings also indicate that the averaging commonly applied to DW-MR images as part of the acquisition protocol should be avoided if possible

Developing a virtual reality environment for petrous bone surgery: a state-of-the-art review

The increasing power of computers has led to the development of sophisticated systems that aim to immerse the user in a virtual environment. The benefits of this type of approach to the training of physicians and surgeons are immediately apparent. Unfortunately the implementation of “virtual reality” (VR) surgical simulators has been restricted by both cost and technical limitations. The few successful systems use standardized scenarios, often derived from typical clinical data, to allow the rehearsal of procedures. In reality we would choose a system that allows us not only to practice typical cases but also to enter our own patient data and use it to define the virtual environment. In effect we want to re-write the scenario every time we use the environment and to ensure that its behavior exactly duplicates the behavior of the real tissue. If this can be achieved then VR systems can be used not only to train surgeons but also to rehearse individual procedures where variations in anatomy or pathology present specific surgical problems. The European Union has recently funded a multinational 3-year project (IERAPSI, Integrated Environment for Rehearsal and Planning of Surgical Interventions) to produce a virtual reality system for surgical training and for rehearsing individual procedures. Building the IERAPSI system will bring together a wide range of experts and combine the latest technologies to produce a true, patient specific virtual reality surgical simulator for petrous/temporal bone procedures. This article presents a review of the “state of the art” technologies currently available to construct a system of this type and an overview of the functionality and specifications such a system requires

Injury prevention strategies at the FIFA 2014 World Cup: perceptions and practices of the physicians from the 32 participating national teams

Purpose The available scientific research regarding injury prevention practices in international football is sparse. The purpose of this study was to quantify current practice with regard to (1) injury prevention of top-level footballers competing in an international tournament, and (2) determine the main challenges and issues faced by practitioners in these national teams. Methods A survey was administered to physicians of the 32 competing national teams at the FIFA 2014 World Cup. The survey included 4 sections regarding perceptions and practices concerning non-contact injuries: (1) risk factors, (2) screening tests and monitoring tools, (3) preventative strategies and (4) reflection on their experience at the World Cup. Results Following responses from all teams (100%), the present study revealed the most important intrinsic (previous injury, accumulated fatigue, agonist:antagonist muscle imbalance) and extrinsic (reduced recovery time, training load prior to and during World Cup, congested fixtures) risk factors during the FIFA 2014 World Cup. The 5 most commonly used tests for risk factors were: flexibility, fitness, joint mobility, balance and strength; monitoring tools commonly used were: medical screen, minutes/matches played, subjective and objective wellness, heart rate and biochemical markers. The 5 most important preventative exercises were: flexibility, core, combined contractions, balance and eccentric. Conclusions The present study showed that many of the National football (soccer) teams’ injury prevention perceptions and practices follow a coherent approach. There remains, however, a lack of consistent research findings to support some of these perceptions and practices

HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells

High-density lipoproteins (HDL) have many biological functions, including reducing endothelial activation and adhesion molecule expression. We recently reported that HDL transport and deliver functional microRNAs (miRNA). Here we show that HDL suppresses expression of intercellular adhesion molecule 1 (ICAM-1) through the transfer of miR-223 to endothelial cells. After incubation of endothelial cells with HDL, mature miR-223 levels are significantly increased in endothelial cells and decreased on HDL. However, miR-223 is not transcribed in endothelial cells and is not increased in cells treated with HDL from miR-223−/− mice. HDL inhibit ICAM-1 protein levels, but not in cells pretreated with miR-223 inhibitors. ICAM-1 is a direct target of HDL-transferred miR-223 and this is the first example of an extracellular miRNA regulating gene expression in cells where it is not transcribed. Collectively, we demonstrate that HDL’s anti-inflammatory properties are conferred, in part, through HDL-miR-223 delivery and translational repression of ICAM-1 in endothelial cells

Acid gases and aerosol measurements in the UK (1999–2015): regional distributions and trends

The UK Acid Gases and Aerosol Monitoring Network (AGANet) was established in 1999 (12 sites, increased to 30 sites from 2006), to provide long-term national monitoring of acid gases (HNO3, SO2, HCl) and aerosol components (NO3-, SO42-, Cl-, Na+, Ca2+, Mg2+). An extension of a low-cost denuder-filter pack system (DELTA) that is used to measure NH3 and NH4+ in the UK National Ammonia Monitoring Network (NAMN) provides additional monthly speciated measurements for the AGANet. A comparison of the monthly DELTA measurement with averaged daily results from an annular denuder system showed close agreement, while the sum of HNO3 and NO3- and the sum of NH3 and NH4+ from the DELTA are also consistent with previous filter pack determination of total inorganic nitrogen and total inorganic ammonium, respectively. With the exception of SO2 and SO42-, the AGANet provides for the first time the UK concentration fields and seasonal cycles for each of the other measured species. The largest concentrations of HNO3, SO2, and aerosol NO3- and SO42- are found in south and east England and smallest in western Scotland and Northern Ireland, whereas HCl are highest in the southeast, southwest and central England, that may be attributed to dual contribution from anthropogenic (coal combustion) and marine sources (reaction of sea salt with acid gases to form HCl). Na+ and Cl- are spatially correlated, with largest concentrations at coastal sites, reflecting a contribution from sea salt. Temporally, peak concentrations in HNO3 occurred in late winter and early spring attributed to photochemical processes. NO3- and SO42- have a spring maxima that coincides with the peak in concentrations of NH3 and NH4+, and are therefore likely attributable to formation of NH4NO3 and (NH4)2SO4 from reaction with higher concentrations of NH3 in spring. By contrast, peak concentrations of SO2, Na+ and Cl- during winter are consistent with combustion sources for SO2 and marine sources in winter for sea salt aerosol. Key pollutant events were captured by the AGANet. In 2003, a spring episode with elevated concentrations of HNO3 and NO3¬- was driven by meteorology and transboundary transport of NH4NO3 from Europe. A second, but smaller episode occurred in September 2014, with elevated concentrations of SO2, HNO3, SO42-, NO3- and NH4+ that was shown to be from the Icelandic Holuhraun volcanic eruptions. Since 1999, AGANet has shown substantial decrease in SO2 concentrations relative to HNO3 and NH3, consistent with estimated decline in UK emissions. At the same time, large reductions and changes in the aerosol components provides evidence of a shift in the particulate phase from (NH4)2SO4 to NH4NO3. The potential for NH4NO3 to release NH3 and HNO3 in warm weather, together with the surfeit of NH3 also means that a larger fraction of the reduced and oxidised N is remaining in the gas phase as NH3 and HNO3 as indicated by the increasing trend in ratios of NH3:NH4+ and HNO3:NO3- over the 16 year period. Due to different removal rates of the component species by wet and dry deposition, this change is expected to affect spatial patterns of pollutant deposition with consequences for sensitive habitats with exceedance of critical loads of acidity and eutrophication. The changes are also relevant for human health effects assessment, particularly in urban areas as NH4NO3 constitutes a significant fraction of fine particulate matter (< 2.5 µm) that are linked to increased mortality from respiratory and cardiopulmonary diseases

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640

Finding Our Way through Phenotypes

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p&lt;0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p&lt;0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark