Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists

New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes

Project Retrosight. Understanding the returns from cardiovascular and stroke research: Case Studies

Copyright @ 2011 RAND Europe. All rights reserved. The full text article is available via the link below.This project explores the impacts arising from cardiovascular and stroke research funded 15-20 years ago and attempts to draw out aspects of the research, researcher or environment that are associated with high or low impact. The project is a case study-based review of 29 cardiovascular and stroke research grants, funded in Australia, Canada and UK between 1989 and 1993. The case studies focused on the individual grants but considered the development of the investigators and ideas involved in the research projects from initiation to the present day. Grants were selected through a stratified random selection approach that aimed to include both high- and low-impact grants. The key messages are as follows: 1) The cases reveal that a large and diverse range of impacts arose from the 29 grants studied. 2) There are variations between the impacts derived from basic biomedical and clinical research. 3) There is no correlation between knowledge production and wider impacts 4) The majority of economic impacts identified come from a minority of projects. 5) We identified factors that appear to be associated with high and low impact. This report presents the key observations of the study and an overview of the methods involved. It has been written for funders of biomedical and health research and health services, health researchers, and policy makers in those fields. It will also be of interest to those involved in research and impact evaluation.This study was initiated with internal funding from RAND Europe and HERG, with continuing funding from the UK National Institute for Health Research, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada and the National Heart Foundation of Australia. The UK Stroke Association and the British Heart Foundation provided support in kind through access to their archives

Separator fluid volume requirements in multi-infusion settings

INTRODUCTION. Intravenous (IV) therapy is a widely used method for the administration of medication in hospitals worldwide. ICU and surgical patients in particular often require multiple IV catheters due to incompatibility of certain drugs and the high complexity of medical therapy. This increases discomfort by painful invasive procedures, the risk of infections and costs of medication and disposable considerably. When different drugs are administered through the same lumen, it is common ICU practice to flush with a neutral fluid between the administration of two incompatible drugs in order to optimally use infusion lumens. An important constraint for delivering multiple incompatible drugs is the volume of separator fluid that is sufficient to safely separate them. OBJECTIVES. In this pilot study we investigated whether the choice of separator fluid, solvent, or administration rate affects the separator volume required in a typical ICU infusion setting. METHODS. A standard ICU IV line (2m, 2ml, 1mm internal diameter) was filled with methylene blue (40 mg/l) solution and flushed using an infusion pump with separator fluid. Independent variables were solvent for methylene blue (NaCl 0.9% vs. glucose 5%), separator fluid (NaCl 0.9% vs. glucose 5%), and administration rate (50, 100, or 200 ml/h). Samples were collected using a fraction collector until <2% of the original drug concentration remained and were analyzed using spectrophotometry. RESULTS. We did not find a significant effect of administration rate on separator fluid volume. However, NaCl/G5% (solvent/separator fluid) required significantly less separator fluid than NaCl/NaCl (3.6 ± 0.1 ml vs. 3.9 ± 0.1 ml, p <0.05). Also, G5%/G5% required significantly less separator fluid than NaCl/NaCl (3.6 ± 0.1 ml vs. 3.9 ± 0.1 ml, p <0.05). The significant decrease in required flushing volume might be due to differences in the viscosity of the solutions. However, mean differences were small and were most likely caused by human interactions with the fluid collection setup. The average required flushing volume is 3.7 ml. CONCLUSIONS. The choice of separator fluid, solvent or administration rate had no impact on the required flushing volume in the experiment. Future research should take IV line length, diameter, volume and also drug solution volumes into account in order to provide a full account of variables affecting the required separator fluid volume

ESICM LIVES 2017 : 30th ESICM Annual Congress. September 23-27, 2017.

INTRODUCTION. Unplanned readmission to intensive care is highly undesirable in that it contributes to increased variance in care, disruption, difficulty in resource allocation and may increase length of stay and mortality particularly if subject to delays. Unlike the ICU admission from the ward, readmission prediction has received relatively little attention, perhaps in part because at the point of ICU discharge, full physiological information is systematically available to the clinician and so it is expected that readmission should be largely due to unpredictable factors. However it may be that there are multidimensional trends that are difficult for the clinician to perceive that may nevertheless be predictive of readmission. OBJECTIVES. We investigated whether machine learning (ML) techniques could be used to improve on the simple published SWIFT score [1] for the prediction of unplanned readmission to ICU within 48 hours. METHODS. We extracted systolic BP, pulse pressure, heart and respiration rate, temperature, SpO2, bilirubin, creatinine, INR, lactate, white cell count, platelet count, pH, FiO2, and total Glasgow Coma Score from ICU stays of over 2000 adult patients from our hospital electronic patient record system. We trained our own custom multidimensional / time-sensitive algorithmic ML system to predict failed discharges defined as either readmission or unexpected death within 48 hours of discharge. We used 10-fold cross validation to assess performance. We also assessed the effect of augmenting our system by transfer learning (TL) with 44,000 additional cases from the MIMIC III database. RESULTS. The SWIFT score performed relatively poorly with an AUROC of around 0.6 which our ML system trained on local data was also able to match. However when augmented with an additional dataset by TL, the AUROC for the ML system improved statistically and clinically significantly to over 0.7. CONCLUSIONS. Machine learning is able to improve on predictors based on simple multiple logistic regression. Thus there is likely to be information in the trends and in combinations of variables. A disadvantage with this technique is that ML approaches require large amounts of data for training. However, ML approaches can be improved by TL. Basing prediction models on locally derived data augmented by TL is a potentially novel approach to generating tools that customised to the institution yet can exploit the potential power of ML algorithms. REFERENCES [1] Gajic O, Malinchoc M, Comfere TB, et al. The Stability and Workload Index for Transfer score predicts unplanned intensive care unit patient readmission: initial development and validation. Crit Care Med. 2008;36(3):676–82. Grant Acknowledgement This work was internally funded

Epidemiology of Injury in English Women's Super league Football: A Cohort Study

INTRODUCTION: The epidemiology of injury in male professional football has been well documented (Ekstrand, Hägglund, & Waldén, 2011) and used as a basis to understand injury trends for a number of years. The prevalence and incidence of injuries occurring in womens super league football is unknown. The aim of this study is to estimate the prevalence and incidence of injury in an English Super League Women’s Football squad. METHODS: Following ethical approval from Leeds Beckett University, players (n = 25) signed to a Women’s Super League Football club provided written informed consent to complete a self-administered injury survey. Measures of exposure, injury and performance over a 12-month period was gathered. Participants were classified as injured if they reported a football injury that required medical attention or withdrawal from participation for one day or more. Injuries were categorised as either traumatic or overuse and whether the injury was a new injury and/or re-injury of the same anatomical site RESULTS: 43 injuries, including re-injury were reported by the 25 participants providing a clinical incidence of 1.72 injuries per player. Total incidence of injury was 10.8/1000 h (95% CI: 7.5 to 14.03). Participants were at higher risk of injury during a match compared with training (32.4 (95% CI: 15.6 to 48.4) vs 8.0 (95% CI: 5.0 to 10.85)/1000 hours, p 28 days) of which there were three non-contact anterior cruciate ligament (ACL) injuries. The epidemiological incidence proportion was 0.80 (95% CI: 0.64 to 0.95) and the average probability that any player on this team will sustain at least one injury was 80.0% (95% CI: 64.3% to 95.6%) CONCLUSION: This is the first report capturing exposure and injury incidence by anatomical site from a cohort of English players and is comparable to that found in Europe (6.3/1000 h (95% CI 5.4 to 7.36) Larruskain et al 2017). The number of ACL injuries highlights a potential injury burden for a squad of this size. Multi-site prospective investigations into the incidence and prevalence of injury in women’s football are require

iPS Cells for Modelling and Treatment of Human Diseases

The field of reprogramming somatic cells into induced pluripotent stem cells (iPSC) has moved very quickly, from bench to bedside in just eight years since its first discovery. The best example of this is the RIKEN clinical trial this year in Japan, which will use iPSC derived retinal pigmented epithelial (RPE) cells to treat macular degeneration (MD). This is the first human disease to be tested for regeneration and repair by iPSC-derived cells and others will follow in the near future. Currently, there is an intense worldwide research effort to bring stem cell technology to the clinic for application to treat human diseases and pathologies. Human tissue diseases (including those of the lung, heart, brain, spinal cord, and muscles) drive organ bioengineering to the forefront of technology concerning cell replacement therapy. Given the critical mass of research and translational work being performed, iPSCs may very well be the cell type of choice for regenerative medicine in the future. Also, basic science questions, such as efficient differentiation protocols to the correct cell type for regenerating human tissues, the immune response of iPSC replacement therapy and genetic stability of iPSC-derived cells, are currently being investigated for future clinical applications

Psr1p interacts with SUN/sad1p and EB1/mal3p to establish the bipolar spindle

Regular Abstracts - Sunday Poster Presentations: no. 382During mitosis, interpolar microtubules from two spindle pole bodies (SPBs) interdigitate to create an antiparallel microtubule array for accommodating numerous regulatory proteins. Among these proteins, the kinesin-5 cut7p/Eg5 is the key player responsible for sliding apart antiparallel microtubules and thus helps in establishing the bipolar spindle. At the onset of mitosis, two SPBs are adjacent to one another with most microtubules running nearly parallel toward the nuclear envelope, creating an unfavorable microtubule configuration for the kinesin-5 kinesins. Therefore, how the cell organizes the antiparallel microtubule array in the first place at mitotic onset remains enigmatic. Here, we show that a novel protein psrp1p localizes to the SPB and plays a key role in organizing the antiparallel microtubule array. The absence of psr1+ leads to a transient monopolar spindle and massive chromosome loss. Further functional characterization demonstrates that psr1p is recruited to the SPB through interaction with the conserved SUN protein sad1p and that psr1p physically interacts with the conserved microtubule plus tip protein mal3p/EB1. These results suggest a model that psr1p serves as a linking protein between sad1p/SUN and mal3p/EB1 to allow microtubule plus ends to be coupled to the SPBs for organization of an antiparallel microtubule array. Thus, we conclude that psr1p is involved in organizing the antiparallel microtubule array in the first place at mitosis onset by interaction with SUN/sad1p and EB1/mal3p, thereby establishing the bipolar spindle.postprin

Removal of antagonistic spindle forces can rescue metaphase spindle length and reduce chromosome segregation defects

Regular Abstracts - Tuesday Poster Presentations: no. 1925Metaphase describes a phase of mitosis where chromosomes are attached and oriented on the bipolar spindle for subsequent segregation at anaphase. In diverse cell types, the metaphase spindle is maintained at a relatively constant length. Metaphase spindle length is proposed to be regulated by a balance of pushing and pulling forces generated by distinct sets of spindle microtubules and their interactions with motors and microtubule-associated proteins (MAPs). Spindle length appears important for chromosome segregation fidelity, as cells with shorter or longer than normal metaphase spindles, generated through deletion or inhibition of individual mitotic motors or MAPs, showed chromosome segregation defects. To test the force balance model of spindle length control and its effect on chromosome segregation, we applied fast microfluidic temperature-control with live-cell imaging to monitor the effect of switching off different combinations of antagonistic forces in the fission yeast metaphase spindle. We show that spindle midzone proteins kinesin-5 cut7p and microtubule bundler ase1p contribute to outward pushing forces, and spindle kinetochore proteins kinesin-8 klp5/6p and dam1p contribute to inward pulling forces. Removing these proteins individually led to aberrant metaphase spindle length and chromosome segregation defects. Removing these proteins in antagonistic combination rescued the defective spindle length and, in some combinations, also partially rescued chromosome segregation defects. Our results stress the importance of proper chromosome-to-microtubule attachment over spindle length regulation for proper chromosome segregation.postprin

Phytochemical Omics in Medicinal Plants

Medicinal plants are used to treat diseases and provide health benefits, and their applications are increasing around the world. A huge array of phytochemicals have been identified from medicinal plants, belonging to carotenoids, flavonoids, lignans, and phenolic acids, and so on, with a wide range of biological activities. In order to explore our knowledge of phytochemicals with the assistance of modern molecular tools and high-throughput technologies, this book collects recent innovative original research and review articles on subtopics of mechanistic insights into bioactivities, treatment of diseases, profiling, extraction and identification, and biotechnology