SCIRIA Openmind seminar series, autonomatic

SCIRIA ‘OpenMind’ was a regular seminar series for University of the Arts London staff, MA and PhD students and the public. The seminars were hosted at Camberwell College of Arts and Chelsea College of Art and Design. The footage, audio and flyers offer an insight into the research processes and activities of SCIRIA members, associates and external speakers

Long-Term Blocking of Calcium Channels in mdx Mice Results in Differential Effects on Heart and Skeletal Muscle

The disease mechanisms underlying dystrophin-deficient muscular dystrophy are complex, involving not only muscle membrane fragility, but also dysregulated calcium homeostasis. Specifically, it has been proposed that calcium channels directly initiate a cascade of pathological events by allowing calcium ions to enter the cell. The objective of this study was to investigate the effect of chronically blocking calcium channels with the aminoglycoside antibiotic streptomycin from onset of disease in the mdx mouse model of Duchenne muscular dystrophy (DMD)

Should rehabilitated hedgehogs be released in winter? A comparison of survival, nest use and weight change in wild and rescued animals

The rehabilitation of sick or injured wildlife and their subsequent release back into the wild is considered important, not only for the welfare of the individual animal but also for the conservation and management of endangered and threatened wildlife. The European hedgehog Erinaceus europaeus has declined by 25% in Britain over the last decade and is the most common mammal admitted to wildlife rehabilitation centres in Britain, with a large proportion of individuals admitted to gain body weight overwinter prior to release in the spring. Consequently, many thousands of hedgehogs are housed overwinter which incurs significant costs for rehabilitation centres, and has potentially animal welfare issues, such as, stress in captivity, reintroduction stress, increased mortality risk and impaired or altered behaviour. To determine if releasing rehabilitated hedgehogs during autumn and winter had an effect on their survival, body weight or nesting behaviour, we compared these factors between 34 rehabilitated hedgehogs with 23 wild hedgehogs across five sites in England over four different winters. Overwinter survival was high for both wild and rehabilitated hedgehogs, with a significant decrease in survival across both groups when hedgehogs became active post hibernation in spring. We found no differences in the survival rates up to 150 days post release, in weight change, or nest use between wild- and winter-released rehabilitated hedgehogs. Our results suggest that under the correct conditions, rehabilitated hedgehogs can be released successfully during winter, therefore avoiding or reducing time in captivity

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Crafting communities

The aim of this workshop was, 'to explore the processes through which craft connects individuals and groups, in person and virtually, through communities of knowledge, skill and interest, shared memories and values, a mutual commitment to activism or sustainable living, a need to establish alternative ways of working,or simply the desire to decorate oneʼs home or improve quality of life'. Carol Tulloch was invited to be part of the 30 delegates of this closed workshop, to contribute to group discussions

Pervasive supply of therapeutic lysosomal enzymes in the CNS of normal and Krabbe-affected non-human primates by intracerebral lentiviral gene therapy.

Metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD or Krabbe disease) are severe neurodegenerative lysosomal storage diseases (LSD) caused by arylsulfatase A (ARSA) and galactosylceramidase (GALC) deficiency, respectively. Our previous studies established lentiviral gene therapy (GT) as a rapid and effective intervention to provide pervasive supply of therapeutic lysosomal enzymes in CNS tissues of MLD and GLD mice. Here, we investigated whether this strategy is similarly effective in juvenile non-human primates (NHP). To provide proof of principle for tolerability and biological efficacy of the strategy, we established a comprehensive study in normal NHP delivering a clinically relevant lentiviral vector encoding for the human ARSA transgene. Then, we injected a lentiviral vector coding for the human GALC transgene in Krabbe-affected rhesus macaques, evaluating for the first time the therapeutic potential of lentiviral GT in this unique LSD model. We showed favorable safety profile and consistent pattern of LV transduction and enzyme biodistribution in the two models, supporting the robustness of the proposed GT platform. We documented moderate inflammation at the injection sites, mild immune response to vector particles in few treated animals, no indication of immune response against transgenic products, and no molecular evidence of insertional genotoxicity. Efficient gene transfer in neurons, astrocytes, and oligodendrocytes close to the injection sites resulted in robust production and extensive spreading of transgenic enzymes in the whole CNS and in CSF, leading to supraphysiological ARSA activity in normal NHP and close to physiological GALC activity in the Krabbe NHP, in which biological efficacy was associated with preliminary indication of therapeutic benefit. These results support the rationale for the clinical translation of intracerebral lentiviral GT to address CNS pathology in MLD, GLD, and other neurodegenerative LSD