The Development of Technology-supported Approaches to the LO Process for Accredited Engineering Programs

Tracking graduate outcomes is a new requirement for engineering education in Canada.  Working closely with curriculum developers and educational technologists, the School of Engineering at the University of Guelph has shown it is possible to put in place an effective process.  The process requires engaged participants, an open-mindedness and integrated technologies to collect and report the data.  Combining people, process and technology provides a way for data analysis to satisfy accreditation requirements and internal quality education metrics.  This paper describes the approach taken and identifies strengths, challenges, and opportunities to be successful, and support the ultimate goal of curriculum improvement

Gap junction proteins and their role in spinal cord injury

© 2015 Tonkin, Mao, O'Carroll, Nicholson, Green, Gorrie and Moalem-Taylor. Gap junctions are specialized intercellular communication channels that are formed by two hexameric connexin hemichannels, one provided by each of the two adjacent cells. Gap junctions and hemichannels play an important role in regulating cellular metabolism, signaling, and functions in both normal and pathological conditions. Following spinal cord injury (SCI), there is damage and disturbance to the neuronal elements of the spinal cord including severing of axon tracts and rapid cell death. The initial mechanical disruption is followed by multiple secondary cascades that cause further tissue loss and dysfunction. Recent studies have implicated connexin proteins as playing a critical role in the secondary phase of SCI by propagating death signals through extensive glial networks. In this review, we bring together past and current studies to outline the distribution, changes and roles of various connexins found in neurons and glial cells, before and in response to SCI. We discuss the contribution of pathologically activated connexin proteins, in particular connexin 43, to functional recovery and neuropathic pain, as well as providing an update on potential connexin specific pharmacological agents to treat SCI

Electrical Perceptual Threshold Testing - validation study

Study Design : Prospective experimental Objectives : To investigate inter-rater and intra-rater reliability of electrical perceptual threshold (EPT) testing in assessing somatosensory function in healthy volunteers. Setting: Spinal Injuries Unit, Royal North Shore Hospital, Sydney, NSW, Australia Methods: Cutaneous electrical stimulation of 4 dermatomes at American Spinal Injuries Association (ASIA) sensory key points (C3, T1, L3, S2) was performed on 40 control subjects. The lowest ascending stimulus intensity at which sensation was perceived was recorded as the EPT. Mean EPT values for each dermatome, as determined by 2 testers at two time points, were examined and plotted against a normative template. Differences and associations between intra- and inter-rater measurements, and left-right measurements were investigated. EPT results for 2 people with spinal cord injuries were also examined. Results : EPT measurements from left and right sides, obtained from the two time points and two testers, were found to be strongly associated, with the exception of left and right side measurements at the S2 dermatome. No significant differences in the mean EPT for tester or time period were found. The intra- and inter-rater reliability was good for all dermatomes tested. Mean EPT measurements fell within the range of a normative template at each of the 4 dermatomes tested. Conclusion : EPT is an objective, reproducible and quantifiable method of assessing sensation in a control group. However, caution should be applied in certain dermatomes such as S2 where there was large variation between left and right side measurements. Sponsorship : New South Wales Office of Science and Medical Researc

Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats

© 2017, Springer-Verlag GmbH Germany. Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis. A second cohort received intraperitoneal injections of Peptide5 or a scrambled peptide and was culled at 8 or 24 h post-injury for the analysis of connexin proteins and systemic cytokine profile. We found that Peptide5 did not cross the blood-spinal cord barrier in control animals, but reached the lesion area in the spinal cord-injured animals without entering non-injured tissue. There was no evidence that the systemic administration of Peptide5 modulates Connexin43 protein expression or hemichannel closure in the heart and lung tissue of SCI animals. The expression levels of other major connexin proteins including Connexin30 in astrocytes, Connexin36 in neurons and Connexin47 in oligodendrocytes were also unaltered by systemic delivery of Peptide5 in either the injured or non-injured spinal cords. In addition, systemic delivery of Peptide5 had no significant effect on the plasma levels of cytokines, chemokines or growth factors. These data indicate that the systemic delivery of Peptide5 is unlikely to cause any off-target or adverse effects and may thus be a safe treatment option for traumatic SCI

Rapid GFAP and Iba1 Expression Changes in the Female Rat Brain following Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition often associated with sleep disorders, mood change and depression. Evidence suggests that rapid changes to supporting glia may predispose individuals with SCI to such comorbidities. Here, we interrogated the expression of astrocyte- and microglial-specific markers glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) in the rat brain in the first 24 hours following spinal cord injury (SCI). Female Sprague Dawley rats underwent thoracic laminectomy; half of the rats received a mild contusion injury at the level of the T10 vertebral body (SCI group), the other half did not (Sham group). Twenty-four hours post-surgery the rats were sacrificed, and the amygdala, periaqueductal grey, prefrontal cortex, hypothalamus, lateral thalamus, hippocampus (dorsal and ventral) were collected. GFAP and Iba1 mRNA and protein levels were measured by real-time qPCR and Western blot. In SCI rats, GFAP mRNA and protein expression increased in the amygdala and hypothalamus (*p<0.05). In contrast, gene and protein expression decreased in the thalamus (**p<0.01) and dorsal hippocampus (*p<0.05 and **p<0.01, respectively). Interestingly, Iba1 transcripts and proteins were significantly diminished only in the dorsal (*p<0.05 and **p<0.01, respectively) and ventral hippocampus, where gene expression diminished (*p<0.05 for both mRNA and protein). Considered together, these findings demonstrate that as early as 24 hours post-SCI there are region-specific disruptions of GFAP and Iba1 transcript and protein levels in higher brain regions

L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury

© 2018, The Author(s). There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress

Fit for purpose? A cross-sectional study to evaluate the acceptability and usability of HeadUp, a novel neck support collar for neurological neck weakness

The HeadUp collar (previously known as the Sheffield Support Snood) provides support for neck weakness caused by amyotrophic lateral sclerosis (ALS) and has shown to be superior to alternative options in a small cohort of patients from one single center. Here we report the assessment of the HeadUp collar in a larger cohort of patients, exploring the use in other neurological conditions and expanding to other centers across the UK and Ireland. An interventional cross-sectional study design was implemented to investigate the usability and acceptability of the HeadUp collar. A total of 139 patients were recruited for the study, 117 patients had a diagnosis of ALS and 22 patients presented with neck weakness due to other neurological conditions. Participants were assessed at baseline, fitted a HeadUp collar and followed-up one month later. The performance of the HeadUp collar was rated favorably compared to previously worn collars in terms of the ability to eat, drink and swallow. Findings suggest that the collar also permitted a more acceptable range of head movements whilst maintaining a good level of support. We conclude that the HeadUp collar is a suitable option for patients with neck weakness due to ALS and other neurological conditions

Uncertainty quantification of reference-based cellular deconvolution algorithms

This is the final version. Available on open access from Routledge via the DOI in this recordData and code availability: The DNAm data used in this study are available as R packages or via GEO (see Supplementary Table 2 for details). We have provided the code for calculating the CETYGO score as an R package available via GitHub (https://github.com/ds420/CETYGO). The code to reproduce the analyses in this manuscript using our R package are also available via GitHub (https://github.com/ejh243/CETYGOAnalyses).The majority of epigenetic epidemiology studies to date have generated genome-wide profiles from bulk tissues (e.g., whole blood) however these are vulnerable to confounding from variation in cellular composition. Proxies for cellular composition can be mathematically derived from the bulk tissue profiles using a deconvolution algorithm; however, there is no method to assess the validity of these estimates for a dataset where the true cellular proportions are unknown. In this study, we describe, validate and characterize a sample level accuracy metric for derived cellular heterogeneity variables. The CETYGO score captures the deviation between a sample's DNA methylation profile and its expected profile given the estimated cellular proportions and cell type reference profiles. We demonstrate that the CETYGO score consistently distinguishes inaccurate and incomplete deconvolutions when applied to reconstructed whole blood profiles. By applying our novel metric to >6,300 empirical whole blood profiles, we find that estimating accurate cellular composition is influenced by both technical and biological variation. In particular, we show that when using a common reference panel for whole blood, less accurate estimates are generated for females, neonates, older individuals and smokers. Our results highlight the utility of a metric to assess the accuracy of cellular deconvolution, and describe how it can enhance studies of DNA methylation that are reliant on statistical proxies for cellular heterogeneity. To facilitate incorporating our methodology into existing pipelines, we have made it freely available as an R package (https://github.com/ds420/CETYGO).Biotechnology and Biological Sciences Research Council (BBSRC)Engineering and Physical Sciences Research Council (EPSRC)Medical Research Council (MRC)Alzheimer’s Societ