Neuroimaging as a selection tool and endpoint in preclinical and clinical trials

Standard imaging in acute stroke enables the exclusion of non-stroke structural CNS lesions and cerebral haemorrhage from clinical and pre-clinical ischaemic stroke trials. In this review, the potential benefit of imaging (e.g., angiography and penumbral imaging) as a translational tool for trial recruitment and the use of imaging endpoints are discussed for both clinical and pre-clinical stroke research. The addition of advanced imaging to identify a “responder” population leads to reduced sample size for any given effect size in phase 2 trials and is a potentially cost-efficient means of testing interventions. In pre-clinical studies, technical failures (failed or incomplete vessel occlusion, cerebral haemorrhage) can be excluded early and continuous multimodal imaging of the animal from stroke onset is feasible. Pre- and post-intervention repeat scans provide real time assessment of the intervention over the first 4–6 h. Negative aspects of advanced imaging in animal studies include increased time under general anaesthesia, and, as in clinical studies, a delay in starting the intervention. In clinical phase 3 trial designs, the negative aspects of advanced imaging in patient selection include higher exclusion rates, slower recruitment, overestimated effect size and longer acquisition times. Imaging may identify biological effects with smaller sample size and at earlier time points, compared to standard clinical assessments, and can be adjusted for baseline parameters. Mechanistic insights can be obtained. Pre-clinically, multimodal imaging can non-invasively generate data on a range of parameters, allowing the animal to be recovered for subsequent behavioural testing and/or the brain taken for further molecular or histological analysis

Preliminary endurance tests of water vaporizers for resistojet applications

Three water vaporizers designed for resistojet applications were built and tested for periods up to 500 h and 250 thermal cycles. Two of the vaporizers were not sensitive to orientation with respect to gravity, an indication of likely compatibility with low-gravity environments. Some temperatures and pressures in the third were impacted by orientation, although operation was always stable. The pressure drop across the sand-filled version increased by 147 percent in 38 h and 19 thermal cycles. Bonding of the sand granules in the downstream end of the heat exchanger was the suspected cause of failure of this vaporizer. Pressure drops across the two sintered stainless steel-filled versions were more gradual. One, with a pore size of 60 microns, showed an 80 percent increase in 500 h and 250 thermal cycles and another, with a 10 microns poresize, showed a 29 percent increase in 350 h and 175 thermal cycles. Testing of the latter metal-filled vaporizer was ongoing as of this writing. Oxidation of the porous metal packing materials in these vaporizers, with subsequent deposition of oxide particles within the pores, was believed to have caused the observed increases in pressure drops

Pain in traumatic upper limb amputees in Sierra Leone.

Data on 40 upper limb amputees (11 bilateral) with regard to stump pain, phantom sensation and phantom pain is presented. All the patients lost their limbs as a result of violent injuries intended to terrorise the population and were assessed 10-48 months after the injury. All amputees reported stump pain in the month prior to interview and ten of the 11 bilateral amputees had bilateral pain. Phantom sensation was common (92.5%), but phantom pain was only present in 32.5% of amputees. Problems in translation and explanation may have influenced the low incidence of phantom pain and high incidence of stump pain. In the bilateral amputees phantom sensation, phantom pain and telescoping all showed bilateral concordance, whereas stump pain and neuromas did not show concordance. About half the subjects (56%) had lost their limb at the time of injury (primary) while the remainder had an injury, then a subsequent amputation in hospital (secondary). There was no association between the incidence of phantom pain and amputation irrespective of being primary or secondary

Hyperglycaemia does not increase perfusion deficits after focal cerebral ischaemia in male Wistar rats

Background: Hyperglycaemia is associated with a worse outcome in acute ischaemic stroke patients; yet the pathophysiological mechanisms of hyperglycaemia-induced damage are poorly understood. We hypothesised that hyperglycaemia at the time of stroke onset exacerbates ischaemic brain damage by increasing the severity of the blood flow deficit. Methods: Adult, male Wistar rats were randomly assigned to receive vehicle or glucose solutions prior to permanent middle cerebral artery occlusion. Cerebral blood flow was assessed semi-quantitatively either 1 h after middle cerebral artery occlusion using 99mTc-D, L-hexamethylpropyleneamine oxime (99mTc-HMPAO) autoradiography or, in a separate study, using quantitative pseudo-continuous arterial spin labelling for 4 h after middle cerebral artery occlusion. Diffusion weighted imaging was performed alongside pseudo-continuous arterial spin labelling and acute lesion volumes calculated from apparent diffusion coefficient maps. Infarct volume was measured at 24 h using rapid acquisition with refocused echoes T2-weighted magnetic resonance imaging. Results: Glucose administration had no effect on the severity of ischaemia when assessed by either 99mTc-HMPAO autoradiography or pseudo-continuous arterial spin labelling perfusion imaging. In comparison to the vehicle group, apparent diffusion coefficient–derived lesion volume 2–4 h post-middle cerebral artery occlusion and infarct volume 24 h post-middle cerebral artery occlusion were significantly greater in the glucose group. Conclusions: Hyperglycaemia increased acute lesion and infarct volumes but there was no evidence that the acute blood flow deficit was exacerbated. The data reinforce the conclusion that the detrimental effects of hyperglycaemia are rapid, and that treatment of post-stroke hyperglycaemia in the acute period is essential but the mechanisms of hyperglycaemia-induced harm remain unclear

Using a hypothetical scenario to assess public preferences for colorectal surveillance following screening-detected, intermediate-risk adenomas: annual home-based stool test vs. triennial colonoscopy

Background To assess public preferences for colorectal cancer (CRC) surveillance tests for intermediate-risk adenomas, using a hypothetical scenario. Methods Adults aged 45–54 years without CRC were identified from three General Practices in England (two in Cumbria, one in London). A postal survey was carried out during a separate study on preferences for different first-line CRC screening modalities (non- or full-laxative computed tomographic colonography, flexible sigmoidoscopy, or colonoscopy). Individuals were allocated at random to receive a pack containing information on one first-line test, and a paragraph describing CRC surveillance recommendations for people who are diagnosed with intermediate-risk adenomas during screening. All participants received a description of two surveillance options: annual single-sample, home-based stool testing (consistent with Faecal Immunochemical Tests; FIT) or triennial colonoscopy. Invitees were asked to imagine they had been diagnosed with intermediate-risk adenomas, and then complete a questionnaire on their surveillance preferences. Results 22.1 % (686/3,100) questionnaires were returned. 491 (15.8 %) were eligible for analysis. The majority of participants stated a surveillance preference for the stool test over colonoscopy (60.8 % vs 31.0 %; no preference: 8.1 %; no surveillance: 0.2 %). Women were more likely to prefer the stool test than men (66.7 % vs. 53.6 %; p = .011). The primary reason for preferring the stool test was that it would be done more frequently. The main reason to prefer colonoscopy was its superiority at finding polyps. Conclusions A majority of participants stated a preference for a surveillance test resembling FIT over colonoscopy. Future research should test whether this translates to greater adherence in a real surveillance setting

TRA-957: LONDON ON BIKES – LONDON’S CYCLING MASTER PLAN STRATEGIC CHANGES TO IMPROVE LONDON’S CYCLING CULTURE & INFRASTRUCTURE

The City of London, Canada has been implementing cycling infrastructure since the 1980s. The City’s formal cycling master planning efforts to improve the cycling culture within the City were successfully “launched” in 2005 with the development and adoption of the City’s first Cycling Master Plan. The first master plan was followed by a strategic implementation plan which was completed in 2007 and used to guide planning, design and engineering efforts by City staff. The completion and adoption of both of these plans has led to the development of comprehensive off-road network of cycling facilities along the City’s premier Thames River Valley and an initial on-road network

ECONOMIC ANALYSIS OF USING A BORDER TREATMENT FOR REDUCING ORGANOPHOSPHATE USE IN SEED POTATO PRODUCTION

Recent research shows initial colonization of potato fields by winged green peach aphid is concentrated at field edges. This suggests that insecticides applied only to field margins during initial colonization would largely eliminate a colonizing aphid population, conserve natural enemies in the field center, and reduce insecticide use. To better understand the costs and benefits of reducing organophosphate use, the six participating growers were interviewed to ascertain their reason for participating and their satisfaction with the border only treatment method as well as their estimated net economic benefits. Five of the farms ranked cost reduction as the most important reason for participating. The sixth farm ranked reducing virus spread as the most important reason with cost reduction as their second most important reason. The average cost savings over all 28 participating fields of using the border treatment is estimated to be $23.85 per acre for the entire field-a 93% savings. Almost all the farmers found the border treatment method to be successful at aphid control. None of the farmers observed any impact on the physical yield of seed potato. All the fields were certified during the summer except for one of Farmer F's fields that was lost because of off type. In conclusion, the border treatment method seems likely to be adopted by many farmers since the potential cost saving is large and farmers dislike Monitor. However, some farmers may resist the method due to scouting requirements and costs. Also, farmers with fields that do not meet the uniformity requirements of the border treatment will not be successful in their use of the border method.Crop Production/Industries,