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Introduction: The effectiveness of intravenous alteplase is highly time dependent, and very short door-to-needle times (DNT) of 30 minutes or less have been reported in single centre hospitals, but never in an entire population. QuICR (Quality Improvement and Clinical Research) Alberta Stroke Program aimed to reduce DNT to a median of 30 minutes across the Canadian province of Alberta. Methods: We used the Improvement Collaborative Methodology from early 2015 to September 2016 with participation from all 17 Stroke Centres in Alberta. This methodology included 4 face-to-face workshops, site visits, webinars, data collection, data feedback, intensive process mapping, and process improvements. We compared data in the pre-intervention period from 2009-2014 (collected during the Alberta Provincial Stroke Strategy) to data in the post-intervention period from March 2016-February 2017 (collected during the QuICR DTN Collaborative). Data from January 2015-February 2016 were excluded, as improvements were being implemented during this time. Results: There were a total of 2,322 treated cases in the pre- and post-intervention periods. The results show that the median DNT dropped from 68 minutes (n=1846) in the pre-intervention period to 36 minutes (n=476) in the post-intervention period (p<0.001). There were reductions in DNT across all hospital types: median DNT dropped from 63 to 32 minutes in Urban Tertiary Centres (p<0.001), from 73 to 32 minutes in Community with 24/7 neurology (p<0.001), from 85 to 62 minutes in Community with limited/no neurology (p<0.001), and from 74 to 52.5 minutes in rural centres (p<0.001). Conclusion: There were 21.5 to 41 minute reductions in median DNT across all hospital types including smaller rural and community hospitals. A targeted multi-site improvement collaborative can be an effective intervention to reduce DNT across an entire population.
Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups, with Group 3 MB having the worst prognosis due to the highest rate of metastatic dissemination and relapse. In this work, we describe the epigenetic regulator Bmi1 as a novel therapeutic target for treatment of recurrent Group 3 MB. Through comparative profiling of primary and recurrent MB, we show that Bmi1 defines a treatment-refractory cell population that is uniquely targetable by a novel class of small molecule inhibitors. We have optimized an in vivo mouse-adapted therapy model that has the advantage of generating recurrent, human, treatment-refractory MBs. Our preliminary studies showed that although chemoradiotherapy administered to mice engrafted with human MB showed reduction in tumour size, Bmi1 expression was enriched in the post-treatment residual tumour. Furthermore, we found that knockdown of Bmi1 in human recurrent MB cells decreases proliferation and self-renewing capacities of MB cells in vitro as well as both tumour size and extent of spinal leptomeningeal metastases in vivo. Oral administration of a potent Bmi1 inhibitor, PTC 028, resulted in a marked reduction in tumour burden and an increased survival in treatment cohort. Bmi1 inhibitors showed high specificity for MB cells and spared normal human neural stem cells, when treated with doses relevant for MB cells. As Group 3 medulloblastoma is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious agent such as Bmi1 inhibitor could be rapidly transitioned to clinical trials.
It has been known that non spherical silicate particles of a size comparable to the wavelength of light, and aggregates of such particles, produce negative polarization in the backscattering region (e.g. Xing & Hanner 1997, Yanamandra-Fisher & Hanner, 1999). It has now been shown that large aggregates of small absorbing particles of fractal dimension about 2 produce a slightly negative polarization at small phase angles (Levasseur-Regourd et al., 1997). The phase-curves strongly differ from those of Mie spheroidal particles. They are likely to be due to scattering by irregular dust particles and/or fluffy aggregates of numerous submicronic absorbing particles (Levasseur-Regourd et al., 1997; Lumme et al., 1997).
Surveys with ISO (Kessler et al 1996), in particular with the CAM (Cesarsky et al 1996) and PHOT (Lemke et al 1996) instruments, will greatly extend our understanding of extra-galactic populations and their cosmological evolution. The main advantages that ISO surveys have over e.g IRAS are increased sensitivity/depth and wavelength coverage. Within the Guaranteed and Open Time programmes there are many field surveys which will efficiently map the limits in these parameters. In this talk I will briefly overview those surveys before concentrating in more detail on one survey in particular, the ISO survey of the Hubble Deep Field (HDF), to illustrate the kind of results that can be expected.
Olfactory dysfunction is common. The reliability of self-assessment tools for smell testing is still controversial. This study aimed to provide new data about the accuracy of olfactory self-assessment compared with a standardised smell test.
Prospective, controlled, cohort study of patients with olfactory disorders and healthy controls.
Ninety-six patients with a smell deficit and 71 controls were asked to rate their sense of smell on a visual analogue scale. Their olfactory abilities were also evaluated with the Sniffin' Sticks tests.
The whole cohort showed a significant correlation between visual analogue scale smell scores and Sniffin' Sticks total scores. This correlation was also significant in the patient group, but not in the control group. These results were independent of olfactory deficit aetiology and subject age.
Self-assessment of olfaction is only a reliable indicator in smell-impaired patients, not in healthy controls. For an accurate assessment of olfaction, reliable, standardised tests are needed.
Red deer, sheep and reindeer grazing on their normal hill ranges were examined at intervals over a period of four years. Samples from the digestive tract were taken at different seasons and processed in the field. The Red deer and reindeer were killed before samples were taken; rumen samples from the sheep were taken by stomach tube, but a number of animals were also killed at different seasons to correlate stomach tube and whole rumen samples. The animals sampled were representative of the general condition of the herds. Examinations were made for parasites and any pathological conditions. In most instances parasitic infections were slight. Apparent seasonal changes were found in the compositions of the diets. The Red deer and sheep ate principally heather and grass, the proportion of heather increasing in the winter. The reindeer ate mainly grass in the summer, with lichens and grass forming the winter diet, and these animals seemed to have a higher nutritional status in the winter than did the other two species. The weights of the animals and of their rumen contents, the concentrations of rumen ammonia and volatile fatty acid, and the rates at which different dietary components were fermented are recorded. Rumen fermentation was low in winter and the diets were generally inadequate for the animals. A lack of nitrogen seemed to be a major factor.
Discontinuities in nanoindentation loading curves are frequently observed in ceramic materials. These normally occur at fairly random loads and displacements, probably due to the random distance of pre-existing defects from the indent location. Here we report the observation of reproducible, sudden indent-depth changes which occur over a very narrow distribution of depths and loads, for GaAs and a range of related epitaxial layer systems. The surface preparation and material defect density have a significant influence. Different tip geometries have been used to gain insights into the deformation processes which cause these discontinuities.
Self-propagating reactions in free-standing multilayer foils provide a unique opportunity to study very rapid, diffusion-based transformations in non-equilibrium material systems. To fully understand the coupling between mass and thermal diffusion controlling these reactions and to optimize the commercial use of reactive foils, we have undertaken analytical and numerical modeling. Our analytical model predicts an increase in the reaction velocities with decreasing bilayer thickness down to a critical bilayer thickness and a reversal in this trend below the critical thickness. Predicting reaction characteristics such as the flame thermal width, the reaction zone width and the effect of variations in material properties with temperature has proven analytically intractable. To overcome these limitations, we have also used numerical methods to determine the composition and temperature profiles ahead of the reaction front for different multilayer periods and premixing. The results are compared with experimental values where possible.
Biaxial zero creep experiments were performed on Ni/Ag multilayer films on sapphire substrates. The equilibrium curvature was measured using a scanning laser and position sensitive photodetector. The experiments were designed to measure the free energy of Ni/Ag interfaces and to investigate their effect on the structural stability of multilayered materials. For the Ni/Ag multilayers studied, significant plastic straining occurs at temperatures above 400°C, enabling the growth stresses and thermal stresses in the multilayers to decay to zero. After a long time at elevated temperatures, the equilibrium curvature is reached for the film/substrate couple. This curvature is determined by the number and the energy of the Ni/Ag interfaces. Using this equilibrium technique, a free energy of 0.44 ± 0.03 N/m was measured for Ni/Ag interfaces at an equilibrium temperature of 550°C.
The deformation behavior of both ion-implanted and deposited amorphous Si (a-Si) films has been studied using spherical nanoindentation, followed by analysis using Raman spectroscopy and cross-sectional transmission electron microscopy (XTEM). Indentation was carried out on both unannealed a-Si films (the so-called unrelaxed state) and in ion implanted films that were annealed to 450°C to fully relax the amorphous film. The dominant mode of deformation in unrelaxed films was via plastic flow of the amorphous phase rather than phase transformation, with measured hardness being typically 75–85% of that of crystalline Si. In contrast, deformation via phase transformation was clearly observed in the relaxed state of ion implanted a-Si, with the load-unload curves displaying characteristic discontinuities and Raman and XTEM indicating the presence of high-pressure crystalline phases Si-III and Si-XII following pressure release. In such cases the measured hardness was within 5% of that of the crystalline phase.
Nanoimprint and a number of other related techniques are a collection of surface patterning technologies that involve direct contact of a master template with the target surface. As such, they are governed by the laws of contacting bodies, and the mechanics involved can readily be investigated by existing indentation methods or close variants thereof. Among the many demonstrated applications of nanoimprint, lithographic resist processing has generated considerable interest due to its combination of high resolution with rapid throughput over wide areas. Pattern transfer can be achieved by the application of heat and pressure to the stamp (hot embossing), or solely by the generation of shear stress at the contact (cold forming.) In both cases we have found that elastic and viscoplastic strains are present during the forming process, the former of which can considerably alter the characteristics of the pattern transfer. The use of depth sensing instrumented indentation in conjunction with specially designed stamps and a variety of microscopy techniques has allowed us to isolate, control, and measure many of the stresses and strains directly during the imprint process. Further, in a more standard role, the indenter can be used to characterize the mechanical properties of imprinted structures. In this paper we summarize our experimental findings and conclusions on the role of important factors influencing the fidelity of the imprint process including elastic stresses, plastic deformation mechanisms, complexities in the confined deformation rheology, and choices in the form of applied stress. These are illustrated by a series of idealized experiments ranging from the squeeze flow of prepared coupons to the flat punch indentation of thin films and back extrusion into isolated cavities. A connection between these more localized experiments and the established findings and requirements of applications such as wide area lithography and functional polymer patterning will be made to establish the concept of “instrumented imprint”.
A five year collaborative study of influenza in volunteer families from 1973–78 covered a period in which there were outbreaks every year but no major epidemics of influenza. Volunteers over the age of 15 years were bled before and after each of the five winters, and virus isolation was attempted from as many as possible when they reported episodes of illness. Children under 15 in the volunteer families were also swabbed when they were ill. Although most families experienced one or more attacks by influenza viruses, there was little transmission within families.