Using Stories in Coach Education

The purpose of this paper is to illustrate how storied representations of research can be used as an effective pedagogical tool in coach education. During a series of continuing professional development seminars for professional golf coaches, we presented our research in the form of stories and poems which were created in an effort to evoke and communicate the lived experiences of elite professional golfers. Following these presentations, we obtained written responses to the stories from 53 experienced coaches who attended the seminars. Analysis of this data revealed three ways in which coaches responded to the stories: (i) questioning; (ii) summarising; and (iii) incorporating. We conclude that these responses illustrate the potential of storied forms of representation to enhance professional development through stimulating reflective practice and increasing understanding of holistic, person-centred approaches to coaching athletes in high-performance sport

Beamlines of the biomedical imaging and therapy facility at the Canadian Light Source - Part 2

Volume: 425The BioMedical Imaging and Therapy (BMIT) facility provides a world class facility with unique synchrotron-specific imaging and therapy capabilities. This paper describes Insertion Device (ID) beamline 05ID-2 with the beam terminated in the first experimental hutch: POE-2. The experimental methods available in POE-2 include: Microbeam Radiation Therapy (MRT), Synchrotron Stereotactic Radiation Therapy (SSRT) and absorption imaging (projection and Computed Tomography (CT)). The source for the ID beamline is a multi-pole superconductive 4.3 T wiggler, which can generate ∼30 kW of radiative power and deliver dose as high as 3000 Gy/s required for MRT program. The optics in POE-1 hutch prepares either monochromatic or filtered white beam that is used in POE-2. The Double Crystal (DC), bent Laue monochromator will prepare a beam over 10 cm wide at sample point, while spanning an energy range appropriate for imaging studies of animals (20-100+ keV). The experimental hutch will have a flexible positioning system that can handle subjects up to 120 kg. Several different cameras will be available with resolutions ranging from 4 μm to 150 μm. The latest update on the status of 05B1-1 bending magnet (BM) beamline, described in Part 1 [1], is also included. © 2013 IOP Publishing Ltd.Non peer reviewe

Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer

Conceptual models of carcinogenesis typically consist of an evolutionary sequence of heritable changes in genes controlling proliferation, apoptosis, and senescence. We propose that these steps are necessary but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia and acidosis that develop as cells proliferate into the lumen and away from the underlying vessels. This requires evolution of glycolytic and acid-resistant phenotypes that, we hypothesise, is critical for emergence of invasive cancer. Mathematical models demonstrate severe hypoxia and acidosis in regions of intraductal tumours more than 100 m from the basement membrane. Subsequent evolution of glycolytic and acid-resistant phenotypes leads to invasive proliferation. Multicellular spheroids recapitulating ductal carcinoma in situ (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptation to hypoxia followed by growth into normoxic regions in qualitative agreement with model predictions. Clinical specimens of DCIS exhibit periluminal distribution of GLUT-1 and Na+/H+ exchanger (NHE) indicating transcriptional activation by hypoxia and clusters of the same phenotype in the peripheral, presumably normoxic regions similar to the pattern predicted by the models and observed in spheroids. Upregulated GLUT-1 and NHE-1 were observed in microinvasive foci and adjacent intraductal cells. Adaptation to hypoxia and acidosis may represent key events in transition from in situ to invasive cancer

Dynamics of liquid 4He in Vycor

We have measured the dynamic structure factor of liquid 4He in Vycor using neutron inelastic scattering. Well-defined phonon-roton (p-r) excitations are observed in the superfluid phase for all wave vectors 0.3 < Q < 2.15. The p-r energies and lifetimes at low temperature (T = 0.5 K) and their temperature dependence are the same as in bulk liquid 4He. However, the weight of the single p-r component does not scale with the superfluid fraction (SF) as it does in the bulk. In particular, we observe a p-r excitation between T_c = 1.952 K, where SF = 0, and T_(lambda)=2.172 K of the bulk. This suggests, if the p-r excitation intensity scales with the Bose condensate, that there is a separation of the Bose-Einstein condensation temperature and the superfluid transition temperature T_c of 4He in Vycor. We also observe a two-dimensional layer mode near the roton wave vector. Its dispersion is consistent with specific heat and SF measurements and with layer modes observed on graphite surfaces.Comment: 3 pages, 4 figure

Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels

Tumour recurrence frequently occurs after radiotherapy, but the characteristics, intratumoural localization and post-irradiation behaviour of radioresistant cancer cells remain largely unknown. Here we develop a sophisticated strategy to track the post-irradiation fate of the cells, which exist in perinecrotic regions at the time of radiation. Although the perinecrotic tumour cells are originally hypoxia-inducible factor 1 (HIF-1)-negative, they acquire HIF-1 activity after surviving radiation, which triggers their translocation towards tumour blood vessels. HIF-1 inhibitors suppress the translocation and decrease the incidence of post-irradiation tumour recurrence. For the first time, our data unveil the HIF-1-dependent cellular dynamics during post-irradiation tumour recurrence and provide a rational basis for targeting HIF-1 after radiation therapy

Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy

Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tumour radioresistance; therefore, it is recognised as an excellent target during radiation therapy. However, the inhibition of HIF-1 in unsuitable timing can suppress rather than enhance the effect of radiation therapy because its anti-angiogenic effect increases the radioresistant hypoxic fraction. In this study, we imaged changes of HIF-1 activity after treatment with radiation and/or an HIF-1 inhibitor, YC-1, and optimised their combination. Hypoxic tumour cells were reoxygenated 6 h postirradiation, leading to von Hippel-Lindau (VHL)-dependent proteolysis of HIF-1α and a resultant decrease in HIF-1 activity. The activity then increased as HIF-1α accumulated in the reoxygenated regions 24 h postirradiation. Meanwhile, YC-1 temporarily but significantly suppressed HIF-1 activity, leading to a decrease in microvessel density and an increase in tumour hypoxia. On treatment with YC-1 and then radiation, the YC-1-mediated increase in tumour hypoxia suppressed the effect of radiation therapy, whereas on treatment in the reverse order, YC-1 suppressed the postirradiation upregulation of HIF-1 activity and consequently delayed tumour growth. These results indicate that treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the therapeutic effect of radiation, and the suppression of the postirradiation upregulation of HIF-1 activity is important for the best therapeutic benefit

Blood Transfusion Requirements for Patients With Sarcomas Undergoing Combined Radio- and Chemotherapy

Patients with bony and soft tissue sarcomas may require intensive treatment with chemotherapy and radiotherapy, which often leads to a fall in haemoglobin levels, requiring blood transfusion. There may be advantages in predicting which patients will require transfusion, partly because anaemia and hypoxia may worsen the response of tumours to chemotherapy and radiotherapy. Between 1997 and 2003, a total of 26 patients who received intensive treatment with curative intent were identified. Transfusions were given to maintain the haemoglobin at 10g/dl or above during chemotherapy, and at 12 g/dl or above during radiotherapy. Eighteen (69%) required a transfusion, the majority as a result of both the chemotherapy and RT criteria. There were 78 transfusion episodes, and 181 units of blood given. In the 18 patients who required transfusion, the average number of units was 10.1, but seven patients required more blood than this. The most significant factor influencing blood transfusion was choice of intensive chemotherapy. Intensive chemotherapy and presenting Hb less than 11.6 g/dl identified 13 out of 18 patients who needed transfusion. Adding a drop in haemoglobin of greater than 1.7 g/dl after one cycle of chemotherapy identified 16 out of 18 patients who required transfusion. The seven patients who had heavy transfusion requirements were identified by age 32 or less, intensive chemotherapy and a presenting Hb of 12 g/dl or less. Erythropoietin might be a useful alternative to transfusion in selected patient groups, especially those with heavy transfusion requirements

Uptake Rate of Cationic Mitochondrial Inhibitor MKT-077 Determines Cellular Oxygen Consumption Change in Carcinoma Cells

<div><h3>Objective</h3><p>Since tumor radiation response is oxygen-dependent, radiosensitivity can be enhanced by increasing tumor oxygenation. Theoretically, inhibiting cellular oxygen consumption is the most efficient way to increase oxygen levels. The cationic, rhodacyanine dye-analog MKT-077 inhibits mitochondrial respiration and could be an effective metabolic inhibitor. However, the relationship between cellular MKT-077 uptake and metabolic inhibition is unknown. We hypothesized that rat and human mammary carcinoma cells would take up MKT-077, causing a decrease in oxygen metabolism related to drug uptake.</p> <h3>Methods</h3><p>R3230Ac rat breast adenocarcinoma cells were exposed to MKT-077. Cellular MKT-077 concentration was quantified using spectroscopy, and oxygen consumption was measured using polarographic electrodes. MKT-077 uptake kinetics were modeled by accounting for uptake due to both the concentration and potential gradients across the plasma and mitochondrial membranes. These kinetic parameters were used to model the relationship between MKT-077 uptake and metabolic inhibition. MKT-077-induced changes in oxygen consumption were also characterized in MDA-MB231 human breast carcinoma cells.</p> <h3>Results</h3><p>Cells took up MKT-077 with a time constant of ∼1 hr, and modeling showed that over 90% of intracellular MKT-077 was bound or sequestered, likely by the mitochondria. The uptake resulted in a rapid decrease in oxygen consumption, with a time constant of ∼30 minutes. Surprisingly the change in oxygen consumption was proportional to uptake rate, not cellular concentration. MKT-077 proved a potent metabolic inhibitor, with dose-dependent decreases of 45–73% (p = 0.003).</p> <h3>Conclusions</h3><p>MKT-077 caused an uptake rate-dependent decrease in cellular metabolism, suggesting potential efficacy for increasing tumor oxygen levels and radiosensitivity <em>in vivo</em>.</p> </div

CT imaging of small animals using monochromatized synchrotron x rays

Rats and chicken embryos were imaged in vivo with a prototype Multiple Energy Computed Tomography (MECT) system using monochromatized x rays from the X17 superconducting wiggler at the National Synchrotron Light Source. The CT configuration coated of a horizontal low-divergence, fan-shaped beam, 70 mm wide and 0.5 mm high, and a subject rotating about a vertical aids. A linear-array high-purity Ge detector with 140 elements, each 0.5 mm wide and 6 mm thick, was used with a data acquisition system that provides a linear response over almost six orders of magnitude of detector current. The dual photon absorptiometry (DPA) algorithm was applied to images of the rat head acquired at 20 and 45 keV to obtain two new images, one representing the low-Z, and the other the intermediate-Z clement group. The results indicate that the contrast resolution and the quantification accuracy of the images improve stepwise; first, with the monochromatic beam and, second, the DPA method. The system is a prototype for a brain scanner