Culture change in elite sport performance teams: Examining and advancing effectiveness in the new era

Reflecting the importance of optimizing culture for elite teams, Fletcher and Arnold (2011) recently suggested the need for expertise in culture change. Acknowledging the dearth of literature on the specific process, however, the potential effectiveness of practitioners in this area is unknown. The present paper examines the activity's precise demands and the validity of understanding in sport psychology and organizational research to support its delivery. Recognizing that sport psychologists are being increasingly utilized by elite team management, initial evidence-based guidelines are presented. Finally, to stimulate the development of ecologically valid, practically meaningful knowledge, the paper identifies a number of future research directions

Comparison of the Ki-67 score and S-phase fraction as prognostic variables in soft-tissue sarcoma

Immunohistochemically determined Ki-67 scores and flow cytometrically determined S-phase fractions were successfully evaluated from the primary tumours of 123 patients with soft-tissue sarcoma. All patients had either limb or superficial trunk tumours. Ki-67 score correlated strongly with ploidy, S-phase fraction and grade. Ki-67 did not correlate with the size of the primary tumour. When analysed as a continuous variable, Ki-67 was a stronger predictor of both metastasis-free survival and disease-specific overall survival (P= 0.003 and 0.04 respectively) than was the S-phase fraction (P= 0.06 and 0.07 respectively). We tested the relevance of different cut-point values by dividing the whole material into two parts at every 10% (e.g. 10% of patients vs. the remaining 90%, 20% vs. 80%, etc.). We counted the relative risk and confidence interval at all these cut-off points. Ki-67 had good prognostic discriminating power irrespective of the cut-point value, but S-phase fraction lost its prognostic power at higher cut-point values. In conclusion, we found that Ki-67 is a useful prognostic tool in the treatment of soft-tissue sarcoma patients irrespective of the cut-point value. S-phase fraction can be used at lower cut-point values. © 1999 Cancer Research Campaig

Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells

BackgroundThe canonical Wnt signalling pathway is activated in most sporadic colorectal cancers (CRCs). We previously reported that FZD7 functions as a receptor for the canonical Wnt signalling pathway in colon cancer cells.Methods and resultsIn this study, we examined the function of FZD7 in survival, invasion and metastatic capabilities of colon cancer cells. FZD7_siRNA transfection decreased cell viability of HT-29 and HCT-116 colon cancer cells. Expression of c-Jun, phosphorylation of JNK and c-Jun, and activation of RhoA were suppressed after FZD7_siRNA transfection into HCT-116 cells. In vitro invasion activity and Wnt target gene expression were also reduced in HCT-116 cells transfected with FZD7_siRNA. Liver metastasis of stable FZD7_siRNA HCT-116 cell transfectants in scid mice was decreased to 40-50% compared to controls. The mRNA levels of FZD7 in 135 primary CRC tissues were examined by real-time PCR. FZD7 mRNA levels were significantly higher in stage II, III or IV tumours than in non-tumour tissues (P<0.005), and overall survival was shorter in those patients with higher FZD7 expression (P<0.001).ConclusionThese data suggest that FZD7 may be involved in enhancement of survival, invasion and metastatic capabilities of colon cancer cells through non-canonical Wnt signalling pathways as well as the canonical pathway

Inhibition of Fibroblast Growth by Notch1 Signaling Is Mediated by Induction of Wnt11-Dependent WISP-1

Fibroblasts are an integral component of stroma and important source of growth factors and extracellular matrix (ECM). They play a prominent role in maintaining tissue homeostasis and in wound healing and tumor growth. Notch signaling regulates biological function in a variety of cells. To elucidate the physiological function of Notch signaling in fibroblasts, we ablated Notch1 in mouse (Notch1Flox/Flox) embryonic fibroblasts (MEFs). Notch1-deficient (Notch1−/−) MEFs displayed faster growth and motility rate compared to Notch1Flox/Flox MEFs. Such phenotypic changes, however, were reversible by reconstitution of Notch1 activation via overexpression of the intracellular domain of Notch1 (NICD1) in Notch1-deficient MEFs. In contrast, constitutive activation of Notch1 signaling by introducing NICD1 into primary human dermal fibroblasts (FF2441), which caused pan-Notch activation, inhibited cell growth and motility, whereas cellular inhibition was relievable when the Notch activation was countered with dominant-negative mutant of Master-mind like 1 (DN-MAML-1). Functionally, “Notch-activated” stromal fibroblasts could inhibit tumor cell growth/invasion. Moreover, Notch activation induced expression of Wnt-induced secreted proteins-1 (WISP-1/CCN4) in FF2441 cells while deletion of Notch1 in MEFs resulted in an opposite effect. Notably, WISP-1 suppressed fibroblast proliferation, and was responsible for mediating Notch1's inhibitory effect since siRNA-mediated blockade of WISP-1 expression could relieve cell growth inhibition. Notch1-induced WISP-1 expression appeared to be Wnt11-dependent, but Wnt1-independent. Blockade of Wnt11 expression resulted in decreased WISP-1 expression and liberated Notch-induced cell growth inhibition. These findings indicated that inhibition of fibroblast proliferation by Notch pathway activation is mediated, at least in part, through regulating Wnt1-independent, but Wnt11-dependent WISP-1 expression

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

The Ki-67 antigen is used to evaluate the proliferative activity of breast cancer (BC); however, Ki-67's role as a prognostic marker in BC is still undefined. In order to better define the prognostic value of Ki-67/MIB-1, we performed a meta-analysis of studies that evaluated the impact of Ki-67/MIB-1 on disease-free survival (DFS) and/or on overall survival (OS) in early BC. Sixty-eight studies were identified and 46 studies including 12 155 patients were evaluable for our meta-analysis; 38 studies were evaluable for the aggregation of results for DFS, and 35 studies for OS. Patients were considered to present positive tumours for the expression of Ki-67/MIB-1 according to the cut-off points defined by the authors. Ki-67/MIB-1 positivity is associated with higher probability of relapse in all patients (HR=1.93 (95% confidence interval (CI): 1.74–2.14); P<0.001), in node-negative patients (HR=2.31 (95% CI: 1.83–2.92); P<0.001) and in node-positive patients (HR=1.59 (95% CI: 1.35–1.87); P<0.001). Furthermore, Ki-67/MIB-1 positivity is associated with worse survival in all patients (HR=1.95 (95% CI: 1.70–2.24; P<0.001)), node-negative patients (HR=2.54 (95% CI: 1.65–3.91); P<0.001) and node-positive patients (HR=2.33 (95% CI: 1.83–2.95); P<0.001). Our meta-analysis suggests that Ki-67/MIB-1 positivity confers a higher risk of relapse and a worse survival in patients with early BC

Aging and Visual Counting

Much previous work on how normal aging affects visual enumeration has been focused on the response time required to enumerate, with unlimited stimulus duration. There is a fundamental question, not yet addressed, of how many visual items the aging visual system can enumerate in a "single glance", without the confounding influence of eye movements.We recruited 104 observers with normal vision across the age span (age 21-85). They were briefly (200 ms) presented with a number of well- separated black dots against a gray background on a monitor screen, and were asked to judge the number of dots. By limiting the stimulus presentation time, we can determine the maximum number of visual items an observer can correctly enumerate at a criterion level of performance (counting threshold, defined as the number of visual items at which ≈63% correct rate on a psychometric curve), without confounding by eye movements. Our findings reveal a 30% decrease in the mean counting threshold of the oldest group (age 61-85: ∼5 dots) when compared with the youngest groups (age 21-40: 7 dots). Surprisingly, despite decreased counting threshold, on average counting accuracy function (defined as the mean number of dots reported for each number tested) is largely unaffected by age, reflecting that the threshold loss can be primarily attributed to increased random errors. We further expanded this interesting finding to show that both young and old adults tend to over-count small numbers, but older observers over-count more.Here we show that age reduces the ability to correctly enumerate in a glance, but the accuracy (veridicality), on average, remains unchanged with advancing age. Control experiments indicate that the degraded performance cannot be explained by optical, retinal or other perceptual factors, but is cortical in origin

Retinotopic Maps, Spatial Tuning, and Locations of Human Visual Areas in Surface Coordinates Characterized with Multifocal and Blocked fMRI Designs

The localization of visual areas in the human cortex is typically based on mapping the retinotopic organization with functional magnetic resonance imaging (fMRI). The most common approach is to encode the response phase for a slowly moving visual stimulus and to present the result on an individual's reconstructed cortical surface. The main aims of this study were to develop complementary general linear model (GLM)-based retinotopic mapping methods and to characterize the inter-individual variability of the visual area positions on the cortical surface. We studied 15 subjects with two methods: a 24-region multifocal checkerboard stimulus and a blocked presentation of object stimuli at different visual field locations. The retinotopic maps were based on weighted averaging of the GLM parameter estimates for the stimulus regions. In addition to localizing visual areas, both methods could be used to localize multiple retinotopic regions-of-interest. The two methods yielded consistent retinotopic maps in the visual areas V1, V2, V3, hV4, and V3AB. In the higher-level areas IPS0, VO1, LO1, LO2, TO1, and TO2, retinotopy could only be mapped with the blocked stimulus presentation. The gradual widening of spatial tuning and an increase in the responses to stimuli in the ipsilateral visual field along the hierarchy of visual areas likely reflected the increase in the average receptive field size. Finally, after registration to Freesurfer's surface-based atlas of the human cerebral cortex, we calculated the mean and variability of the visual area positions in the spherical surface-based coordinate system and generated probability maps of the visual areas on the average cortical surface. The inter-individual variability in the area locations decreased when the midpoints were calculated along the spherical cortical surface compared with volumetric coordinates. These results can facilitate both analysis of individual functional anatomy and comparisons of visual cortex topology across studies

IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.</p> <p>Methods</p> <p>We used an <it>ex vivo </it>culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. <it>In vitro </it>data were correlated with <it>in vivo </it>findings by comparing the results with published expression datasets on human cancer biopsies.</p> <p>Results</p> <p>Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (<it>P </it>= 0.029 - Norway/Stanford and <it>P </it>= 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (<it>P </it>= 0.007 - Bhattacharjee and <it>P </it>= 0.008 - Garber dataset).</p> <p>Conclusion</p> <p>Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.</p> <p>See the related commentary by Werner and Bruchim: <url>http://www.biomedcentral.com/1741-7015/8/2</url></p