Combination of celecoxib with percutaneous radiotherapy in patients with localised prostate cancer – a phase I study

BACKGROUND: Current approaches for the improvement of bNED for prostate cancer patients treated with radiotherapy mainly focus on dose escalation. However molecularly targeted approaches may also turn out to be of value. In this regard cyclooxygenase (COX)-2 inhibitors have been shown to exert some anti-tumour activities in human prostate cancer in vivo and in vitro. Although in vitro data indicated that the combination of COX-2 inhibition and radiation was not associated with an increased toxicity, we performed a phase I trial using high dose celecoxib together with percutaneous radiation therapy. METHODS: In order to rule out any increases of more than 20% incidence for a given side effect level 22 patients were included in the trial. Celecoxib was given 400 mg twice daily with onset of the radiation treatment. Risk adapted radiation doses were between 70 and 74 Gy standard fractionation. RTOG based gastrointestinal (GI) and genitourinary (GU) acute toxicity scoring was performed weekly during radiation therapy, at six weeks after therapy and three month after completing radiation treatment. RESULTS: Generally no major increase in the level and incidence of side effects potentially caused by the combined treatment was observed. In two cases a generalised skin rash occurred which immediately resolved upon discontinuation of the drug. No grade 3 and 4 toxicity was seen. Maximal GI toxicity grade 1 and 2 was observed in 85% and 10%, respectively. In terms of GU toxicity 80 % of the patients experienced a grade 1 toxicity and 10 % had grade 2 symptoms. CONCLUSION: The combination of irradiation to the prostate with concurrent high dose celecoxib was not associated with an increased level of side effects

Diagnosing and mapping pulmonary emphysema on X-ray projection images

To assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution. Lungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology. Transmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology. In a murine model, the complementary information provided by X-ray transmission and dark-field images adds incremental diagnostic value in detecting pulmonary emphysema and visualizing its regional distribution as compared to conventional X-ray projections

Semantics of the Painted Image in Hugo von Hofmannsthal’s Tod des Tizian

Form theories in Hofmannstahl’s aesthetic program aim at a reciprocal empowerment of life and art. Titian’s last painting in Tod des Tizian (1892) has to express a concept of unity and totality of all living things. Most disciples are not able to understand this, as they can’t get free of the model of existence of the aesthete, who rejects life, perceiving it as abandoned to chaos and disorder, but is incapable of replacing it with any other form because he exalts art as an object of mere idolatry, as a pure and simple instrument of defence from the pitfalls of life

Characterizing Triviality of the Exponent Lattice of A Polynomial through Galois and Galois-Like Groups

The problem of computing \emph{the exponent lattice} which consists of all the multiplicative relations between the roots of a univariate polynomial has drawn much attention in the field of computer algebra. As is known, almost all irreducible polynomials with integer coefficients have only trivial exponent lattices. However, the algorithms in the literature have difficulty in proving such triviality for a generic polynomial. In this paper, the relations between the Galois group (respectively, \emph{the Galois-like groups}) and the triviality of the exponent lattice of a polynomial are investigated. The \bbbq\emph{-trivial} pairs, which are at the heart of the relations between the Galois group and the triviality of the exponent lattice of a polynomial, are characterized. An effective algorithm is developed to recognize these pairs. Based on this, a new algorithm is designed to prove the triviality of the exponent lattice of a generic irreducible polynomial, which considerably improves a state-of-the-art algorithm of the same type when the polynomial degree becomes larger. In addition, the concept of the Galois-like groups of a polynomial is introduced. Some properties of the Galois-like groups are proved and, more importantly, a sufficient and necessary condition is given for a polynomial (which is not necessarily irreducible) to have trivial exponent lattice.Comment: 19 pages,2 figure

The construction of identities in narratives about serious leisure occupations

Engagement in occupation contributes to the shaping of identity throughout the human life. The act of telling about such engagement involves interaction based on symbolic meaning; the speaker constructing an identity by conveying how the occupation is personally meaningful. This study explored meaning in narratives told by people who engage in serious leisure occupations. A total of 78 narratives were extracted from interviews with 17 people who invest considerable time and other resources into their leisure. Analysis focused on the content, structure and performance of each narrative in order to explore meaning. The meanings were organised into a framework based around three dimensions: the located self, the active self and the changing self. Each dimension has facets that the individual might emphasise, constructing a unique identity. The framework offers a structured basis for conceptualising how occupation contributes to the shaping of the internalised self and the socially situated identity

When veiled silences speak: reflexivity, trouble and repair as methodological tools for interpreting the unspoken in discourse-based data

Researchers who have attempted to make sense of silence in data have generally considered literal silences or such things as laughter. We consider the analysis of veiled silences where participants speak, but their speaking serves as ‘noise’ that ‘veils’, or masks, their inability or unwillingness to talk about a (potentially sensitive) topic. Extending Lisa Mazzei’s ‘problematic of silence’ by using our performativity-performance analytical method, we propose the purposeful use of ‘unusual conversational moves’, the deployment of researcher reflexivity, and the analysis of trouble and repair as methods to expose taken-for-granted normative frameworks in veiled silences. We illustrate the potential of these research practices through reference to our study on men’s involvement in reproductive decision-making, in which participants demonstrated an inability to engage with the topic. The veiled silence that this produced, together with what was said, pointed to the operation of procreative heteronormativity