Risk estimation of distant metastasis in node-negative, estrogen receptor-positive breast cancer patients using an RT-PCR based prognostic expression signature

<p>Abstract</p> <p>Background</p> <p>Given the large number of genes purported to be prognostic for breast cancer, it would be optimal if the genes identified are not confounded by the continuously changing systemic therapies. The aim of this study was to discover and validate a breast cancer prognostic expression signature for distant metastasis in untreated, early stage, lymph node-negative (N-) estrogen receptor-positive (ER+) patients with extensive follow-up times.</p> <p>Methods</p> <p>197 genes previously associated with metastasis and ER status were profiled from 142 untreated breast cancer subjects. A "metastasis score" (MS) representing fourteen differentially expressed genes was developed and evaluated for its association with distant-metastasis-free survival (DMFS). Categorical risk classification was established from the continuous MS and further evaluated on an independent set of 279 untreated subjects. A third set of 45 subjects was tested to determine the prognostic performance of the MS in tamoxifen-treated women.</p> <p>Results</p> <p>A 14-gene signature was found to be significantly associated (p < 0.05) with distant metastasis in a training set and subsequently in an independent validation set. In the validation set, the hazard ratios (HR) of the high risk compared to low risk groups were 4.02 (95% CI 1.91–8.44) for the endpoint of DMFS and 1.97 (95% CI 1.28 to 3.04) for overall survival after adjustment for age, tumor size and grade. The low and high MS risk groups had 10-year estimates (95% CI) of 96% (90–99%) and 72% (64–78%) respectively, for DMFS and 91% (84–95%) and 68% (61–75%), respectively for overall survival. Performance characteristics of the signature in the two sets were similar. Ki-67 labeling index (LI) was predictive for recurrent disease in the training set, but lost significance after adjustment for the expression signature. In a study of tamoxifen-treated patients, the HR for DMFS in high compared to low risk groups was 3.61 (95% CI 0.86–15.14).</p> <p>Conclusion</p> <p>The 14-gene signature is significantly associated with risk of distant metastasis. The signature has a predominance of proliferation genes which have prognostic significance above that of Ki-67 LI and may aid in prioritizing future mechanistic studies and therapeutic interventions.</p

The Gift and the meaning-giving subject: A Reading of Given Time

In this essay the relation between justice and the gift in Derrida’s thinking is explored. The essay shows that an understanding of the ontological difference or the relation between Being and beings in Heidegger’s thinking as well as Freud’s speculations on the death drive are essential to comprehend the ‘concept’ or ‘notion’ of différance as well as the gift in Derrida’s thinking. The analysis points to the complexity of Derrida’s thinking in his contemplation of the relation between justice and law and the need for a broader investigation to understand what is at stake in this regard. An exploration of the gift shows that Derrida’s thinking on justice is not ‘relativistic’ as is often assumed and that the gift can in a certain way function as a ‘guide’ in questions of constitutional interpretation

Deconstructive Aporias: Quasi-Transcendental and Normative

This paper argues that Derrida’s aporetic conclusions regarding moral and political concepts, from hospitality to democracy, can only be understood and accepted if the notion of différance and similar infrastructures are taken into account. This is because it is the infrastructures that expose and commit moral and political practices to a double and conflictual (thus aporetic) future: the conditional future that projects horizonal limits and conditions upon the relation to others, and the unconditional future without horizons of anticipation. The argument thus turns against two kinds of interpretation: the first accepts normative unconditionality in ethics but misses its support by the infrastructures. The second rejects unconditionality as a normative commitment precisely because the infrastructural support for unconditionality seems to rule out that it is normatively required. In conclusion, the article thus reconsiders the relation between a quasi-transcendental argument and its normative implications, suggesting that Derrida avoids the naturalistic fallacy

Equal consideration of all – an aporetic project?

The article considers the relationships among three arguments that purport to establish the intrinsically contradictory or paradoxical nature of the modern project aiming at the equal consideration of all. The claim that the inevitable historical insertion of universal-egalitarian norms leads to always particular and untransparent interpretations of grammatically universal norms may be combined with the claim that the logic of determination of political communities tends to generate exclusions. The combination of these two claims lends specific force to the third argument according to which equal consideration perpetually requires the non-egalitarian project of understanding (excluded) individuals on their own terms. Hence, taking off from a recent debate between Christoph Menke and Jürgen Habermas, I argue that the former is right to diagnose an aporetic self-reflection in egalitarian universalism, while agreeing with the latter about the indispensability of deliberative democratic frameworks for the defence of both egalitarian and non-egalitarian norms

Life and the Technical Transformation of Différance: Stiegler and the Noopolitics of Becoming Non-Inhuman

Through a re-articulation of Derridean différance, Bernard Stiegler claims that the human is defined by an originary default that displaces all psychic and social life onto technical supplements. His philosophy of technics re-articulates the logic of the supplement as concerning both human reflexivity and its supports, and the history of the différance of life itself. This has been criticised for reducing Derrida’s work to a metaphysics of presence, and for instituting a humanism of the relation to the inorganic. By refuting these claims, this article will show that Stiegler’s doubling of différance enables him to articulate the human as constituted by both the individuation characteristic of ‘life’, and that of a technical, psychic and collective individuation. Putting forward a reading of the logic of the trace in life, and emphasising the aspects of Leroi-Gourhan, Simondon, and Canguilhem that Stiegler uses in his reading of Derrida, I will demonstrate that the political stakes of adaption and adoption in Noo-Politics require this re-articulation of différance. Technics shapes the human future, arising from this differential mutation; marking the invention of the human as the site of the political

Luminescent bacteria and deep-sea macrourids (Pisces: gadiformes) from the Gulf of Mexico

Vita.A taxonomic analysis of luminescent bacteria from the light organs of five different species (four genera) of fishes of the family Macrouridae, 39 non-symbiotic luminescent isolants from nearshore and offshore marine environments, and non-luminescent bacteria from fishes and nearshore environments, was conducted to assess ecologic relationships between organisms found in various environments and those from photophores of macrourid fishes. Four species of luminescent bacteria described in the literature are present in the Gulf of Mexico. Luminescent bacteria from the macrourid photophore were all found to be strains of Photobacterium phosphoreum. Strain differences appeared to be more related to geographic origin than to host. Beneckea harveyi organisms were found in nearshore sediment and water samples. Photobacterium fischeri organisms were isolated from both nearshore and offshore water and sediment samples. Photobacterium leiognathi were found in the alimentary canal of a chlorophthalmid fish. The results indicate that a single luminescent bacteria species occurs in the photophores of macrourid fishes in the Gulf of Mexico. Data from growth requirement analysis indicate that host factors together with physical characteristics of the deep-sea environment probably influence the microecology of the light organ such that one specific luminescent bacterial form exists in that organ

Hikari Michi: Studying Immersion in Games Using the Oculus Rift and Leap Motion Controller

Game developers are always searching for new, creative ways to immerse players into their games, whether it be through gameplay, input, or output. As aspiring games developers ourselves, we pursued this project with the goal of building a game that made an enriching and engaging experience through its gameplay, input, and output. For this game, we made use of the Leap Motion hand and finger movement capturing device and the Oculus Rift virtual reality head mounted display alongside the C4 Game Engine. Through this project, we hope to provide players with a fun, immersive game play experience and hopefully be a source of inspiration for virtual reality game developers in the future