Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

We analysed the molecular genetic profiles of breast cancer samples before and after neoadjuvant chemotherapy with combination doxorubicin and cyclophosphamide (AC). DNA was obtained from microdissected frozen breast core biopsies from 44 patients before chemotherapy. Additional samples were obtained before the second course of chemotherapy (D21) and after the completion of the treatment (surgical specimens) in 17 and 21 patients, respectively. Microarray-based comparative genome hybridisation was performed using a platform containing approx5800 bacterial artificial chromosome clones (genome-wide resolution: 0.9 Mb). Analysis of the 44 pretreatment biopsies revealed that losses of 4p, 4q, 5q, 12q13.11–12q13.12, 17p11.2 and 17q11.2; and gains of 1p, 2p, 7q, 9p, 11q, 19p and 19q were significantly associated with oestrogen receptor negativity. 16q21–q22.1 losses were associated with lobular and 8q24 gains with ductal types. Losses of 5q33.3–q4 and 18p11.31 and gains of 6p25.1–p25.2 and Xp11.4 were associated with HER2 amplification. No correlations between DNA copy number changes and clinical response to AC were found. Microarray-based comparative genome hybridisation analysis of matched pretreatment and D21 biopsies failed to identify statistically significant differences, whereas a comparison between matched pretreatment and surgical samples revealed a statistically significant acquired copy number gain on 11p15.2–11p15.5. The modest chemotherapy-driven genomic changes, despite profound loss of cell numbers, suggest that there is little therapeutic selection of resistant non-modal cell lineages.

No pain, no gain? Torture and ethics in the war on terror

Is the use of torture ever justified? This article argues that torture cannot be justified, even in so called ticking bomb cases, but that in such extreme situations it may be necessary. In those situations, judgements about whether the use of torture is legitimate must balance the imminence and gravity of the threat with the need to prevent future occurrences of torture and maintain a normative environment that is hostile to its use. The article begins by observing that the use of torture and/or cruel and degrading treatment has become a core component of the global war on terror. It tests the claim that the use of coercive interrogation techniques does not constitute torture, showing that similar arguments were levelled by both the British and French governments in relation to Northern Ireland and Algeria respectively and found wanting. It then evaluates and rejects Dershowitz's claim for the legalization of torture and the more limited claim that torture may be permissible in ticking bomb scenarios. In the final section, the article questions how we might maintain the prohibition on torture while acknowledging that it may be necessary in some hypothetical cases.

On the relative complexity of labelled modal tableaux

We investigate the relative complexity of two free-variable labelled modal tableaux(KEM and Single Step Tableaux, SST). We discuss the reasons why p-simulation is not a proper measure of the relative complexity of tableaux-like proof systems, and we propose an improved comparison scale (p-search-simulation). Finally we show that KEM p-search-simulates SST while SST cannot p-search-simulate KEM.

Minimum description length, regularisation and multi-modal data

Relationships between clustering, description length, and regularisation are pointed out, motivating the introduction of a cost function with a description length interpretation and the unusual and useful property of having its minimum approximated by the densest mode of a distribution. A simple inverse kinematics example is used to demonstrate that this property can be used to select and learn one branch of a multi-valued mapping. This property is also used to develop a method for setting regularisation parameters according to the scale on which structure is exhibited in the training data. The regularisation technique is demonstrated on two real data sets, a classification problem and a regression problem.