From the Bench to Bedside: Biological and Methodology Considerations for the Future of Companion Diagnostics in Nonsmall Cell Lung Cancer

Companion diagnostics are an emerging and exciting field in the care of oncology patients. These tests accompany standard diagnostic investigations in cancer patients and function as an aid in treatment decision making. A great number of new compounds are under clinical and laboratory testing in nonsmall cell lung cancer (NSCLC). As the variety of therapeutic options expands in the various settings of the disease, it becomes apparent that specific and sensitive molecular tests are necessary to define the subsets of patients who are going to derive clinical benefit. Testing for epidermal growth factor receptor (EGFR) somatic mutations for the appropriate administration of tyrosine kinase inhibitors is just the beginning. Anaplastic lymphoma kinase (ALK) fusion protein detection and molecular histology classification are promising candidate predictors for clinical benefit from crizotinib and pemetrexed, respectively. This paper summarizes such diagnostics and discusses unanswered questions concerning underlying biology and standardization issues

An artificial neural network predictor for tropospheric surface duct phenomena

International audienceIn this work, an artificial neural network (ANN) model is developed and used to predict the presence of ducting phenomena for a specific time, taking into account ground values of atmospheric pressure, relative humidity and temperature. A feed forward backpropagation ANN is implemented, which is trained, validated and tested using atmospheric radiosonde data from the Helliniko airport, for the period from 1991 to 2004. The network's quality and generality is assessed using the Area Under the Receiver Operating Characteristics (ROC) Curves (AUC), which resulted to a mean value of about 0.86 to 0.90, depending on the observation time. In order to validate the ANN results and to evaluate any further improvement options of the proposed method, the problem was additionally treated using Least Squares Support Vector Machine (LS-SVM) classifiers, trained and tested with identical data sets for direct performance comparison with the ANN. Furthermore, time series prediction and the effect of surface wind to the presence of tropospheric ducts appearance are discussed. The results show that the ANN model presented here performs efficiently and gives successful tropospheric ducts predictions

On the Influence of Pulse Shapes on Ionization Probability

We investigate analytical expressions for the upper and lower bounds for the ionization probability through ultra-intense shortly pulsed laser radiation. We take several different pulse shapes into account, including in particular those with a smooth adiabatic turn-on and turn-off. For all situations for which our bounds are applicable we do not find any evidence for bound-state stabilization.Comment: 21 pages LateX, 10 figure

On the absence of bound-state stabilization through short ultra-intense fields

We address the question of whether atomic bound states begin to stabilize in the short ultra-intense field limit. We provide a general theory of ionization probability and investigate its gauge invariance. For a wide range of potentials we find an upper and lower bound by non-perturbative methods, which clearly exclude the possibility that the ultra intense field might have a stabilizing effect on the atom. For short pulses we find almost complete ionization as the field strength increases.Comment: 34 pages Late

Ionization Probabilities through ultra-intense Fields in the extreme Limit

We continue our investigation concerning the question of whether atomic bound states begin to stabilize in the ultra-intense field limit. The pulses considered are essentially arbitrary, but we distinguish between three situations. First the total classical momentum transfer is non-vanishing, second not both the total classical momentum transfer and the total classical displacement are vanishing together with the requirement that the potential has a finite number of bound states and third both the total classical momentum transfer and the total classical displacement are vanishing. For the first two cases we rigorously prove, that the ionization probability tends to one when the amplitude of the pulse tends to infinity and the pulse shape remains fixed. In the third case the limit is strictly smaller than one. This case is also related to the high frequency limit considered by Gavrila et al.Comment: 16 pages LateX, 2 figure

An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1–5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan–Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16–82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up

Multiphoton detachment of electrons from negative ions

A simple analytical solution for the problem of multiphoton detachment from negative ions by a linearly polarized laser field is found. It is valid in the wide range of intensities and frequencies of the field, from the perturbation theory to the tunneling regime, and is applicable to the excess-photon as well as near-threshold detachment. Practically, the formulae are valid when the number of photons is greater than two. They produce the total detachment rates, relative intensities of the excess-photon peaks, and photoelectron angular distributions for the hydrogen and halogen negative ions, in agreement with those obtained in other, more numerically involved calculations in both perturbative and non-perturbative regimes. Our approach explains the extreme sensitivity of the multiphoton detachment probability to the asymptotic behaviour of the bound-state wave function. Rapid oscillations in the angular dependence of the $n$-photon detachment probability are shown to arise due to interference of the two classical trajectories which lead to the same final state after the electron emerges at the opposite sides of the atom when the field is close to maximal.Comment: 27 pages, Latex, and PostScript figures fig1.ps, fig2.ps, fig3.ps, accepted for publication in Phys. Rev.

Coffee consumption and risk of breast cancer: A Mendelian randomization study.

BACKGROUND: Observational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations. RESULTS: One cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80-1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79-1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75-1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80-1.25), weighted median (OR: 0.97, 95% CI: 0.89-1.05) and weighted mode (OR: 1.00, CI: 0.93-1.07). CONCLUSIONS: The results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association

COST292 experimental framework for TRECVID 2008

In this paper, we give an overview of the four tasks submitted to TRECVID 2008 by COST292. The high-level feature extraction framework comprises four systems. The first system transforms a set of low-level descriptors into the semantic space using Latent Semantic Analysis and utilises neural networks for feature detection. The second system uses a multi-modal classifier based on SVMs and several descriptors. The third system uses three image classifiers based on ant colony optimisation, particle swarm optimisation and a multi-objective learning algorithm. The fourth system uses a Gaussian model for singing detection and a person detection algorithm. The search task is based on an interactive retrieval application combining retrieval functionalities in various modalities with a user interface supporting automatic and interactive search over all queries submitted. The rushes task submission is based on a spectral clustering approach for removing similar scenes based on eigenvalues of frame similarity matrix and and a redundancy removal strategy which depends on semantic features extraction such as camera motion and faces. Finally, the submission to the copy detection task is conducted by two different systems. The first system consists of a video module and an audio module. The second system is based on mid-level features that are related to the temporal structure of videos