Treatment and detection of ALK-rearranged NSCLC.

The recent approval of crizotinib for the treatment of anaplastic lymphoma kinase (ALK)-rearranged advanced non-small cell lung cancer (NSCLC) in the US and other countries has provoked intense interest in ALK rearrangements as oncogenic drivers, and promises to revolutionise the way in which NSCLC is diagnosed and treated. Here, we review clinical data to date for the use of crizotinib to treat patients with advanced, ALK-positive NSCLC and consider issues surrounding the detection of ALK-positivity including the use of fluorescence in situ hybridisation and the other potential techniques available, and their suitability for ALK screening. We also discuss the emergence of resistance to crizotinib therapy and the range of other ALK inhibitors currently in development.

Neuropathies diabétiques: tableaux cliniques, détection précoce et appel au spécialiste [Diabetic neuropathies: clinical sub-types, early detection and asking help from the specialist].

In diabetes mellitus, it is expected to see a common, mainly sensitive, distal symmetrical polyneuropathy (DPN) involving a large proportion of diabetic patients according to known risk factors. Several other diabetic peripheral neuropathies are recognized, such as dysautonomia and multifocal neuropathies including lumbosacral radiculoplexus and oculomotor palsies. In this review, general aspects of diabetic neuropathies are examined, and it is discussed why and how the general practionner has to perform a yearly examination. At the present time, some consensuses emerge to ask help from the specialist when faced to other forms of peripheral neuropathies than distal symmetrical DPN.

Phylogeographical structure, postglacial recolonization and barriers to gene flow in the distinctive Valais chromosome race of the common shrew (Sorex araneus).

Using one male-inherited and eight biparentally inherited microsatellite markers, we investigate the population genetic structure of the Valais chromosome race of the common shrew (Sorex araneus) in the Central Alps of Europe. Unexpectedly, the Y-chromosome microsatellite suggests nearly complete absence of male gene flow among populations from the St-Bernard and Simplon regions (Switzerland). Autosomal markers also show significant genetic structuring among these two geographical areas. Isolation by distance is significant and possible barriers to gene flow exist in the study area. Two different approaches are used to better understand the geographical patterns and the causes of this structuring. Using a principal component analysis for which testing procedure exists, and partial Mantel tests, we show that the St-Bernard pass does not represent a significant barrier to gene flow although it culminates at 2469 m, close to the highest altitudinal record for this species. Similar results are found for the Simplon pass, indicating that both passes represented potential postglacial recolonization routes into Switzerland from Italian refugia after the last Pleistocene glaciations. In contrast with the weak effect of these mountain passes, the Rhône valley lowlands significantly reduce gene flow in this species. Natural obstacles (the large Rhône river) and unsuitable habitats (dry slopes) are both present in the valley. Moreover, anthropogenic changes to landscape structures are likely to have strongly reduced available habitats for this shrew in the lowlands, thereby promoting genetic differentiation of populations found on opposite sides of the Rhône valley.

Enhanced sensitivity detection of protein immobilization by fluorescent interference on oxidized silicon.

We present a silicon chip-based approach for the enhanced sensitivity detection of surface-immobilized fluorescent molecules. Green fluorescent protein (GFP) is bound to the silicon substrate by a disuccinimidyl terephtalate-aminosilane immobilization procedure. The immobilized organic layers are characterized by surface analysis techniques, like ellipsometry, atomic force microscopy (AFM) and X-ray induced photoelectron spectroscopy. We obtain a 20-fold enhancement of the fluorescent signal, using constructive interference effects in a fused silica dielectric layer, deposited before immobilization onto the silicon. Our method opens perspectives to increase by an order of magnitude the fluorescent response of surface immobilized DNA- or protein-based layers for a variety of biosensor applications.

Front-Crawl propulsive phase detection using inertial sensors

Front crawl is an alternating swimming stroke technique in which different phases of arm movement induce changes in acceleration of limbs and body. This study proposes a new approach to use inertial body worn sensors to estimate main temporal phases of front crawl. Distinctive features in kinematic signals are used to detect the temporal phases. These temporal phases are key information sources of qualitative and quantitative evaluation of swimming coordination, which have been assessed previously by video analysis. The present method has been evaluated upon a wide range of coordination and showed a difference of 4.9% with video based system. The results are in line with video analysis inter-operator variability yet offering an easy-to-use system for trainers.

Simple method for detection of MYH11 DNA rearrangements in patients with inv(16)(p13q22) and acute myeloid leukemia.

The pericentric inversion on chromosome 16 [inv(16)(p13q22)] and related t(16;16)(p13;q22) are recurrent aberrations associated with acute myeloid leukemia (AML) M4 Eo. Both abberations result in a fusion of the core binding factor beta (CBFB) and smooth muscle myosin heavy chain gene (MYH11). A selected genomic 6.9-kb BamHl probe detects MYH11 DNA rearrangements in 18 of 19 inv(16)/t(16;16) patients tested using HindIII digested DNA. The rearranged fragments were not detectable after remission in two cases tested, while they were present after relapse in one of these two cases tested.

A note on robust detection

We introduce a simple new hypothesis testing procedure, which,based on an independent sample drawn from a certain density, detects which of $k$ nominal densities is the true density is closest to, under the total variation (L_{1}) distance. Weobtain a density-free uniform exponential bound for the probability of false detection.

The application of NMR and MS methods for detection of adulteration of wine, fruit juices, and olive oil. A review

This review covers two important techniques, high resolution nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), used to characterize food products and detect possible adulteration of wine, fruit juices, and olive oil, all important products of the Mediterranean Basin. Emphasis is placed on the complementary use of SNIF-NMR (site-specific natural isotopic fractionation nuclear magnetic resonance) and IRMS (isotope-ratio mass spectrometry) in association with chemometric methods for detecting the adulteration.

Characterization and detection of naturally occurring antibodies against IL-1 alpha and IL-1 beta in normal human plasma.

During the development and testing of a radioreceptor assay (RRA) for human IL-1, we have detected and identified the presence of auto-antibodies to IL-1 in normal human plasma (NHP). The RRA is based on the competition between human 125I-labeled rIL-1 alpha and standard or unknown quantities of IL-1 alpha or IL-1 beta for binding to a limited amounts of IL-1 receptor (IL-1R) isolated from the EL4 mouse thymoma cell line. NHP from 20 out of 100 unselected blood donors were found to completely inhibit the binding of 125I-labeled IL-1 alpha to its receptor, suggesting the presence in these NHP samples of either abnormal amounts of IL-1 or of a factor binding to the 125I-labeled IL-1 alpha. Special care was taken to ascertain that the inhibitory factors were antibodies and not soluble IL-1 receptor antagonist. When plasma samples with inhibiting activity were incubated with labeled IL-1 alpha and chromatographed on a Sephadex G200 column, they were found to contain 125I-labeled complexes with an apparent molecular weight of 150-200kD. The IL-1 binding factor could be eliminated from plasma by incubation with protein A-Sepharose, suggesting that it consisted in IgG antibodies directed against IL-1. Furthermore, the antibody nature of the inhibiting factor was confirmed by its binding to purified rIL-1 coupled to Sepharose. Screening of 200 NHP samples by incubation with 100 pg of 125I-labeled IL-1 followed by precipitation with 12% of polyethylene glycol (PEG) confirmed that about 25% of NHP contain detectable IgG antibodies to IL-1 alpha, while only 2% of NHP contain antibodies to IL-1 beta. No correlation between the presence of these anti-IL-1 antibodies and any particular major histocompatibility complex or any pathological conditions was detected. We suggest that all serum samples assayed for IL-1 alpha or IL-1 beta content should be pretested with the PEG precipitation assay described here.

Molecular basis of odor detection in insects.

Olfactory systems are evolutionarily ancient, underlying the common requirement for all animals to sense and respond to diverse volatile chemical signals in their environment. Odor detection is mediated by odorant receptors (ORs) that, in most olfactory systems, comprise large families of divergent G protein-coupled receptors. Here, I discuss our and others' recent investigations of ORs in the fruit fly, Drosophila melanogaster, which have revealed insights into the distinct evolutionary origin and molecular function of insect ORs. I also describe a bioinformatics strategy that we developed to identify molecules that function with these insect-specific receptors in odor detection.

Exposition de l'enfant a des violences domestiques. Un modèle pluridisciplinaire de détection, d'evaluation et de prise en charge [Children's exposure to domestic violence. A multidisciplinary model of detection, assessment and management].

Children psychological abuse is difficult to identify. However, its consequences on child development can be as serious as physical and sexual abuses. It is therefore essential, to implement in our hospitals, structures whose missions are successively to detect victims, evaluate them on somatic and psychological levels, and elaborate a therapy. We propose a model for the achievement of these objectives through collaboration between the Medical Unit of Violence, the Pediatric CAN Team and the Unit of Les Boréales.