Development of model observers applied to 3D breast tomosynthesis microcalcifications and masses

The development of model observers for mimicking human detection strategies has followed from symmetric signals in simple noise to increasingly complex backgrounds. In this study we implement different model observers for the complex task of detecting a signal in a 3D image stack. The backgrounds come from real breast tomosynthesis acquisitions and the signals were simulated and reconstructed within the volume. Two different tasks relevant to the early detection of breast cancer were considered: detecting an 8 mm mass and detecting a cluster of microcalcifications. The model observers were calculated using a channelized Hotelling observer (CHO) with dense difference-of-Gaussian channels, and a modified (Partial prewhitening [PPW]) observer which was adapted to realistic signals which are not circularly symmetric. The sustained temporal sensitivity function was used to filter the images before applying the spatial templates. For a frame rate of five frames per second, the only CHO that we calculated performed worse than the humans in a 4-AFC experiment. The other observers were variations of PPW and outperformed human observers in every single case. This initial frame rate was a rather low speed and the temporal filtering did not affect the results compared to a data set with no human temporal effects taken into account. We subsequently investigated two higher speeds at 5, 15 and 30 frames per second. We observed that for large masses, the two types of model observers investigated outperformed the human observers and would be suitable with the appropriate addition of internal noise. However, for microcalcifications both only the PPW observer consistently outperformed the humans. The study demonstrated the possibility of using a model observer which takes into account the temporal effects of scrolling through an image stack while being able to effectively detect a range of mass sizes and distributions.

Late removal of retrievable caval filters.

The advent of retrievable caval filters was a game changer in the sense, that the previously irreversible act of implanting a medical device into the main venous blood stream of the body requiring careful evaluation of the pros and cons prior to execution suddenly became a "reversible" procedure where potential hazards in the late future of the patient lost most of their weight at the time of decision making. This review was designed to assess the rate of success with late retrieval of so called retrievable caval filters in order to get some indication about reasonable implant duration with respect to relatively "easy" implant removal with conventional means, i.e., catheters, hooks and lassos. A PubMed search (www.pubmed.gov) was performed with the search term "cava filter retrieval after 30 days clinical", and 20 reports between 1994 and 2013 dealing with late retrieval of caval filters were identified, covering approximately 7,000 devices with 600 removed filters. The maximal duration of implant reported is 2,599 days and the maximal implant duration of removed filters is also 2,599 days. The maximal duration reported with standard retrieval techniques, i.e., catheter, hook and/or lasso, is 475 days, whereas for the retrievals after this period more sophisticated techniques including lasers, etc. were required. The maximal implant duration for series with 100% retrieval accounts for 84 days, which is equivalent to 12 weeks or almost 3 months. We conclude that retrievable caval filters often become permanent despite the initial decision of temporary use. However, such "forgotten" retrievable devices can still be removed with a great chance of success up to three months after implantation. Conventional percutaneous removal techniques may be sufficient up to sixteen months after implantation whereas more sophisticated catheter techniques have been shown to be successful up to 83 months or more than seven years of implant duration. Tilting, migrating, or misplaced devices should be removed early on, and replaced if indicated with a device which is both, efficient and retrievable.

Occupational and non-occupational exposure of non-smokers to environmental tobacco smoke in Switzerland : preliminary results of an original campaig

A passive sampling device called Monitor of NICotine or "MoNIC", was constructed and evaluated by IST laboratory for determining nicotine in Environmental Tobacco Smoke (ETS). Vapour nicotine was passively collected on a potassium bisulfate treated glass fibre filter as collection medium. Analysis of amount of nicotine on the treated filter by gas chromatography equipped with Thermoionic-Specific Detector (GCTSD) after liquid-liquid extraction of 1mL of 5N NaOH : 1 mL of n-heptane saturated with NH3 using quinoline as internal standard. Based on nicotine amount of 0.2 mg/cigarette as reference, the inhaled Cigarette Equivalents (CE) by non-smokers can be calculated. Using the detected CE on the badge for nonsmokers, and comparing with amount of nicotine and cotinine level in saliva of both smokers and exposed non-smokers (N=49), we can confirm the use of the CE concept for estimating exposure to ETS. The Valais CIPRET (Center of information and prevention of the addiction to smoking), is going to organize a big campaign on the subject of the passive addiction to smoking entitled "Smoked passive, we suffer from it, we die from it ". This campaign will take place in 2007 and has for objective to inform clearly the population of Valais of the dangerousness of the passive smoke. More than 1'500 MoNIC badges were gracefully distributed to Swiss population to perform a self-monitoring of population exposure level to ETS, expressed in term of CE. Non-stimulated saliva were also collected to determine ETS biomarkers nicotine/cotinine levels of participating volunteers. Preliminary results of different levels of CE in occupational and non-occupational situations in relation with ETS were presented in this study.

Desarrollo de tecnología Bulk Acoustic Wave

El creciente uso de dispositivos móviles y el gran avance en la mejora de las aplicaciones y sistemas inalámbricos ha impulsado la demanda de filtros paso banda miniaturizados, que trabajen a altas frecuencias y tengan unas prestaciones elevadas. Los filtros basados en resonadores Bulk Acoustic Wave (BAW) están siendo la mejor alternativa a los filtros Surface Acoustic Wave (SAW), ya que funcionan a frecuencias superiores, pueden trabajar a mayores niveles de potencia y son compatibles con la tecnología CMOS. El filtro en escalera, que utiliza resonadores BAW, es de momento la mejor opción, debido a su facilidad de diseño y su bajo coste de fabricación. Aunque el filtro con resonadores acoplados (CRF) presenta mejores prestaciones como mayor ancho de banda, menor tamaño y conversión de modos. El problema de este tipo de filtros reside en su complejidad de diseño y su elevado coste. Este trabajo lleva a cabo el diseño de un CRF a partir de unas especificaciones bastante estrictas, demostrando sus altas prestaciones a pesar de su mayor inconveniente: el coste de fabricación.

Functional diversity decreases with temperature in high elevation ant fauna

1. Severe environmental conditions filter community species compositions, forming clines of functional diversity along environmental gradients. Here, the changes in functional diversity in ant assemblages with severe environmental conditions in the Swiss Alps were investigated. 2. Eight sites were sampled along an elevation gradient (1800-2550 m). The variation in functional diversity was analysed along an elevation gradient considering four traits: social structure (monogynous vs. polygynous), worker size, pupal development, and nest structure. 3. Ant species richness and functional diversity decreased with decreasing temperature. Species found in colder habitats tended to live in subterranean nests rather than in mounds and exhibit a polymorphism in queen number, either within or across populations. The phylogenetic diversity did not decrease at colder temperature: Formicinae and Myrmicinae occupied the full range of elevations investigated. 4. An insulation experiment indicated that mounds are more thermally insulated against the cold compared with soil. The absence of a mound-building ant from high elevations probably results from a reduction in the amount of vegetal materials provided by coniferous trees. 5. More severe abiotic conditions at higher elevations act as a filter on ant assemblages, directly through physiological tolerances to the abiotic conditions and indirectly as the vegetation necessary for nest building shifts with elevation.</list-item

The DART classification of unannotated transcription within the ENCODE regions: associating transcription with known and novel loci

For the ∼1% of the human genome in the ENCODE regions, only about half of the transcriptionally active regions (TARs) identified with tiling microarrays correspond to annotated exons. Here we categorize this large amount of “unannotated transcription.” We use a number of disparate features to classify the 6988 novel TARs—array expression profiles across cell lines and conditions, sequence composition, phylogenetic profiles (presence/absence of syntenic conservation across 17 species), and locations relative to genes. In the classification, we first filter out TARs with unusual sequence composition and those likely resulting from cross-hybridization. We then associate some of those remaining with proximal exons having correlated expression profiles. Finally, we cluster unclassified TARs into putative novel loci, based on similar expression and phylogenetic profiles. To encapsulate our classification, we construct a Database of Active Regions and Tools (DART.gersteinlab.org). DART has special facilities for rapidly handling and comparing many sets of TARs and their heterogeneous features, synchronizing across builds, and interfacing with other resources. Overall, we find that ∼14% of the novel TARs can be associated with known genes, while ∼21% can be clustered into ∼200 novel loci. We observe that TARs associated with genes are enriched in the potential to form structural RNAs and many novel TAR clusters are associated with nearby promoters. To benchmark our classification, we design a set of experiments for testing the connectivity of novel TARs. Overall, we find that 18 of the 46 connections tested validate by RT-PCR and four of five sequenced PCR products confirm connectivity unambiguously.

Comparative gene finding in chicken indicates that we are closing in on the set of multi-exonic widely-expressed human genes

The recent availability of the chicken genome sequence poses the question of whether there are human protein-coding genes conserved in chicken that are currently not included in the human gene catalog. Here, we show, using comparative gene finding followed by experimental verification of exon pairs by RT–PCR, that the addition to the multi-exonic subset of this catalog could be as little as 0.2%, suggesting that we may be closing in on the human gene set. Our protocol, however, has two shortcomings: (i) the bioinformatic screening of the predicted genes, applied to filter out false positives, cannot handle intronless genes; and (ii) the experimental verification could fail to identify expression at a specific developmental time. This highlights the importance of developing methods that could provide a reliable estimate of the number of these two types of genes.

Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces.

A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC-MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm(-2)) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.

Separation of small metabolites and lipids in spectra from biopsies by diffusion-weighted HR-MAS NMR: a feasibility study.

High Resolution Magic Angle Spinning (HR-MAS) NMR allows metabolic characterization of biopsies. HR-MAS spectra from tissues of most organs show strong lipid contributions that are overlapping metabolite regions, which hamper metabolite estimation. Metabolite quantification and analysis would benefit from a separation of lipids and small metabolites. Generally, a relaxation filter is used to reduce lipid contributions. However, the strong relaxation filter required to eliminate most of the lipids also reduces the signals for small metabolites. The aim of our study was therefore to investigate different diffusion editing techniques in order to employ diffusion differences for separating lipid and small metabolite contributions in the spectra from different organs for unbiased metabonomic analysis. Thus, 1D and 2D diffusion measurements were performed, and pure lipid spectra that were obtained at strong diffusion weighting (DW) were subtracted from those obtained at low DW, which include both small metabolites and lipids. This subtraction yielded almost lipid free small metabolite spectra from muscle tissue. Further improved separation was obtained by combining a 1D diffusion sequence with a T2-filter, with the subtraction method eliminating residual lipids from the spectra. Similar results obtained for biopsies of different organs suggest that this method is applicable in various tissue types. The elimination of lipids from HR-MAS spectra and the resulting less biased assessment of small metabolites have potential to remove ambiguities in the interpretation of metabonomic results. This is demonstrated in a reproducibility study on biopsies from human muscle.

Sequential estimation of multipath MIMO-OFDM channels

Wireless “MIMO” systems, employing multiple transmit and receive antennas, promise a significant increase of channel capacity, while orthogonal frequency-division multiplexing (OFDM) is attracting a good deal of attention due to its robustness to multipath fading. Thus, the combination of both techniques is an attractive proposition for radio transmission. The goal of this paper is the description and analysis of a new and novel pilot-aided estimator of multipath block-fading channels. Typical models leading to estimation algorithms assume the number of multipath components and delays to be constant (and often known), while their amplitudes are allowed to vary with time. Our estimator is focused instead on the more realistic assumption that the number of channel taps is also unknown and varies with time following a known probabilistic model. The estimation problem arising from these assumptions is solved using Random-Set Theory (RST), whereby one regards the multipath-channel response as a single set-valued random entity.Within this framework, Bayesian recursive equations determine the evolution with time of the channel estimator. Due to the lack of a closed form for the solution of Bayesian equations, a (Rao–Blackwellized) particle filter (RBPF) implementation ofthe channel estimator is advocated. Since the resulting estimator exhibits a complexity which grows exponentially with the number of multipath components, a simplified version is also introduced. Simulation results describing the performance of our channel estimator demonstrate its effectiveness.

Sequential estimation of time-varying multipath channel for MIMO-OFDM systems

In this paper, we introduce a pilot-aided multipath channel estimator for Multiple-Input Multiple-Output (MIMO) Orthogonal Frequency Division Multiplexing (OFDM) systems. Typical estimation algorithms assume the number of multipath components and delays to be known and constant, while theiramplitudes may vary in time. In this work, we focus on the more realistic assumption that also the number of channel taps is unknown and time-varying. The estimation problem arising from this assumption is solved using Random Set Theory (RST), which is a probability theory of finite sets. Due to the lack of a closed form of the optimal filter, a Rao-Blackwellized Particle Filter (RBPF) implementation of the channel estimator is derived. Simulation results demonstrate the estimator effectiveness.

Upgrading or polarization? occupational change in Britain, Germany, Spain and Switzerland, 1990-2008

This paper analyzes the pattern of occupational change in four Western European countries over the last two decades: what kind of jobs have been expanding -- high-paid jobs, low-paid jobs or both? By addressing this issue, we also examine what theoretical account is consistent with the observed pattern of change: skill-biased technical change, skill supply evolution or wage-setting institutions? Our empirical findings show a picture of massive occupational upgrading that closely matches educational expansion. In all four countries, by far the strongest employment growth occurred at the top of the occupational hierarchy, among managers and professionals. Yet in parallel, in Britain and Switzerland, as well as in Germany and Spain after 1996 and 2002 respectively, relative employment declined more strongly in the middling occupations (among clerks and production workers) than at the bottom (among interpersonal service workers). This slightly polarized pattern of occupational upgrading is consistent with the "routinization" hypothesis that technology is a better substitute for average-paid jobs in production and the office that for low-paid jobs in interpersonal services. However, we find large cross-country differences in the employment evolution at the bottom of the occupational hierarchy, among low-paid services workers: sizeable growth in Britain and Spain, but stagnation in Germany and Switzerland. This results points towards the possibility that wage-setting institutions filter the pattern of occupational change.

Role of intracellular cysteines in ENaC function

The epithelial sodium channel (ENaC) regulates the sodium reabsorption in the collecting duct principal cells of the nephron. ENaC is mainly regulated by hormones such as aldosterone and vasopressin, but also by serine proteases, Na+ and divalent cations. The crystallization of an ENaC/Deg member, the Acid Sensing Ion Channel, has been recently published but the pore-lining residues constitution of ENaC internal pore remains unclear. It has been reported that mutation aS589C of the selectivity filter on the aENaC subunit, a three residues G/SxS sequence, renders the channel permeant to divalent cations and sensitive to extracellular Cd2+. We have shown in the first part of my work that the side chain of aSer589 residue is not pointing toward the pore lumen, permitting the Cd2+ to permeate through the ion pore and to coordinate with a native cysteine, gCys546, located in the second transmembrane domain of the gENaC subunit. In a second part, we were interested in the sulfhydryl-reagent intracellular inhibition of ENaC-mediated Na+ current. Kellenberger et al. have shown that ENaC is rapidly and reversibly inhibited by internal sulfhydryl reagents underlying the involvement of intracellular cysteines in the internal regulation of ENaC. We set up a new approach comprising a Substituted Cysteine Analysis Method (SCAM) using intracellular MTSEA-biotin perfusion coupled to functional and biochemical assays. We were thus able to correlate the cysteine-modification of ENaC by methanethiosulfonate (MTS) and its effect on sodium current. This allowed us to determine the amino acids that are accessible to intracellular MTS and the one important for the inhibition of the channel. RESUME : Le canal épithélial sodique ENaC est responsable de la réabsorption du sodium dans les cellules principales du tubule collecteur rénal. Ce canal est essentiellement régulé par voie hormonale via l'aldostérone et la vasopressine mais également par des sérines protéases, le Na+ lui-même et certains cations divalents. La cristallisation du canal sodique sensible au pH acide, ASIC, un autre membre de la famille ENaC/Deg, a été publiée mais les acides aminés constituant le pore interne d'ENaC restent indéterminés. Il a été montré que la mutation aS589C du filtre de sélectivité de la sous-unité aENaC permet le passage de cations divalents et l'inhibition du canal par le Cd2+ extracellulaire. Dans un premier temps, nous avons montré que la chaîne latérale de la aSer589 n'est pas orientée vers l'intérieur du pore, permettant au Cd2+ de traverser le canal et d'interagir avec une cysteine native du second domaine transrnembranaire de la sous-unité γENaC, γCys546. Dans un second temps, nous nous sommes intéressés au mécanisme d'inhibition d'ENaC par les réactifs sulfhydryl internes. Kellenberger et al. ont montré l'implication de cystéines intracellulaires dans la régulation interne d'ENaC par les réactifs sulfhydryl. Nous avons mis en place une nouvelle approche couplant la méthode d'analyse par substitution de cystéines (SCAM) avec des perfusions intracellulaires de MTSEAbiotine. Ainsi, nous pouvons meure en corrélation les modifications des cystéines d'ENaC par les réactifs methanethiosulfonates (MTS) avec leur effet sur le courant sodique, et donc mettre en évidence les acides aminés accessibles aux MTS intracellulaires et ceux qui sont importants dans la fonction du canal.

Simple estimation of incident HIV infection rates in notification cohorts based on window periods of algorithms for evaluation of line-immunoassay result patterns.

BACKGROUND: Tests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods. METHODS: We classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship 'Prevalence = Incidence x Duration' in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship 'incident = true incident + false incident' and also to the IIR derived from the BED incidence assay. RESULTS: Window periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R(2) = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods. CONCLUSIONS: IIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.