Imaging dielectric relaxation in nanostructured polymers by frequency modulation electrostatic force microscopy

We have developed a method for imaging the temperature-frequency dependence of the dynamics of nanostructured polymer films with spatial resolution. This method provides images with dielectric compositional contrast well decoupled from topography. Using frequency-modulation electrostatic-force-microscopy, we probe the local frequency-dependent (0.1–100 Hz) dielectric response through measurement of the amplitude and phase of the force gradient in response to an oscillating applied electric field. When the phase is imaged at fixed frequency, it reveals the spatial variation in dielectric losses, i.e., the spatial variation in molecular/dipolar dynamics, with 40 nm lateral resolution. This is demonstrated by using as a model system; a phase separated polystyrene/polyvinyl-acetate (PVAc) blend. We show that nanoscale dynamic domains of PVAc are clearly identifiable in phase images as those which light-up in a band of temperature, reflecting the variations in the molecular/dipolar dynamics approaching the glass transition temperature of PVAc

Parallel tagged amplicon sequencing of transcriptome-based genetic markers for Triturus newts with the Ion Torrent next-generation sequencing platform

Next-generation sequencing is a fast and cost-effective way to obtain sequence data for nonmodel organisms for many markers and for many individuals. We describe a protocol through which we obtain orthologous markers for the crested newts (Amphibia: Salamandridae: Triturus), suitable for analysis of interspecific hybridization. We use transcriptome data of a single Triturus species and design 96 primer pairs that amplify c. 180 bp fragments positioned in 3-prime untranslated regions. Next, these markers are tested with uniplex PCR for a set of species spanning the taxonomical width of the genus Triturus. The 52 markers that consistently show a single band of expected length at gel electrophoreses for all tested crested newt species are then amplified in five multiplex PCRs (with a plexity of ten or eleven) for 132 individual newts: a set of 84 representing the seven (candidate) species and a set of 48 from a presumed hybrid population. After pooling multiplexes per individual, unique tags are ligated to link amplicons to individuals. Subsequently, individuals are pooled equimolar and sequenced on the Ion Torrent next-generation sequencing platform. A bioinformatics pipeline identifies the alleles and recodes these to a genotypic format. Next, we test the utility of our markers. baps allocates the 84 crested newt individuals representing (candidate) species to their expected (candidate) species, confirming the markers are suitable for species delineation. newhybrids, a hybrid index and hiest confirm the 48 individuals from the presumed hybrid population to be genetically admixed, illustrating the potential of the markers to identify interspecific hybridization. We expect the set of markers we designed to provide a high resolving power for analysis of hybridization in Triturus

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography

Inter-observer variability of visual analysis of “stress”-only adenosine first-pass myocardial perfusion imaging in relation to clinical experience and reading criteria

To assess the inter-observer agreement of adenosine “stress”-only visual analysis of perfusion MR images in relation to experience and reading criteria. 106 adenosine perfusion MR examinations out of 350, 46 consecutive positive examinations and 60 randomly selected negative examinations were visually analysed by three individual readers (two residents and a technician) with different levels of experience. Readings (blinded for any information) were compared with the reading of an expert radiologist. After a month the examinations were presented again (randomly) without knowledge regarding the first readings. This time readings were performed with the systematical use of reading criteria. Agreement with the expert reading was good for the most experienced resident (k = 0.88). Kappa was 0.48 for the least experienced, and 0.57 for the technician. After the second systematical reading inter-observer agreement increased to 0.9, 0.68 and 0.77 respectively. Overall kappa increased from 0.59 to 0.71. The use of reading criteria significantly improved the performance of the least experienced reader (P = 0.01). Visual analysis of adenosine “stress”-only first-pass perfusion MR images has moderate to very good agreement. Performance is experience related, but the systematic use of reading criteria significantly increased performance for the least experienced observer

Exon expression arrays as a tool to identify new cancer genes

Background: Identification of genes that are causally implicated in oncogenesis is a major goal in cancer research. An estimated 10-20% of cancer-related gene mutations result in skipping of one or more exons in the encoded transcripts. Here we report on a strategy to screen in a global fashion for such exon-skipping events using PAttern based Correlation (PAC). The PAC algorithm has been used previously to identify differentially expressed splice variants between two predefined subgroups. As genetic changes in cancer are sample specific, we tested the ability of PAC to identify aberrantly expressed exons in single samples. Principal Findings: As a proof-of-principle, we tested the PAC strategy on human cancer samples of which the complete coding sequence of eight cancer genes had been screened for mutations. PAC detected all seven exon-skipping mutants among 12 cancer cell lines. PAC also identified exon-skipping mutants in clinical cancer specimens although detection was compromised due to heterogeneous (wild-type) transcript expression. PAC reduced the number candidate genes/exons for subsequent mutational analysis by two to three orders of magnitude and had a substantial true positive rate. Importantly, of 112 randomly selected outlier exons, sequence analysis identified two novel exon skipping events, two novel base changes and 21 previously reported base changes (SNPs). Conclusions: The ability of PAC to enrich for mutated transcripts and to identify known and novel genetic changes confirms its suitability as a strategy to identify candidate cancer genes

Risk factors for atherosclerotic and medial arterial calcification of the intracranial internal carotid artery

_Background and aims:_ Calcifications of the intracranial internal carotid artery (iICA) are an important risk factor for stroke. The calcifications can occur both in the intimal and medial layer of the vascular wall. The aim of this study is to assess whether medial calcification in the iICA is differently related to risk factors for cardiovascular disease, compared to intimal calcification. _Methods:_ Unenhanced thin slice computed tomography (CT) scans from 1132 patients from the Dutch acute stroke study cohort were assessed for dominant localization of calcification (medial or intimal) by one of three observers based on established methodology. Associations between known cardiovascular risk factors (age, gender, body mass index, pulse pressure, eGFR, smoking, hypertension, diabetes mellitus, hyperlipidemia, previous vascular disease, and family history) and the dominant localization of calcifications were assessed via logistic regression analysis. _Results:_ In the 1132 patients (57% males, mean age 67.4 years [SD 13.8]), dominant intimal calcification was present in 30.9% and dominant medial calcification in 46.9%. In 10.5%, no calcification was seen. Age, pulse pressure and family history were risk factors for both types of calcification. Multivariably adjusted risk factors for dominant intimal calcification only were smoking (OR 2.09 [CI 1.27–3.44]) and hypertension (OR 2.09 [CI 1.29–3.40]) and for dominant medial calcification diabetes mellitus (OR 2.39 [CI 1.11–5.14]) and previous vascular disease (OR 2.20 [CI 1.30–3.75]). _Conclusions:_ Risk factors are differently related to the dominant localizations of calcifications, a finding that supports the hypothesis that the intimal and medial calcification represents a distinct etiology

Formal Safety Assessment of a Marine Seismic Survey Vessel Operation, Incorporating Risk Matrix and Fault Tree Analysis

In maritime safety research, risk is assessed usually within the framework of formal safety assessment (FSA), which provides a formal and systematic methodology to improve the safety of lives, assets, and the environment. A bespoke application of FSA to mitigate accidents in marine seismic surveying is put forward in this paper, with the aim of improving the safety of seismic vessel operations, within the context of developing an economically viable strategy. The work herein takes a close look at the hazards in North Sea offshore seismic surveying, in order to identify critical risk factors, leading to marine seismic survey accidents. The risk factors leading to undesirable events are analysed both qualitatively and quantitatively. A risk matrix is introduced to screen the identified undesirable events. Further to the screening, Fault Tree Analysis (FTA) is presented to investigate and analyse the most critical risks of seismic survey operation, taking into account the lack of historical data. The obtained results show that man overboard (MOB) event is a major risk factor in marine seismic survey operation; lack of training on safe work practice, slippery deck as a result of rain, snow or water splash, sea state affecting human judgement, and poor communication are identified as the critical risk contributors to the MOB event. Consequently, the risk control options are focused on the critical risk contributors for decision-making. Lastly, suggestions for the introduction and development of the FSA methodology are highlighted for safer marine and offshore operations in general

Wettbewerb und Regulierung

Wettbewerb und Regulierung werfen sowohl aus einer wirtschafts- als auch aus einer politikwissenschaftlichen Perspektive interessante Fragestellungen auf und haben daher in beiden Disziplinen umfangreiche Beachtung gefunden. Der vorliegende Beitrag gibt eine Übersicht über beide Herangehensweisen. Dabei wer-den zunächst die grundlegenden Unterschiede und Gemeinsamkeiten offengelegt (Abschnitt 2), bevor die disziplinären Schwerpunkte in der Analyse vorgestellt, und aus Sicht der jeweils anderen Disziplin kommentiert werden (Abschnitte 3 und 4). Wir kommen zu dem Ergebnis, dass beide Sichtweisen in erster Linie komplementär sind und sich gegenseitig befruchten können