403 research outputs found

    A Convex Reconstruction Model for X-ray Tomographic Imaging with Uncertain Flat-fields

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    Classical methods for X-ray computed tomography are based on the assumption that the X-ray source intensity is known, but in practice, the intensity is measured and hence uncertain. Under normal operating conditions, when the exposure time is sufficiently high, this kind of uncertainty typically has a negligible effect on the reconstruction quality. However, in time- or dose-limited applications such as dynamic CT, this uncertainty may cause severe and systematic artifacts known as ring artifacts. By carefully modeling the measurement process and by taking uncertainties into account, we derive a new convex model that leads to improved reconstructions despite poor quality measurements. We demonstrate the effectiveness of the methodology based on simulated and real data sets.Comment: Accepted at IEEE Transactions on Computational Imagin

    Client abuse to public welfare workers: theoretical framework and critical incident case study

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    We analyse a case study of workers’ experience of client abuse in a Danish public welfare organisation. We make an original contribution by putting forward two different theoretical expectations of the case. One expectation is that the case follows a pattern of customer abuse processes in a social market economy – in which worker are accorded power and resources, in which workers tend to frame the abuse as the outcome of a co-citizen caught in system failure, and in which workers demonstrate some resilience to abuse. Another expectation is that New Public Management reforms push the case to follow patterns of customer abuse associated with a liberal market economy – in which the customer is treated as sovereign against the relatively powerless worker, and in which workers bear heavy emotional costs of abuse. Our findings show a greater match to the social processes of abuse within a social market economy

    Seasonal sea ice variability in eastern Fram Strait over the last 2000 years

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    We present a high-resolution (ca. 50 years) biomarker-based reconstruction of seasonal sea ice conditions for the West Svalbard continental margin covering the last ca. 2k years. Our reconstruction is based on the distributions of sea ice algal (IP25) and phytoplankton (brassicasterol and HBI III) lipids in marine sediment core MSM5/5-712-1 retrieved in 2007. The individual and combined (PIP25) temporal profiles, together with estimates of spring sea ice concentration [SpSIC (%)] based on a recent calibration, suggest that sea ice conditions during the interval ca. 50–1700 AD may not have been as variable as described in previous reconstructions, with SpSIC generally in the range ca. 35–45 %. A slight enhancement in SpSIC (ca. 50 %) was identified at ca. 1600 AD, contemporaneous with the Little Ice Age, before declining steadily over the subsequent ca. 400 years to near-modern values (ca. 25 %). In contrast to these spring conditions, our data suggest that surface waters during summer months were ice free for the entire record. The decline in SpSIC in recent centuries is consistent with the known retreat of the winter ice margin from documentary sea ice records. This decrease in sea ice is possibly attributed to enhanced inflow of warm water delivered by the North Atlantic Current and/or increasing air temperatures, as shown in previous marine and terrestrial records. Comparison of our biomarker-based sea ice reconstruction with one obtained previously based on dinocyst distributions in a core from a similar location reveals partial agreement in the early–mid part of the records (ca. 50–1700 AD), but a notable divergence in the most recent ca. 300 years. We hypothesise that this divergence likely reflects the individual signatures of each proxy method, especially as the biomarker-based SpSIC estimates during this interval (\u3c25 %) are much lower than the threshold level (\u3e50 % sea ice cover) used for the dinocyst approach. Alternatively, divergence between outcomes may indicate seasonality shifts in sea ice conditions, such that a combined biomarker-dinocyst approach in future studies might provide further insights into this important parameter

    GRANADA consensus on analytical approaches to assess associations with accelerometer-determined physical behaviours (physical activity, sedentary behaviour and sleep) in epidemiological studies.

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    The inter-relationship between physical activity, sedentary behaviour and sleep (collectively defined as physical behaviours) is of interest to researchers from different fields. Each of these physical behaviours has been investigated in epidemiological studies, yet their codependency and interactions need to be further explored and accounted for in data analysis. Modern accelerometers capture continuous movement through the day, which presents the challenge of how to best use the richness of these data. In recent years, analytical approaches first applied in other scientific fields have been applied to physical behaviour epidemiology (eg, isotemporal substitution models, compositional data analysis, multivariate pattern analysis, functional data analysis and machine learning). A comprehensive description, discussion, and consensus on the strengths and limitations of these analytical approaches will help researchers decide which approach to use in different situations. In this context, a scientific workshop and meeting were held in Granada to discuss: (1) analytical approaches currently used in the scientific literature on physical behaviour, highlighting strengths and limitations, providing practical recommendations on their use and including a decision tree for assisting researchers' decision-making; and (2) current gaps and future research directions around the analysis and use of accelerometer data. Advances in analytical approaches to accelerometer-determined physical behaviours in epidemiological studies are expected to influence the interpretation of current and future evidence, and ultimately impact on future physical behaviour guidelines

    Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.

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    Novel APC mutations in Czech and Slovak FAP families: clinical and genetic aspects

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    BACKGROUND: Germline mutations in the adenomatous polyposis gene (APC) result in familial adenomatous polyposis (FAP). FAP is an autosomal dominantly inherited disorder predisposing to colorectal cancer. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extracolonic manifestations. An attenuated form of polyposis (AFAP) is characterized by less than 100 adenomas and later onset of the disease. METHODS: Here, we analyzed the APC gene for germline mutations in 59 Czech and 15 Slovak FAP patients. In addition, 50 apparently APC mutation negative Czech probands and 3 probands of Slovak origin were screened for large deletions encompassing the APC gene. Mutation screening was performed using denaturing gradient gel electrophoresis and/or protein truncation test. DNA fragments showing an aberrant electrophoretic banding pattern were sequenced. Screening for large deletions was performed by multiplex ligation dependent probe amplification. The extent of deletions was analyzed using following microsatellite markers: D5S299, D5S82, D5S134 and D5S346. RESULTS: In the set of Czech and Slovak patients, we identified 46 germline mutations among 74 unrelated probands. Total mutation capture is 62,2% including large deletions. Thirty seven mutations were detected in 49 patients presenting a classical FAP phenotype (75,5%) and 9 mutations in 25 patients with attenuated FAP (36%). We report 20 novel germline APC mutations and 3 large deletions (6%) encompassing the whole-gene deletions and/or exon 14 deletion. In the patients with novel mutations, correlations of the mutation localization are discussed in context of the classical and/or attenuated phenotype of the disease. CONCLUSION: The results of the molecular genetic testing are used both in the establishment of the predictive diagnosis and in the clinical management of patients. In some cases this study has also shown the difficulty to classify clinically between the classical and the attenuated form of FAP according to the established criteria. Interfamilial and/or intrafamilial phenotype variability was also confirmed in some cases which did not fit well with predicted genotype-phenotype correlation. All these findings have to be taken into consideration both in the genetic counselling and in the patient care

    Tropical root responses to global changes:A synthesis

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    Tropical ecosystems face escalating global change. These shifts can disrupt tropical forests' carbon (C) balance and impact root dynamics. Since roots perform essential functions such as resource acquisition and tissue protection, root responses can inform about the strategies and vulnerabilities of ecosystems facing present and future global changes. However, root trait dynamics are poorly understood, especially in tropical ecosystems. We analyzed existing research on tropical root responses to key global change drivers: warming, drought, flooding, cyclones, nitrogen (N) deposition, elevated (e) CO2, and fires. Based on tree species‐ and community‐level literature, we obtained 266 root trait observations from 93 studies across 24 tropical countries. We found differences in the proportion of root responsiveness to global change among different global change drivers but not among root categories. In particular, we observed that tropical root systems responded to warming and eCO2 by increasing root biomass in species‐scale studies. Drought increased the root: shoot ratio with no change in root biomass, indicating a decline in aboveground biomass. Despite N deposition being the most studied global change driver, it had some of the most variable effects on root characteristics, with few predictable responses. Episodic disturbances such as cyclones, fires, and flooding consistently resulted in a change in root trait expressions, with cyclones and fires increasing root production, potentially due to shifts in plant community and nutrient inputs, while flooding changed plant regulatory metabolisms due to low oxygen conditions. The data available to date clearly show that tropical forest root characteristics and dynamics are responding to global change, although in ways that are not always predictable. This synthesis indicates the need for replicated studies across root characteristics at species and community scales under different global change factors

    Determining Frequent Patterns of Copy Number Alterations in Cancer

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    Cancer progression is often driven by an accumulation of genetic changes but also accompanied by increasing genomic instability. These processes lead to a complicated landscape of copy number alterations (CNAs) within individual tumors and great diversity across tumor samples. High resolution array-based comparative genomic hybridization (aCGH) is being used to profile CNAs of ever larger tumor collections, and better computational methods for processing these data sets and identifying potential driver CNAs are needed. Typical studies of aCGH data sets take a pipeline approach, starting with segmentation of profiles, calls of gains and losses, and finally determination of frequent CNAs across samples. A drawback of pipelines is that choices at each step may produce different results, and biases are propagated forward. We present a mathematically robust new method that exploits probe-level correlations in aCGH data to discover subsets of samples that display common CNAs. Our algorithm is related to recent work on maximum-margin clustering. It does not require pre-segmentation of the data and also provides grouping of recurrent CNAs into clusters. We tested our approach on a large cohort of glioblastoma aCGH samples from The Cancer Genome Atlas and recovered almost all CNAs reported in the initial study. We also found additional significant CNAs missed by the original analysis but supported by earlier studies, and we identified significant correlations between CNAs

    Modeling Neurodegeneration in Zebrafish

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    The zebrafish, Danio rerio, has been established as an excellent vertebrate model for the study of developmental biology and gene function. It also has proven to be a valuable model to study human diseases. Here, we reviewed recent publications using zebrafish to study the pathology of human neurodegenerative diseases including Parkinson’s, Huntington’s, and Alzheimer’s. These studies indicate that zebrafish genes and their human homologues have conserved functions with respect to the etiology of neurodegenerative diseases. The characteristics of the zebrafish and the experimental approaches to which it is amenable make this species a useful complement to other animal models for the study of pathologic mechanisms of neurodegenerative diseases and for the screening of compounds with therapeutic potential
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