520 research outputs found

    Cenozoic sedimentary and volcanic rocks of New Zealand: A reference volume of lithology, age and paleoenvironments with maps (PMAPs) and database.

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    This volume presents descriptive geological data and text about each Cenozoic sedimentary and volcanic geological unit to formation and member level (in some cases) exposed on land in New Zealand, including their lithology, stratigraphic age and inferred environment of deposition or emplacement. These data are illustrated as two types of PMAPS: a present-day paleoenvironment map of New Zealand; and as restored paleoenvironment maps, one for each million years from 65 Ma to the present. These information and data underpin the development of a new Cenozoic paleogeographical model of New Zealand

    Understanding Outstanding: quality assurance in colonoscopy

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    Since a couple of years, quality assurance (QA) stands at the core of the attention in the healthcare sector. Especially after the publication in 2000 of the Institute of Medicine’s report ‘To err is human’ the interest in QA has taken a quantum leap and many quality initiatives have been developed. This report revealed that every year in the United States approximately 98,000 patients died because of medical errors. Following this report, within the healthcare sector the awareness arose that the quality of the service had to improve, with special attention to safety and patient experiences. Since then the healthcare sector has learned some important lessons in QA from other industries such as the airline industry and energy sector, which are generally classified as ultra-safe organizations. Gastrointestinal endoscopy has been one of the medicine specialties which enrolled important quality initiatives. Especially since the introduction of colorectal cancer (CRC) screening programs, many efforts have been undertaken to better understand the concept of high quality endoscopy. CRC screening has been proven to decrease the incidence of CRC, and CRC related mortality. Therefore many institutions and societies recommend to screen asymptomatic individuals by fecal occult blood tests, flexible sigmoidoscopy, or colonoscopy. As these screening programs involve healthy individuals, the cost-effectiveness of such programmatic screening approaches is highly dependent on the quality of the procedure, but also on pre- and post-procedure quality aspects to improve screenee experiences and thereby the uptake of and adherence to screening modalities. In the Netherlands, CRC screening is about to start in 2013 by means of biennial fecal immunochemical testing. To attain the highest effect a comprehensive QA program should be enrolled with major focus on endoscopy as secondary screening method, as is recommended now by the European Union. The other diagnostic and therapeutic service

    Assembly-based inference of B-cell receptor repertoires from short read RNA sequencing data with V'DJer

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    Motivation: B-cell receptor (BCR) repertoire profiling is an important tool for understanding the biology of diverse immunologic processes. Current methods for analyzing adaptive immune receptor repertoires depend upon PCR amplification of VDJ rearrangements followed by long read amplicon sequencing spanning the VDJ junctions. While this approach has proven to be effective, it is frequently not feasible due to cost or limited sample material. Additionally, there are many existing datasets where short-read RNA sequencing data are available but PCR amplified BCR data are not. Results: We present here V'DJer, an assembly-based method that reconstructs adaptive immune receptor repertoires from short-read RNA sequencing data. This method captures expressed BCR loci from a standard RNA-seq assay. We applied this method to 473 Melanoma samples from The Cancer Genome Atlas and demonstrate V'DJer's ability to accurately reconstruct BCR repertoires from short read mRNA-seq data

    Machine-learning prediction of tumor antigen immunogenicity in the selection of therapeutic epitopes

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    Current tumor neoantigen calling algorithms primarily rely on epitope/major histocompatibility complex (MHC) binding affinity predictions to rank and select for potential epitope targets. These algorithms do not predict for epitope immunogenicity using approaches modeled from tumor-specific antigen data. Here, we describe peptide-intrinsic biochemical features associated with neoantigen and minor histocompatibility mismatch antigen immunogenicity and present a gradient boosting algorithm for predicting tumor antigen immunogenicity. This algorithm was validated in two murine tumor models and demonstrated the capacity to select for therapeutically active antigens. Immune correlates of neoantigen immunogenicity were studied in a pan-cancer data set from The Cancer Genome Atlas and demonstrated an association between expression of immunogenic neoantigens and immunity in colon and lung adenocarcinomas. Lastly, we present evidence for expression of an out-of-frame neoantigen that was capable of driving antitumor cytotoxic T-cell responses. With the growing clinical importance of tumor vaccine therapies, our approach may allow for better selection of therapeutically relevant tumor-specific antigens, including nonclas-sic out-of-frame antigens capable of driving antitumor immunity

    Comment on "Relay selection for secure cooperative networks with jamming"

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    It is the purpose of the note to point out that the Cumulative Distribution Function (CDF) (Eq. (23)) in Appendix A in the paper "Relay Selection for Secure Cooperative Networks with Jamming" by Krikidis et al. (IEEE Trans. Wireless Commun., vol. 8, no. 10, pp. 5003-5011, Oct. 2009) is not the exact expression but an approximation. We provide the exact solution of the CDF in two forms: one using Beta and hypergeometric functions and the second exploiting a recurrence relationshi

    Prognostic value of B cells in cutaneous melanoma

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    Background: Measures of the adaptive immune response have prognostic and predictive associations in melanoma and other cancer types. Specifically, intratumoral T cell density and function have considerable prognostic and predictive value in skin cutaneous melanoma (SKCM). Less is known about the significance of tumor-infiltrating B cells in SKCM. Our goal was to understand the prognostic and predictive value of B cell phenotypic subsets in SKCM using RNA sequencing. Methods: We used our previously published algorithm, V'DJer, to assemble B cell receptor (BCR) repertoires and estimate diversity from short-read RNA sequencing (RNA-seq). We applied machine learning-based cellular phenotype classifiers to measure relative similarity of bulk tumor sample gene expression profiles and different B cell phenotypes. We assessed these aspects of B cell biology in 473 SKCM from the Cancer Genome Atlas Project (TCGA) as well as in RNA-seq data corresponding to tumor samples procured from patients who received CTLA-4 and PD-1 inhibitors for metastatic SKCM. Results: We found that the BCR repertoire was associated with different clinical factors, such as tumor tissue site and sex. However, increased clonality of the BCR repertoire was favorably prognostic in SKCM and was prognostic even after first conditioning on various clinical factors. Mutation burden was not correlated with any BCR measurement, and no specific mutation had an altered BCR repertoire. Lack of an assembled BCR in pre-treatment tumor tissues was associated with a lack of anti-tumor response to a CTLA-4 inhibitor in metastatic SKCM. Conclusions: These findings suggest an important prognostic and predictive role for B cell characteristics in SKCM. This has implications for melanoma immunobiology and potential development of immunogenomics features to predict survival and response to immunotherapy

    Suspension by regular and groupy waves over bedforms in a large wave flume (SISTEX99)

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    Suspended sand concentrations and bedforms under waves were measured in the controlled environment of a large wave flume. Three suspension conditions are discussed here; those occurring with regular (monochromatic) waves of height 0.55m over anorbital ripples, regular waves 1.0m high over orbital bedforms, and repeating wave groups (with a significant wave height of 0.6m) also over orbital-scale features. In all cases the wave-to-wave variability in suspended load was high (∼30%). Patterns of suspension were dependent on the bedform type and on instrument location relative to the bedform. Regular waves suspended an order of magnitude more sediment than groupy waves with a similar significant wave height illustrating,the importance of sequences of high waves in pumping-up sediment concentration into the water column

    Molecular and clinical characterization of a claudin-low subtype of gastric cancer

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    Purpose Claudin-low molecular subtypes have been identified in breast and bladder cancers and are characterized by low expression of claudins, enrichment for epithelial-to-mesenchymal transition (EMT), and tumor-initiating cell (TIC) features. We evaluated whether the claudin-low subtype also exists in gastric cancer. Materials and Methods Four hundred fifteen tumors from The Cancer Genome Atlas (TCGA) gastric cancer mRNA data set were clustered on the claudin, EMT, and TIC gene sets to identify claudin-low tumors. We derived a 24-gene predictor that classifies gastric cancer into claudin-low and non-claudin-low subtypes. This predictor was validated with the Asian Cancer Research Group(ACRG)data set. We characterized molecular and clinical features of claudin-low tumors. Results We identified 46 tumors that had consensus enrichment for claudin-low features in TCGA data set. Claudin-low tumors were most commonly diffuse histologic type (82%) and originally classified as TCGA genomically stable(GS)subtype (78%). Compared with GS subtype, claudin-low subtype had significant activation in Rho family of GTPases signaling, which appears to play a key role in its EMT and TIC properties. In the ACRG data set, 28 of 300 samples were classified as claudin-low tumors by the 24-gene predictor and were phenotypically similar to the initially derived claudin-low tumors. Clinically, claudin-low subtype had the worst overall survival. Of note, the hazard ratios that compared claudin-low versus GS subtype were 2.10 (95% CI, 1.07 to 4.11) in TCGA and 2.32 (95% CI, 1.18 to 4.55) in the ACRG cohorts, with adjustment for age and pathologic stage. Conclusion We identified a gastric claudin-low subtype that carries a poor prognosis likely related to therapeutic resistance as a result of its EMT and TIC phenotypes

    Population screening for gestational hypertensive disorders using maternal, fetal and placental characteristics

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    Objective: To determine screening performance of maternal, fetal and placental characteristics for selecting pregnancies at risk of gestational hypertension and preeclampsia in a low-risk multi-ethnic population. Method: In a prospective population-based cohort among 7124 pregnant women, we collected maternal characteristics including body mass index, ethnicity, parity, smoking and blood pressure in early-pregnancy. Fetal characteristics included second and third trimester estimated fetal weight and sex determined by ultrasound. Placental characteristics included first and second trimester placental growth factor concentrations and second and third trimester uterine artery resistance indices. Results: Maternal characteristics provided the best screening result for gestational hypertension (area-under-the-curve [AUC] 0.79 [95% Confidence interval {CI} 0.76-0.81]) with 40% sensitivity at 90% specificity. For preeclampsia, the maternal characteristics model led to a screening performance of AUC 0.74 (95% CI 0.70-0.78) with 33% sensitivity at 90% specificity. Addition of second and third trimester placental ultrasound characteristics only improved screening performance for preeclampsia (AUC 0.78 [95% CI 0.75-0.82], with 48% sensitivity at 90% specificity). Conclusion: Routinely measured maternal characteristics, known at the start of pregnancy, can be used in screening for pregnancies at risk of gestational hypertension or preeclampsia within a low-risk multi-ethnic population. Addition of combined second and third trimester placental ultrasound characteristics only improved screening for preeclampsia

    Second and third trimester fetal ultrasound population screening for risks of preterm birth and small-size and large-size for gestational age at birth: a population-based prospective cohort study

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    BACKGROUND: Preterm birth, small size for gestational age (SGA) and large size for gestational age (LGA) at birth are major risk factors for neonatal and long-term morbidity and mortality. It is unclear which periods of pregnancy are optimal for ultrasound screening to identify fetuses at risk of preterm birth, SGA or LGA at birth. We aimed to examine whether single or combined second and third trimes
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