Publications by authors named "Crichton D"

Molecular biomarkers measure discrete components of biological processes that can contribute to disorders when impaired. Great interest exists in discovering early cancer biomarkers to improve outcomes. Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates.

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NASA's Jet Propulsion Laboratory (JPL) is advancing research capabilities for data science with two of the National Cancer Institute's major research programs, the Early Detection Research Network (EDRN) and the Molecular and Cellular Characterization of Screen-Detected Lesions (MCL), by enabling data-driven discovery for cancer biomarker research. The research team pioneered a national data science ecosystem for cancer biomarker research to capture, process, manage, share, and analyze data across multiple research centers. By collaborating on software and data-driven methods developed for space and earth science research, the biomarker research community is heavily leveraging similar capabilities to support the data and computational demands to analyze research data.

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Background: Pancreatic ductal adenocarcinoma (PDAC) is a formidable challenge for patients and clinicians.

Objective: To analyze the distribution of 31 different markers in tumor and stromal portions of the tumor microenvironment (TME) and identify immune cell populations to better understand how neoplastic, non-malignant structural, and immune cells, diversify the TME and influence PDAC progression.

Methods: Whole slide imaging (WSI) and cyclic multiplexed-immunofluorescence (MxIF) was used to collect 31 different markers over the course of nine distinctive imaging series of human PDAC samples.

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Cancer biomarker research has become a data-intensive discipline requiring innovative approaches for data analysis that can combine traditional and data-driven methods. Significant leveraging can be done transferring methodologies and capabilities across scientific disciplines, such as planetary science and astronomy, each of which are grappling with and developing similar solutions for the analysis of massive scientific data.

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Purpose: The purpose of OncoMX knowledgebase development was to integrate cancer biomarker and relevant data types into a meta-portal, enabling the research of cancer biomarkers side by side with other pertinent multidimensional data types.

Methods: Cancer mutation, cancer differential expression, cancer expression specificity, healthy gene expression from human and mouse, literature mining for cancer mutation and cancer expression, and biomarker data were integrated, unified by relevant biomedical ontologies, and subjected to rule-based automated quality control before ingestion into the database.

Results: OncoMX provides integrated data encompassing more than 1,000 unique biomarker entries (939 from the Early Detection Research Network [EDRN] and 96 from the US Food and Drug Administration) mapped to 20,576 genes that have either mutation or differential expression in cancer.

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Background: The potential utility of microRNA as biomarkers for early detection of cancer and other diseases is being investigated with genome-scale profiling of differentially expressed microRNA. Processes for measurement assurance are critical components of genome-scale measurements. Here, we evaluated the utility of a set of total RNA samples, designed with between-sample differences in the relative abundance of miRNAs, as process controls.

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We present multi-wavelength detections of nine candidate gravitationally-lensed dusty star-forming galaxies (DSFGs) selected at 218GHz (1.4mm) from the ACT equatorial survey. Among the brightest ACT sources, these represent the subset of the total ACT sample lying in SPIRE fields, and all nine of the 218GHz detections were found to have bright counterparts.

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Anterior Gradient 2 (AGR2) is a protein expressed in many solid tumor types including prostate, pancreatic, breast and lung. AGR2 functions as a protein disulfide isomerase in the endoplasmic reticulum. However, AGR2 is secreted by cancer cells that overexpress this molecule.

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We present evidence of the gravitational lensing of the cosmic microwave background by 10(13) solar mass dark matter halos. Lensing convergence maps from the Atacama Cosmology Telescope Polarimeter (ACTPol) are stacked at the positions of around 12 000 optically selected CMASS galaxies from the SDSS-III/BOSS survey. The mean lensing signal is consistent with simulated dark matter halo profiles and is favored over a null signal at 3.

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Bio-ontologies provide terminologies for the scientific community to describe biomedical entities in a standardized manner. There are multiple initiatives that are developing biomedical terminologies for the purpose of providing better annotation, data integration and mining capabilities. Terminology resources devised for multiple purposes inherently diverge in content and structure.

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Objectives: This study sought to describe the food retail environment and its use in a deprived urban area in Scotland by mapping all food outlets and determining where residents do their main food shopping as well as investigating the availability of fresh fruit and vegetables (F&V) (as an indicator of healthy eating) and takeaway food.

Study Design: Cross-sectional study.

Methods: The food retail environment, the number, size and food availability of all food outlets, was mapped in Viewpark, a small community located to the east of Glasgow.

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Years of sequence feature curation by UniProtKB/Swiss-Prot, PIR-PSD, NCBI-CDD, RefSeq and other database biocurators has led to a rich repository of information on functional sites of genes and proteins. This information along with variation-related annotation can be used to scan human short sequence reads from next-generation sequencing (NGS) pipelines for presence of non-synonymous single-nucleotide variations (nsSNVs) that affect functional sites. This and similar workflows are becoming more important because thousands of NGS data sets are being made available through projects such as The Cancer Genome Atlas (TCGA), and researchers want to evaluate their biomarkers in genomic data.

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Capturing, sharing, and publishing cancer biomarker research data are all fundamental challenges of enabling new opportunities to research and understand scientific data. Informatics experts from the National Cancer Institute's (NCI) Early Detection Research Network (EDRN) have pioneered a principled informatics infrastructure to capture and disseminate data from biomarker validation studies, in effect, providing a national-scale, real-world successful example of how to address these challenges. EDRN is a distributed, collaborative network and it requires its infrastructure to support research across cancer research institutions and across their individual laboratories.

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What can cities do to increase resilience?

Philos Trans A Math Phys Eng Sci

November 2007

This paper examines climate change mitigation and adaptation from an insurance industry perspective, with particular reference to London and the USA. It illustrates how British insurers are increasingly shaping public policy and using new technology to manage the risks from climate change impacts and makes a plea for society to make more use of insurance expertise in future decision making. In particular, more dialogue is needed between architects, planners and insurers to adapt our buildings and cities for climate change impacts.

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A new cancer gene, HIC-1 (Hypermethylated in Cancer) telomeric to p53 on chromosome 17p may be of clinical importance in sporadic breast cancer. Regional DNA hypermethylation of 17p13.3 resulting in suppression of gene expression has been shown to precede 17p structural changes in human carcinogenesis.

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We analyzed the FEV(1)/FEV(6) and FEV(1)/FVC results of 502 consecutive patients in the spirometric diagnosis of airway obstruction. We also examined the agreement between FEV(6) and FVC in the spirometric diagnosis of restriction. Technically acceptable test results were obtained from 337 subjects (67%).

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Background: In the UK, travel health advice is mainly provided by practice nurses and general practitioners (GPs). The need for their improved education in travel medicine has been highlighted through previous studies and by an increasing number of requests for training.

Methods: A questionnaire-based survey of 3900 GP practices was conducted to assess training requirements and to establish the demand for an academic course in travel medicine.

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Molecular and immunohistochemical studies of genetic events on chromosome 17p were prospectively compared with conventional clinical and pathological parameters and disease behaviour at a minimum of 72 months follow-up. In a series of 91 patients with primary operable breast cancer, 37 out of 91 (41%) patients had disease relapse and 23 out of 91 (25%) had died during the follow-up period. Allelic imbalance at the YNZ22 locus (17p13.

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The pattern of loss of heterozygosity (LOH) on chromosome 17 in human breast cancer is complicated and shows many different regions of loss. In an attempt to narrow down the relevant regions of LOH on chromosome 17, we have studied the deletion pattern and its association with clinical parameters in 1280 breast carcinoma-venous blood lymphocyte pairs. In total, 42 different chromosome 17 loci were investigated, and between 25 and 625 cases were analyzed at each locus.

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The chromosome region 17p13.3 is thought to encode a tumour suppressor gene involved in sporadic breast cancer and other malignancies. Physical ordering of markers has been carried out by a series of multicolour fluorescent in situ hybridisation (FISH) experiments, using isolated yeast artificial chromosomes (YACs) and cosmids.

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This article describes certain innovations and aspects of surgical technique together with some surgical assessments of results in a series of 58 operations for gender reassignment undertaken by the author over the past 24 years. The salient new features described are: (i) to prevent the early and late vaginal contractures that commonly follow previously accepted methods of neo-vagina construction, the technique of dissecting a new vaginal canal has been improved, and an improved skin graft (double-layered) is added to the peno-scroto-perineal flaps used to line the vaginal canal--these split-skin grafts, superimposed upon a meshed thick dermal graft, do not contract nearly as much as solitary split-skin grafts; (ii) the vagina is suspended laterally by the testicular cords, threaded above the superior pubic rami; and (iii) repeated intermittent use of a vaginal vibrator is substituted for an indwelling vaginal mould, resulting in better compliance and a more pliable vagina.

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Dinucleotide repeat sequences ('microsatellites') have been used as polymorphic genetic markers following amplification in the polymerase chain reaction (PCR). We have compared several methods of analysing the PCR products. The most reliable and unambiguous results were obtained when the PCR products were probed with a specific dinucleotide repeat oligonucleotide, so that only the microsatellite-containing products were detectable.

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