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Biomedical subjects

D J Thomas

Publications and source records attributed to D J Thomas.

At least 19 recordsLinked to original sources

The UCSC genome browser database: update 2007.

The University of California, Santa Cruz Genome Browser Database contains, as of September 2006, sequence and annotation data for the genomes of 13 vertebrate and 19 invertebrate species. The Genome Browser displays a wide variety of annotations at all scales from the single nucleotide level up to a full chromosome and includes assembly data, genes and gene predictions, mRNA and EST alignments, and comparative genomics, regulation, expression and variation data. The database is optimized for fast interactive performance with web tools that provide powerful visualization and querying capabilities for mining the data. In the past year, 22 new assemblies and several new sets of human variation annotation have been released. New features include VisiGene, a fully integrated in situ hybridization image browser; phyloGif, for drawing evolutionary tree diagrams; a redesigned Custom Track feature; an expanded SNP annotation track; and many new display options. The Genome Browser, other tools, downloadable data files and links to documentation and other information can be found at http://genome.ucsc.edu/.

Animals↗

The UCSC Genome Browser Database: update 2006.

The University of California Santa Cruz Genome Browser Database (GBD) contains sequence and annotation data for the genomes of about a dozen vertebrate species and several major model organisms. Genome annotations typically include assembly data, sequence composition, genes and gene predictions, mRNA and expressed sequence tag evidence, comparative genomics, regulation, expression and variation data. The database is optimized to support fast interactive performance with web tools that provide powerful visualization and querying capabilities for mining the data. The Genome Browser displays a wide variety of annotations at all scales from single nucleotide level up to a full chromosome. The Table Browser provides direct access to the database tables and sequence data, enabling complex queries on genome-wide datasets. The Proteome Browser graphically displays protein properties. The Gene Sorter allows filtering and comparison of genes by several metrics including expression data and several gene properties. BLAT and In Silico PCR search for sequences in entire genomes in seconds. These tools are highly integrated and provide many hyperlinks to other databases and websites. The GBD, browsing tools, downloadable data files and links to documentation and other information can be found at http://genome.ucsc.edu/.

Amino Acid Sequence↗

Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study.

OBJECTIVES: This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors. METHODS: Patients (n=1115) with asymptomatic internal carotid artery (ICA) stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6-84 (mean 37.1) months. Stenosis was graded using duplex, and clinical and biochemical risk factors were recorded. RESULTS: The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method, but S-shaped if expressed by the NASCET method. In addition to the ECST grade of stenosis (RR 1.6; 95% CI 1.21-2.15), history of contralateral TIAs (RR 3.0; 95% CI 1.90-4.73) and creatinine in excess of 85 micromol/L (RR 2.1; 95% CI 1.23-3.65) were independent risk predictors. The combination of these three risk factors can identify a high-risk group (7.3% annual event rate and 4.3% annual stroke rate) and a low risk group (2.3% annual event rate and 0.7% annual stroke rate). CONCLUSIONS: Linearity between ECST per cent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used. Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy.

Brain Ischemia↗

Modelling of neutron survey instrument performance and experimental validation of those calculated response data.

Three moderator-type neutron survey instruments have been modelled for energy and angle dependence of the response, in greater detail than before. These response data have been verified by comparison with published experimental measurements and measurements made specifically for this project. Influences on the instrument response have also been investigated. These have included its mode-of-use and perturbations caused by variations in the instrument manufacture. The implications of these new response data have been assessed by an extensive programme of folding the responses with workplace energy distributions.

Computer Simulation↗

Factors associated with mortality in patients with asymptomatic carotid stenosis: results from the ACSRS Study.

AIM: This study determines the factors associated with mortality in patients with asymptomatic carotid stenosis. METHODS: Patients (n=1,101) with asymptomatic internal carotid artery stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6 to 84 (median 38) months. Stenosis was graded using duplex scanning and expressed as a percentage of the carotid bulb diameter. Clinical and biochemical risk factors were recorded. The end-points were ipsilateral ischemic stroke, cardiovascular death and all cause mortality. RESULTS: In a Cox multivariate analysis 6 factors emerged as independent predictors of risk. Age, male gender, cardiac failure, left ventricular hypertrophy on electrocardiogram (ECG) and myocardial ischemia on ECG were associated with increased risk. Antiplatelet therapy was associated with decreased risk. Based on these risk factors a high-risk group consisting of one third of the population with a 40% cumulative cardiovascular death rate and a 66% all cause death rate at 7 years could be identified. The remaining 2/3 consisted of a low-risk group with a 10% cumulative cardiovascular death rate and a 21% all cause death rate at 7 years (P<0.0001 compared to the high risk group). There was not any significant difference in the cumulative ipsilateral stroke rate, which was 12% in the low and 13% in the high cardiovascular risk group (Log Rank P>0.05). CONCLUSIONS: The methodology and findings from the ACSRS natural history study need to be applied to randomized controlled trials on the value of carotid endarterectomy or stenting in patients with asymptomatic carotid stenosis. They may help refine the indications for intervention in patients with carotid endarterectomy.

Cardiovascular Diseases↗

Angle dependence of response characteristics of neutron survey instruments.

Neutron area survey instruments are designed to have an approximately isotropic response. In practice, the response cannot be perfectly isotropic for instruments that do not have spherical symmetry, and for all instruments it is modified by the inclusion of batteries, electronics, handles, etc. This affects the ability of the survey instrument to measure accurately an isotropic dose equivalent quantity. Measurements of the angle dependence of response for four of the most commonly used designs of survey instrument (Harwell 0949, Mark 7 NRM, NM2 and Studsvik 2202D) have been performed in a low-scatter room using radionuclide and monoenergetic neutron sources. The Monte Carlo code MCNP has been used to model the responses and to investigate their sensitivity to the polyethylene density, counting gas pressure and other manufacturing tolerances. Preliminary modelling results are presented here.

Environmental Exposure↗

A realistic field facility to simulate reactor spectra.

The design construction and characterisation of a simulated realistic neutron workplace field is described. Utilising a low-energy primary source of neutrons based on the 7Li(p,n) reaction, and a heavy water moderator, a broad spectrum is produced with energies extending from thermal to about 1 MeV. The field simulates the type of spectra encountered around UK gas-cooled reactors.

Body Burden↗

Practical implications of neutron survey instrument performance.

Improvements have been made to the Monte Carlo modelling used to calculate the response of the neutron survey instruments most commonly used in the UK, for neutron energies up to 20 MeV. The improved modelling of the devices includes the electronics and battery pack, allowing better calculations of both the energy and angle dependence of response. These data are used to calculate the response of the instruments in rotationally and fully isotropic, as well as unidirectional fields. Experimental measurements with radionuclide sources and monoenergetic neutron fields have been, and continue to be made, to test the calculated response characteristics. The enhancements to the calculations have involved simulation of the sensitivity of the response to variations in instrument manufacture, and will include the influence of the user and floor during measurements. The practical implications of the energy and angle dependence of response, variations in manufacture, and the influence of the user are assessed by folding the response characteristics with workplace energy and direction distributions.

Algorithms↗

Characterisation of the IRSN CANEL/T400 facility producing realistic neutron fields for calibration and test purposes.

The new CANEL/T400 facility has been set-up at the Institute for Radiological Protection and Nuclear Safety (IRSN) to produce a realistic neutron field. The accurate characterisation of this neutron field is mandatory since this facility will be used as a reference neutron source. For this reason an international measuring campaign, involving four laboratories with extensive expertise in neutron metrology and spectrometry, was organised through a concerted EUROMET project. Measurements were performed with Bonner sphere (BS) systems to determine the energy distribution of the emitted neutrons over the whole energy range (from thermal energy up to a few MeV). Additional measurements were performed with proton recoil detectors to provide detailed information in the energy region above 90 keV. The results obtained by the four laboratories are in agreement with each other and are compared with a calculation performed with the MCNP4C Monte-Carlo code. As a conclusion of this exercise, a reliable characterisation of the CANEL/T400 neutron field is obtained.

Algorithms↗

TEPC measurements in commercial aircraft.

The collaborative project involving the Mullard Space Science Laboratory (MSSL), Virgin Atlantic Airways (VAA), the UK Civil Aviation Authority (CAA) and the UK National Physical Laboratory (NPL) has been performing tissue-equivalent proportional counter measurements of cosmic ray doses in commercial aircraft since January 2000. In that time data have been recorded on over 700 flights, including over 150 flights with Air New Zealand (ANZ). This substantial set of data from the southern hemisphere is an ideal complement to the London-based measurements performed primarily on VAA flights. Although some ANZ data remains to be analysed, dose information from 111 flights has been compared with the CARI and EPCARD computer codes. Overall, the agreement between the measurements and EPCARD was excellent (within 1% for the total ambient dose equivalent), and the difference in the total effective doses predicted by EPCARD and CARI was <5%.

Aircraft↗

The UCSC Genome Browser Database.

The University of California Santa Cruz (UCSC) Genome Browser Database is an up to date source for genome sequence data integrated with a large collection of related annotations. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The Genome Browser Database, browsing tools and downloadable data files can all be found on the UCSC Genome Bioinformatics website (http://genome.ucsc.edu), which also contains links to documentation and related technical information.

Animals↗

Cytologic analysis of ureteral washings is informative in patients with grade 2 upper tract TCC considering endoscopic treatment.

OBJECTIVES: To determine the diagnostic accuracy of ureteroscopic biopsy and whether exfoliated cell cytology can improve diagnostic accuracy. METHODS: Sixty-two cases of upper tract transitional cell carcinoma were diagnosed by ureteroscopic biopsy and treated by nephroureterectomy. Stage and grade evaluation was possible in 51 cases. Cytology for exfoliated cells from the ureter/pelvis was available in 48 cases. RESULTS: Biopsies were staged as Tis in 3, Ta in 35, and T1 in 13 and graded as G1 in 6, G2 in 32, and G3 in 13. Cytology was positive/suspicious in 40% (19 of 48). The biopsy grade accurately predicted the pathologic grade (P <0.0001) and stage (P = 0.001). The biopsy stage was not associated with the final stage (P = 0.112, Fisher's exact test). Biopsy G3 accurately predicted high-grade (G3) transitional cell carcinoma in 92% (12 of 13) of cases. The remaining 1 case was G2 by final histologic examination. No case of high-grade (G3) disease was found in the 6 G1 biopsies (100%). Of 32 G2 biopsies, 9 were upgraded to G3. Cytology was available for 8 of the 9 and 5 (63%) were positive. For patients with G2 biopsies, combining cytology and biopsy grade improved the sensitivity and specificity of high-grade tumor detection from 43% to 55% and 23% to 85%, respectively. CONCLUSIONS: The results of this study have shown that biopsy grade reflects the pathologic stage and grade. Combining exfoliated cell cytology improved the predictive power of biopsy G2 disease for high-risk specimen grade. Exfoliated cell cytology in combination with biopsy grade is recommended as part of the evaluation of upper tract transitional cell carcinoma selected for endoscopic management.

Adult↗