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131.
PreCimp: Pre‐collapsing imputation approach increases imputation accuracy of rare variants in terms of collapsed variables
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Young Jin Kim Juyoung Lee Bong‐Jo Kim TD‐Genes Consortium Taesung Park 《Genetic epidemiology》2017,41(1):41-50
Imputation is widely used for obtaining information about rare variants. However, one issue concerning imputation is the low accuracy of imputed rare variants as the inaccurate imputed rare variants may distort the results of region‐based association tests. Therefore, we developed a pre‐collapsing imputation method (PreCimp) to improve the accuracy of imputation by using collapsed variables. Briefly, collapsed variables are generated using rare variants in the reference panel, and a new reference panel is constructed by inserting pre‐collapsed variables into the original reference panel. Following imputation analysis provides the imputed genotypes of the collapsed variables. We demonstrated the performance of PreCimp on 5,349 genotyped samples using a Korean population specific reference panel including 848 samples of exome sequencing, Affymetrix 5.0, and exome chip. PreCimp outperformed a traditional post‐collapsing method that collapses imputed variants after single rare variant imputation analysis. Compared with the results of post‐collapsing method, PreCimp approach was shown to relatively increase imputation accuracy about 3.4–6.3% when dosage r2 is between 0.6 and 0.8, 10.9–16.1% when dosage r2 is between 0.4 and 0.6, and 21.4 ~ 129.4% when dosage r2 is below 0.4. 相似文献
132.
Induction of nuclear aberrations by smokeless tobacco in epithelial cells of human oral mucosa 总被引:3,自引:0,他引:3
G K Livingston R N Reed B L Olson J E Lockey 《Environmental and molecular mutagenesis》1990,15(3):136-144
Cytologic and cytogenetic studies were performed to assess the prevalence of somatic cell genetic damage in 48 young adults equally divided to represent users and nonusers of smokeless tobacco. Exposure was ascertained by measuring saliva cotinine using capillary gas chromatography. Squamous epithelial cells sampled from the oral mucosa demonstrated significant cytologic alterations associated with tobacco exposure. The frequency of micronucleated cells was significantly (P less than .01) higher in the labial mucosa of exposed (2.22%) compared to unexposed (0.27%) individuals. The frequency of micronuclei varied widely between exposed subjects but was higher in heavily (2.48%) compared to lightly (1.29%) exposed individuals as measured by saliva cotinine levels. Morphologic classification of epithelial cell nuclei showed that the frequency of cells with normal nuclear structure was significantly (P less than .01) reduce in exposed individuals. Analysis of oral epithelial cells of five additional nonusers of smokeless tobacco but wearers of orthodontic appliances to stimulate abrasion demonstrated no difference from the nonexposed control group. Unlike the case with cigarette smokers, peripheral lymphocyte sister-chromatid exchange frequency was not affected by exposure to smokeless tobacco. The oral cytology data, however, support an interpretation of exposure-dependent nuclear alterations, including micronuclei, in the oral epithelium associated with the use of smokeless tobacco. Altogether, results suggest that use of smokeless tobacco may cause genetic damage to cells in the oral epithelium. 相似文献
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OBJECTIVE: To investigate the factors which influence decision making by experienced emergency physicians when they decide whether to (a) pronounce 'life extinct' in adult patients with non traumatic cardiac arrest while in the ambulance, or (b) bring them into the resuscitation room in the Emergency Department for further assessment/management. DESIGN: Qualitative study involving semi structured interviews and a focus group. SETTING: Accident & Emergency (A&E) departments in the Yorkshire region. PARTICIPANTS: Fifteen emergency physicians (two clinical fellows, nine specialist registrars and four consultants) working in the Yorkshire region. RESULTS: Six main themes were identified that impacted upon the decision making process: the doctor's past experience, ambulance service issues, prehospital care, patient characteristics, presence and views of relatives, and organisational issues. CONCLUSION: The reasoning behind decisions made when a patient arrives at the Emergency Department in cardiac arrest is multifactorial. Strict guidelines would be difficult to construct since individuals vary in the importance they attach to different factors. 相似文献
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Katy E. Beck Melanie Chaplin Michael Stack Rosemary E. Sallis Sarah Simonini Richard Lockey John Spiropoulos 《Brain pathology (Zurich, Switzerland)》2010,20(2):313-322
Primary isolation of bovine spongiform encephalopathy (BSE) in RIII mice generates a lesion profile believed to be reproducible and distinct from that produced by classical scrapie. This profile, which is characterized by peaks at gray matter areas 1, 4 and 7 (dorsal medulla, hypothalamus and septal nuclei), is used to diagnose BSE on primary isolation. The aim of this study was to investigate whether the BSE agent could be present in sheep diagnosed with classical scrapie, using lesion profiles in RIII mice as a discriminatory method. Sixty-two positive scrapie field cases were collected from individual farms between 1996 and 1999 and bioassayed in RIII mice. Fifty-five of these isolates transmitted successfully to at least one mouse. Of the 31 that produced adequate data to allow lesion profile analysis, 10 showed a consistent profile with peaks at brain areas 1, 4 and 7. All inocula for this subgroup were derived from sheep of genotype ARQ/ARQ. While the 1-4-7-scrapie profile exhibited similarities to BSE in RIII mice at primary isolation, it was distinguishable based on histopathology, immunohistochemistry and cluster analysis. We conclude that caution should be taken to distinguish this profile from BSE and that additional parameters should be considered to reach a final diagnosis. 相似文献
138.
The survival after traumatic cardiac arrest is low but similar to out-of-hospital cardiac arrest of any cause. Potential reversible pathologies must be addressed immediately, regardless of patient location at the time of diagnosis. Resuscitative thoracotomy is a well-established surgical intervention that may result in a neurologically good outcome for some patients in traumatic cardiac arrest. This paper describes a simple approach to resuscitative thoracotomy that can be used by a doctor in the pre-hospital environment and in the emergency department. 相似文献
139.
Gail E. Chapman Richard Lockey Katy E. Beck Chris Vickery Mark Arnold Leigh Thorne Jemma K. Thorne Sarah R. Walker Lucien van Keulen Cristina Casalone Peter C. Griffiths Marion M. Simmons Linda A. Terry John Spiropoulos 《Transboundary and Emerging Diseases》2020,67(5):1872-1878
The resistance of H‐type and L‐type BSE prions to autoclaving under EU regulation conditions for specified risk material is unknown. We employed transgenic mouse (bovinized line tg1896) bioassay to assess the efficacy of such decontamination on L‐ and H‐type BSE. For each source, titre calculation was based on the comparison of incubation period and attack rate prior to and after decontamination. The infectious titre of L‐type BSE was reduced by at least 9.40 log10 and of H‐type BSE by at least 3.94 log10. In fact, no infectivity was detected for L‐type or H‐type BSE post‐inactivation even at a 10–1 dilution. 相似文献
140.
Soluble kit receptor in human serum 总被引:3,自引:1,他引:3
Wypych J; Bennett LG; Schwartz MG; Clogston CL; Lu HS; Broudy VC; Bartley TD; Parker VP; Langley KE 《Blood》1995,85(1):66-73
c-kit encodes the transmembrane receptor tyrosine kinase (Kit) for the recently described ligand stem cell factor (SCF). We have developed an enzyme-linked immunosorbent assay for measuring soluble human Kit and we have used the assay to show high levels of soluble Kit in human serum. The distribution of soluble Kit levels was investigated among 112 normal human serum donors. The mean serum level (+/- SD) was found to be 324 +/- 105 ng/mL with the values falling between 163 ng/mL and 788 ng/mL. No correlation between soluble Kit levels and the sexes or ages of the donors was found. Partial purification using immunoaffinity chromatography allowed us to characterize the soluble Kit from pooled human serum. Antibodies generated to a 497-amino acid recombinant human soluble Kit corresponding to the N-terminal extracellular domain of the receptor recognized the serum-derived soluble Kit by immunoblotting. We found that the serum-derived soluble Kit is glycosylated, with mostly N- linked but also O-linked carbohydrate, and with terminal sialic acid residues. When compared with the recombinant human soluble Kit, the serum-derived material was similar both in size and glycosylation pattern. CNBr cleavage of the isolated serum-derived material followed by amino terminal sequencing confirmed the presence of five peptides expected for the extracellular portion of the Kit molecule. The immunoaffinity purified serum-derived soluble Kit inhibited binding of [125I]SCF to membrane-bound receptor in an in vitro assay. These results indicate that soluble Kit could modulate the activity and functions of SCF in vivo. 相似文献