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排序方式: 共有89条查询结果,搜索用时 390 毫秒
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Loredana Bury Karyn Megy Jonathan C. Stephens Luigi Grassi Daniel Greene Nick Gleadall Karina Althaus David Allsup Tadbir K. Bariana Mariana Bonduel Nora V. Butta Peter Collins Nicola Curry Sri V. V. Deevi Kate Downes Daniel Duarte Kim Elliott Emanuela Falcinelli Bruce Furie David Keeling Michele P. Lambert Rachel Linger Sarah Mangles Rutendo Mapeta Carolyn M. Millar Christopher Penkett David J. Perry Kathleen E. Stirrups Ernest Turro Sarah K. Westbury John Wu NIHR BioResource Keith Gomez Kathleen Freson Willem H. Ouwehand Paolo Gresele Ilenia Simeoni 《Human mutation》2020,41(1):277-290
The heterogeneous manifestations of MYH9‐related disorder (MYH9‐RD), characterized by macrothrombocytopenia, Döhle‐like inclusion bodies in leukocytes, bleeding of variable severity with, in some cases, ear, eye, kidney, and liver involvement, make the diagnosis for these patients still challenging in clinical practice. We collected phenotypic data and analyzed the genetic variants in more than 3,000 patients with a bleeding or platelet disorder. Patients were enrolled in the BRIDGE‐BPD and ThromboGenomics Projects and their samples processed by high throughput sequencing (HTS). We identified 50 patients with a rare variant in MYH9. All patients had macrothrombocytes and all except two had thrombocytopenia. Some degree of bleeding diathesis was reported in 41 of the 50 patients. Eleven patients presented hearing impairment, three renal failure and two elevated liver enzymes. Among the 28 rare variants identified in MYH9, 12 were novel. HTS was instrumental in diagnosing 23 patients (46%). Our results confirm the clinical heterogeneity of MYH9‐RD and show that, in the presence of an unclassified platelet disorder with macrothrombocytes, MYH9‐RD should always be considered. A HTS‐based strategy is a reliable method to reach a conclusive diagnosis of MYH9‐RD in clinical practice. 相似文献
3.
Yvonne Linger Alexander Kukhtin Julia Golova Alexander Perov Amine Lambarqui Lexi Bryant George B. Rudy Kim Dionne Stefanie L. Fisher Nicole Parrish Darrell P. Chandler 《Journal of clinical microbiology》2014,52(6):2100-2107
We developed a simplified microarray test for detecting and identifying mutations in rpoB, katG, inhA, embB, and rpsL and compared the analytical performance of the test to that of phenotypic drug susceptibility testing (DST). The analytical sensitivity was estimated to be at least 110 genome copies per amplification reaction. The microarray test correctly detected 95.2% of mutations for which there was a sequence-specific probe on the microarray and 100% of 96 wild-type sequences. In a blinded analysis of 153 clinical isolates, microarray sensitivity for first-line drugs relative to phenotypic DST (true resistance) was 100% for rifampin (RIF) (14/14), 90.0% for isoniazid (INH) (36/40), 70% for ethambutol (EMB) (7/10), and 89.1% (57/64) combined. Microarray specificity (true susceptibility) for first-line agents was 95.0% for RIF (132/139), 98.2% for INH (111/113), and 98.6% for EMB (141/143). Overall microarray specificity for RIF, INH, and EMB combined was 97.2% (384/395). The overall positive and negative predictive values for RIF, INH, and EMB combined were 84.9% and 98.3%, respectively. For the second-line drug streptomycin (STR), overall concordance between the agar proportion method and microarray analysis was 89.5% (137/153). Sensitivity was 34.8% (8/23) because of limited microarray coverage for STR-conferring mutations, and specificity was 99.2% (129/130). All false-susceptible discrepant results were a consequence of DNA mutations that are not represented by a specific microarray probe. There were zero invalid results from 220 total tests. The simplified microarray system is suitable for detecting resistance-conferring mutations in clinical M. tuberculosis isolates and can now be used for prospective trials or integrated into an all-in-one, closed-amplicon consumable. 相似文献
4.
Jeremy D. Keenan Takele Lakew Wondu Alemayehu Muluken Melese Travis C. Porco Elizabeth Yi Jenafir I. House Zhaoxia Zhou Kathryn J. Ray Nisha R. Acharya John P. Whitcher Bruce D. Gaynor Thomas M. Lietman 《The American journal of tropical medicine and hygiene》2010,82(3):482-487
It is unclear how the prevalence of clinically active trachoma correlates with the prevalence of ocular chlamydial infection at the community level. In 24 villages from a cluster-randomized clinical trial of mass azithromycin distributions in Ethiopia, the correlation between the prevalence of clinical activity (on examination) and chlamydial infection (by polymerase chain reaction) was moderately strong before mass antibiotic treatments (Pearson''s correlation coefficient r = 0.75, 95% confidence interval [CI] = 0.52–0.87), but decreased at each time point during four biannual treatments (at 24 months, r = 0.15, 95% CI = −0.14–0.41). One year after the final treatment, the correlation coefficient had increased, but not to the pre-treatment level (r = 0.55, 95% CI = 0.30–0.73). In a region with hyperendemic trachoma, conjunctival examination was a useful indicator of the prevalence of chlamydial infection before treatments, less useful during mass treatments, but regained utility by one year after treatments had stopped. 相似文献
5.
Yeast expands its role from eukaryotic genetics and genomics to drug discovery. 相似文献
6.
The purpose of this paper is to examine how West Virginia University Medical School used the AAMC Curriculum Management Information Tool (CurrMIT) to map the undergraduate medical school curriculum. Information gleaned from this analysis identified what students are expected to learn, how they learn and how they are assessed. Information about the curriculum was entered into CurrMIT, creating a comprehensive picture of the curricular landscape. Learning outcomes were parceled out according to a competence-based framework. In addition, learning methods and assessment measures were identified. A total of 639 learning outcomes were identified across several competences. A total of 13 learning methods and 13 assessment measures were also identified in the undergraduate curriculum. The results suggest that students are expected to acquire varied knowledge, skills and attitudes. Further, students are presented with diverse learning methods and assessment measures. The curriculum map ascertains whether the program's components, such as learning outcomes, learning approaches and assessment methods, are designed and linked to further students' learning. This analysis will lead to curricular improvements. The implications of this work can help faculty, students and other academic stakeholders shift tacit expectations of learning and development to a curricular reality and, in turn, help prepare future physicians for the changing field of medicine. 相似文献
7.
Miller K Pakpour N Yi E Melese M Alemayehu W Bird M Schmidt G Cevallos V Olinger L Chidambaram J Gaynor B Whitcher J Lietman T 《The British journal of ophthalmology》2004,88(6):750-751
AIM: Face seeking flies have long been thought to transmit Chlamydia trachomatis, the causative agent of trachoma, but this has never been proven. The four criteria proposed by Barnett, previously used to incriminate other arthropods suspected of transmitting disease, were examined. One of these criteria remains unmet: the repeated demonstration of the presence of C trachomatis on flies. The authors used polymerase chain reaction (PCR) to look for the presence of C trachomatis DNA on flies in the Gurage Zone of Ethiopia. METHODS: Using sticky paper, one fly was collected from the face of each of 103 children aged 1-10 years. The piece of fly paper to which the fly was attached was cut out, followed by the collection of an empty piece from an arbitrary area of the fly paper, which served as control. Roche Amplicor PCR kits were used to detect C trachomatis DNA. RESULTS: Evidence of C trachomatis by PCR was found on 15 of 103 flies versus 0 of 103 controls (p = 0.0001). CONCLUSION: These results meet the final criterion needed to incriminate flies as a vector of trachoma. However, interventional studies will be needed to show the importance of fly control. 相似文献
8.
Controversy regarding patient exposure to mercury from dental amalgam is more than 150 years old. Researchers continue to investigate the amount of mercury vapor released from amalgam both in vivo and in vitro. In this investigation, an in vitro testing method previously described in the literature was used to quantify the effect of operator-controlled variables on mercury release from dental amalgam. The variables tested were alloy morphology (spherical, admixed or atomized irregular particle), operator skill (inexperienced, novice and expert), operator technique (overfill and evenly fill) and cavity design (standard Class I, double volume and double surface area). Preparations fabricated in sections of acrylic rod were filled with dental amalgam, placed in 25 mL glass bottles and sealed. Mercury vapor concentrations were measured using a Jerome M-411 at specified times. Standardized mean concentrations for each time and total mercury released over time were calculated and analyzed with ANOVA and Tukey HSD. Statistically significant differences ((alpha = 0.05) were identified for all variables tested. Total mercury vapor release was consistently found to be greater for admixed as compared to spherical amalgam. Amalgam restorations prepared by an inexperienced operator demonstrated statistically less mercury vapor than a novice or experienced clinician for both spherical and admixed morphologies. A statistically significant difference in mercury vapor using different condensation and carving techniques was found for the spherical amalgam but not for the admixed material. Restoration design demonstrated significant differences in total mercury vapor dependent on volume and exposed surface area of the amalgam restoration. In this in vitro investigation, mercury vapor release from amalgam was dependent on alloy morphology, operator experience, operator technique and restoration design. 相似文献
9.
Melese M Alemayehu W Bayu S Girma T Hailesellasie T Khandekar R Worku A Courtright P 《The British journal of ophthalmology》2003,87(6):677-680
AIM: To determine the magnitude and causes of low vision and blindness in the Gurage zone, central Ethiopia. METHODS: A cross sectional study using a multistage cluster sampling technique was used to identify the study subjects. Visual acuity was recorded for all adults 40 years and older. Subjects who had a visual acuity of <6/18 were examined by an ophthalmologist to determine the cause of low vision or blindness. RESULTS: From the enumerated population, 2693 (90.8%) were examined. The prevalence of blindness (<3/60 better eye presenting vision) was 7.9% (95% CI 6.9 to 8.9) and of low vision (6/24-3/60 better eye presenting vision) was 12.1% (95% CI 10.9 to 13.3). Monocular blindness was recorded in 16.3% of the population. Blindness and low vision increased with age. The odds of low vision and blindness in women were 1.8 times that of the men. The leading causes of blindness were cataract (46.1%), trachoma (22.9%), and glaucoma (7.6%). While the prevalence of vision reducing cataract increased with age, the prevalence of trachoma related vision loss did not increase with age, suggesting that trichiasis related vision loss in this population might not be cumulative. CONCLUSION: The magnitude of low vision and blindness is high in this zone and requires urgent intervention, particularly for women. Further investigation of the pattern of vision loss, particularly as a result of trachomatous trichiasis, is warranted. 相似文献
10.
Kathryn J Ray Travis C Porco Kevin C Hong David C Lee Wondu Alemayehu Muluken Melese Takele Lakew Elizabeth Yi Jenafir House Jaya D Chidambaram John P Whitcher Bruce D Gaynor Thomas M Lietman 《BMC infectious diseases》2007,7(1):1-10