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51.
Mireille Claustres Viktor Ko?ich Els Dequeker Brain Fowler Jayne Y Hehir-Kwa Konstantin Miller Cor Oosterwijk Borut Peterlin Conny van Ravenswaaij-Arts Uwe Zimmermann Orsetta Zuffardi Ros J Hastings David E Barton 《European journal of human genetics : EJHG》2014,22(2):160-170
Genetic test results can have considerable importance for patients, their parents and more remote family members. Clinical therapy and surveillance, reproductive decisions and genetic diagnostics in family members, including prenatal diagnosis, are based on these results. The genetic test report should therefore provide a clear, concise, accurate, fully interpretative and authoritative answer to the clinical question. The need for harmonizing reporting practice of genetic tests has been recognised by the External Quality Assessment (EQA), providers and laboratories. The ESHG Genetic Services Quality Committee has produced reporting guidelines for the genetic disciplines (biochemical, cytogenetic and molecular genetic). These guidelines give assistance on report content, including the interpretation of results. Selected examples of genetic test reports for all three disciplines are provided in an annexe.Diagnostic genetic testing is an extremely rapidly expanding area encompassing a broad range of laboratory investigations to analyse chromosomes (from classical karyotype to molecular cytogenetics), nucleic acids (DNA, RNA), proteins and metabolites used to detect heritable or somatic mutations, genotypes or phenotypes related to disease and health. Genetic testing requires particular consideration in that it is usually performed only once in a patient''s lifetime, and the results may have considerable importance for lifetime decisions not only for the individuals being tested but also for children and family. Interpreting and reporting variation in germline chromosomes, DNA sequences or their products is a heavy clinical responsibility for prediction of susceptibility to disease, patient diagnosis, prognosis, counselling, treatment or family planning. Providing a set of reporting frameworks that can be customised for different testing contexts but share some common principles could be beneficial to the practice of a number of laboratories, including non-OECD members and/or laboratories that do not participate in External Quality Assessments (EQA), and to laboratories with blurred boundaries between research and genetic testing services.Although several guidelines already exist for reporting the results of genetic testing,1,2,3 these focus on molecular genetic testing and do not cover the other two branches of laboratory genetics, namely biochemical genetics and cytogenetics. Based on recent surveys of EQA results presented by some European EQA providers and the request from genetic laboratories for comprehensive reporting guidelines, it was considered that a unifying attempt to harmonise the reporting practice of genetic tests in Europe and neighbouring countries would be welcome. 相似文献
52.
W. Al‐Hertani V.A. Hastings J. McGowan‐Jordan J. Hurteau Gail E. Graham MD MSc FRCPC FCCMG 《American journal of medical genetics. Part A》2013,161(1):153-157
We report a male infant with 22q11.2 deletion syndrome and very severe multi‐sutural craniosynostosis associated with increased intracranial pressure, marked displacement of brain structures, and extensive erosion of the skull. While uni‐ or bi‐sultural craniosynostosis is a recognized (though relatively uncommon) feature of 22q11 deletion syndrome, a severe multi‐sutural presentation of this nature has never been reported. SNP Microarray was otherwise normal and the patient did not have common mutations in FGFR2, FGFR3, or TWIST associated with craniosynostosis. While markedly variable expressivity is an acknowledged feature of deletion 22q11 syndrome, herein we also consider and discuss the possibility that this infant may have been additionally affected with an undiagnosed single gene disorder. © 2012 Wiley Periodicals, Inc. 相似文献
53.
Interactions between clock gene mutation, circadian phenotype and tumor growth in mice 总被引:1,自引:0,他引:1
The relation between circadian physiology (rest-activity and body temperature) and the growth of a grafted tumor (Glasgow osteosarcoma-GOS) was investigated in the mice with mutation of clock gene (ClockDelta19(-)) or gene controlled by the clock (Vpac(-/-)). Circadian rhythms in temperature and activity were stable, with an approximately 24-h period in all the mice synchronized by the alternation of 12 h of light and 12 h of darkness (LD 12:12). Following exposure to constant darkness (DD), both rhythms persisted in ClockDelta19(-), yet with a lengthening of the period by 4.5 h compared to wild type. In DD, the amplitude increased by 45.9% for the temperature rhythm (p<0.001) and by 17.4% for the activity one (p=0.08) as compared to LD 12:12 in ClockDelta19(-). The improvement of circadian coordination and/or the lengthening of the circadian period observed in ClockDelta19(-) kept in DD was associated with a moderate slowing down of tumor growth. Although the exposure to DD ablated the activity and temperature rhythms in Vpac(-/-), no modification in tumor growth was observed as compared to wide type or Vpac(-/-) in LD 12:12. Major alternations of circadian physiology can result from interactions between photoperiodic environment and mutation of clock gene or gene controlled by the clock. In these conditions, we have shown that the alternation of the circadian phenotype does not seem to constitute an essential determinant of the growth of a grafted tumor. 相似文献
54.
Isolation and composition of the extracellular slime made by coagulase-negative staphylococci in a chemically defined medium 总被引:6,自引:0,他引:6
Slime isolated after growth of four strains of coagulase-negative staphylococci on chemically defined medium plus agar was rich in galactose. However, when sterile agar plates were extracted with saline, high-molecular-weight material with similar properties was obtained that also was galactose-rich. Most of the dry weight attributed to slime, and probably all the galactose, originated from agar. Slime isolated by gel and ion-exchange chromatography from liquid culture in the same medium contained glycerol phosphate, glucose (no galactose), glucosamine, alanine, uronate, an unidentified component, and protein. Separation of protein from carbohydrate was achieved by affinity chromatography. [14C]glucose in the medium labeled the carbohydrate polymer; [14C]amino acids chiefly labeled extracellular proteins. Slime from bacteria grown on medium solidified with silica gel or on dialysis membrane above an agar surface showed essentially the same composition and behavior after purification as the material isolated from liquid culture. 相似文献
55.
To resolve the apparent conflict between a lubricating glycoprotein,
'lubricin', as the active ingredient in synovial fluid (SF) and surface-
active phospholipid (SAPL) present in SF (and adsorbed to articular
cartilage) as the boundary lubricant reducing friction to such low
physiological levels, lubricin was isolated from bovine SF following the
original procedure of Swann et al. (Arthritis Rheum 1981;24:22-30).
Analysis of the lipid extract by thin-layer chromatography and phosphorus
determination demonstrated a phospholipid component of 11.1 +/- 1.7% (N =
5) which corresponds very closely to the 9.2-13.0% of lubricin which had
hitherto remained unidentified and which has previously been shown to be
transferable to the articular surface to impart lubrication. These results
would appear to resolve any theoretical conflict in that lubricin is,
indeed, an active ingredient within SF. Yet, as a large water-soluble
molecule, it really functions as a carrier for the highly insoluble SAPL
which it deposits on the articular surface as the oligolamellar layer
visualized in previous studies. However, it is this deposited SAPL, rather
than lubricin, which actually lubricates.
相似文献
56.
目的分析影响大学生饮酒模式的因素,针对饮酒教育及酒精政策提出建议。方法采用整群抽样方法,选择来自北京和郑州的530名大学生完成有效问卷调查。采用 Epidata 录入数据,SAS 12.0和 R 2.7.2进行数据描述和分析。结果74.5%的大学生在过去1年内饮过酒,啤酒是饮酒者的主要选择(85.9%),餐馆和家里是饮酒比较频繁的场所,饮用酒多来自同学/朋友及家庭成员提供,25.3%饮酒者并无特别原因饮酒,各有约1/5的饮酒者是出于社交目的或喜欢饮酒的感觉。认为“饮酒有助于社交暠或“饮酒促进交流暠者、父母及同学/朋友饮酒者、来自农村地区或小城镇者及吸烟者更容易发生饮酒行为(均 P 〈0.05),男生大学生、规律饮酒者更容易遭遇强迫劝酒场面、更易发生醉酒(均 P 〈0.05)。超过一半饮酒者出现酒后脸红、肌肉软弱无力等生理反应,饮酒对被调查大学生产生的社会心理影响依次是记忆丧失(23.9%)、宿醉(14.6%)、做了后悔的事(低于10%)等。结论目前大学生仍保持着一种低风险饮酒模式。大学生饮酒教育应提供关于饮酒利弊的科学信息,使其对饮酒保持一种现实的期望。应制定针对性酒精政策和教育鼓励和支持低风险且满足社交功能的饮酒模式,控制高风险饮酒模式。 相似文献
57.
Abdallah El Sabbagh Vishal G. Patel Omar M. Jeroudi Tesfaldet T. Michael Mohammed E. Alomar Owen Mogabgab Eric Fuh Michele Roesle Bavana V. Rangan Shuaib Abdullah Jeffrey L. Hastings Jerrold Grodin Dharam J. Kumbhani Dimitrios Alexopoulos Panayotis Fasseas Subhash Banerjee Emmanouil S. Brilakis 《International journal of cardiology》2014
Background
The efficacy and safety profile of retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We sought to perform a weighted meta-analysis of the success and complication rates of retrograde CTO PCI.Methods
We conducted a meta-analysis of 26 studies published between 2006 and April 2013 reporting in-hospital outcomes of retrograde CTO PCI. Data on procedural success, frequency of death, emergent coronary artery bypass graft surgery (CABG), stroke, myocardial infarction (MI), perforation, tamponade, stent thrombosis, major vascular or bleeding events, contrast nephropathy, and radiation skin injury were collected.Results
A total of 26 studies with 3482 patients and 3493 target CTO lesions were included. Primary retrograde CTO PCI was attempted in 52.4%. Pooled estimates of outcomes were as follows: procedural success 83.3% [95% confidence interval (CI): 79.0% to 87.7%]; death 0.7% (95% CI: 0.5% to 1.2%); urgent CABG 0.7% (95% CI: 0.4% to 1.2%); tamponade 1.4% (95% CI: 1.0% to 2.2%); collateral perforation 6.9% (95% CI: 4.6% to 10.4%); coronary perforation 4.3% (95% CI: 1.2% to 15.4%); donor vessel dissection 2% (95% CI: 0.9% to 4.5%); stroke 0.5% (95% CI: 0.2% to 1.0%); MI 3.1% (95% CI: 0.2% to 5.0%); Q wave MI 0.6% (95% CI: 0.4% to 1.1%); vascular access complications 2% (95% CI: 0.9% to 4.5%); contrast nephropathy 1.8% (95% CI: 0.8% to 3.7%); and wire fracture and equipment entrapment 1.2% (95% CI: 0.6% to 2.5%).Conclusions
Retrograde CTO PCI is associated with high procedural success rate and acceptable risk for procedural complications. 相似文献58.
Michael Abouyannis Russell Dacombe Isaias Dambe James Mpunga Brian Faragher Francis Gausi Henry Ndhlovu Chifundo Kachiza Pedro Suarez Catherine Mundy Hastings T Banda Ishmael Nyasulu S Bertel Squire 《Bulletin of the World Health Organization》2014,92(11):798-806
Objective
To document the prevalence of multidrug resistance among people newly diagnosed with – and those retreated for – tuberculosis in Malawi.Methods
We conducted a nationally representative survey of people with sputum-smear-positive tuberculosis between 2010 and 2011. For all consenting participants, we collected demographic and clinical data, two sputum samples and tested for human immunodeficiency virus (HIV).The samples underwent resistance testing at the Central Reference Laboratory in Lilongwe, Malawi. All Mycobacterium tuberculosis isolates found to be multidrug-resistant were retested for resistance to first-line drugs – and tested for resistance to second-line drugs – at a Supranational Tuberculosis Reference Laboratory in South Africa.Findings
Overall, M. tuberculosis was isolated from 1777 (83.8%) of the 2120 smear-positive tuberculosis patients. Multidrug resistance was identified in five (0.4%) of 1196 isolates from new cases and 28 (4.8%) of 581 isolates from people undergoing retreatment. Of the 31 isolates from retreatment cases who had previously failed treatment, nine (29.0%) showed multidrug resistance. Although resistance to second-line drugs was found, no cases of extensive drug-resistant tuberculosis were detected. HIV testing of people from whom M. tuberculosis isolates were obtained showed that 577 (48.2%) of people newly diagnosed and 386 (66.4%) of people undergoing retreatment were positive.Conclusion
The prevalence of multidrug resistance among people with smear-positive tuberculosis was low for sub-Saharan Africa – probably reflecting the strength of Malawi’s tuberculosis control programme. The relatively high prevalence of such resistance observed among those with previous treatment failure may highlight a need for a change in the national policy for retreating this subgroup of people with tuberculosis. 相似文献59.
Sharmistha Dev MD MPH Andrew A. Gonzalez MD JD MPH Jessica Coffing MPH James E. Slaven MS Shantanu Dev BS Stan Taylor MA Carrie Ballard S. Nicole Hastings MD MHSc Dawn M. Bravata MD 《Academic emergency medicine》2023,30(4):349-358
Objectives
Frailty is a clinical syndrome characterized by decreased physiologic reserve that diminishes the ability to respond to stressors such as acute illness. Veterans Health Administration (VA) emergency departments (ED) are the primary venue of care for Veterans with acute illness and represent key sites for frailty recognition. As questionnaire-based frailty instruments can be cumbersome to implement in the ED, we examined two administratively derived frailty scores for use among VA ED patients.Methods
This national retrospective cohort study included all VA ED visits (2017–2020). We evaluated two administratively derived scores: the Care Assessment Needs (CAN) score and the VA Frailty Index (VA-FI). We categorized all ED visits across four frailty groups and examined associations with outcomes of 30-day and 90-day hospitalization and 30-day, 90-day, and 1-year mortality. We used logistic regression to assess the model performance of the CAN score and the VA-FI.Results
The cohort included 9,213,571 ED visits. With the CAN score, 28.7% of the cohort were classified as severely frail; by VA-FI, 13.2% were severely frail. All outcome rates increased with progressive frailty (p-values for all comparisons < 0.001). For example, for 1-year mortality based on the CAN score frailty was determined as: robust, 1.4%; prefrail, 3.4%; moderately frail, 7.0%; and severely frail, 20.2%. Similarly, for 90-day hospitalization based on VA-FI, frailty was determined as prefrail, 8.3%; mildly frail, 15.3%; moderately frail, 29.5%; and severely frail, 55.4%. The c-statistics for CAN score models were higher than for VA-FI models across all outcomes (e.g., 1-year mortality, 0.721 vs. 0.659).Conclusions
Frailty was common among VA ED patients. Increased frailty, whether measured by CAN score or VA-FI, was strongly associated with hospitalization and mortality and both can be used in the ED to identify Veterans at high risk for adverse outcomes. Having an effective automatic score in VA EDs to identify frail Veterans may allow for better targeting of scarce resources. 相似文献60.
Phillip E. Posch Alice E. Hastings Sandra Rosen-Bronson John R. Richert Carolyn Katovich Hurley 《European journal of immunology》1996,26(8):1884-1891
Definition of peptide binding motifs for DR molecules has proven difficult as the peptides that bind to a DR molecule have shown extensive variability at putative motif positions. Recent studies suggest that specific peptide anchor residues (motif positions) and specific DR residues can differ in importance for peptide binding to a DR molecule. To assess further the relevance of individual peptide anchor residues, the binding of serial alanine-substituted analogs of influenza virus hemagglutinin (HA) 306–318 and human myelin basic protein (MBP) 152–165 to a panel of transfected wild-type DR molecules was examined. This analysis included DR molecules from a wide range of allelic families and, unlike most earlier studies, multiple members of single DR allelic families. The data show that different peptide residues serve as critical anchors for binding to different DR molecules. For example, MBP binding to DR(α,β1*0303) required peptide residues F154 (i), R159 (i + 5) and R162 (i + 8). In contrast, MBP binding to DR(α,β1*0102) required peptide residues I153 (i) and L156 (i + 3). More importantly, the combination of critical anchor residues in HA and MBP differed for binding to a single DR molecule [e.g. V309 (i) for HA and I153 (i) and L156 (i + 3) for MBP binding to DR(α,β1*0102)]. Although the location of the binding pocket in each DR molecule compared to the DR (α,β1*0101) crystal is expected to be similar and suggests a common extended DR binding motif, the present results suggest that the relative importance of individual peptide anchor residues and of the corresponding DR binding pockets will differ for each DR/peptide complex. 相似文献