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51.
Thomson R Quinn S McKay J Silver J Bahlo M FitzGerald L Foote S Dickinson J Stankovich J 《Human genetics》2007,121(3-4):459-468
Dense sets of hundreds of thousands of markers have been developed for genome-wide association studies. These marker sets
are also beneficial for linkage analysis of large, deep pedigrees containing distantly related cases. It is impossible to
analyse jointly all genotypes in large pedigrees using the Lander–Green Algorithm, however, as marker density increases it
becomes less crucial to analyse all individuals’ genotypes simultaneously. In this report, an approximate multipoint non-parametric
technique is described, where large pedigrees are split into many small pedigrees, each containing just two cases. This technique
is demonstrated, using phased data from the International Hapmap Project to simulate sets of 10,000, 50,000 and 250,000 markers,
showing that it becomes increasingly accurate as more markers are genotyped. This method allows routine linkage analysis of
large families with dense marker sets and represents a more easily applied alternative to Monte Carlo Markov Chain methods. 相似文献
52.
V. Vedam-Mai N. Krock M. Ullman K. D. Foote W. Shain K. Smith A. T. Yachnis D. Steindler B. Reynolds S. Merritt F. Pagan J. Marjama-Lyons P. Hogarth A. S. Resnick P. Zeilman M. S. Okun 《Cell and tissue banking》2011,12(3):219-231
Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51?C92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval. 相似文献
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The production learning of vocalizations by manipulation of the sound production organs to alter the physical structure of sound has been demonstrated in only a few mammals. In this natural experiment, we document the vocal behaviour of two juvenile killer whales, Orcinus orca, separated from their natal pods, which are the only cases of dispersal seen during the three decades of observation of their populations. We find mimicry of California sea lion (Zalophus californianus) barks, demonstrating the vocal production learning ability for one of the calves. We also find differences in call usage (compared to the natal pod) that may reflect the absence of a repertoire model from tutors or some unknown effect related to isolation or context. 相似文献
55.
Alexander S T Papadopulos Andrew J Helmstetter Owen G Osborne Aaron A Comeault Daniel P Wood Edward A Straw Laurence Mason Michael F Fay Joe Parker Luke T Dunning Andrew D Foote Rhian J Smith Jackie Lighten 《Molecular biology and evolution》2021,38(9):3724
The impact of human-mediated environmental change on the evolutionary trajectories of wild organisms is poorly understood. In particular, capacity of species to adapt rapidly (in hundreds of generations or less), reproducibly and predictably to extreme environmental change is unclear. Silene uniflora is predominantly a coastal species, but it has also colonized isolated, disused mines with phytotoxic, zinc-contaminated soils. To test whether rapid, parallel adaptation to anthropogenic pollution has taken place, we used reduced representation sequencing (ddRAD) to reconstruct the evolutionary history of geographically proximate mine and coastal population pairs and found largely independent colonization of mines from different coastal sites. Furthermore, our results show that parallel evolution of zinc tolerance has occurred without gene flow spreading adaptive alleles between mine populations. In genomic regions where signatures of selection were detected across multiple mine-coast pairs, we identified genes with functions linked to physiological differences between the putative ecotypes, although genetic differentiation at specific loci is only partially shared between mine populations. Our results are consistent with a complex, polygenic genetic architecture underpinning rapid adaptation. This shows that even under a scenario of strong selection and rapid adaptation, evolutionary responses to human activities (and other environmental challenges) may be idiosyncratic at the genetic level and, therefore, difficult to predict from genomic data. 相似文献
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A Fallah EA Akl S Ebrahim GM Ibrahim A Mansouri CJ Foote Y Zhang MG Fehlings 《PloS one》2012,7(8):e43407
Objective
To estimate the effectiveness of anterior cervical discectomy with arthroplasty (ACDA) compared to anterior cervical discectomy with fusion (ACDF) for patient-important outcomes for single-level cervical spondylosis.Data sources
Electronic databases (MEDLINE, EMBASE, Cochrane Register for Randomized Controlled Trials, BIOSIS and LILACS), archives of spine meetings and bibliographies of relevant articles.Study selection
We included RCTs of ACDF versus ACDA in adult patients with single-level cervical spondylosis reporting at least one of the following outcomes: functionality, neurological success, neck pain, arm pain, quality of life, surgery for adjacent level degeneration (ALD), reoperation and dysphonia/dysphagia. We used no language restrictions. We performed title and abstract screening and full text screening independently and in duplicate.Data synthesis
We used random-effects model to pool data using mean difference (MD) for continuous outcomes and relative risk (RR) for dichotomous outcomes. We used GRADE to evaluate the quality of evidence for each outcome.Results
Of 2804 citations, 9 articles reporting on 9 trials (1778 participants) were eligible. ACDA is associated with a clinically significant lower incidence of neurologic failure (RR = 0.53, 95% CI = 0.37–0.75, p = 0.0004) and improvement in the Neck pain visual analogue scale (VAS) (MD = 6.56, 95% CI = 3.22–9.90, p = 0.0001; Minimal clinically important difference (MCID) = 2.5. ACDA is associated with a statistically but not clinically significant improvement in Arm pain VAS and SF-36 physical component summary. ACDA is associated with non-statistically significant higher improvement in the Neck Disability Index Score and lower incidence of ALD requiring surgery, reoperation, and dysphagia/dysphonia.Conclusions
There is no strong evidence to support the routine use of ACDA over ACDF in single-level cervical spondylosis. Current trials lack long-term data required to assess safety as well as surgery for ALD. We suggest that ACDA in patients with single level cervical spondylosis is an option although its benefits and indication over ACDF remain in question. 相似文献58.
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