Gorlov IP, Gorlova OY, Frazier ML, Spitz MR, Amos CI. Evolutionary evidence of the effect of rare variants on disease etiology. The common disease/common variant hypothesis has been popular for describing the genetic architecture of common human diseases for several years. According to the originally stated hypothesis, one or a few common genetic variants with a large effect size control the risk of common diseases. A growing body of evidence, however, suggests that rare single‐nucleotide polymorphisms (SNPs), i.e. those with a minor allele frequency of less than 5%, are also an important component of the genetic architecture of common human diseases. In this study, we analyzed the relevance of rare SNPs to the risk of common diseases from an evolutionary perspective and found that rare SNPs are more likely than common SNPs to be functional and tend to have a stronger effect size than do common SNPs. This observation, and the fact that most of the SNPs in the human genome are rare, suggests that rare SNPs are a crucial element of the genetic architecture of common human diseases. We propose that the next generation of genomic studies should focus on analyzing rare SNPs. Further, targeting patients with a family history of the disease, an extreme phenotype, or early disease onset may facilitate the detection of risk‐associated rare SNPs. 相似文献
OBJECTIVE: Our aim was to compare the effectiveness of mammography and MRI in the detection of multifocal, multicentric breast cancer. SUBJECTS AND METHODS: Ninety patients with planned mastectomies (nine bilateral) underwent mammography and dynamic gadolinium-enhanced MRI. Off-site reviewers aware of the entry criterion (planned mastectomy) evaluated both examinations for the presence of malignant foci, recording the density pattern on mammography. The gold standard was pathologic examination of the whole excised breast (slice thickness, 5 mm). RESULTS: Of 99 breasts, pathologic findings revealed 52 unifocal, 29 multifocal, and 18 multicentric cancers for a total of 188 malignant foci (158 invasive and 30 in situ). Overall sensitivity was 66% (124/188) for mammography and 81% (152/188) for MRI (p < 0.001); 72% (113/158) and 89% (140/158) for invasive foci (p < 0.001); and 37% (11/30) and 40% (12/30) for in situ foci (p > 0.05, not significant), respectively. Mammography and MRI missed 64 and 36 malignant foci, respectively, with median diameters of 8 and 5 mm (p = 0.033) and an invasive-noninvasive ratio of 2.4:1 (45:19) and 1.0:1 (18:18) (p = 0.043), respectively. The overall positive predictive value (PPV) was 76% (124/164) for mammography and 68% (152/222) for MRI (not significant). In breasts with an almost entirely fatty pattern, sensitivity was 75% for mammography and 80% for MRI (not significant), and the PPV was 73% and 65% (not significant), respectively. In breasts with fibroglandular or dense pattern, the sensitivity was 60% and 81% (p < 0.001), and the PPV was 78% and 71% (not significant), respectively. CONCLUSION: MRI was more sensitive than mammography for the detection of multiple malignant foci in fibroglandular or dense breasts. Mammography missed larger and more invasive cancer foci than MRI. A relatively low PPV was a problem for both techniques. 相似文献
With nurse education in a state of flux the opportunity exists to reappraise the teaching methods currently used and to consider which will be the most appropriate to prepare the practitioner of the future. This paper examines the possible contribution of one particular teaching medium — the academic game — by describing the development and evaluation of a new game called ‘Consolidate or bust’. The game was introduced as part of a wider programme of curriculum development aimed at providing a more balanced introductory course for new student nurses. The results to date indicate that the application of experiential methods in general, and gaming in particular, constitute a valuable addition to more formal approaches and one that may be perceived very prositively by student nurses. The paper concludes with a call for nurse educators to critically examine their present practice and consider the wider application of less formal methods. 相似文献
To assess the clinical value of three‐dimensional (3D) printing technology for treatment strategies for complex double outlet right ventricle (DORV).
Methods
Twenty‐five patients with complex double outlet right ventricle were enrolled in this study. The patients were divided into two groups: 3D printing group (eight patients) and a non‐3‐D printing control group (17 patients). The cardiac images of patients in the 3D printing group were transformed to Digital Imaging and Communications and were segmented and reconstructed to create a heart model. No cardiac models were created in the control group. A Pearson coefficient analysis was used to assess the correlation between measurements of 3D printed models and computed tomography angiography (CTA) data. Pre‐operative assessment and planning were performed with 3D printed models, and then operative time and recovery time were compared between the two groups.
Results
There was good correlation (r = 0.977) between 3D printed models and CTA data. Patients in the 3D printing group had shorter aortic cross‐clamp time (102.88 vs 127.76 min, P= 0.094) and cardiopulmonary bypass time (151.63 vs 184.24 min; P = 0.152) than patients in the control group. Patients with 3D printed models had significantly lower mechanical ventilation time (56.43 vs 96.76 h, P = 0.040) and significantly shorter intensive care unit time (99.04 vs 166.94 h, P = 0.008) than patients in the control group.
Conclusions
3D printed models can accurately demonstrate anatomic structures and are useful for pre‐operative treatment strategies in DORV. 相似文献
Tuberculosis remains a worldwide health problem, as well as its complications including arthritis in various joints. End-stage arthritis in weight-bearing joint would require surgery either arthroplasty or arthrodesis, in order to achieve painless and stable gait. In general, staged surgery consisted of debridement and subsequent definitive procedure is accepted. However, multiple surgery would be disadvantageous in terms of clinical and economic burdens. This study reported the short-term result of one-stage debridement and fusion for ankle joint tuberculosis.
Methods
Retrospective evaluation of twenty-six patients with history of one-stage debridement and ankle fusion was conducted. Basic anthropometric measurement, local status, and surgical technique were recorded. Functional score using Foot and Ankle Ability Measures (FAAM) activities of daily living (ADL) was assessed pre-operatively and at two and half year post-surgery follow-up visit along with radiological fusion rate. Paired t test was used to analyse the improvement of the clinical scores.
Results
There was improvement in FAAM score from 43.38 ± 9.51 to 62.19 ± 6.63% (p < 0.001). All sinuses had been subsided, albeit at various time spans. Modified radiographic union score for tibia (RUST) revealed various fusion rate results, ranged from 5 to 11.
Conclusion
One-stage debridement and fusion is proven efficacious for end-stage joint tuberculosis, with less surgery occasion compared with staged surgery. However, patient selection is important since any comorbidities or secondary infection may complicate the fusion.