Purpose The purpose of this prospective multicenter study was to assess the accuracy of a computer-aided surgical simulation (CASS) protocol for orthognathic surgery. Materials and Methods The ...accuracy of the CASS protocol was assessed by comparing planned outcomes with postoperative outcomes of 65 consecutive patients enrolled from 3 centers. Computer-generated surgical splints were used for all patients. For the genioplasty, 1 center used computer-generated chin templates to reposition the chin segment only for patients with asymmetry. Standard intraoperative measurements were used without the chin templates for the remaining patients. The primary outcome measurements were the linear and angular differences for the maxilla, mandible, and chin when the planned and postoperative models were registered at the cranium. The secondary outcome measurements were the maxillary dental midline difference between the planned and postoperative positions and the linear and angular differences of the chin segment between the groups with and without the use of the template. The latter were measured when the planned and postoperative models were registered at the mandibular body. Statistical analyses were performed, and the accuracy was reported using root mean square deviation (RMSD) and the Bland-Altman method for assessing measurement agreement. Results In the primary outcome measurements, there was no statistically significant difference among the 3 centers for the maxilla and mandible. The largest RMSDs were 1.0 mm and 1.5° for the maxilla and 1.1 mm and 1.8° for the mandible. For the chin, there was a statistically significant difference between the groups with and without the use of the chin template. The chin template group showed excellent accuracy, with the largest positional RMSD of 1.0 mm and the largest orientation RMSD of 2.2°. However, larger variances were observed in the group not using the chin template. This was significant in the anteroposterior and superoinferior directions and the in pitch and yaw orientations. In the secondary outcome measurements, the RMSD of the maxillary dental midline positions was 0.9 mm. When registered at the body of the mandible, the linear and angular differences of the chin segment between the groups with and without the use of the chin template were consistent with the results found in the primary outcome measurements. Conclusions Using this computer-aided surgical simulation protocol, the computerized plan can be transferred accurately and consistently to the patient to position the maxilla and mandible at the time of surgery. The computer-generated chin template provides greater accuracy in repositioning the chin segment than the intraoperative measurements.
Background Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can ...identify novel asthma genes by enabling prioritization of putative functional variants for association testing. Objective We evaluated 6706 cis-acting expression-associated variants (eSNPs) identified through a genome-wide eQTL survey of CD4+ lymphocytes for association with asthma. Methods eSNPs were tested for association with asthma in 359 asthmatic patients and 846 control subjects from the Childhood Asthma Management Program, with verification by using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by using formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. Results Cis-acting eSNPs demonstrated associations with asthma in both cohorts. We confirmed the previously reported association of ORMDL3 / GSDMB variants with asthma (combined P = 2.9 × 10−8 ). Reproducible associations were also observed for eSNPs in 3 additional genes: fatty acid desaturase 2 ( FADS2 ; P = .002), N-acetyl-α-D-galactosaminidase ( NAGA ; P = .0002), and Factor XIII, A1 ( F13A1 ; P = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4+ lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. Conclusions Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes and provide evidence for the importance of FADS2 , NAGA , and F13A1 in the pathogenesis of asthma.
Abstract Background Ambient temperature is an important risk factor for human health. However, little evidence is available on the attributable burden, such as absolute or relative excess of ...mortality, due to temperature. We investigated the burden ofdeath attributable toambient temperature in China. Methods We used the national database comprising daily death data for 89 Chinese communities for 2007–2013, covering 106·1 million permanent residents, according to China's 2010 population census. A distributed lag non-linear model was used to estimate the community-specific mortality effects of daily mean temperature. Pooled estimates of national and regional effects (southern, northern, western and eastern; rural and urban), were then calculated through multivariate meta-analysis. Attributable deaths were calculated for cold and heat, defined as ambient temperatures below and above the minimum-mortality temperature. This study was approved by the ethics committee of the Chinese Center for Disease Control and Prevention (201214). Findings Our analysis included 1 727 143 non-accidental deaths during the study period, with a total of 228 213 (95% empirical CI 192 835–244 597) deaths attributed to non-optimum ambient temperatures. The national attributable fraction was 13·21% (95% empirical CI 11·34–14·16), most of which was linked to low temperatures (11·96%, 10·04–12·94). There was significant between-region heterogeneity in the attributable fractions for non-optimal temperature (I2 =56·1%, p<0·0001, ranging from 12·18% (8·49–14·33) in northern regions to 18·16% (8·73–22·92) in western regions. Death burdens attributed to ambient temperatures were similar between urban (13·37%, 10·68–15·09) and rural regions (13·46%, 10·46–15·08). Interpretation Ambient temperature was responsible for 13·21% of deaths in China, and the burden attributable to this factor varied significantly across different regions. Most of this burden was caused by low temperature. This study has implications for policymakers developing protective strategies to mitigate the health effects of adverse ambient temperatures. Funding National Basic Research Program of China (973 Program) ( Grant No 2012CB955504 ). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Purpose The purpose of the present study was to evaluate the accuracy of our newly developed approach to digital dental model articulation. Materials and Methods Twelve sets of stone dental models ...from patients with craniomaxillofacial deformities were used for validation. All the models had stable occlusion and no evidence of early contact. The stone models were hand articulated to the maximal intercuspation (MI) position and scanned using a 3-dimensional surface laser scanner. These digital dental models at the MI position served as the control group. To establish an experimental group, each mandibular dental model was disarticulated from its original MI position to 80 initial positions. Using a regular office personal computer, they were digitally articulated to the MI position using our newly developed approach. These rearticulated mandibular models served as the experimental group. Finally, the translational, rotational, and surface deviations in the mandibular position were calculated between the experimental and control groups, and statistical analyses were performed. Results All the digital dental models were successfully articulated. Between the control and experimental groups, the largest translational difference in mandibular position was within 0.2 mm ± 0.6 mm. The largest rotational difference was within 0.1° ± 1.1°. The averaged surface deviation was 0.08 ± 0.07. The results of the Bland and Altman method of assessing measurement agreement showed tight limits for the translational, rotational, and surface deviations. In addition, the final positions of the mandibular articulated from the 80 initial positions were absolutely agreed on. Conclusion The results of our study have demonstrated that using our approach, the digital dental models can be accurately and effectively articulated to the MI position. In addition, the 3-dimensional surface geometry of the mandibular teeth played a more important role in digital dental articulation than the initial position of the mandibular teeth.
Background This study was conducted to assess expression of Galectin-3 (Gal-3) in patients with different types of left ventricle (LV) hypertrophy geometry, and the relationship between Gal-3 ...expression and LV remodelling in patients with aortic valve stenosis (AS). Methods Galectin-3 expression was measured in the plasma and myocardia of AS patients who underwent an aortic valve replacement procedure. Results The study enrolled 77 consecutive patients with severe AS. Fifty-five (71.43%) of the enrolled patients had concentric hypertrophy (CH group), and had the highest degree of fibrosis (27.10 ± 5.25%; p < 0.001) and expression of Gal-3 in both plasma (19.11 ± 2.06 ng/mL) and myocardial tissue (3.01 ± 0.79). There was a strong positive correlation between the levels of fibrosis and Gal-3 expression in both plasma (r = 0.584, p < 0.001) and myocardium (r = 0.522, p < 0.001). Relative wall thickness (RWT) was strongly correlated with Gal-3 expression in both myocardium (r = 0.594, p < 0.001) and plasma (r = 0.323, p = 0.005). Additionally, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were positively correlated with both fibrosis (r = 0.313, p = 0.036) and LV mass index (r = 0.559, p < 0.001). Conclusions Concentric hypertrophy geometry was the most common type of myocardium remodelling, and AS patients with CH geometry showed the highest levels of Gal-3 expression. Galectin-3 levels were positively correlated with fibrosis and RWT, both of which are crucial indicators of geometric remodelling. Galectin-3 and NT-proBNP levels may be valuable prognostic predictors in AS patients with myocardial remodelling.
The genetic risk factors for susceptibility to chronic obstructive pulmonary disease (COPD) are still largely unknown. Additional genetic variants are likely to be identified by genome-wide ...association studies in larger cohorts or specific subgroups. We sought to identify risk loci for moderate to severe and severe COPD with data from several cohort studies.
We combined genome-wide association analysis data from participants in the COPDGene study (non-Hispanic white and African-American ethnic origin) and the ECLIPSE, NETT/NAS, and Norway GenKOLS studies (self-described white ethnic origin). We did analyses comparing control individuals with individuals with moderate to severe COPD and with a subset of individuals with severe COPD. Single nucleotide polymorphisms yielding a p value of less than 5 × 10(-7) in the meta-analysis at loci not previously described were genotyped in individuals from the family-based ICGN study. We combined results in a joint meta-analysis (threshold for significance p<5 × 10(-8)).
Analysis of 6633 individuals with moderate to severe COPD and 5704 control individuals confirmed association at three known loci: CHRNA3 (p=6·38 × 10(-14)), FAM13A (p=1·12 × 10(-14)), and HHIP (p=1·57 × 10(-12)). We also showed significant evidence of association at a novel locus near RIN3 (p=5·25 × 10(-9)). In the overall meta-analysis (ie, including data from 2859 ICGN participants), the association with RIN3 remained significant (p=5·4 × 10(-9)). 3497 individuals were included in our analysis of severe COPD. The effect estimates for the loci near HHIP and CHRNA3 were significantly stronger in severe disease than in moderate to severe disease (p<0·01). We also identified associations at two additional loci: MMP12 (overall joint meta-analysis p=2·6 × 10(-9)) and TGFB2 (overall joint meta-analysis p=8·3 × 10(-9)).
We have confirmed associations with COPD at three known loci and identified three new genome-wide significant associations. Genetic variants other than in α-1 antitrypsin increase the risk of COPD.
US National Heart, Lung, and Blood Institute; the Alpha-1 Foundation; the COPD Foundation through contributions from AstraZeneca, Boehringer Ingelheim, Novartis, and Sepracor; GlaxoSmithKline; Centers for Medicare and Medicaid Services; Agency for Healthcare Research and Quality; and US Department of Veterans Affairs.
PDF
