Testing association with interactions by partitioning chi-squares

Gene-gene interaction plays an important role in association studies for complex diseases. There have been different approaches to incorporating gene-gene interactions in candidate gene or genome-wide association studies, especially for those genes with no marginal effects but with interaction effects. However, there is no general agreement on how interaction should be tested and how main effects and interaction effects act on a significance signal. In this paper, we propose a test of the null hypothesis of no association in terms of interaction effects for two unlinked loci, which is a 4 degrees of freedom (df) chi-square for two SNPs. The test, derived by contrasting inter-locus disequilibrium measures between cases and controls, can be viewed as the interaction component of the total Pearson chi-square. The remaining portion of the total chi-square can also be used for association analysis, which emphasizes main effects. Simulation studies show that in most situations our interaction test is similar in power to the test based on a logistic regression model but has more power when the genes have no marginal effects. Results also show that single-locus marginal tests can lose much power if interaction effects dominate main effects. For some specific genetic models, the interaction test may be further partitioned into four 1-df chi-squares for individual interaction effect. The interaction pattern can best be demonstrated by the 1-df chi-square components. Simulation results show that there is substantial power gain if interaction patterns are properly incorporated in association analysis.     

Three-Dimensional Computed Tomographic Findings of Bilateral Tracheal Bronchus

A newborn male was admitted with cyanosis and respiratory distress. Echocardiography showed a right heart isomerism associated with a single right ventricle, a double-outlet right ventricle, and pulmonary atresia. Chest X-ray demonstrated severe left upper lobe emphysema and a shift of the mediastinal structures to the right. Two-dimensional computed tomography (CT) exhibited left upper lobe emphysema and right upper lobe atelectasis. Three-dimensional (3D) spiral CT angiography showed a bilateral tracheal bronchus. The left tracheal bronchus branch was compressed between the descending aorta and the ductus arteriosus. After a right arteriopulmonary shunt operation, the patient’s respiratory condition improved dramatically, with spontaneous closure of the ductus arteriosus. Subsequently, 3D-CT clearly exhibited the disappearance of tracheal compression. This combination of bilateral tracheal bronchus and congenital heart anomaly is extremely rare. The 3D-CT is a powerful noninvasive means for dynamically demonstrating the special relationships of arterial and tracheal anomalies.     

Analysis of ET‐A and ET‐B receptors using an isolated perfused rat lung preparation

Aims and Methods: The pulmonary and vascular effects of endothelin‐1 receptor activation were studied in isolated perfused and ventilated lung preparations from rat. The responses to endothelin‐1 (ET‐1) and the endothelin B (ET_B) receptor agonist sarafotoxin 6c (S6c) were characterized using the endothelin A (ET_A)‐receptor antagonist FR 139317, the ET_B‐receptor antagonist BQ 788 and the combined ET_A/ET_B‐receptor antagonist Bosentan. The respiratory parameter airway conductance (G_aw) and the vascular parameter perfusion flow were analysed simultaneously. Results: Concentration–response curves for ET‐1 administered intra‐arterially revealed that its most potent effect was on the vascular side while S6c had a more potent effect on airway conductance. ET‐1, given as a bolus dose intra‐arterially (100 μL of 0.2 nm ), induced a strong‐ and long‐lasting contraction of the vasculature while only a less pronounced contraction was seen in the airways. Neither of the antagonists had a significant effect per se on G_aw or perfusion flow. FR 139317 reduced the effect of ET‐1 on perfusion flow by about 50%, while airway conductance was augmented. BQ 788 enhanced the decrease in perfusion flow by ET‐1 while G_aw was not influenced. The combined ET_A/ET_B antagonist Bosentan powerfully prevented the ET‐1‐induced decrease in G_aw but did not alter its reduction in perfusion flow. Conclusions: The potent effect of ET‐1 on the vascular side of the lung is mediated mainly through ET_A receptors, whereas both ET_A and ET_B receptors are involved in G_aw in the rat lung.     

Are difficulties during transbronchial lung biopsy/brushing through a fiberoptic bronchoscope based on the bronchial anatomy?

Some of the difficulties encountered during transbronchial lung biopsy through a flexible bronchofiberscope are due to anatomical reasons, namely the branching angles of some subsegmental bronchi from their mother bronchi are large, and differences in branching angles during respiration may also be large. This makes insertion of forceps difficult. We have sometimes experienced difficulties reaching the target lesion during a transbronchial approach. Which subsegmental bronchi make transbronchial lung biopsy/brushing difficult, and are such difficulties due to anatomical reasons? To answer these questions, we firstly surveyed 10 bronchologists regarding which five subsegmental bronchi they considered to be the most difficult for transbronchial biopsy/brushing. We then measured the branching angles of subsegmental bronchi in 106 cadaver lungs. Finally, in six volunteers, we also measured differences in branching angles of the subsegmental bronchi between the point of forced inspiration and the point of forced expiration on CT images. According to the survey, left B¹⁺²c was considered to be the most difficult for insertion by nine doctors, followed by bilateral B⁶a by seven, right B¹a by five, left B³a by five and left B¹⁺²a by four. The results of our dissections showed that a branching angle of over 60º was present in more than 10% of specimens in B³a, B⁶a and B⁶c in the right lung and in B¹⁺²c, B³a, B⁶a and B⁶c in the left lung. In addition, three-dimensional reconstructed images revealed that the angles of some subsegmental bronchi changed during respiration. Inter-individual variations were present in most subsegmental bronchi. The direction of movement of each subsegmental bronchus during respiration varied. In addition, maximum degrees of difference in angles between volunteers were sometimes as much as 80°. In conclusion, branching angles of subsegmental bronchi from their mother bronchi are large in B³a, B⁶a and B⁶c in the right lung and in B¹⁺²c, B³a, B⁶a and B⁶c in the left lung. Most of these correspond to those which many bronchologists felt to be difficult for insertion. In addition, changes in the angles of subsegmental bronchi during respiration are likely to partially account for difficulties encountered during transbronchial approaches.     

青少年特发性脊柱侧凸腰主弯患者腰椎-骨盆的生物力学分析

文题释义： 青少年特发性脊柱侧凸：为脊柱三维平面上的畸形,会导致青少年脊柱结构发生明显的改变,结构的改变会导致椎骨及椎间盘应力发生相应的改变,且腰椎、骨盆在人体中的力学作用极为重要,青少年时期为人体脊柱生长发育的高峰期,脊柱结构及应力的改变在该时期的进展尤为明显。 背景：青少年特发性脊柱侧凸导致脊柱结构和应力发生改变,腰椎在脊柱中承受的载荷最大,骨盆也起着传导重力的作用,故青少年特发性脊柱侧凸腰主弯患者腰椎骨盆的生物力学分析尤为重要。 目的：建立青少年特发性脊柱侧凸腰主弯腰椎-骨盆三维数字化模型并进行有限元分析。 方法：根据1例13岁女性特发性脊柱侧凸腰主弯患者的腰椎-骨盆CT薄层数据,应用Mimics 15.0软件重建三维数字化模型,以Pro/E 5.0软件建立初步几何模型并导入Hypermesh 13.0进行网格划分,最终通过Abaqus 6.14软件对该模型进行有限元分析。分析有限元模型在6种载荷条件下的位移、应力变化及该模型各椎体及椎间盘的应力变化。患者家属对试验方案知情同意,且得到医院伦理委员会批准。 结果与结论：①建立了青少年特发性脊柱侧凸腰主弯患者的腰椎-骨盆的三维有限元模型;②模型在6种载荷条件下,L₁椎体上部在左、右侧屈时位移变化最大,骶骨下端在前屈时位移最大;③椎间盘右缘在右侧屈运动条件下所受应力最大;前屈位时,腰椎间盘所受应力为前缘最大,左缘所受应力最小;后伸位时后缘所受应力最大,而右缘所受应力最小;侧屈位及旋转位时,右缘所受应力最大,前缘所受应力最小;④L₅在6种运动中应力均最大,其中应力集中于上下关节突及椎弓根,尤其以右侧最为集中;⑤提示青少年特发性脊柱侧凸不同载荷会引起椎体或椎间盘不同位置受力及位移有相应变化,研究结果对脊柱侧凸的治疗和预防具有重要意义。 ORCID: 0000-0001-5810-6674(张聪) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

On the organization of olfactory and vomeronasal cortices

Classically, the olfactory and vomeronasal pathways are thought to run in parallel non-overlapping axes in the forebrain subserving different functions. The olfactory and vomeronasal epithelia project to the main and accessory olfactory bulbs (primary projections), which in turn project to different areas of the telencephalon in a non-topographic fashion (secondary projections) and so on (tertiary projections). New data indicate that projections arising from the main and accessory olfactory bulbs converge widely in the rostral basal telencephalon. In contrast, in the vomeronasal system, cloning two classes of vomeronasal receptors (V1R and V2R) has led to the distinction of two anatomically and functionally independent pathways that reach some common, but also some different, targets in the amygdala. Tertiary projections from the olfactory and vomeronasal amygdalae are directed to the ventral striatum, which thus becomes a site for processing and potential convergence of chemosensory stimuli. Functional data indicate that the olfactory and vomeronasal systems are able to detect and process volatiles (presumptive olfactory cues) as well as pheromones in both epithelia and bulbs. Collectively, these data indicate that the anatomical and functional distinction between the olfactory and vomeronasal systems should be re-evaluated. Specifically, the recipient cortex should be reorganized to include olfactory, vomeronasal (convergent and V1R and V2R specific areas) and mixed (olfactory and vomeronasal) chemosensory cortices. This new perspective could help to unravel olfactory and vomeronasal interactions in behavioral paradigms.     

右肺门支气管和血管在横断面上的配布特点

目的：探讨有肺门支气管、肺动脉和肺静脉在横断面上的配布特点。方法：在44例成人胸部连续横断层标本和5例螺旋CT图像上，追踪观察了有侧第一、二、三肺门处支气管、肺动脉和肺静脉的分支(或属支)及其毗邻关系。结果：从气管权开始，至底段上、下静脉出现，以7个典型横断面便可清晰显示有肺门管道结构的配布规律：①在气管权层面，尖段动脉、尖段支气管和后段静脉于奇静脉弓右侧由内向外依次排列；②在右肺上叶支气管层面，后段静脉居后段支气管与前段支气管之间；③在中间支气管层面，右肺上叶动脉上行于中间支气管前方，两者的深面为尖段静脉、前段静脉和后段静脉；④在叶间动脉层面，右肺上叶静脉、叶间动脉和中间支气管由前向后依次排列，在33例(75％)标本中可见到下叶上段动脉的起源；⑤于中间支气管权层面，中、下叶动脉走行于中、下叶支气管外侧；⑥于基底干支气管层面，在11例(25％)标本中可见中叶静脉直接汇入左心房，内侧底段支气管常与上段静脉段问支同时出现；⑦于底段上、下静脉层面，以各底段支气管为中心，相应动脉呈周围性分布，底段上、下静脉呈向心性走行。结论：通过寻找标志性结构，在横断面上可准确识别有肺门处肺叶和肺段的支气管、肺动脉和肺静脉。     

Induced sputum and bronchial mucosal expression of interleukin-13 is not increased in chronic obstructive pulmonary disease

Background:  The Th2 cytokine interleukin-13 (IL-13) has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). We sought to examine IL-13 expression in COPD subjects in induced sputum and bronchus specimens. We hypothesized that inflammatory cells expressing IL-13 localize to the airway smooth muscle bundle and bronchial glands.
Methods:  Interleukin-13 was measured in sputum samples from subjects with COPD ( n  = 34) across a range of severity (Global initiative for chronic Obstructive Lung Disease 2–4) and controls ( n  = 14) using ELISA. IL-13+ cells and inflammatory cells were enumerated within surgically resected proximal airway using immunohistochemical techniques from subjects with COPD ( n  = 10), smoking ( n  = 10) and nonsmoking controls ( n  = 8).
Results:  Sputum IL-13 was measurable in only 6/34 subjects with COPD and was not found in the smoking or nonsmoking control subjects. In subjects with COPD and controls there was a paucity of IL-13+ cells. The distribution of inflammatory cells within different airway compartments was similar in COPD and controls except for an increase in CD3⁺ lymphocytes within bronchial glands in COPD ( P  = 0.04).
Conclusions:  Our findings do not support a role for IL-13 in COPD. However, the tissue localization of inflammatory cells to airway compartments, particularly the increase of T cells in glands in COPD may be important in disease.