Bayesian consensus clustering for multivariate longitudinal data

In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co-existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker-specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data.     

肠炎清合剂治疗慢性复发型溃疡性结肠炎大肠湿热证的临床观察

目的:观察肠炎清合剂对慢性复发型溃疡性结肠炎(UC)大肠湿热证患者诱导缓解效果及维持治疗对复发的影响,并从神经-内分泌-免疫炎症网络方面探讨了其作用机制。方法:将112例符合要求的患者随机分成对照组55例和观察组57例。对照组内服美沙拉嗪肠溶片,1.0 g/次,4次/d;Mayo评分系统≥7分者,加服醋酸泼尼松片,0.75 mg·kg^-1·d^-1;加用双歧杆菌活菌散剂,1包/次,2次/d,餐后温水冲服。观察组在对照组治疗的基础上服用肠炎清合剂,1包/次,分早晚2次服用。两组疗程均为连续治疗6周,再每周门诊复诊1次。进入缓解期后,两组患者均给予美沙拉嗪肠溶片,0.5 g/次,3次/d,维持治疗;观察组仍内服肠炎清合剂内服,至大肠湿热证评分减少≥90%以上。记录进入6周内缓解期的人数和缓解时间;进行治疗前后结肠镜检查,并进行Geboes指数和Baron法评价;进行治疗前后大肠湿热证评分和Mayo评分;检测治疗前后外周血白细胞介素-6(IL-6),IL-8,IL^-10,IL^-17,血管活性肠肽(VIP),胃动素(MTL)和神经肽Y(NPY);随访24周,记录复发情况。结果:经6周治疗后,观察组临床有效率为100%,黏膜愈合率为96.4%,均分别高于对照组的89.09%和81.82%(P<0.05),两组患者内镜应答率均为100%;经6周治疗后,观察组临床缓解率为91.23%,高于对照组的76.36%(χ2=4.581,P<0.05),观察组平均缓解时间短于对照组(P<0.01);治疗后观察组结肠黏膜评分,Geboes指数、大肠湿热证评分和Mayo评分均低于对照组(P<0.01);观察组患者外周血IL-6,IL-8和IL^-17水平均低于对照组(P<0.01),IL^-10水平高于对照组(P<0.01);观察组患者外周血VIP,MTL水平均低对照组(P<0.01),NPY水平高于对照组(P<0.01);观察组复发率为17.54%,低于对照组的38.18%(χ2=5.955,P<0.05);观察组平均复发时间长于对照组(P<0.01)。结论:在常规西医治疗的基础上,肠炎清合剂用于慢性复发型UC大肠湿热证的治疗,可诱导病情缓解,缩短病程,并能降低复发率,推迟复发时间,并对神经-内分泌-免疫炎症网络具有调节作用,从而可改善病情。     

Multivariate modelling of responses to conditional items: New possibilities for latent class analysis

Questionnaire data may contain missing values because certain questions do not apply to all respondents. For instance, questions addressing particular attributes of a symptom, such as frequency, triggers or seasonality, are only applicable to those who have experienced the symptom, while for those who have not, responses to these items will be missing. This missing information does not fall into the category ‘missing by design’, rather the features of interest do not exist and cannot be measured regardless of survey design. Analysis of responses to such conditional items is therefore typically restricted to the subpopulation in which they apply. This article is concerned with joint multivariate modelling of responses to both unconditional and conditional items without restricting the analysis to this subpopulation. Such an approach is of interest when the distributions of both types of responses are thought to be determined by common parameters affecting the whole population. By integrating the conditional item structure into the model, inference can be based both on unconditional data from the entire population and on conditional data from subjects for whom they exist. This approach opens new possibilities for multivariate analysis of such data. We apply this approach to latent class modelling and provide an example using data on respiratory symptoms (wheeze and cough) in children. Conditional data structures such as that considered here are common in medical research settings and, although our focus is on latent class models, the approach can be applied to other multivariate models. Copyright © 2009 John Wiley & Sons, Ltd.     

Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of <Emphasis Type="Italic">Hydrangea macrophylla</Emphasis> var. <Emphasis Type="Italic">Otaksa</Emphasis>, with special reference to its antimalarial activity

Febrifugine and isofebrifugine alkaloid mixtures extracted from the leaves and buds of Hydrangea macrophylla var. Otaksa, collected during different months, in Japan, were quantified using high-performance liquid chromatography. Leaves collected during the flowering season, namely from June to August, contained 0.16–0.31 mg/g of the alkaloid mixture, whereas those collected from September to December had less than 0.03 mg/g of the mixture. However, extracts of buds harvested from October to February contained a consistently larger amount (more than 0.49 mg/g) of the alkaloids. Hot-water extracts from the leaves and buds collected during different seasons were evaluated for antimalarial activity against Plasmodium yoelii 17XL in mice. The extract of leaves collected in August demonstrated high antimalarial activity, and all mice that received the extract survived the infection. In contrast, the extract of leaves collected in December showed little activity. The extract of buds collected in December cleared parasites, but with subsequent mortality to mouse. The present results show that the amount of antimalarial agent—febrifugine and isofebrifugine mixture—in H. macrophylla var. Otaksa is both part- and season-dependent, suggesting that the choice of plant parts and their harvesting season are important factors worth considering in the pharmacological use of medicinal plants.     

地黄合剂降血糖作用的实验性研究

本文通过用四氧嘧啶复制小白鼠糖尿病模型,以血清中血糖及胰岛素水平为指标,研究了地黄合剂对高糖动物的降血糖作用。结果表明,注射四氧嘧啶前小白鼠血糖为173.47±5.23mg/100ml注射后血糖升高至419.78±22.70mg/100ml(P<0.01),差异有高度显著性。实验组服用地黄合剂后,血糖值从410.25±2739mg/100ml下降至313.51±29.39mg/100ml(P<0.05)差异有显著性。因而认为地黄合剂对于四氧嘧啶性糖尿病有显著的降血糖作用。     

温经化瘀合剂临床疗效观察与研究

目的:验证"温经化瘀舍剂"对妇女寒凝血瘀型痛经的治疗效果;方法:将符合中医诊断标准寒凝血瘀型痛经患者,随机分为2组,分别给予"温经化瘀合剂"和"痛经宁冲剂"进行治疗;结果:治疗组总有效率达95%,对照组总有效率80.5%,治疗组优于对照组,治疗组痊愈率48.3%,对照组痊愈率14.6%,治疗组明显优于对照组.实验动物无明显急性毒性反应,能减轻二甲苯引起的小鼠耳肿胀度,减少缩宫素所致大鼠扭体反应次数,和前列腺素E1所致小鼠扭体反应次数,对大鼠离体子宫有双向调节作用,证明"温经化瘀舍剂"具有镇痛、抗炎作用.     

Continuous flow synthesis of peptides using a polyacrylamide gel resin (Expansin™)

The continuous flow syntheses of endothelin 1, proendothelin 2. ATP binding site of the CDC2 kinase 3, and fragment 18-30 of an actin 4, have been performed by using a polyacrylamide gel resin Expansin? (about 0.6 mmol NH₂/g) with the glycolamidic ester handle as labile anchorage. In addition, we report here a method of air oxidation which reduces the formation of side-products related to the formation of intermolecular disulfide bridges.     

Classification of spatiotemporal hemodynamics from brain perfusion MR images using expectation-maximization estimation with finite mixture of multivariate gaussian distributions.

The ability to cluster different perfusion compartments in the brain is critical for analyzing brain perfusion. This study presents a method based on a mixture of multivariate Gaussians (MoMG) and the expectation-maximization (EM) algorithm to dissect various perfusion compartments from dynamic susceptibility contrast (DSC) MR images so that each compartment comprises pixels of similar signal-time curves. This EM-based method provides an objective way to 1) delineate an area to serve as the in-plane arterial input function (AIF) of the feeding artery for adjacent tissues to better quantify the relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT); 2) demarcate regions with abnormal perfusion derangement to facilitate diagnosis; and 3) obtain parametric maps with supplementary information, such as temporal scenarios and recirculation of contrast agent. Results from normal subjects show that perfusion cascade manifests (in order of appearance) the arteries, gray matter (GM), white matter (WM), veins and sinuses, and choroid plexus mixed with cerebrospinal fluid (CSF). The averaged rCBV, rCBF, and MTT ratios between GM and WM are in good agreement with those in the literature. Results from a patient with cerebral arteriovenous malformation (CAVM) showed distinct spatiotemporal characteristics between perfusion patterns, which allowed differentiation between pathological and nonpathological areas.     

人参银杏合剂对模拟海拔8000米低氧大鼠的保护作用研究

目的 :研究人参银杏合剂对模拟海拔 80 0 0米低氧大鼠脑组织及血液内丙二酰二甲醛 (MDA)、乳酸含量的影响 ,并探讨其机理。方法 :用成年 SD大白鼠随机分为常氧对照组 (NC组 ) ,急性低氧组 (AH组 ) ,人参银杏合剂加低氧组 (GH组 ) ;分别测定各组的脑含水量、脑组织和血液 MDA和乳酸的含量。结果 :(1)与 NC组相比 ,AH组的脑含水量明显增高 (P<0 .0 1) ,GH组脑含水量较 AH组显著降低 (P<0 .0 5 )。(2 ) AH组脑组织匀浆和血液 MDA含量明显高于 NC组 (P<0 .0 1) ,GH组的 MDA含量较 AH组显著降低 (P<0 .0 1)。 (3) AH组脑组织匀浆和血液乳酸含量明显高于 NC组 (P<0 .0 1) ,GH组的乳酸含量较 AH组显著降低 (P<0 .0 1)。结论 :人参银杏合剂对高原缺氧脑损伤具有保护作用 ,其机理与其抗氧自由基、与膜脂质过氧化作用、改善细胞能量代谢有关。