Constrained empirical-likelihood confidence regions in nonignorable covariate-missing data problems

Missing covariates in regression analysis are a pervasive problem in medical, social, and economic researches. We study empirical-likelihood confidence regions for unconstrained and constrained regression parameters in a nonignorable covariate-missing data problem. For an assumed conditional mean regression model, we assume that some covariates are fully observed but other covariates are missing for some subjects. By exploitation of a probability model of missingness and a working conditional score model from a semiparametric perspective, we build a system of unbiased estimating equations, where the number of equations exceeds the number of unknown parameters. Based on the proposed estimating equations, we introduce unconstrained and constrained empirical-likelihood ratio statistics to construct empirical-likelihood confidence regions for the underlying regression parameters without and with constraints. We establish the asymptotic distributions of the proposed empirical-likelihood ratio statistics. Simulation results show that the proposed empirical-likelihood methods have a better finite-sample performance than other competitors in terms of coverage probability and interval length. Finally, we apply the proposed empirical-likelihood methods to the analysis of a data set from the US National Health and Nutrition Examination Survey.     

Semi-perfusion cultures of suspension MDCK cells enable high cell concentrations and efficient influenza A virus production

Control and prevention of rapid influenza spread among humans depend on the availability of efficient and safe seasonal and pandemic vaccines, made primarily from inactivated influenza virus particles. Current influenza virus production processes rely heavily on embryonated chicken eggs or on cell culture as substrate for virus propagation. Today’s efforts towards process intensification in animal cell culture could innovate viral vaccine manufacturing using high-yield suspension cells in high cell density perfusion processes. In this work, we present a MDCK cell line adapted to grow as single cell suspension with a doubling time of less than 20 h, achieving cell concentrations over 1 × 10⁷ cells/mL in batch mode. Influenza A virus titer obtained in batch infections were 3.6 log₁₀(HAU/100 µL) for total- and 10⁹ virions/mL for infectious virus particles (TCID₅₀), respectively. In semi-perfusion mode concentrations up to 6 × 10⁷ cells/mL, accumulated virus titer of 4.5 log₁₀(HAU/100 µL) and infectious titer of almost 10¹⁰ virions/mL (TCID₅₀) were possible. This exceeds results reported previously for cell culture-based influenza virus propagation by far and suggests perfusion cultures as the preferred method in viral vaccine manufacturing.     

Echocardiographic assessment at rest and during stress in patients with intermittent claudication

Objective. Skeletal muscle perfusion during walking relies on complex interactions between cardiac activity and vascular control mechanisms, why cardiac dysfunction may contribute to intermittent claudication (IC) symptoms. The study aims were to describe cardiac function at rest and during stress in consecutive IC patients, to explore the relations between cardiac function parameters and treadmill performance, and to test the hypothesis that clinically silent myocardial ischemia during stress may contribute to IC limb symptomatology. Design. Patients with mild to severe IC (n?=?111, mean age 67 y, 52% females, mean treadmill distance 195 m) underwent standard echocardiography, dobutamine stress echocardiography (SE) and treadmill testing. The patient cohort was separated in two groups based on treadmill performance (HIGH and LOW performance). Results. Ten patients (9%) had regional wall motion abnormalities of which three had left ventricular ejection fraction <50% at standard echocardiography. A majority had lower than expected systolic- and diastolic ventricular volumes. LOW performers had smaller diastolic left ventricular volumes and lower global peak systolic velocity during dobutamine stress. No patient demonstrated significant cardiac dysfunction during dobutamine provocation that was not also evident at standard echocardiography. Conclusions. Most IC patients were without signs of ischemic heart disease or cardiac failure. The majority had small left ventricular volumes. The hypothesis that clinically silent myocardial ischemia impairing left ventricular function during stress may contribute to IC limb symptomatology was not supported.

Trial registration: ClinicalTrials.gov identifier: NCT01219842.     

甲状腺功能减退与子宫内膜癌的相关性分析

 目的 探讨甲状腺功能减退与子宫内膜癌（EC）的关系及EC患者癌组织分化程度和雌激素受体（ER）、孕激素受体（PR）的表达与甲状腺功能之间的关系。方法 选取2015年1月—2018年7月我院收治的EC患者113例，同时随机选取年龄与EC组相匹配的此段时间内我院健康体检的妇女156例作为对照组，检测血清促甲状腺激素（TSH）、甲状腺激素（FT4）。比较两组间甲状腺功能减退的患病率，并利用免疫组织化学法测定EC患者手术切除标本的癌组织中ER、PR的表达，分析EC患者癌组织分化程度及癌组织中ER、PR的表达与甲状腺功能之间的相关性。结果 EC组甲状腺功能减退的患病率较对照组高（P<0.000）。低分化EC患者的TSH高于中分化EC患者（P=0.025）。EC手术切除标本的癌组织中ER、PR阳性与阴性患者的TSH、FT4差异无统计学意义（P>0.05）。结论 甲状腺功能减退与EC具有相关性。     

Liguzinediol对阿霉素诱导的慢性心衰大鼠心功能的影响

目的 通过阿霉素（Dox）复制大鼠慢性心力衰竭（CHF）模型，观察Liguzinediol对CHF大鼠心功能的影响。方法 通过血流动力学观察Liguzinediol对Dox（腹腔注射，2 mg/kg）诱导的CHF大鼠左心室内压最大上升/下降速率(±dp/dt_max)、左心室内压(LVSP)、动脉收缩压(ASP)、动脉舒张压(ADP)和心率(HR)的变化；观察Liguzinediol对血清一氧化氮（NO）、一氧化氮合成酶（NOS）、超氧化物歧化酶（SOD）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）以及血浆中丙二醛（MDA）的影响。结果 Liguzinediol能增加LVSP、+dp/dt_max、ASP、ADP、AP、HR，降低-dp/dt_max(P<0.05~0.01)；降低NO、iNOS以及MDA的浓度，同时增强了SOD的活性(P<0.05~0.01)；抑制IL-6和TNF-α的生成(P<0.05~0.01)。结论 Liguzinediol可明显改善Dox诱导的CHF大鼠血流动力学指标，减少模型大鼠炎症因子的释放以及抑制氧自由基的生成。      

氯吡格雷联合前列地尔对急性脑梗死患者疗效、血流动力学及凝血功能水平的影响

目的：探讨氯吡格雷联合前列地尔对急性脑梗死患者的疗效及对患者血流动力学、凝血功能水平的影响。方法：选取2015年6月-2017年6月某院收治的急性脑梗死患者90例，按照随机数字表法分为对照组与观察组，每组各45例。对照组患者在常规治疗基础上给予氯吡格雷治疗，观察组患者在对照组治疗基础上给予前列地尔治疗。比较2组患者临床治疗效果；检测治疗前、后2组患者血浆黏度（PV）、血浆纤维蛋白原（FIB）、血小板聚集率（PAR）、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、D-二聚体（D-D）水平。结果：对照组患者治疗后临床总有效率为64.44%；观察组患者治疗后临床总有效率为86.67%。两者比较差异有显著性（P<0.05）。治疗前，2组患者血流动力学指标PV、FIB、PAR及凝血功能指标PT、APTT、D-D水平比较，差异无显著性（P>0.05）。治疗后，对照组及观察组患者PV、FIB、PAR及D-D水平均明显低于本组治疗前，PT、APTT水平均明显高于本组治疗前；观察组患者治疗后PV、FIB、PAR及D-D水平均明显低于对照组治疗后，PT、APTT水平均明显高于对照组治疗后，差异均有显著性（P<0.05）。结论：氯吡格雷联合前列地尔对急性脑梗死患者具有较好的临床疗效，可通过抑制血小板活性及降低血液黏度，起到改善患者血流动力学水平，调节患者凝血功能的作用。     

唤醒状态联合中央沟定位切除脑运动区胶质瘤对患者运动功能保护作用探讨

目的 探究唤醒状态联合中央沟定位对脑运动区胶质瘤切除术患者运动功能的保护作用。方法 选取本院2016年12月—2017年10月期间收治的脑运动区胶质瘤患者70例。所有患者均行唤醒状态联合中央沟定位运动区胶质瘤切除术。观察患者术后复发情况及术后第6、12个月的Kamofsky评分,并记录并发症发生情况。结果 所有患者均成功完成手术,未出现术中大出血、死亡等严重并发症。70例患者中,有40例全切除,26例次全切除,4例大部分切除。术后,感觉减退者有6例,肌力下降者有5例,肌力下降伴感觉减退者有2例,并发症发生率为18.57%(13/70)。6个月后,应用增强MRI显示有4例患者肿瘤灶周围明显强化,进一步使用正电子发射断层显像发现有1例患者肿瘤复发。术前及术后第6、12个月的Kamofsky评分分别为(89.62±11.88)及(80.73±9.91)、(65.82±12.36)。结论 唤醒状态联合中央沟定位能最大限度切除脑运动区胶质瘤,提高患者预后效果。