Principal stratification designs to estimate input data missing due to death

We consider studies of cohorts of individuals after a critical event, such as an injury, with the following characteristics. First, the studies are designed to measure "input" variables, which describe the period before the critical event, and to characterize the distribution of the input variables in the cohort. Second, the studies are designed to measure "output" variables, primarily mortality after the critical event, and to characterize the predictive (conditional) distribution of mortality given the input variables in the cohort. Such studies often possess the complication that the input data are missing for those who die shortly after the critical event because the data collection takes place after the event. Standard methods of dealing with the missing inputs, such as imputation or weighting methods based on an assumption of ignorable missingness, are known to be generally invalid when the missingness of inputs is nonignorable, that is, when the distribution of the inputs is different between those who die and those who live. To address this issue, we propose a novel design that obtains and uses information on an additional key variable-a treatment or externally controlled variable, which if set at its "effective" level, could have prevented the death of those who died. We show that the new design can be used to draw valid inferences for the marginal distribution of inputs in the entire cohort, and for the conditional distribution of mortality given the inputs, also in the entire cohort, even under nonignorable missingness. The crucial framework that we use is principal stratification based on the potential outcomes, here mortality under both levels of treatment. We also show using illustrative preliminary injury data that our approach can reveal results that are more reasonable than the results of standard methods, in relatively dramatic ways. Thus, our approach suggests that the routine collection of data on variables that could be used as possible treatments in such studies of inputs and mortality should become common.     

Focus: Rare Disease: Behçet’s Disease and Pregnancy: A Retrospective Case-control Study

Background: Behçet’s disease (BD) is a rare chronic multisystemic vasculitis of unknown etiology. It is usually diagnosed between the 2^nd and 4^th decades of life, so its association with pregnancy is not unusual. This study aims to characterize the evolution of pregnancy in a group of pregnant women with BD and the impact of this pathology in embryo-fetal morbidity. Methods: A retrospective case-control study included 49 pregnancies in women suffering from BD, followed in our institution. Pregnancy outcomes were compared with a control group of healthy pregnant women. Two controls per case were randomly selected. Statistical analysis used SPSS 25.0, and a p-value of 0.05 was considered statistically significant. Results: Forty-nine pregnancies were included in 27 patients with BD. BD exacerbation occurred in 32.6% of the pregnancies. There were no significant statistical differences between the two groups regarding the rate of preterm delivery, gestational diabetes, and preeclampsia (p>0.05). In the BD group, we found a higher rate of miscarriage (24.5%) and fetal growth restriction (FGR, 13.3%, p<0.05). In the study group, 13 (32.5%) of the pregnant patients did not need treatment. The cesarean rate was significantly higher in the BD group (43.2% vs 20.4% in the control group, p<0.05), and there were no significant differences in median gestational age at the time of delivery (p>0.05). The birth weight of newborns did not differ significantly between the groups. There was no association of BD with maternal morbidity and neonatal complications. Conclusion: In this study, the majority of pregnant with BD did not present clinical exacerbation of their pathology. However, BD may have an adverse influence on pregnancy outcomes. FGR and miscarriage rates were significantly higher in the study group.     

孕期规律运动与妊娠期糖代谢异常关系的研究

目的探讨不同方式干预孕期运动与妊娠期糖代谢异常的关系及对妊娠结局的影响。方法将300例孕14周单胎孕妇按阶段分为两组各150例,干预组对孕妇进行评估,建立孕妇档案,孕期通过个体化运动干预,给予孕妇个体化、具体的适度运动处方及给予督导规律运动;对照组采用传统的产前检查及常规护理。观察比较两组孕妇血糖变化、体重增长及妊娠结局。结果干预组空腹,餐后2h血糖值,妊娠末期体重,发生糖代谢异常,早产儿、新生儿窒息、巨大儿以及剖宫产率均低于对照组,差异有统计学意义(P0.05)。结论通过个体化护理对孕期运动进行干预,有效控制血糖值,降低母婴并发症的发生。     

Plasmodium falciparum: Assessment of parasite-infected red blood cell binding to placental chondroitin proteoglycan and bovine tracheal chondroitin sulfate A

In pregnant women infected with Plasmodium falciparum, the infected red blood cells (IRBCs) sequester in placenta by binding to the chondroitin 4-sulfate (C4S) chains of low sulfated chondroitin sulfate proteoglycan (CSPG). Placental CSPG, the natural receptor for IRBC adherence in the placenta, is the ideal molecule for studying structural interactions in IRBC adhesion to C4S, adhesion inhibitory antibody responses, and identification of parasite adhesive protein(s). However, because of difficulty involved in purifying placental CSPG, the commercially available bovine tracheal chondroitin sulfate A (bCSA), a copolymer having structural features of both C4S and C6S, has been widely used. To determine the validity of bCSA for C4S-IRBC interaction studies, we comparatively evaluated the characteristics of IRBC binding to placental CSPG and bCSA using three commonly used parasite strains. The results indicate that, in all three parasites studied, the characteristics of IRBC binding to placental CSPG and bCSA are qualitatively similar, but the binding capacity with respect to both the number of IRBCs bound per unit area of coated surface and binding strength is significantly higher for CSPG than bCSA regardless of whether parasites were selected on CSPG or bCSA. These results demonstrate that placental CSPG is best suited for studying interactions between parasite adhesive protein(s) and C4S, and have implications in understanding C4S-IRBC structural interactions.     

Transitions of interaction outcomes in a uni-directional consumer-resource system

A uni-directional consumer-resource system of two species is analyzed. Our aim is to understand the mechanisms that determine how the interaction outcomes depend on the context of the interaction; that is, on the model parameters. The dynamic behavior of the model is described and, in particular, it is demonstrated that no periodic orbits exist. Then the parameter (factor) space is shown to be divided into four regions, which correspond to the four forms of interaction outcomes; i.e. mutualism, commensalism, parasitism and amensalism. It is shown that the interaction outcomes of the system transition smoothly among these four forms when the parameters of the system are varied continuously. Varying each parameter individually or varying pairs of parameters can also lead to smooth transitions between the interaction outcomes. The analysis leads to both conditions for which each species achieves its maximal density, and situations in which periodic oscillations of the interaction outcomes emerge.     

西安地区妊娠妇女不同孕期血清铁蛋白、叶酸和维生素B12的水平及临床意义

目的：探讨西安地区妊娠妇女不同孕期血清铁蛋白、叶酸和维生素B12的水平及临床意义。方法：收集2012 年8 月至2013年1 月在本院进行产前检查的750 例妊娠期妇女及86 例健康非妊娠妇女的血清标本。采用全自动化学发光免疫分析法测定其血清铁蛋白、叶酸和维生素B12的含量。结果：孕妇血清铁蛋白、叶酸和维生素B12的含量随孕期的增长而逐渐降低。早、中、晚孕期妇女叶酸的含量较对照组相比,并无显著差异（P〉0.05）。中、晚孕期妇女血清铁蛋白和维生素B12含量均显著低于对照组,差异有统计学意义（P〈0.05）。结论：西安地区中、晚孕期的孕妇体内存在铁蛋白和维生素B12缺乏,但并不缺乏叶酸。在重视补充叶酸的同时,也应该重视对铁和维生素B12的补充。     

硒对铅暴露致神经损伤的拮抗作用研究

目的:研究铅暴露诱导的神经毒性损伤作用,明确铅暴露引发神经毒性损伤的部分机制以及硒的保护作用。方法:通过哺乳期染铅及补充硒建立铅暴露动物模型;通过TUNEL实验确定铅暴露引发的神经损伤;通过Western blot实验检测Bax、Bcl-2、Caspase-3水平确定铅暴露对凋亡途径的启动;并确证补硒在铅神经毒性作用下对机体的保护作用。结果:1.哺乳期铅暴露能够引起仔鼠海马神经细胞凋亡的发生;2.铅暴露能够诱导Bax/Bcl-2水平改变,激活Caspase-3。3.同时给予硒干预后,机体抗铅神经毒性能力显著增加。结论:1.铅暴露能够诱导海马部位神经毒性损伤,损伤可能通过启动凋亡途径而发生,2.补硒能够通过拮抗凋亡发生从而拮抗铅的神经毒性,产生保护作用。