两性霉素B联合氟康唑治疗艾滋病合并新型隐球菌性脑膜脑炎的疗效预测因素分析

目的:探讨两性霉素B联合氟康唑治疗艾滋病合并新型隐球菌性脑膜脑炎(简称"艾滋病合并隐脑")的疗效预测因素。方法:回顾性收集2010年1月1日-2016年12月31日58例在首都医科大学附属北京佑安医院住院治疗且接受两性霉素B联合氟康唑治疗的艾滋病合并隐脑患者的临床资料,分析其疗效预测因素及预测价值。结果:根据预后将患者分为好转组(38例)和死亡组(20例),单因素分析结果显示两组之间CD4+T细胞计数、脑脊液细胞计数比较有统计学差异(P分别为0.032,0.001)。Logistic回归多因素分析结果显示脑脊液细胞计数是两性霉素B联合氟康唑治疗艾滋病合并隐脑的疗效预测因素(P=0.023),Exp(B)=1.01,95%置信区间为1.00-1.03。ROC曲线对脑脊液细胞计数的预测价值进行分析,结果显示曲线下面积为0.889,预测阈值为261个/mm3,对应的敏感性=0.684,特异性=1.0。结论:脑脊液细胞计数是两性霉素B联合氟康唑治疗艾滋病合并新型隐球菌性脑膜脑炎良好的疗效预测参考因素。     

畸变汉字语义启动的ERP 效应

运用事件相关电位技术,采用词汇判断作业,考察字形畸变和语境对低频汉字识别的影响。行为结果显示,启动效应的主效应显著,启动条件和字形畸变的交互作用显著。脑电结果显示,150-300ms窗口,字形畸变的主效应显著。300-450ms时间窗口,启动效应的主效应显著。靶字畸变和靶字清晰条件下,均得到了语义相关和语义无关条件的显著差异。得出结论,汉字通透性是影响汉字加工的重要因素。RP与视知觉分析有关,N400和语义的自动加工有关。     

高功能自闭症儿童面孔加工的ERP研究

目的：探讨7-9岁高功能自闭症儿童面孔加工时事件相关电位（Electrical event-relateds,ERP）的变化及其意义。方法：选择7-9岁自闭症儿童（实验组）与普通儿童（对照组）各15名,以中国人中性面孔及常见物件为刺激材料,记录和比较两类儿童在面孔刺激下的脑电成分。结果：剔除无效数据后,有效被试：实验组12人、对照组14人,两组年龄和性别组成无显著性差异（P〉0.05）。而,自闭症组按键反应时间、面孔反应时间显著长于对照组（按键反应F=9.26,P〈0.05;面孔反应t=5.32,P〈0.05）。在面孔刺激因素下,自闭症组平均波峰明显小于对照组（t=4.62,P〈0.05）。在物件刺激因素下,两组平均波峰无显著差异（t=0.21,P〉0.05）。而两组的潜伏期组别主效应不显著（F=1.63,P〉0.05）。结论：自闭症儿童面孔结构编码过程异常,对面孔的关注度比普通儿童低。本文证实了自闭症儿童知觉/认知缺陷的存在,为更进一步研究提供了理论依据。     

鞘内注射两性霉素 B 治疗隐球菌脑膜炎的 META 分析

目的 评价鞘内注射两性霉素B用于隐球菌脑膜炎患者治疗的有效性和安全性.方法 采用循证医学系统评价方法,检索Cochran图书馆注册临床对照试验数据库2012年第1期,PubMed、Ovid、Springer、外文生物医学期刊全文数据库,中国生物医学文献数据库、中文生物医学期刊文献数据库、中国知网、万方数据库、维普中文期刊数据库、中华医学会数字期刊数据库.文献检索时间从建库至2012年2月,纳入探讨鞘内注射两性霉素B治疗隐球菌脑膜炎的临床对照试验,并逐个进行质量评价和资料提取,运用RevMan 5.1.6软件进行统计分析.结果 共检出89篇文献,最终纳入6篇,涉及临床对照试验6项,纳入患者175例.Meta分析提示:鞘内注射给药组较对照组有效率高[OR =4.59,95％CI (2.19,9.64),P＜0.0001].可使脑膜刺激征持续时间平均缩短8.56 d(95％CI-11.74～-5.38,P＜0.000 01),但相应不良反应较多.结论 鞘内注射两性霉素B治疗隐球菌脑膜炎可以提高疗效,但较多的不良反应限制了其广泛应用,能否作为首选治疗手段有待于更大样本的高质量临床对照研究证实.     

框架描述对医疗资源分配公平感的影响

目的:初步探讨医疗资源分配方案设置及框架描述对人们感知公平的影响。方法:以120名大学生为研究对象,自编情境问题,分别依据Miller定义的平等、需求、责任及付出原则制定医疗资源分配分配方案,采用正、负及平衡框架进行描述。被试被随机分为三组,每组被试需要评估同一框架下,四种分配方案的公平性。结果:结果显示,分配方案主效应显著(F=7.27,P0.01),按照需求原则分配医疗资源,被试感到不公平(t=-2.04,P0.01),而以付出原则分配,被试感到公平(t=2.87,P0.01),以按责与平等原则分配,被试没有显著的公平或不公平感(P.05)。框架描述主效应显著(F=6.08,P.05),以正框架描述,公平感评估显著高于平衡框架与负框架。框架描述与分配原则交互作用显著(F=3.93,P0.01),在正框架下,分配方案效应不显著(F=1.29,P0.05),在负框架与平衡框架下,分配方案效应显著(F平衡=9.23,P0.01;F负=4.69,P0.01)。依据按需与按责原则制定的分配方案受到框架描述影响(F按需=12.88,P0.01;F按责=4.12,P0.05),而依据平等原则、付出原则制定的分配方案不会受到框架描述的影响。结论:分配原则及框架描述均能显著影响人们对医疗资源分配的公平感知。     

IGF-1基因对长白×蓝塘猪资源群生产性能的遗传效应分析

利用F2代设计建立了由216头F2代个体组成的长白×蓝塘猪资源群,应用PCR-RFLP方法检测F2代个体IGF-1基因的多态性;通过固定模型方法估计了IGF-1不同基因型的最小二乘均值,同时采用混合模型方法分析不同性状IGF-1基因型的遗传效应,并由此计算IGF-1基因的加性和显性效应.固定模型和混合模型方法的分析结果都表明,IGF-1不同基因型对猪断奶后日增重有显著影响,AA型的遗传效应显著比AB型高20.58 g(P=0.0347),IGF-1基因对该性状的加性和显性效应分别为1.78 g和-18.81 g;对胴体组成性状也有影响,AA型和AB型对骨率的遗传效应分别极显著低于BB型5.22%(P= 0.0008)和5.19%(P=0.0007),IGF-1基因对该性状的加性和显性效应分别为-2.61%和-2.58%;AA型胴体瘦肉量的遗传效应显著比AB型少0.45 kg(P=0.0264),IGF-1基因对该性状的加性和显效应分别为0.16 kg和0.61 kg;AA型和AB型皮脂率的遗传效应比BB型分别高8.81%(P=0.0206)和7.64%(P=0.0431),对该性状的加性和显性效应分别为4.41%和3.24%.因此,IGF-1基因的遗传效应分析说明该基因对断奶后日增重、骨率、胴体瘦肉量和皮脂率等4个性状有显著的遗传影响;而加性和显性效应估计值的大小表明,IGF-1基因的遗传效应只有在皮脂率性状上加性效应相对显性效应比较高,可以作为主基因对该性状进行有效选择.     

高功能自闭症儿童面孔加工的ERP研究

目的:探讨7-9岁高功能自闭症儿童面孔加工时事件相关电位(Electrical event-relateds,ERP)的变化及其意义。方法:选择7-9岁自闭症儿童(实验组)与普通儿童(对照组)各15名,以中国人中性面孔及常见物件为刺激材料,记录和比较两类儿童在面孔刺激下的脑电成分。结果:剔除无效数据后,有效被试:实验组12人、对照组14人,两组年龄和性别组成无显著性差异(P0.05)。而,自闭症组按键反应时间、面孔反应时间显著长于对照组(按键反应F=9.26,P0.05;面孔反应t=5.32,P0.05)。在面孔刺激因素下,自闭症组平均波峰明显小于对照组(t=4.62,P0.05)。在物件刺激因素下,两组平均波峰无显著差异(t=0.21,P0.05)。而两组的潜伏期组别主效应不显著(F=1.63,P0.05)。结论:自闭症儿童面孔结构编码过程异常,对面孔的关注度比普通儿童低。本文证实了自闭症儿童知觉/认知缺陷的存在,为更进一步研究提供了理论依据。     

大隐静脉曲张不同手术治疗方法比较

目的：探讨大隐静脉高位结扎加腔内激光治疗大隐静脉曲张的临床意义。方法：150例大隐静脉曲张患者分为A、B两组,其中A组70例,采用大隐静脉高位结扎加剥脱术治疗,B组80例,采用高位结扎加腔内激光治疗,比较两组在手术过程、术后疼痛、术后恢复及并发症发生率等方面的差别。结果：B组患者切口个数、手术时间、术中出血量、止痛药使用百分比和平均住院时间均少于A组（P〈0.01或0.05）,而两组间24hNRE评分、首次下床时间和并发症发生率比较差异无显著性（P〉0.05）。结论：大隐静脉高位结扎加腔内激光术的临床疗效优于传统的高位结扎加剥脱术,且患者损伤小、恢复快、疼痛轻,值得临床推广。     

视觉中文词汇识别的整体优先效应和词内核证原则:来自ERPs的证据

目的:以视觉的汉语真假双字词为材料,用词汇判断任务考察词汇加工过程与表征的关系.方法:记录了16名被试者的行为数据和ERPs数据.结果:①真词的反应时间显著短于假词.②真词和假词均诱发了明显的N1、P2、N2、P3、N400、P600成分.③假词的N2波幅显著大于真词;假词的P3波幅、潜伏期显著小于真词.④假词的N400波幅显著小于真词,假词减真词的差异波波幅表现出显著的半球效应,左半球大于右半球.⑤假词的P600潜伏期显著长于真词.结论:N2、P3成分分别反映了词汇认知加工早期对心理表征的匹配和评价、注意的分配;N400、P600成分分别反映了词汇认知加工晚期词素之间的语义冲突和词素之间语义、句法等关系的整合.研究结果证明了中文双字词识别的整体优先效应和词内核证原则,支持了词汇后加工的观点,为假词反应时长于真词提供了电生理证据.     

维-汉双语语义认知的事件相关电位特征研究

为了研究维-汉双语者维吾尔语和汉语双语语义认知特点,本实验使用事件相关电位(event-related potentials,ERP)技术,以"图片-词语"语义启动范式研究了维-汉双语者的维吾尔语和汉语N400波的特点及差异波脑电地形图分布特点。结果显示:双语均有明显的语义启动效应,双语者两种语言的N400波的平均波幅没有语言间的差异,仅在汉语中存在语言与电极位置的交互作用,F3、F4、PZ三点波幅比其余电极波幅显著偏负;差异波脑电地形图显示,维吾尔语激活了几乎所有脑区(除了枕叶激活较弱),汉语的激活较维吾尔语弱,但也有大部分脑区激活,左右额叶和顶叶的激活明显。以上结果表明,维-汉双语者的两种语言均对语义启动敏感,额叶、顶叶参与两种语言间的转换,不熟练的维-汉晚双语者的双语语义加工过程均为大脑两半球共同协作的结果,没有明显的偏侧化。     

Implicit associations with social status: the effects of relationship involvement

The study tested the proposition that relationship involvement influences the implicit responses of women to high- and low-status professions. It was hypothesized that when a high-involvement context was primed, women would have more positive implicit associations with high-status occupations than when a low-involvement context was primed. In contrast, when a high-involvement context was primed, women would have more negative associations with low-status occupations than when a low-involvement context was primed. To test the hypothesis, 123 female participants received a high or low relationship involvement prime. Then the participants completed a single category implicit associations test designed to measure the participants' associations with either high- or low-status occupations. As predicted, the relationship involvement prime influenced the positivity of associations made with high- and low-status occupations. The study pointed to the possibility that persons possess evolutionary-based implicit associations.     

弹性支撑状态下人—板系统的优化

为了有效地控制人－板系统,我们在本文中提出了基于人－板方程的隐函数泛函极值问题,并给出其数值解法,考虑到实际应用,我们把多项式函数看作挖优化控制函数,通过这种方法,隐这泛函优化问题就转化为用Mount Garlo方法解的数学规划问题,最终,我们获得了一个标准的压力板控制函数。     

Leap-dynamics: efficient sampling of conformational space of proteins and peptides in solution

A molecular simulation scheme, called Leap-dynamics, that provides efficient sampling of protein conformational space in solution is presented. The scheme is a combined approach using a fast sampling method, imposing conformational 'leaps' to force the system over energy barriers, and molecular dynamics (MD) for refinement. The presence of solvent is approximated by a potential of mean force depending on the solvent accessible surface area. The method has been successfully applied to N-acetyl-L-alanine-N-methylamide (alanine dipeptide), sampling experimentally observed conformations inaccessible to MD alone under the chosen conditions. The method predicts correctly the increased partial flexibility of the mutant Y35G compared to native bovine pancreatic trypsin inhibitor. In particular, the improvement over MD consists of the detection of conformational flexibility that corresponds closely to slow motions identified by nuclear magnetic resonance techniques.     

A Photometric Method for Determining the Growth Rate of Yeast (Saccharomyces cereviciae)

There have been several investigations into students' conceptions of animal classification. Previous research has generally failed to study the criteria of classification used by the students. This study shows that students prefer to classify creatures along the criteria of habitat and locomotion (method of movement). They continue using these criteria even after learning the categories of biological taxonomy. The results lead to the assumption of an implicit theory of natural kinship of animals. The educational consequences for biology instruction, especially with regard to biological taxonomy, biodiversity, and evolution, are discussed.     

An efficient protocol for obtaining accurate hydration free energies using quantum chemistry and reweighting from molecular dynamics simulations

The non-Boltzmann Bennett (NBB) free energy estimator method is applied to 21 molecules from the blind subset of the SAMPL4 challenge. When NBB is applied with the SMD implicit solvent model, and the OLYP/DZP level of quantum chemistry, highly accurate hydration free energy calculations are obtained with respect to experiment (RMSD = 0.89 kcal·mol⁻¹). Other quantum chemical methods are also tested, and the effects of solvent model, density functional, basis set are explored in this benchmarking study, providing a framework for improvements in calculating hydration free energies. We provide a practical guide for using the best QM-NBB protocols that are consistently more accurate than either pure QM or pure MM alone. In situations where high accuracy hydration free energy predictions are needed, the QM-NBB method with SMD implicit solvent should be the first choice of quantum chemists.     

Motor-maps, navigation and implicit space representation in the hippocampus

Multiple sensory-motor maps located in the brainstem and the cortex are involved in spatial orientation. Guiding movements of eyes, head, neck and arms they provide an approximately linear relation between target distance and motor response. This involves especially the superior colliculus in the brainstem and the parietal cortex. There, the natural frame of reference follows from the retinal representation of the environment. A model of navigation is presented that is based on the modulation of activity in those sensory-motor maps. The actual mechanism chosen was gain-field modulation, a process of multimodal integration that has been demonstrated in the parietal cortex and superior colliculus, and was implemented as attraction to visual cues (colour). Dependent on the metric of the sensory-motor map, the relative attraction to these cues implemented as gain field modulation and their position define a fixed point attractor on the plane for locomotive behaviour. The actual implementation used Kohonen-networks in a variant of reinforcement learning that are well suited to generate such topographically organized sensory-motor maps with roughly linear visuo-motor response characteristics. In the following, it was investigated how such an implicit coding of target positions by gain-field parameters might be represented in the hippocampus formation and under what conditions a direction-invariant space representation can arise from such retinotopic representations of multiple cues. Information about the orientation in the plane—as could be provided by head direction cells—appeared to be necessary for unambiguous space representation in our model in agreement with physiological experiments. With this information, Gauss-shaped “place-cells” could be generated, however, the representation of the spatial environment was repetitive and clustered and single cells were always tuned to the gain-field parameters as well     

Dynamics and cooperativity of Trp-cage folding

In this study, multiple independent molecular dynamics (MD) simulations on Trp-cage folding were performed at 300, 325 and 375 K using generalized Born (GB) implicit solvent model. The orientational movement of the side-chain of Trp6 to form a hydrophobic core with 3₁₀-helix was observed. The breaking/formation of a salt bridge between Asp9 and Arg16 was proposed to be the prerequisite for Trp-cage folding/refolding. Our results demonstrate that the cooperation between the salt bridge and the Trp6 orientation leads to a stable tertiary structure of Trp-cage. Analyses on backbone concerted motions at different temperatures indicate that interactions between Trp6 and 3₁₀-helix & Pro18 and between Pro12 and Pro17 & Pro18 are weakened at 375 K but strengthened at lower temperatures, suggesting that they could be the potential driving force of hydrophobic collapse.     

Topology and thermodynamics of gaseous ligands diffusion paths in human neuroglobin

The physiological role of recently discovered human neuroglobin (Ngb) is still unknown. Sound hypothesis says that it protects brain during hypoxia. In this paper the advanced potential of mean force by implicit ligand sampling (PMF/ILS) method is used to study the free energy landscape of Ngb for O(2), NO and CO ligands. The multiple diffusion paths are discovered and four ligand binding cavities are determined. The data show that certain regions are easily accessible by O(2) and NO but are protected from CO. Free energy landscapes provide realistic data for stochastic models of ligand diffusion in proteins.     

Causal inference in biomolecular pathways using a Bayesian network approach and an Implicit method

We introduce here the concept of Implicit networks which provide, like Bayesian networks, a graphical modelling framework that encodes the joint probability distribution for a set of random variables within a directed acyclic graph. We show that Implicit networks, when used in conjunction with appropriate statistical techniques, are very attractive for their ability to understand and analyze biological data. Particularly, we consider here the use of Implicit networks for causal inference in biomolecular pathways. In such pathways, an Implicit network encodes dependencies among variables (proteins, genes), can be trained to learn causal relationships (regulation, interaction) between them and then used to predict the biological response given the status of some key proteins or genes in the network. We show that Implicit networks offer efficient methodologies for learning from observations without prior knowledge and thus provide a good alternative to classical inference in Bayesian networks when priors are missing. We illustrate our approach by an application to simulated data for a simplified signal transduction pathway of the epidermal growth factor receptor (EGFR) protein.