Risk assessment for quantitative responses using a mixture model

A problem that frequently occurs in biological experiments with laboratory animals is that some subjects are less susceptible to the treatment than others. A mixture model has traditionally been proposed to describe the distribution of responses in treatment groups for such experiments. Using a mixture dose-response model, we derive an upper confidence limit on additional risk, defined as the excess risk over the background risk due to an added dose. Our focus will be on experiments with continuous responses for which risk is the probability of an adverse effect defined as an event that is extremely rare in controls. The asymptotic distribution of the likelihood ratio statistic is used to obtain the upper confidence limit on additional risk. The method can also be used to derive a benchmark dose corresponding to a specified level of increased risk. The EM algorithm is utilized to find the maximum likelihood estimates of model parameters and an extension of the algorithm is proposed to derive the estimates when the model is subject to a specified level of added risk. An example is used to demonstrate the results, and it is shown that by using the mixture model a more accurate measure of added risk is obtained.     

Concerted Evolution of a Highly Repetitive DNA Family in Eptatretidae (Cyclostomata, Agnatha) Implies Specifically Differential Homogenization and Amplification Events in Their Germ Cells

In eight hagfish species, it is known that chromosome elimination occurs during early embryogenesis, and some highly repetitive DNA families, restricted to germ cells, have been isolated. One of these families, ``EEEo2,' has been isolated as DNA fragments by restriction enzyme analyses from Eptatretus okinoseanus and E. cirrhatus. In this study, EEEo2 sequences were isolated from germline DNA in E. burgeri, Paramyxine sheni, and P. atami using PCR methods. Sequence analysis revealed that these sequences are intraspecifically homogeneous, except in E. burgeri, and are interspecifically conserved with heterogeneity. The intraspecific sequence variability tends to decrease as the copy number increases. These results indicate that EEEo2 has evolved in a concerted manner. Moreover, an ancestral repeating motif consisting of triplicate subrepeats was deduced. These results suggest that EEEo2 arose as an initial amplification of this subrepeat and has evolved by saltatory replication. Phylogenetic analyses suggested the possibility that EEEo2 in E. okinoseanus and E. cirrhatus has been subjected to strong homogenizing forces for concerted evolution, whereas the force is weak in E. burgeri. In addition, EEEo2 in P. sheni and P. atami appear to have been incompletely subjected to these forces. Chromosomal in situ hybridization experiments revealed that EEEo2 sequences were located along almost their entire length of several heterochromatic chromosomes that are restricted to germ cells. These chromosomes are disposed to form a secondary association during the first meiotic metaphases, except in P. sheni. This chromosomal distribution may promote a concerted mode of sequence evolution in both nonhomologous chromosomes and homologous chromosomes and reflect the differential driving forces between species. Received: 17 April 1999 / Accepted: 10 September 1999     

A mechanistic study of thermal C-H reductive elimination from a six-coordinate d iridium complex

The thermolysis of trans-IrL₂(CO)Cl(H)(C₆H₅) (1abd; L=P(i-Pr)₃; H trans to CO) produces benzene and the Vaska-type complex IrL₂(CO)Cl. A mechanistic study of the reaction has shown that 1a reversibly loses CO at 120 °C (as evidenced by the incorporation of ¹³CO) and isomerizes to the previously unreported 1b (H trans to Cl). It was found that 1b is the complex primarily responsible for the formation of benzene upon thermolysis under CO atmosphere; direct loss of benzene from 1a was determined to be, at most, a minor pathway. Benzaldehyde was also formed as a product of thermolysis of 1a under CO atmosphere. The first-order rate constant for benzene elimination in the absence of CO was found to be 8.5 × 10⁻⁵ s⁻¹. The presence of only 5 Torr CO results in a decrease to 2.0 × 10⁻⁵ s⁻¹, but little further inhibition is observed above 5 Torr CO. Added dihydrogen (100 Torr) was found to effect a novel catalysis of benzene elimination from 1a in the absence of CO atmosphere; it is suggested that trace amounts of dihydrogen, present in solutions of 1a, are responsible for the enhanced rate of elimination in the absence of CO. The thermolysis of 1-d₆ in toluene was found to proceed without any toluene incorporation, implying that arene loss is irreversible.     

沙棘共生固氮根瘤及其内生弗兰克氏菌

用透射电镜研究了中国沙棘（Ｈｉｐｐｏｐｈａｅ ｒｈａｍｎｏｙｄｅｓ Ｌ．）根瘤的超微结构。它的侵梁细胞位于皮层中部,非侵染细胞与之间排列,富含多酚和淀粉粒。在根瘤的发育过程中,具有以下特征：（１）早期侵染细胞中具有核仁联合体;（２）由内生菌丝趋核生长而形成的核膜内陷处,有许多核孔出现;（３）在中期侵染细胞的内生菌丝和泡囊的荚膜附近,有成束的微管存在;（４）在４、５月瘤样的维管束细胞、非侵染细胞及早     

浙江天台山甜槠群落研究

以分布在浙江省天台山的甜储群落为对象,分析了群落的特征和性质。甜储群落中,甜储的优势突出,呈单优势群落。群落垂直结构复杂,可分为乔木层、灌木层、草本层,亦有一定数量的层间植物。乔木层的物种多样性指数偏低,这与特定生境所形成的单优势群落有关。各样地间的植物种类具有较高的相似性,群落内种类组成相对一致。群落内优势种群甜储、木荷的年龄结构属稳定型或增长型,它们在各样地的分布格局均呈集群分布。     

Capture–recapture analysis with a latent class model allowing for local dependence and observed heterogeneity

In epidemiology, capture–recapture models are commonly used to estimate the size of an unknown population based on several incomplete lists of individuals. The method operates under two main assumptions: independence between the lists (local independence) and homogeneity of capture probabilities of individuals. In practice, these assumptions are rarely satisfied. We introduce a multinomial latent class model that can account for both list dependence and heterogeneity. Parameter estimation is performed by maximizing the conditional likelihood function with the use of the EM algorithm. In addition, a new approach for evaluating the standard errors of the parameter estimates is discussed, which considerably reduces the computational burden associated with the evaluation of the variance of the population size estimate.     

不同临床病理特征的乳腺非特殊型浸润性癌分子亚型分析

目的:探讨不同临床病理特征的乳腺非特殊型浸润性癌的分子亚型分布特点。方法:回顾性分析309例乳腺非特殊型浸润性癌患者的临床资料,根据患者年龄、绝经情况、组织学分级和淋巴结转移情况分组,每组再根据免疫组化雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(HER-2)结果分为4种不同的分子亚型,分析各组中不同分子亚型的分布特点。结果:309例乳腺非特殊型浸润性癌中Lumina A型为137例(44.3%),Lumina B型为64例(20.7%),HER-2/neu型为63例(20.4%),basal cell-like型为45例(14.6%)。不同年龄段、绝经与否、不同组织学分级和淋巴结转移情况患者的分子亚型差异均具有统计学意义(P0.05)。结论:非特殊型浸润性癌的分子亚型以Luminal A型为主,其中异型性高,转移广泛的basal cell-like型的年龄分布呈现年轻化趋势。