Population inference with mortality and attrition in longitudinal studies on aging: a two-stage multiple imputation method

A major challenge for inference regarding aging-related change in longitudinal studies is that of study attrition and population mortality. Inferences in longitudinal studies can account for attrition and mortality-related change as distinct processes, but this is made difficult when follow-up of all individuals (i.e., age at death) is not complete. This is a common problem because most longitudinal studies of aging either have incomplete follow-up or are still collecting data on subsequent outcomes, including time of death. A statistical approach is suggested for including time-to-death as a predictor in models with incomplete follow-up using a two-stage multiple-imputation procedure. An empirical example using data from the OCTO-Twin study is presented that shows the utility of his procedure for making inferences conditional on mortality when mortality data are incomplete.     

Primary ovarian carcinoid heart disease curatively treated with a two-stage procedure

Primary ovarian carcinoid disease with cardiac involvement is a very rare syndrome, which requires interdisciplinary management. We report on a patient with primary ovarian carcinoid tumor with severe tricuspid valve insufficiency who was curatively treated after successful tumor resection and tricuspid valve replacement.     

Two novel antigens associated with group B streptococci identified by a rapid two-stage radioimmunoassay

A two-stage radioimmunoassay (RIA) has been developed that identifies type-specific antigens on the surfaces of group B streptococci. In addition to detecting the type-specific carbohydrate antigens Ia, Ib, II, and III, the RIA identified four unique antigens reactive with the Centers for Disease Control's c-protein typing antiserum. Analysis of hot-acid extracts by immunoelectrophoresis confirmed that two of these reactivities corresponded to the reported alpha and beta antigens of the c-protein marker. In addition, the identification of two heretofore unidentified antigens, gamma and delta, by the two-stage RIA is detailed in this report. The assay uses intact bacteria and does not require hot-acid extraction, a procedure thus enabling detection of acid-labile antigens in their native unmodified form. The semiquantitative RIA requires less typing reagent than does precipitin testing and is more objective, reproducible, and rapid. The assay described here could be applied to the detection of any cell surface antigen for which a monospecific antiserum is available.     

Esophageal carcinoma with humoral hypercalcemia and leukocytosis successfully treated by a two-stage operation: report of a case

We herein report a patient demonstrating esophageal carcinoma with humoral hypercalcemia and leukocytosis. A 56-year-old Japanese man complained of a 2-month history of pyrexia. The radiological and endoscopic findings showed advanced esophageal carcinoma with a giant intraabdominal lymph node metastasis. Preoperative examination suggested that the tumor, consisting of squamous cell carcinoma, produced both parathyroid hormone-related protein and granulocyte colony-stimulating factor. We first performed an extirpation of the giant metastatic tumor to reduce the degree of humoral secretion and to improve his general condition. Thereafter, the hypercalcemia, leukocytosis, and other associated symptoms all improved. As a result, we were then able to safely perform an esophagectomy 2 months later. The patient has been doing well during the 10-month follow-up period, and is presently alive more than 1 year since hypercalcemia and leukocytosis were first observed. This is the first report of esophageal carcinoma with humoral hypercalcemia and leukocytosis that was successfully treated by an operation.     

冠心病患者生存质量评定量表构建

目的 探讨评价冠心病患生存质量评定量表，并进行效度及信度分析，为进一步广泛应用提供根据。资料和方法量表设计为四部分30项分测验，分别为生理、心理／精神状态、社会适应能力和对冠心病防治知识认知水平。信度(Reliability)评估采用重测信度法，计算总分值及各分值的相关系数r来评估重测信度。效度(Validity)分析采用因子分析法评价结构效度及内容效度。同时对已被广泛应用的普适性SF-36量表进行因子分析及二表比较，以便对量表进一步评价。结果 所设计量表总分值和各分值重测信度r在0．7～0．9，达到0．7标准，可认为量表信度较好。因子分析显示三个公因子所包含的条目具有设计所预想的逻辑关系，即所构想的量表结构与测定结果吻合程度较好。结论 本研究设计的冠心病生存质量量表信度和效度评估符合标准，认为量表可以应用。     

A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver

Current techniques for the alteration of gene expression in the liver have a number of limitations, including the lack of stable somatic gene transfer and the technical challenges of germline transgenesis. Rapid and stable genetic engineering of the liver would allow systematic, in vivo testing of contributions by many genes to disease. After fumaryl acetoacetate hydrolase (Fah) gene transfer to hepatocytes, selective repopulation of the liver occurs in FAH-deficient mice. This genetic correction is readily mediated with transposons. Using this approach, we show that genes with biological utility can be linked to a selectable Fah transposon cassette. First, net conversion of Fah(-/-) liver tissue to transgenic tissue, and its outgrowth, was monitored by bioluminescence in vivo from a luciferase gene linked to the FAH gene. Second, coexpressed short hairpin RNAs (shRNAs) stably reduced target gene expression, indicating the potential for loss-of-function assays. Third, a mutant allele of human alpha1-antitrypsin (hAAT) was linked to Fah and resulted in protein inclusions within hepatocytes, which are the histopathological hallmark of hAAT deficiency disorder. Finally, oncogenes linked to Fah resulted in transformation of transduced hepatocytes. Conclusion: Coexpression with FAH is an effective technique for lifelong expression of transgenes in adult hepatocytes with applicability to a wide variety of genetic studies in the liver.     

Experimental calibration of a two-stage prism-grating system for measuring cell velocity

A new optical system for the measurement of the erythrocyte velocity in microvessels is extensively applied for the first time. It is based on the projection of the erythrocyte image onto two photodiodes through a prism grating. The differential signal of the photodiodes is proportional to the velocity. The system is comparable to those of M. Anliker, M. Casty, P. Friedli, R. Kubli, and H. Keller ((1977). Noninvasive measurement of blood flow. In “Cardiovascular Flow Dynamics and Measurement” (N. H. Hwang and N. Normann, eds.), pp. 43–88. Univ. Park Press, Baltimore) and D. W. Slaaf, J. P. S. M. Rood, G. J. Tangelder, and T. Arts ((1979). Microvasc. Res.17, S173). It measures an instantaneous velocity. The system is calibrated by a velocity which is constant over the total measuring field and by a known flow rate and profile. Concerning applicability and results the device is compared to the two-slit methods, the laser-Doppler-anemometry and high-speed cinematography.     

Developing ultra deformable vesicular transportation of a bioactive alkaloid in pursuit of vitiligo therapy

ObjectiveTo develop transfersomal formulation integrated with piperine intended for vitiligo.MethodsFilm hydration technique was employed in the preparation of transfersomes. Modified diffusion cell, consistency tester were fabricated for ex vivo diffusion studies and spreadability studies respectively while tape stripping method was integrated with tissue extraction in the determination of tissue drug concentration.ResultsWhen film hydration technique was used for, ultradeformable vesicles (transfersomes) of piperine in soabean phosphatidylcholine was formed with (67.11±0.22) to (70.55±3.62) and (60.12±1.04) to (80.43±0.14) mean size (μ) and entrapment efficiency (%) respectively. Transfersomes are capable of crossing the pores in permeability barriers extremely efficient even if the transfersome radius (t_r) is much greater than the pore size (r_pore) ie., tr/r_pore? 0.25 the driven flux rate depends on the transdermal osmotic gradient. The vesicles describes elasto-mechanical character of vesicles while penetrating through the pores. The proviso is that the vesicular membrane elasticity is dynamically to the local stress by the external. Diffusion and Spreadability studies showed maximum diffusion when the lipid was kept minimum. Tape stripping and tissue extraction method for the tissue drug retention showed that (75.25±1.72)% drug was retained in the dermis.ConclusionSpan 80 was preferred over tween 80 in terms of dermal retention. Size and encapsulation was slightly altered by phosphatidylcholine concentration. The kinetics, efficiency and the transfersome mediated transport can be tailored for trans-epidermal, deep tissues and systemic depending on the vesicular composition, dose and form. Thus we have offered a successful drug delivery of piperine targeting the deep epidermis.     

Mycobacterium tuberculosis lineage: a naming of the parts

There have been many reports of groups of related Mycobacterium tuberculosis strains described variously as lineages, families or clades. There is no objective definition of these groupings, making it impossible to define relationships between those groups with biological advantages. Here we describe two groups of related strains obtained from an epidemiological study in Tanzania, which we define as the Kilimanjaro and Meru lineages on the basis of IS6110 restriction fragment length polymorphism (RFLP), polymorphic GC rich sequence (PGRS) RFLP and mycobacterial interspersed repeat unit (MIRU) typing. We investigated the concordance between each of the typing techniques and the dispersal of the typing profiles from a core pattern. The Meru lineage is more dispersed than the Kilimanjaro lineage and we speculate that the Meru lineage is older. We suggest that this approach provides an objective definition that proves robust in this epidemiological study. Such a framework will permit associations between a lineage and clinical or bacterial phenomenon to be tested objectively. This definition will also enable new putative lineages to be objectively tested.     

用遗传操纵防治蚊媒的研究进展

近年,由于蚊媒对杀虫剂的抗药性等多种原因,致使现有蚊媒防治措施的实施受到限制。因而人们把蚊媒病的防治策略转到了遗传操纵上,其目的是减少和替代目标种群,改变其作为疾病媒介的特性。早在30多年前研究者就在遗传防治方面展开了研究,通过改变媒介昆虫的染色体,产生大量绝育雄虫然后将其释放到野外,以控制种群数量,达到防治目的。但是,由于实践操作上的限制而被否定。近年来,随着分子生物学技术的发展,遗传防治被赋予了新的涵义,例如利用转基因技术,对媒介昆虫进行基因转化,定向地改变生物学性状,培育对病原体不易感、自身繁殖能力或传媒能力下降、对杀虫剂敏感性增加等性状的新型转基因昆虫,然后释放至自然界,最终达到控制危害的目的。     

Integration of CAD models with product assembly planning in a Web-based 3D visualized environment

Product assembly planning plays an important role in the product life cycle management. Product assembly planning consists of the product representation, assembly sequence generation, and the sequence optimization. An efficient assembly planning depends on the integration of CAD models with product assembly analysis. However, existing product modeling systems are separated from the product assembly planning. 3D CAD models cannot be directly used by most of the product assembly planning systems. The data extraction from CAD models becomes a critical process in the integrated product development system. This paper presents an integration method of CAD models with product assembly planning. Product data are extracted from product CAD-VRML models and stored in MySQL database. The extracted data are regrouped for product assembly reasoning and 3D visualization. The 3D animation is developed to visually validate the generated assembly plan. The product assembly process is simulated by manipulating the geometry using VRML external authoring interface.     

Familial discrepancy between the one-stage and two-stage factor VIII methods in a subgroup of patients with haemophilia A

A higher result for plasma factor VIII:C measured by the one-stage as compared with the twostage method has been described in some patients with haemophilia A or with von Willebrand's disorder. We used both methods to measure FVIII:C in 95 patients with haemophilia A. The results were equivalent in all 21 patients with severe haemophilia (16 families) and in 45 of the patients with mild or moderate haemophilia (18 families). However, the results were discrepant (FVIII: C by one-stage assay 2-7-fold higher than by two-stage assay) in the other 29 patients with mild or moderate haemophilia (12 other families). For each patient with discrepant FVIII: C results the classification was the same for all other affected members of his family. In some families with haemophilia A the gene defect leads to a discrepancy between the one-stage and twostage FVIII: C results and may be more widespread than previously recognized.