Stratified or Multicentre Analysis with Extended Mantel–Haenszel Statistics

Since its introduction in 1959 the ability of the classical Mantel-Haenszel (M–H) procedure for combining the odds ratios of a set of I 2 × 2 tables has led to its use also in stratified or multicentre type clinical trials. A familiar application is the M–H logrank test in survival analysis. An extension of the M–H procedure covering the case of 2 × K contingency tables (MANTEL , 1963) with ordered levels retains the essential property of pooling the results of I homogeneous tables (i.e. in absence of qualitative interactions). The assignment of some score for the K columns of a table is essential for the use of the method (in comparing 2 treatments). Some possibilities of score assignment are discussed: for clinical outcome variables such as the degree of severity of a disease, pain and so on, the score is at hand in a natural way. A less well-known type of scoring consists in ranking the observations of a continuous variable, leading to cell sizes of 1 or 0. In this case, however, if equidistant ranking was used, the E–M–H procedure appears as an extension of Wilcoxon's rank sum test and represents a powerful non-parametric approach in stratified or multicentre type designs with non normally distributed outcome variables. The results of some Monte-Carlo simulations for 2 possible equidistant ranking procedures are presented, which indicate only a moderate gain in power as compared to Wilcoxon's rank sum test under the common situation of centre effects not exceeding treatment effects. Use of the E–M–H pro?edure is also recommended as a simple method to overcome the potential bias due to unequally distributed prognostic factors among treatment groups.     

Seed quality effects in bulb onions (Allium cepa L.)

The nature and persistence of seed quality effects produced by a range of seed production treatments was investigated in the autumn-sown onion crop. Genotypically equivalent seed lots raised in different glasshouses within the same year were found to germinate at significantly different rates. The seed lot which emerged earlier produced larger seedlings and this difference in size persisted throughout the growing period. In a comparison between the effects of hand crossing and self-pollination techniques the hand crossing method produced a much lower total seed yield but heavier seeds and larger plants. The induced effects persisted throughout the year but were not significant in the mature bulb characters. The implications of these results upon the control of seed production for plant breeding and genetical experiments is discussed.     

Regression Models for Clinical Trials with Correlated Categorical Responses

Regression models for correlated categorical data are presented in which the covariance is a function of measured effects. The regression and covariance parameters are estimated by extended least square methods. A numerical example of a clinical trial comparing two antiemetic treatment regimes for patients receiving chemotherapy is given to illustrate the approach.     

Agronomic and chemical performance of field‐grown tobacco engineered for triterpene and methylated triterpene metabolism

Squalene is a linear intermediate to nearly all classes of triterpenes and sterols and is itself highly valued for its use in wide range of industrial applications. Another unique linear triterpene is botryococcene and its methylated derivatives generated by the alga Botryococcus braunii race B, which are progenitors to fossil fuel deposits. Production of these linear triterpenes was previously engineered into transgenic tobacco by introducing the key steps of triterpene metabolism into the particular subcellular compartments. In this study, the agronomic characteristics (height, biomass accumulation, leaf area), the photosynthetic capacity (photosynthesis rate, conductance, internal CO₂ levels) and triterpene content of select lines grown under field conditions were evaluated for three consecutive growing seasons. We observed that transgenic lines targeting enzymes to the chloroplasts accumulated 50–150 times more squalene than the lines targeting the enzymes to the cytoplasm, without compromising growth or photosynthesis. We also found that the transgenic lines directing botryococcene metabolism to the chloroplast accumulated 10‐ to 33‐fold greater levels than the lines where the same enzymes were targeted to in the cytoplasm. However, growth of these high botryococcene accumulators was highly compromised, yet their photosynthesis rates remained unaffected. In addition, in the transgenic lines targeting a triterpene methyltransferase (TMT) to the chloroplasts of high squalene accumulators, 55%–65% of total squalene was methylated, whereas in the lines expressing a TMT in the cytoplasm, only 6%–13% of squalene was methylated. The growth of these methylated triterpene‐accumulating lines was more compromised than that of nonmethylated squalene lines.     

Recent advances in gene‐enhanced bone tissue engineering

The loss of bone tissue represents a critical clinical condition that is frequently faced by surgeons. Substantial progress has been made in the area of bone research, providing insight into the biology of bone under physiological and pathological conditions, as well as tools for the stimulation of bone regeneration. The present review discusses recent advances in the field of gene‐enhanced bone tissue engineering. Gene transfer strategies have emerged as highly effective tissue engineering approaches for supporting the repair of the musculoskeletal system. By contrast to treatment with recombinant proteins, genetically engineered cells can release growth factors at the site of injury over extended periods of time. Of particular interest are the expedited technologies that can be applied during a single surgical procedure in a cost‐effective manner, allowing translation from bench to bedside. Several promising methods based on the intra‐operative genetic manipulation of autologous cells or tissue fragments have been developed in preclinical studies. Moreover, gene therapy for bone regeneration has entered the clinical stage with clinical trials for the repair of alveolar bone. Current trends in gene‐enhanced bone engineering are also discussed with respect to the movement of the field towards expedited, translational approaches. It is possible that gene‐enhanced bone tissue engineering will become a clinical reality within the next few years.