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As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas Ligand (FasL). As an important note, and in contrast to somatic cell therapy trials, there are no reported deaths due to therapeutic vector administration in any cancer gene therapy trial. That said, from our studies and from the published literature, the issue of gene delivery remains the major obstacle to successfully employing gene therapy for cancer treatment. Numerous laboratories are studying this with many different approaches. My co-workers and I have focused on the delivery issue by using various approaches that address tumor targeting and transgene expression. In addition, we are focusing on enhancing tumor cell killing via the bystander effect and through use of small molecules to enhance bystander activity.Cancer Gene Therapy (2006) 13, 1045–1051. doi:10.1038/sj.cgt.7700965; published online 9 June 2006 [ABSTRACT FROM AUTHOR]

We used Cox regression analyses to assess mortality outcomes in a combined cohort of 7675 women who received diethylstilbestrol (DES) through clinical trial participation or prenatal care. In the combined cohort, the RR for DES in relation to all-cause mortality was 1.06 (95% CI = 0.98-1.16), and 1.11 (95% CI = 1.02-1.21) after adjusting for covariates and omitting breast cancer deaths. The RR was 1.07 (95% CI = 0.94-1.23) for overall cancer mortality, and remained similar after adjusting for covariates and omitting breast cancer deaths. The RR was 1.27 (95% CI = 0.96-1.69) for DES and breast cancer, and 1.38 (95% CI=1.03-1.85) after covariate adjustment. The RR was 1.82 in trial participants and 1.12 in the prenatal care cohort, but the DES-cohort interaction was not significant (P = 0.15). Diethylstilbestrol did not increase mortality from gynaecologic cancers. In summary, diethylstilbestrol was associated with a slight but significant increase in all-cause mortality, but was not significantly associated with overall cancer or gynaecological cancer mortality. The association with breast cancer mortality was more evident in trial participants, who received high DES doses. [ABSTRACT FROM AUTHOR]

Exploring whether the positive association between birth weight and breast cancer risk differs by other breast cancer risk factors may help inform speculation about biological mechanism. In these data, high birth weight was associated with breast cancer risk in younger and in more educated women, but was not associated overall. [ABSTRACT FROM AUTHOR]

Objectives: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES.Methods: A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates.Results: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis.Conclusions: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out. [ABSTRACT FROM AUTHOR]

It is well known that the room-temperature shapes of unsymmetric laminates do not always conform to the predictions of classical lamination theory. Instead of being saddle shaped, as classical lamination theory predicts, the room-temperature shapes of unsymmetrically laminated composites are often cylindrical in nature. In addition, a second cylindrical shape can sometimes be obtained from the first by a simple snap-through action. Hyer examined the class of all square unsymmetric cross-ply laminates which can be fabricated from four layers, i.e., [0/0/0/90], [0/0/90/0], [0/90/0/90], [0/0/90/90], and developed an extended classical lamination theory to predict whether these laminates have a saddle shape or one or two cylindrical shapes. Finite element analysis (FEA) has just recently been used for the calculation of the room-temperature shapes of unsymmetric laminates because more sophisticated finite element codes are now available and the calculations can be made in an acceptable time. The hope is to get more accurate results for the shape and the stresses and forces that occur during the snap-through action. These results are needed for the development of active deformable composite structures based on unsymmetric laminates and incorporated shape memory alloy wires [1]. Results for different lay-ups are presented and compared. [ABSTRACT FROM AUTHOR]

The paper describes the drawbacks of an electromagnetic forcing device, of the type commonly used to study forced vibration of structures, and presents details of a feedback control system designed to overcome them. The work described was initiated when attempting to generate sinusoidal forcing in a nonlinear beam-vibration study. Magnetic-material nonlinearities and spatial inhomogenieties in the magnetic field led to unwanted harmonics in the force the beam experienced, and feedback was used to reduce these effects. A brief description of the principles of feedback control is presented and the problems encountered in applying the concepts to the electromagnetic forcing device are discussed. Details of the system, its problems, operating characteristics and limitations are presented. [ABSTRACT FROM AUTHOR]