Automated analysis and classification of infected macrophages using bright-field amplitude contrast data.

This article presents a methodology for acquisition and analysis of bright-field amplitude contrast image data in high-throughput screening (HTS) for the measurement of cell density, cell viability, and classification of individual cells into phenotypic classes. We present a robust image analysis pipeline, where the original data are subjected to image standardization, image enhancement, and segmentation by region growing. This work develops new imaging and analysis techniques for cell analysis in HTS and successfully addresses a particular need for direct measurement of cell density and other features without using dyes.

Live birth following preimplantation genetic screening for trisomy 21. Should aneuploidy screening be offered to all older patients undergoing IVF?

A 42-year-old female patient with history of secondary infertility was referred to our assisted conception unit for in vitro fertilization (IVF). Before her referral, she had two cycles of IVF at another centre; the first was unsuccessful and, after conceiving at the second attempt, the pregnancy was terminated at 14 weeks' gestation following a positive nuchal translucency scan and a diagnosis of trisomy 21 (Down syndrome) by a chorionic villous biopsy performed in the first trimester. The screening tests for trisomy 21 were offered to the patient in view of her advanced age. Subsequent karyotyping revealed that both partners had a normal chromosomal complement. Following genetic counselling, the couple were offered IVF treatment along with preimplantation genetic screening for trisomy 21. Four of the five embryos were suitable for biopsy, and one blastomere from each embryo was analyzed using fluorescent in situ hybridization for chromosome 21. The analysis revealed that two embryos had trisomy 21, one had monosomy 21, and only one embryo was diploid for chromosome 21. The single diploid embryo was transferred to the uterus on day 3, and resulted in an uneventful pregnancy and delivery of a healthy live-born male.

RSV604, a novel inhibitor of respiratory syncytial virus replication.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections worldwide, yet no effective vaccine or antiviral treatment is available. Here we report the discovery and initial development of RSV604, a novel benzodiazepine with submicromolar anti-RSV activity. It proved to be equipotent against all clinical isolates tested of both the A and B subtypes of the virus. The compound has a low rate of in vitro resistance development. Sequencing revealed that the resistant virus had mutations within the nucleocapsid protein. This is a novel mechanism of action for anti-RSV compounds. In a three-dimensional human airway epithelial cell model, RSV604 was able to pass from the basolateral side of the epithelium effectively to inhibit virus replication after mucosal inoculation. RSV604, which is currently in phase II clinical trials, represents the first in a new class of RSV inhibitors and may have significant potential for the effective treatment of RSV disease.

Academia-industry partnerships in drug discovery.

The movement of ideas and innovation from academia into the world of business has a long and fruitful history. Ironically, it might be argued that the recent pressure put on universities and basic research organisations to protect and exploit their intellectual property has, in many ways, created a less conducive environment to successful commercialisation than existed 30 years ago. This movement has been concurrent with the drift of the Pharmaceutical industry towards a more risk-averse R&D strategy in which it has increasingly concentrated its resources on a reductionist drug discovery process and later stage clinical development. In effect, these two strategies have created a discontinuity between academic scientific output and industry at a time when academia as a source of innovation is perhaps more important to industry than ever.

Long term follow up of the cruciate fascial sling for women with genuine stress incontinence.

OBJECTIVE: To determine the long term success of the cruciate fascial sling procedure for the treatment of genuine stress incontinence in women. DESIGN: In 1998, a pre-validated questionnaire was sent to all women who had a cruciate fascial sling between 1979 and 1996 under the care of the senior author at a District General Hospital and in private practice. PARTICIPANTS: Questionnaires were sent to 246 women; 198 (80%) were returned. RESULTS: Overall, 142 women felt that they were much improved or cured. The success rate was 74% (95% CI 70%-81%) in women having the sling as a primary procedure and 67% (95% CI 54%-81%) in women having the sling as a secondary procedure. There was no relationship between symptom severity score and age at time surgery, duration of follow up, current weight or body mass index, previous surgery for stress incontinence or concomitant surgery. Of the 103 women with six or more years of follow up, 29 felt that their operation had failed, 16 of whom thought that it lasted between five and 10 years. Urgency was experienced by 29% of women, three needed to perform intermittent self-catheterisation, and 9% found it difficult to empty their bladder. Thirty-seven women (19%) experienced problems that they attributed to the abdominal wound. CONCLUSION: Although inevitably there are some failures over time, the cruciate fascial sling has good long term success rates. Direct comparison with the literature is impossible, as few studies have relied on properly validated questionnaires.