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Purpose: We evaluated the impact of personal melanoma genomic risk information on sun-related behaviors and psychological outcomes., Methods: In this parallel group, open, randomized controlled trial, 1,025 Australians of European ancestry without melanoma and aged 18-69 years were recruited via the Medicare database (3% consent). Participants were randomized to the intervention (n = 513; saliva sample for genetic testing, personalized melanoma risk booklet based on a 40-variant polygenic risk score, telephone-based genetic counseling, educational booklet) or control (n = 512; educational booklet). Wrist-worn ultraviolet (UV) radiation dosimeters (10-day wear) and questionnaires were administered at baseline, 1 month postintervention, and 12 months postbaseline., Results: At 12 months, 948 (92%) participants completed dosimetry and 973 (95%) the questionnaire. For the primary outcome, there was no effect of the genomic risk intervention on objectively measured UV exposure at 12 months, irrespective of traditional risk factors. For secondary outcomes at 12 months, the intervention reduced sunburns (risk ratio: 0.72, 95% confidence interval: 0.54-0.96), and increased skin examinations among women. Melanoma-related worry was reduced. There was no overall impact on general psychological distress., Conclusion: Personalized genomic risk information did not influence sun exposure patterns but did improve some skin cancer prevention and early detection behaviors, suggesting it may be useful for precision prevention. There was no evidence of psychological harm., (© 2021. The Author(s).)

Background: Reducing ultraviolet radiation (UV) exposure and improving early detection may reduce melanoma incidence, mortality and health system costs. This study aims to evaluate the efficacy and cost-effectiveness of providing information on personal genomic risk of melanoma in reducing UV exposure at 12 months, according to low and high traditional risk., Methods: In this randomized controlled trial, participants (target sample = 892) will be recruited from the general population, and randomized (1:1 ratio, intervention versus control). Intervention arm participants provide a saliva sample, receive personalized melanoma genomic risk information, a genetic counselor phone call, and an educational booklet on melanoma prevention. Control arm participants receive only the educational booklet. Eligible participants are aged 18-69 years, have European ancestry and no personal history of melanoma. All participants will complete a questionnaire and wear a UV dosimeter to objectively measure their sun exposure at baseline, 1- and 12-month time-points, except 1-month UV dosimetry will be limited to ~250 participants. The primary outcome is total daily Standard Erythemal Doses at 12 months. Secondary outcomes include objectively measured UV exposure for specific time periods (e.g. midday hours), self-reported sun protection and skin-examination behaviors, psycho-social outcomes, and ethical considerations surrounding offering genomic testing at a population level. A within-trial and modelled economic evaluation will be undertaken from an Australian health system perspective to assess the intervention costs and outcomes., Discussion: This trial will inform the clinical and personal utility of introducing genomic testing into the health system for melanoma prevention and early detection at a population-level., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12617000691347., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Basiliximab is an anti-CD25 monoclonal antibody used as induction therapy in solid-organ transplantation. In this study we aim to determine whether pre-operative administration of basiliximab is beneficial in preventing early heart allograft rejection., Methods: In this investigation we assess the effect of pre-implantation basiliximab on CD25 count and on acute rejection in children undergoing cardiothoracic transplantation. The notes of all children undergoing cardiothoracic transplantation at the Great Ormond Street Hospital between January 2000 and June 2007 were retrospectively reviewed. One hundred twenty-one heart transplant recipients were included: 29 patients did not receive basiliximab; 33 patients received basiliximab after coming off cardiopulmonary bypass (CPB); and 59 patients received basiliximab prior to organ implantation., Results: All patients receiving basiliximab had an effectively suppressed CD25 count (<0.2%) on Days 1 and 10 post-transplant. Freedom from Grade 3A or greater rejection in the first year was significantly greater in the pre-implantation basiliximab group than in the post-implantation and no-basiliximab groups (95%, 70% and 72%, respectively; p = 0.02). Induction regimen was the only significant explanatory variable after multivariate Cox regression., Conclusions: The results of this study confirm that basiliximab is effective at suppressing CD25 count whether given pre- or post-CPB. Basiliximab before transplantation appeared to reduce acute rejection, whereas post-CPB administration did not suggest similar effects. These findings require independent validation in randomized trials and further studies should seek to mechanistically delineate these observations.

The correlation between angiogenesis as assessed by endothelial cell proliferation in blood/lymphatic vessels in primary breast carcinomas, and axillary lymph-node metastasis was studied using a case-control design. Primary breast carcinomas, < 2 cm in diameter, from 26 axillary node positive patients (case), were compared with neoplasms from 45 node-negative patients (control). Vascularity, as assessed by vessel density, and endothelial cell proliferation were measured in a single tissue section using a double immunohistochemical staining technique using MIBI (Ki-67) and FVIII antibodies. No association between vascularity and node status was found (P > 0.70). Node positive breast carcinomas had, on average, significantly smaller proliferating vessels (140+/-7 microm in perimeter) in the primary lesion when compared with node negative tumours (164+/-7 microm in perimeter (P < 0.02). In addition, the frequency of relatively small vessels (less than 180 microm in perimeter) with proliferating endothelium was higher in node positive carcinomas than lymph-node negative neoplasms (P < 0.03). This association between node status and the size and frequency of blood/lymphatic vessels with proliferating endothelium in primary carcinoma may have important implications in metastasis.

The mouse mammary gland undergoes rapid proliferation during puberty, then cyclical proliferation and involution during adulthood within a 5-day estrous cycle. Although proliferation of mammary epithelial cells is directed by elevated serum levels of estrogen acting via the estrogen receptor (ER), the ER status of the proliferating cells remains unknown. We examined the ER expression of proliferating epithelial cell types during pubertal development and normal adult growth using simultaneous immunohistochemistry for ER and tritiated thymidine (3H-Tdr) autoradiography. These studies demonstrate that during pubertal growth (4-6 weeks) ER-negative cells comprise more than 50% of the epithelial cell populations in the terminal end buds (TEBs) and ducts. Furthermore, the majority of proliferating cells in both TEBs and ducts are ER-negative. These findings indicate that proliferation of cells within both the TEBs and the mammary ducts contribute to pubertal growth of the mammary gland and that the greater proportion of dividing cells are ER-negative. Similar patterns of cell growth were observed in the normal estrous cycle when the majority of dividing cells were ER-negative during both pro-estrous and estrous. Intensive labelling of cells with 3H-Tdr was used to identify long-lived mammary epithelial cells which retained 3H-Tdr 2 weeks following labelling (i.e., following 3 estrous cycles). Of the small number of mammary epithelial cells retaining 3H-Tdr label, most were ER-positive luminal cells and only a few were ER-negative basal cells. This study indicates that pubertal growth of the mammary gland comprises division of ER-negative cap cells and of both ER-negative and ER-positive cells in the body of the TEBs and elongating mammary ducts. Similarly, estrogen-driven proliferation of ER-negative and ER-positive luminal cells and ER-negative basal cells maintains the differentiated mammary gland in the adult mouse.

Since the description of the original technique of field alternation gel electrophoresis (FAGE) about ten years ago there have been significant developments in the area. Between 1983 and early 1987 dramatic improvements in the technique and apparatus resulted in a 500- to 600-fold increase in the functional separation capacity of conventional agarose gel electrophoresis. Details of the improvements in technique and equipment was the subject of an earlier review [H. J. S. Dawkins, J. Chromatogr., 492 (1989) 615]. This review concentrates on the application of FAGE technology. The FAGE technique is no longer restricted to simply separating large DNA fragments. This method is presently being used for electrophoretic karyotyping, long-range genomic mapping, cloning of large DNA fragments into new vectors, the study of pathogenic chromosomal alterations and the structural analysis of chromosomes. The applications of FAGE in molecular biology and genetics is constantly expanding, with the full potential of this technique still to be realised.

The techniques for large DNA separation have developed from a seminal idea for field alternation which has transformed the field of DNA electrophoresis. This single innovation of pulsed field-gradient electrophoresis (PFGE) and the subsequent modifications have made a significant impact on molecular biology, eukaryote genetics, biopolymer research and diagnostic research. The apparatus types used for large DNA separation are depicted and critically compared with relation to molecular mass separation capabilities, straight-lane migration of samples, band sharpness and ease of operation. With these criteria in mind PFGE and orthogonal field alternation gel electrophoresis systems had a number of drawbacks, the principle one being the inability of these systems to give straight-lane migration. To a large extent this has restricted the widespread use of these systems. Field inversion gel electrophoresis produces straight-lane migration but was subject to an upper molecular mass limitation of 2 megabase pairs and tended to produce broader bands in the higher-molecular-mass areas. Transverse alternating field electrophoresis, rotating gel electrophoresis and contour-clamped homogeneous electric field electrophoresis systems where superior to all the other systems. They gave straight-lane migration, separation of chromosomes up to 10 megabase pairs, good resolution of bands and were all relatively simple to operate. Very little was found to separate these three electrophoresis systems. Field alternation electrophoresis has enabled a 500-fold increase in the size of DNA molecules that can be resolved in agar gels. Consequently, electrophoretic karyotypes of a number of organisms have been produced, while genome maps, gene locations and sequences of large areas of mammalian genomes are now being undertaken. The ability to separate entire chromosomes or large DNA fragments has, in conjunction with novel molecular biology techniques, enabled scientists to work backwards from large purified fragments or entire chromosomes to construct long-range genetic maps. The time saving alone when compared with the old techniques of using very small fragments to construct a picture of the gene or gene complex is commendable. The diagnostic role of large DNA separation and electrophoretic karyotyping is beginning to be explored, while the use of this technique for clinical studies of genetic disorders is well advanced. Very few innovations in nucleic acid separation have had as marked an influence on as many areas as field alternation electrophoresis. These techniques have brought mapping of the mammalian genome into the realms of possibility and is contributing in many sphere

In an outbreak of Salmonella ealing infections in November and December, 1985, the proportion of infants infected was in excess of the normal distribution pattern and the cases were geographically widespread. All the infected infants had been fed with a dried-milk product from one manufacturer. Despite intensive efforts to isolate S ealing from packets of the product, it was found only in low numbers in 4 of 267 sealed packets. The source of infection was traced to the factory spray-drier, which had a hole in its inner lining, allowing escape of powder and its return from contaminated insulation material. The plant was closed and the equipment scrapped and later replaced. It is recommended that raw milk and whey, which frequently contain salmonellae, should not be allowed onto the site of milk-drying plants.