A descriptive study of UK cancer genetics services: an emerging clinical response to the new genetics

The objective was to describe NHS cancer genetic counselling services and compare UK regions. The study design was a cross-sectional study over 4 weeks and attendee survey. The setting was 22 of the 24 regional cancer genetics services in the UK NHS. Participants were individuals aged over 18 attending clinics at these services. Outcome measures were staff levels, referral rates, consultation rates, follow-up plans, waiting time. There were only 11 dedicated cancer geneticists across the 22 centres. Referrals were mainly concerned with breast (63%), bowel (18%) and ovarian (12%) cancers. Only 7% of referrals were for men and 3% were for individuals from ethnic minorities. Referral rates varied from 76 to 410 per million per annum across the regions. Median waiting time for an initial appointment was 19 weeks, ranging across regions from 4 to 53 weeks. Individuals at population-level genetic risk accounted for 27% of consultations (range 0%, 58%). Shortfalls in cancer genetics staff and in the provision of genetic testing and cancer surveillance have resulted in large regional variations in access to care. Initiatives to disseminate referral and management guidelines to cancer units and primary care should be adequately resourced so that clinical genetics teams can focus on the genetic testing and management of high-risk families. © 2001 Cancer Research Campaign http://www.bjcancer.co

Design, construction and testing of a low carbon thin-shell concrete flooring system

Rapid global urbanisation and population growth is driving unprecedented levels of building construction, with the total worldwide floor area expected to almost double over the next 40 years. Since most of the structural material in a building exists within the floors, these present a significant opportunity for structural engineers to contribute to a more sustainable construction industry. This paper examines a novel flooring system of textile-reinforced concrete shells with a foamed concrete fill, which has the potential to halve the amount of materials in a building’s entire structure. A new design and geometry optimisation method is described, as well as the construction and testing of two prototypes; each 18mm thick, 2m in span and 200mm tall. These textile-reinforced concrete shells are unconventional in their low total depth, low reinforcement content and lack of rigid supports. Both were reinforced with AR-glass fibre textile and constructed using fine-grained concrete, however only one featured a foamed concrete fill. Each was tested to destruction under an asymmetric load. In both cases, a hinged collapse mechanism was formed rather than sudden catastrophic failure, with positive implications for safety and robustness. A non-linear finite element model was developed which replicated the observed behaviour well, including cracking patterns. Inaccuracies in geometry arising from the hand-made construction methods were measured and their structural impact was assessed and found to be small. The investigations confirm the strength, robustness and buildability of the structural system, and establish a reliable analysis method.This research is supported by the EPSRC Centre for Decarbonisation of the Built Environment (dCarb) [grant number EP/L016869/1], the Building Research Establishment Trust (BRE) and the Cambridge University Department of Engineering

An ex vivo human tumour assay reveals distinct patterns of EGFR trafficking in squamous cell carcinoma correlating to therapeutic outcomes

EGFR overexpression is associated with squamous cell carcinoma development. Altered endocytosis and polarization of receptor tyrosine kinases, including EGFR, affect migration and invasion in 3D culture. These studies have been completed via genetic sequencing, cell line or 3D in vitro and in vivo murine models. Here we describe an imaging method that allows ex-vivo examination of ligand-induced endocytosis of EGFR in non-dissociated human tumours. We analyzed sets of tumour samples from advanced cutaneous squamous cell carcinoma and Head and Neck squamous cell carcinoma, actinic keratosis, intra-epidermal carcinoma and cutaneous squamous cell carcinoma. We demonstrate that EGFR endocytosis is dysregulated in advanced SCC and correlates with anti-EGFR monoclonal antibody therapy outcomes. In actinic keratosis, intra-epidermal carcinoma and well-differentiated cutaneous squamous cell carcinoma different patterns of epidermal growth factor ligand uptake and binding were observed at the leading edge of different dysplastic lesions, suggesting that these differences in EGFR endocytosis might influence the metastatic potential of dysplastic squamous epithelium. These studies in live ex-vivo human tumours confirm that endocytosis dysregulation is a physiological event in human tumours and has therapeutic implications

Organization and Variation Analysis of 5S rDNA in Different Ploidy-level Hybrids of Red Crucian Carp × Topmouth Culter

Through distant crossing, diploid, triploid and tetraploid hybrids of red crucian carp (Carassius auratus red var., RCC♀, Cyprininae, 2n = 100) × topmouth culter (Erythroculter ilishaeformis Bleeker, TC♂, Cultrinae, 2n = 48) were successfully produced. Diploid hybrids possessed 74 chromosomes with one set from RCC and one set from TC; triploid hybrids harbored 124 chromosomes with two sets from RCC and one set from TC; tetraploid hybrids had 148 chromosomes with two sets from RCC and two sets from TC. The 5S rDNA of the three different ploidy-level hybrids and their parents were sequenced and analyzed. There were three monomeric 5S rDNA classes (designated class I: 203 bp; class II: 340 bp; and class III: 477 bp) in RCC and two monomeric 5S rDNA classes (designated class IV: 188 bp, and class V: 286 bp) in TC. In the hybrid offspring, diploid hybrids inherited three 5S rDNA classes from their female parent (RCC) and only class IV from their male parent (TC). Triploid hybrids inherited class II and class III from their female parent (RCC) and class IV from their male parent (TC). Tetraploid hybrids gained class II and class III from their female parent (RCC), and generated a new 5S rDNA sequence (designated class I–N). The specific paternal 5S rDNA sequence of class V was not found in the hybrid offspring. Sequence analysis of 5S rDNA revealed the influence of hybridization and polyploidization on the organization and variation of 5S rDNA in fish. This is the first report on the coexistence in vertebrates of viable diploid, triploid and tetraploid hybrids produced by crossing parents with different chromosome numbers, and these new hybrids are novel specimens for studying the genomic variation in the first generation of interspecific hybrids, which has significance for evolution and fish genetics

The role of CD4 T help in multiple vaccinations when using minimal CD8 T cell epitope peptides

Background: The fact that some cancers and viral infections can be controlled by effector CD8 T cells led to the possibility of utilising minimal CD8 T cell epitope peptides as vaccines. However using minimal CD8 T cell epitope peptide immunisations and a tumour protection model in mice, we have previously shown that functional memory CD8 T cells are not generated unless CD4 T help is provided at the time of CD8 T cell priming. Short-lived effector cells nevertheless are generated in the absence of T help. Aim: To determine the role of CD4 T help in multiple immunisations. Method: Minimal CD8 T cell peptides of HPV16 E7 protein and Ovalbumin were used (with adjuvants Quil-A or IFA) as immunogens in C57BL mice. The presence of effector CD8 T cells were determined by tumour protection assays and was quantified by IFN-gamma ELISPOT assays. Results: In the present study we show that unless T help is provided at the time CD8 T cells are primed, no CD8 effector cells are generated when boosted with the vaccine again in the absence of T help. Our results further show that this failure could be prevented by the inclusion of a T helper peptide during the primary or booster immunisations

Software marketing on the Internet: the use of samples and repositories

This paper examines one of the most important marketing strategies by software producers on the Internet. That is whether to offer free samples and, if so, whether to list the samples on shareware repositories. I show that firms with higher value products have a greater incentive to offer free samples but are more reluctant to do so if they are well known, and even when they do are less likely to be listed on shareware repositories. I then proceed to use four types of Probit-based models to corroborate the findings from the theoretical model.shareware, software, Internet, brand, search, sample,