Does the Child Health Computing System adequately identify children with cerebral palsy?

Background This paper assesses the usefulness of the Child Health Computing System as a source of information about children with cerebral palsy.

Methods A comparative survey of information held on the Child Health Computing System (CHCS) and the Northern Ireland Cerebral Palsy Register (NICPR) in one Health and Social Services Board in Northern Ireland was carried out. The sample comprised children with cerebral palsy aged 5–9 years.

Results Of the 135 cases recorded on the NICPR, 47 per cent were not found on the CHCS; the majority of these children had no computer record of any medical diagnosis. Of the 82 cases recorded on the CHCS, 10(12 per cent) were not found on the NICPR; five of these cases (6 per cent) were found on follow–up not to have CP.

Conclusions Unless improvements are made in case ascertainment, case validation and recording activities, the evidence suggests that the CHCS will not be able to provide the same quality of information for needs assessment and surveillance of very low birthweight infants in relation to cerebral palsy as is provided by a specialist case register.

BRCA1 transcriptionally regulates genes associated with the basal breast cancer phenotype

Background Ten to twenty per cent of breast tumours exhibit a basallike genetic profile and these tumours carry a poor prognosis. Breast tumours which contain germline mutations for BRCA1 commonly exhibit a molecular profile similar to basal breast tumours. BRCA1 is a tumour suppressor gene which is mutated in up to 5–10% of breast cancer cases and is involved in multiple cellular processes including DNA damage control, cell cycle checkpoint control, apoptosis, ubiquitination and transcriptional regulation.

Methods Microarray-based profiling was carried out using the HCC1937EV and HCC1937BR breast cancer cell lines. Basal gene and protein expression levels were analysed by qRT-PCR and western blotting. ChIP analyses were performed and demonstrated that BRCA1 regulates basal gene expression through a transcriptional mechanism involving c-myc.

Results We have previously carried out microarray-based expression profiling to examine differences in gene expression when BRCA1 is reconstituted in BRCA1 mutated HCC1937 breast cancer cells. We observed that p-cadherin and the cytokeratin 5 and cytokeratin 17 genes, which are strongly correlated with the basal phenotype, are differentially expressed when BRCA1 is reconstituted. In addition, qRT-PCR and ChIP analysis of BRCA1 reconstituted cells show that BRCA1 represses the expression of these basal genes by a transcriptional mechanism. Furthermore, abrogation of endogenous BRCA1 protein in the T47D cell line using siRNA results in reexpression of these basal genes, suggesting that BRCA1 expression levels may be important in basal gene expression. We have also demonstrated that BRCA1 is physically associated with the promoter regions of basal genes through an association with c-myc. Consequently, we have confirmed that siRNA inhibition of c-myc in T47D cells results in re-expression of these genes.

Conclusions Our results suggest that BRCA1 is involved in the transcriptional regulation of genes associated with the basal phenotype and that BRCA1 controls basal gene expression through a transcriptional mechanism involving c-myc. Further work is now concentrating on defining the relationship between BRCA1 and basal gene expression and how this may affect clinical responses to breast cancer chemotherapy.

The role of the Professional Engineer in the 21st century

In light of the current world economic and environmental crisis due in part to
unsustainable development and poor financial planning, 21st Century engineers are faced with unprecedented challenges of developing a sustainable world in balance with the forces of nature to combat global environmental, social and economic crises. The European Union, the United States of America and a number of other countries have identified that smart solutions and highly skilled professionals are needed to survive climate change and create long-term prosperity. In this paper the evolution of the changing career of the engineer will be presented. The policy background to the current system of engineering education at bachelor’s and graduate level in Ireland will be introduced and perceptions of engineering as a profession by society in general, and by
school leavers selecting third level courses will be discussed. The role of the engineer as a specialist, expert or generalist will also be studied in terms of the changing demands and needs of society. Finally the responsibility of universities, through broad-based multidisciplinary teaching and training, to prepare the next crop of engineers will be examined.

Do different 'magnocellular tasks' probe the same neural substrate?

The sensory abnormalities associated with disorders such as dyslexia, autism and schizophrenia have often been attributed to a generalized deficit in the visual magnocellular-dorsal stream and its auditory homologue. To probe magnocellular function, various psychophysical tasks are often employed that require the processing of rapidly changing stimuli. But is performance on these several tasks supported by a common substrate? To answer this question, we tested a cohort of 1060 individuals on four 'magnocellular tasks': detection of low-spatial-frequency gratings reversing in contrast at a high temporal frequency (so-called frequency-doubled gratings); detection of pulsed low-spatial-frequency gratings on a steady luminance pedestal; detection of coherent motion; and auditory discrimination of temporal order. Although all tasks showed test-retest reliability, only one pair shared more than 4 per cent of variance. Correlations within the set of 'magnocellular tasks' were similar to the correlations between those tasks and a 'non-magnocellular task', and there was little consistency between 'magnocellular deficit' groups comprising individuals with the lowest sensitivity for each task. Our results suggest that different 'magnocellular tasks' reflect different sources of variance, and thus are not general measures of 'magnocellular function'.