The labour ward analgesic service at King Edward VIII Hospital, Durban

The provision of analgesic services to the labour ward at King Edward VIII Hospital was studied during a 1-week period. Of 249 patients, 113 (45%) received no analgesia whatsoever. Intramuscular pethidine was the commonest form of analgesia and was used in 97 patients (39%). Thirty-six patients (14%) received epidural analgesia and only 4 inhalational analgesia using nitrous oxide and oxygen (Entonox). A significant proportion of patients who received pethidine were given the drug between 1 and 3 hours before delivery, increasing the potential for opiate-related neonatal depression. Of the patients given opiate analgesia, 22 (23%) proceeded to caesarean section and could have been at increased risk of aspiration of gastric contents owing to delayed gastric emptying caused by the opiate. One hundred and eleven mothers (76%) who had an obstetric indication for epidural analgesia were denied it because of lack of medical staffing

ESTIMATING GENOME-WIDE COPY NUMBER USING ALLELE SPECIFIC MIXTURE MODELS

Genomic changes such as copy number alterations are thought to be one of the major underlying causes of human phenotypic variation among normal and disease subjects [23,11,25,26,5,4,7,18]. These include chromosomal regions with so-called copy number alterations: instead of the expected two copies, a section of the chromosome for a particular individual may have zero copies (homozygous deletion), one copy (hemizygous deletions), or more than two copies (amplifications). The canonical example is Down syndrome which is caused by an extra copy of chromosome 21. Identification of such abnormalities in smaller regions has been of great interest, because it is believed to be an underlying cause of cancer. More than one decade ago comparative genomic hybridization (CGH)technology was developed to detect copy number changes in a high-throughput fashion. However, this technology only provides a 10 MB resolution which limits the ability to detect copy number alterations spanning small regions. It is widely believed that a copy number alteration as small as one base can have significant downstream effects, thus microarray manufacturers have developed technologies that provide much higher resolution. Unfortunately, strong probe effects and variation introduced by sample preparation procedures have made single-point copy number estimates too imprecise to be useful. CGH arrays use a two-color hybridization, usually comparing a sample of interest to a reference sample, which to some degree removes the probe effect. However, the resolution is not nearly high enough to provide single-point copy number estimates. Various groups have proposed statistical procedures that pool data from neighboring locations to successfully improve precision. However, these procedure need to average across relatively large regions to work effectively thus greatly reducing the resolution. Recently, regression-type models that account for probe-effect have been proposed and appear to improve accuracy as well as precision. In this paper, we propose a mixture model solution specifically designed for single-point estimation, that provides various advantages over the existing methodology. We use a 314 sample database, constructed with public datasets, to motivate and fit models for the conditional distribution of the observed intensities given allele specific copy numbers. With the estimated models in place we can compute posterior probabilities that provide a useful prediction rule as well as a confidence measure for each call. Software to implement this procedure will be available in the Bioconductor oligo packagehttp://www.bioconductor.org)