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Michael Watson

Publications and source records attributed to Michael Watson.

At least 19 recordsLinked to original sources
PubMed2006

CoXpress: differential co-expression in gene expression data.

BACKGROUND: Traditional methods of analysing gene expression data often include a statistical test to find differentially expressed genes, or use of a clustering algorithm to find groups of genes that behave similarly across a dataset. However, these methods may miss groups of genes which form differential co-expression patterns under different subsets of experimental conditions. Here we describe coXpress, an R package that allows researchers to identify groups of genes that are differentially co-expressed. RESULTS: We have developed coXpress as a means of identifying groups of genes that are differentially co-expressed. The utility of coXpress is demonstrated using two publicly available microarray datasets. Our software identifies several groups of genes that are highly correlated under one set of biologically related experiments, but which show little or no correlation in a second set of experiments. The software uses a re-sampling method to calculate a p-value for each group, and provides several methods for the visualisation of differentially co-expressed genes. CONCLUSION: coXpress can be used to find groups of genes that display differential co-expression patterns in microarray datasets.

Algorithms↗
PubMed2006

large-scale serologic testing program to assess the immunogenicity of inactivated hepatitis a vaccine (VAQTA) in prefilled syringes following product recall in Germany.

A voluntary recall of VAQTA in prefilled syringes was implemented in Europe in late 2001 after the manufacturer noted a slight decrease in the antigen content of a small percentage of the syringes manufactured over a particular time frame. In Germany, a large-scale serologic testing program was implemented. The assay results were conveyed to the subject's physician, and free vaccine was provided for anyone requesting revaccination. An analysis was performed on a subset of 58,546 vaccine recipients with hepatitis A antibody results. Of the 28,681 persons who received either two 25 units (25 U) or two 50 units (50 U) doses of VAQTA, the seropositivity rate (SPR) was 99.5% after receipt of 2 doses, similar to the results in prelicensure clinical trials. The SPR was similar among recipients of lots that had been manufactured over the time frame associated with the recalled lots versus those receiving lots not associated with the recalled lots (25U: 99.7% versus 99,7%; 50U: 98.6% versus 99.6%, respectively). There were less recipients of 25U doses of the affected lots, who had high hepatitis A antibody titers (> or =100 mIU/mL), compared to recipients of unaffected lots.

Germany↗
PubMed2006

A randomised controlled study of the reactogenicity of an acellular pertussis-containing pentavalent infant vaccine compared to a quadrivalent whole cell pertussis-containing vaccine and oral poliomyelitis vaccine, when given concurrently with meningococcal group C conjugate vaccine to healthy UK infants at 2, 3 and 4 months of age.

Two hundred forty-one healthy infants were enrolled in an open randomised controlled study of three doses of DTaP-IPV-Hib (Group 1) or DTwP/Hib+OPV (Group 2) at 2, 3 and 4 months of age given concurrently with a meningitis C conjugate vaccine. After each dose, local reactions (any grade) were less common in Group 1 than Group 2 (p<0.03). Axillary temperature >37.5 degrees C, decreased feeding, reduced activity, irritability and crying in the week after vaccination were also less common in Group 1 than Group 2 (p<0.05 for each symptom, all doses combined). Severe local reactions and systemic symptoms were uncommon and occurred equally in both groups. The pentavalent DTaP-IPV-Hib vaccine was less reactogenic than the quadrivalent DTwP-Hib vaccine, as expected when changing from whole cell pertussis (wP) to an acellular pertussis (aP) component.

Bacterial Vaccines↗
PubMed2006

Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle.

The deficiency of dystrophin, a critical membrane stabilizing protein, in the mdx mouse causes an elevation in intracellular calcium in myocytes. One mechanism that could elicit increases in intracellular calcium is enhanced influx via the L-type calcium channels. This study investigated the effects of the dihydropyridines BAY K 8644 and nifedipine and alterations in dihydropyridine receptors in dystrophin-deficient mdx hearts. A lower force of contraction and a reduced potency of extracellular calcium (P < 0.05) were evident in mdx left atria. The dihydropyridine agonist BAY K 8644 and antagonist nifedipine had 2.7- and 1.9-fold lower potencies in contracting left atria (P < 0.05). This corresponded with a 2.0-fold reduction in dihydropyridine receptor affinity evident from radioligand binding studies of mdx ventricular homogenates (P < 0.05). Increased ventricular dihydropyridine receptor protein was evident from both radioligand binding studies and Western blot analysis and was accompanied by increased mRNA levels (P < 0.05). Patch-clamp studies in isolated ventricular myocytes showed no change in L-type calcium current density but revealed delayed channel inactivation (P < 0.05). This study indicates that a deficiency of dystrophin leads to changes in dihydropyridine receptors and L-type calcium channel properties that may contribute to enhanced calcium influx. Increased influx is a potential mechanism for the calcium overload observed in dystrophin-deficient cardiac muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2006

The regional genetic and newborn screening service collaboratives: the first two years.

Newborn screening and genetic technologies are expanding and changing rapidly, increasing the demand for genetic specialty services. Because of the scarcity and geographic maldistribution of genetic specialty services, access to these services is a critical issue. This article discusses some of the efforts initiated by the Maternal and Child Health Bureau of the Health Resources and Services Administration, particularly the establishment of regional genetic and newborn screening collaboratives to improve access to these services and expertise.

Cooperative Behavior↗
PubMed2006

Protecting the environment: the role of environmental management systems.

Environmental management and auditing systems are increasingly important. They have significant roles to play in relation to environmental protection, workplace safety and public health. Businesses and non-commercial organisations adopt such systems for a variety of reasons. The extent to which they are used varies very considerably between developed countries. The effectiveness of national regulatory systems seems to be a major factor. In the United Kingdom environmental regulators have traditionally sought the voluntary compliance of businesses. This strategy is closely associated with the near absence of administrative penalties. It seems that a wide range of environmental administrative penalties will be introduced in the near future. This may greatly encourage more firms to introduce environmental management and auditing systems.

Certification↗
PubMed2005

ProGenExpress: visualization of quantitative data on prokaryotic genomes.

BACKGROUND: The integration of genomic information with quantitative experimental data is a key component of systems biology. An increasing number of microbial genomes are being sequenced, leading to an increasing amount of data from post-genomics technologies. The genomes of prokaryotes contain many structures of interest, such as operons, pathogenicity islands and prophage sequences, whose behaviour is of interest during infection and disease. There is a need for simple and novel tools to display and analyse data from these integrated datasets, and we have developed ProGenExpress as a tool for visualising arbitrarily complex numerical data in the context of prokaryotic genomes. RESULTS: Here we describe ProGenExpress, an R package that allows researchers to easily and quickly visualize quantitative measurements, such as those produced by microarray experiments, in the context of the genome organization of sequenced prokaryotes. Data from microarrays, proteomics or other whole-genome technologies can be accurately displayed on the genome. ProGenExpress can also search for novel regions of interest that consist of groups of adjacent genes that show similar patterns across the experimental data set. We demonstrate ProGenExpress with microarray data from a time-course experiment involving Salmonella typhimurium. CONCLUSION: ProGenExpress can be used to visualize quantitative data from complex experiments in the context of the genome of sequenced prokaryotes, and to find novel regions of interest.

Computational Biology↗
PubMed2005

Collection of soluble variants of membrane proteins for transcriptomics and proteomics.

The existence of a soluble splice variant for a gene encoding a transmembrane protein suggests that this gene plays a role in intercellular signalling, particularly in immunological processes. Also, the absence of a splice variant of a reported soluble variant suggests exclusive control of the solubilisation by proteolytic cleavage. Soluble splice variants of membrane proteins may also be interesting targets for crystallisation as their structure may be expected to preserve, at least partially, their function as integral membrane proteins, whose structures are most difficult to determine. This paper presents a dataset derived from the literature in an attempt to collect all reported soluble variants of membrane proteins, be they splice variants or shedded. A list of soluble variants is derived in silico from Ensembl. These are checked on their presence in multiple organisms and their number of membranespanning regions is inspected. The findings then are confirmed by a comparison with identified proteins of a recent global proteomics study of human blood plasma. Finally, a tool to determine novel soluble variants by proteomics is provided.

Animals↗
PubMed2005

How useful are home safety behaviours for predicting childhood injury? A cohort study.

Little work has examined the utility of home safety behaviours in predicting childhood injury. This study examines the relationship between safety behaviours and child injury using a cohort of 1717 families, with 2357 children aged 0-7 years. Safety behaviours, and sociodemographic and family characteristics were measured using a validated questionnaire, and medically attended injuries were ascertained from medical records. Hospital admission rates were lower amongst children from families with fitted and working smoke alarms [incidence rate ratio (IRR) 0.55, 95% confidence interval (CI) 0.31-0.96], who stored sharp objects safely (IRR 0.44, 95% CI 0.23-0.84) and who had fitted stair gates (IRR 0.57, 95% CI 0.31-1.03). Not having a stair gate and not storing sharp objects safely had high sensitivities and negative predictive values for predicting hospital admission. These findings are unlikely to be explained by reductions in the risk of injuries these items are designed to prevent. Families with a range of safety behaviours may also be 'safer' in other ways. Further exploration of factors that may explain lower injury rates in these families is required. Information on safety behaviours may be useful for targeting and monitoring injury prevention activity.

Child↗
PubMed2005

Relationships between child, family and neighbourhood characteristics and childhood injury: a cohort study.

There has been little research into the role of neighbourhood effects in childhood injury. We report results from a cohort study, comprising 1717 families (2357 children aged 0-7 years) registered at 47 general practices in Nottingham, UK. Multi-level Poisson regression examined relationships between electoral ward (neighbourhood), family and child characteristics and medically attended injury rates. Primary care attendance rates were higher for children in rented accommodation and those aged 2-3 years. An n-shaped relationship was found between geographical access to services and the primary care attendance rate. Accident and Emergency (A&E) department attendance rates were higher amongst boys, children in rented accommodation, with a teenage mother, aged 2-5 years and living in wards with a higher number of parks and play areas. They were lower for children whose families had a smoke alarm. Hospital admission rates were higher amongst children living in more deprived wards and wards with higher violent crime rates. They were lower in children whose families had smoke alarms, stair gates and stored sharp objects safely. Primary care and A&E attendance rates varied significantly between families. Variation between wards in the A&E attendance rate was explained by family characteristics. We conclude that characteristics of wards, families and children are associated with medically attended childhood injury rates. This study did not find a neighbourhood effect for A&E attendances that could not be explained by family level characteristics. Studies with greater power and a measure of injury severity independent of health service utilisation are needed to explore the relationship between neighbourhood effects and more severe injuries. The greater variation in injury rates vary between families than between neighbourhoods suggests reducing inequalities in injury rates may be achieved more effectively by focussing prevention at families rather than neighbourhoods, but in practice interventions at both levels are likely to be necessary.

Child↗
PubMed2005

A genomic analysis of chicken cytokines and chemokines.

As most mechanisms of adaptive immunity evolved during the divergence of vertebrates, the immune systems of extant vertebrates represent different successful variations on the themes initiated in their earliest common ancestors. The genes involved in elaborating these mechanisms have been subject to exceptional selective pressures in an arms race with highly adaptable pathogens, resulting in highly divergent sequences of orthologous genes and the gain and loss of members of gene families as different species find different solutions to the challenge of infection. Consequently, it has been difficult to transfer to the chicken detailed knowledge of the molecular mechanisms of the mammalian immune system and, thus, to enhance the already significant contribution of chickens toward understanding the evolution of immunity. The availability of the chicken genome sequence provides the opportunity to resolve outstanding questions concerning which molecular components of the immune system are shared between mammals and birds and which represent their unique evolutionary solutions. We have integrated genome data with existing knowledge to make a new comparative census of members of cytokine and chemokine gene families, distinguishing the core set of molecules likely to be common to all higher vertebrates from those particular to these 300 million-year-old lineages. Some differences can be explained by the different architectures of the mammalian and avian immune systems. Chickens lack lymph nodes and also the genes for the lymphotoxins and lymphotoxin receptors. The lack of functional eosinophils correlates with the absence of the eotaxin genes and our previously reported observation that interleukin- 5 (IL-5) is a pseudogene. To summarize, in the chicken genome, we can identify the genes for 23 ILs, 8 type I interferons (IFNs), IFN-gamma, 1 colony-stimulating factor (GM-CSF), 2 of the 3 known transforming growth factors (TGFs), 24 chemokines (1 XCL, 14 CCL, 8 CXCL, and 1 CX3CL), and 10 tumor necrosis factor superfamily (TNFSF) members. Receptor genes present in the genome suggest the likely presence of 2 other ILs, 1 other CSF, and 2 other TNFSF members.

Amino Acid Sequence↗
PubMed2004

Providing child safety equipment to prevent injuries: randomised controlled trial.

OBJECTIVE: To assess the effectiveness of safety advice and safety equipment in reducing unintentional injuries for families with children aged under 5 years and living in deprived areas. DESIGN: Randomised controlled trial. SETTING: 47 general practices in Nottingham. PARTICIPANTS: 3428 families with children under 5. INTERVENTION: A standardised safety consultation and provision of free and fitted stair gates, fire guards, smoke alarms, cupboard locks, and window locks. MAIN OUTCOME MEASURES: Primary outcome measures were whether a child in the family had at least one injury that required medical attendance and rates of attendance in primary and secondary care and of hospital admission for injury over a two year period. Secondary outcome measures included possession of safety equipment and safety practices. RESULTS: No significant difference was found in the proportion of families in which a child had a medically attended injury (odds ratio 1.14, 95% confidence interval 0.98 to 1.50) or in the rates of attendance in secondary care (incidence rate ratio 1.02, 0.90 to 1.13) or admission to hospital (1.02, 0.70 to 1.48). However, children in the intervention arm had a significantly higher attendance rate for injuries in primary care (1.37, 1.11 to 1.70, P = 0.003). At both one and two years' follow up, families in the intervention arm were significantly more likely to have a range of safety practices, but absolute differences in the percentages were relatively small. CONCLUSIONS: The intervention resulted in significant improvements in safety practices for up to two years but did not reduce injuries that necessitated medical attendance. Although equipment was provided and fitted free of charge, the observed changes in safety practices may not have been large enough to affect injury rates.

Accident Prevention↗
PubMed2004

Intradermal radioisotope is superior to peritumoral blue dye or radioisotope in identifying breast cancer sentinel nodes.

BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy have emerged as the technique of choice for axillary staging of breast cancer. Several methods have been developed to identify SLNs, including peritumoral or intradermal injection of isosulfan blue dye or technetium sulfur colloid (TSC). We hypothesize that intradermal TSC is the optimal mapping technique and can be used alone to identify SLNs. STUDY DESIGN: From March 1997 through January 2001, 180 women with T1 and T2 invasive breast cancer and clinically negative axilla underwent SLN mapping and biopsy. Peritumoral TSC was injected in 74 patients, 62 of whom also received peritumoral blue dye. Intradermal TSC (above tumor) was performed in 94 patients, 76 of whom also received peritumoral blue dye. Technetium-rich nodes were identified intraoperatively using a hand-held gamma probe and blue nodes were identified visually. Hematoxylin- and eosin-stained SLN sections were examined by light microscopy for breast cancer metastases. RESULTS: Overall, the SLN mapping procedures were successful in 91% of patients. Peritumoral and intradermal TSC were successful in identifying SLNs in 78% and 97% of patients, respectively. Peritumorally injected isosulfan blue was successful in identifying 83% of SLNs. Intradermal TSC was found to be superior to peritumoral TSC and peritumoral blue dye in identifying SLNs (p = 0.00094, chi-squared, and p = 0.020, ANOVA). CONCLUSIONS: SLN mapping by intradermal TSC has a significantly higher success rate than peritumoral TSC or blue dye. There was minimal benefit in identifying additional SLNs with addition of peritumoral blue dye to intradermal TSC. So, SLN mapping and biopsy using intradermal-injected TSC can be used alone to effectively stage the axilla for breast cancer.

Breast Neoplasms↗
PubMed2004

Invasive pneumococcal disease in Australia, 2003.

There were 2,174 cases of invasive pneumococcal disease (IPD) notified to the National Notifiable Diseases Surveillance System (NNDSS) in Australia in 2003; a rate of 10.9 per 100,000 population. The notification rate varied between states and territories and by geographical region with the highest rates in the north of the country. Invasive pneumococcal disease was reported most frequently in children aged less than two years (98.8 cases per 100,000 population). Enhanced surveillance for IPD in 2003 was carried out in all states and territories, providing additional data on 1,842 (85%) of all notified cases. Rates of IPD in Indigenous Australians were three times the rate in non-Indigenous Australians. There were 125 deaths attributed to IPD resulting in an overall case fatality rate of 6.8 per cent. Seventy-one percent of all pneumococcal isolates serotyped were serotypes in the seven-valent conjugate vaccine and 91 per cent were serotypes in the 23-valent polysaccharide pneumococcal vaccine. The clinical presentation and risk factors for IPD varied between Indigenous and non-Indigenous cases and non-vaccine serotypes occurred more frequently among Indigenous children and adults. Data from three years of surveillance indicate an early impact of the 7-valent vaccine in the target population.

Adolescent↗
PubMed2004

Laboratory surveillance of invasive pneumococcal disease in Australia, 2003 predicting the future impact of the universal childhood conjugate vaccine program.

A comprehensive invasive pneumococcal disease (IPD) laboratory surveillance program was carried out in Australia in 2003. This program provided data on the prevalence of pneumococcal serotypes and antimicrobial resistance. There were 1,995 isolates tested with 34 per cent (683) from children aged less than five years and 27 per cent (535) from the elderly aged more than 65 years. One thousand eight hundred and sixty were isolates from blood, 79 from CSF and 56 from other sterile sites. In young children, 84 per cent of isolates were a serotype and 92 per cent a serogroup in the 7-valent pneumococcal conjugate vaccine (7vPCV). Of penicillin resistant isolates in children less than five years of age 85 per cent and 98 per cent were a serotype and serogroup in the 7vPCV respectively. When the universal 7vPCV vaccine program in young children is introduced in 2005, a proportion of cases of IPD should also be prevented in young adults (estimated reduction of 54 cases annually) and elderly Australians (an estimated reduction of 110 cases annually) as a result of improved herd immunity. Pneumococcal serotypes with higher rates of penicillin resistance (19F, 14 and 6B) were more prevalent in the elderly than in young children. In contrast, erythromycin resistance was more common in children less than five years of age (24%) compared to the elderly (15%). The predominant serotype with erythromycin resistance in Australia was serotype 14 and thus there is likely to be a major reduction in erythromycin resistance as a result of 7vPCV vaccination. Continued surveillance of pneumococcal serotype distribution and antibiotic susceptibility will be essential in order to identify serotype replacement by non-vaccine serotypes and to monitor the overall impact of current and future vaccine programs on invasive pneumococcal disease in Australia, not only in young children but also in other age groups.

Age Distribution↗
PubMed2003

Invasive pneumococcal disease in Australia, 2002.

There were 2,271 cases of invasive pneumococcal disease (IPD) notified to the National Notifiable Diseases Surveillance System in Australia in 2002; a rate of 11.5 cases per 100,000 population. The notification rate varied between states and territories and by geographical region with the highest rates in the north of the country. Invasive pneumococcal disease was reported most frequently in children aged less than five years (57.3 per 100,000 population). Enhanced surveillance for IPD in 2002 was carried out in all states and territories, providing additional data on 1,929 (85%) of all notified cases. Rates of IPD in Indigenous Australians were 2.7 times the rate in non-Indigenous Australians. The clinical presentation of IPD was most commonly pneumonia (44%) and bacteraemia (35%). There were 175 deaths attributed to IPD resulting in an overall case fatality rate of 9.2 per cent. Forty-two per cent of all cases had a recognised risk factor for IPD. Seventy-five per cent of all pneumococcal isolates serotyped were serotypes in the seven-valent conjugate vaccine and 93 per cent were serotypes in the 23-valent polysaccharide pneumococcal vaccine. The clinical presentation and rates of risk factors varied between Indigenous and non-Indigenous cases and non-vaccine serotypes occurred more frequently among Indigenous children and adults.

Adolescent↗
PubMed2003

Laboratory surveillance of invasive pneumococcal disease in Australia in 2001 to 2002--implications for vaccine serotype coverage.

This paper reports the results of comprehensive laboratory surveillance of invasive pneumococcal disease (IPD) in Australia during 2001 and 2002. The 7-valent conjugate pneumococcal vaccine was introduced for high risk paediatric groups, including Indigenous children, in late 2001. Of 1,355 isolates from non-Indigenous children, 86 per cent belonged to serotypes and 93 per cent to serogroups represented in the 7-valent pneumococcal conjugate vaccine. Thirteen per cent and 24 per cent of isolates had reduced susceptibility to penicillin and erythromycin, respectively and of these, more than 99 per cent belonged to serogroups represented in the 7-valent vaccine. Of the 1,504 isolates from non-Indigenous adults, 96 per cent belonged to serotypes included in the 23-valent polysaccharide vaccine; 14 per cent and 15 per cent had reduced susceptibility to penicillin and erythromycin, respectively and more than 95 per cent of these belonged to serotypes included in the 7-valent conjugate vaccine. In Western Australia and the Northern Territory (the only states for which Indigenous status was consistently available), there were 29 cases of IPD in Indigenous children, of which 21 were due to 7-valent vaccine serotypes in 2001, compared with 24 cases, including 10 due to vaccine serotypes, in 2002. This represents a statistically significant increase in the proportion of total isolates due to non-vaccine serotypes (chi2 = 3.93, p = 0.048) following the introduction of the 7-valent conjugate vaccine, principally due to serotypes 7F and 12F. The number of episodes due to penicillin resistant isolates decreased from nine in 2001 to two in 2002. Ninety per cent of isolates from Indigenous adults were included in the 23-valent polysaccharide vaccine and six per cent and five per cent had reduced susceptibility to penicillin and erythromycin, respectively. Conjugate pneumococcal vaccines can be expected to reduce the incidence of IPD due to vaccine serotypes in vaccinated children and potentially, their adult contacts. It may also impact favourably on the incidence of IPD due to penicillin and erythromycin resistant strains. Continued surveillance of both serotype distribution and antibiotic susceptibility are required to identify serotype replacement by non-vaccine serotypes and to monitor the overall impact of current and future vaccine programs on invasive pneumococcal disease in Australia.

Adolescent↗