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M Clements

Publications and source records attributed to M Clements.

At least 19 recordsLinked to original sources
PubMed2007

Predicting case numbers during infectious disease outbreaks when some cases are undiagnosed.

We describe a method for calculating 95 per cent bounds for the current number of hidden cases and the future number of diagnosed cases during an outbreak of an infectious disease. A Bayesian Markov chain Monte Carlo approach is used to fit a model of infectious disease transmission that takes account of undiagnosed cases. Assessing this method on simulated data, we find that it provides conservative 95 per cent bounds for the number of undiagnosed cases and future case numbers, and that these bounds are robust to modifications in the assumptions generating the simulated data. Moreover, the method provides a good estimate of the initial reproduction number, and the reproduction number in the latter stages of the outbreak. Applying the approach to SARS data from Hong Kong, Singapore, Taiwan and Canada, the bounds on future diagnosed cases are found to be reliable, and the bounds on hidden cases suggests that there were few hidden cases remaining at the end of the outbreaks in each region. We estimate that the initial reproduction numbers lay between 1.5 and 3, and the reproduction numbers in the later stages of the outbreak lay between 0.36 and 0.6.

Bayes Theorem↗
PubMed2004

The relationship between fast bowling workload and injury in first-class cricketers: a pilot study.

This study examined the relationship between the bowling workload of first-class fast bowlers and injury with the aim of identifying a "safe" fast bowling workload threshold. Twelve male fast bowlers (mean age 25 years) from an Australian state cricket squad were observed for the 1999--2000 cricket season. Workload was quantified by examining fixture scorecards and conducting surveillance at training sessions. Injury data were obtained from Cricket Australia's Injury Surveillance System. The seasonal incidence of injury was high with seven bowlers sustaining nine injuries. Whilst injured bowlers did not tend to bowl a greater number of deliveries on the day of injury, a significant increase in deliveries per session was observed in the 8-21 days prior to the date of injury (mean= 77) as compared with the rest of the season (mean= 60, p< 0.02). Bowlers with a weekly bowling workload above the mean of 203 deliveries were at an increased risk of injury (Risk Ratio (RR)= 6.0, 95% confidence interval (CI) 1.00-35.91). Those bowlers who bowled in five or more sessions in any 7-day period were also at an increased risk of injury (RR= 4.5, 95% CI 1.02 to 20.12). A consistent relationship between high bowling workload and injury was observed. The risk of injury was much higher for those bowlers with a sessional, weekly and monthly bowling workload above the group mean, especially when this high workload was consistent and sustained.

Adult↗
PubMed2001

Expression of the cysteinyl leukotriene 1 receptor in normal human lung and peripheral blood leukocytes.

The cysteinyl leukotrienes (CysLTs) are important mediators of human asthma. Pharmacologic and clinical studies show that the CysLTs exert most of their bronchoconstrictive and proinflammatory effects through activation of a putative, 7-transmembrane domain, G-protein-coupled receptor, the CysLT1 receptor. The initial molecular characterization of the CysLT1 receptor showed by in situ hybridization, the presence of CysLT1 receptor messenger RNA (mRNA) in human lung smooth-muscle cells and lung macrophages. We confirmed the results of these in situ hybridization analyses for the CysLT1 receptor, and produced the first immunohistochemical characterization of the CysLT1 receptor protein in human lung. The identification of the CysLT1 receptor in the lung is consistent with the antibronchoconstrictive and antiinflammatory actions of CysLT1 receptor antagonists. We also report the expression of CysLT1 receptor mRNA and protein in most peripheral blood eosinophils and pregranulocytic CD34+ cells, and in subsets of monocytes and B lymphocytes.

Blood↗
PubMed2001

Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders.

The homeobox gene Hesx1/HESX1 has been implicated in the establishment of anterior pattern in the central nervous system (CNS) in a number of vertebrate species. Its role in pituitary development has been documented through loss-of-function studies in the mouse. A homozygous missense point mutation resulting in a single amino acid substitution, Arg160Cys (R160C), is associated with a heritable form of the human condition of septo-optic dysplasia (SOD). We have examined the phenotype of affected members in this pedigree in more detail and demonstrate for the first time a genetic basis for midline defects associated with an undescended or ectopic posterior pituitary. A similar structural pituitary abnormality was observed in a second patient heterozygous for another mutation in HESX1, Ser170Leu (S170L). Association of S170L with a pituitary phenotype may be a direct consequence of the HESX1 mutation since S170L is also associated with a dominant familial form of pituitary disease. However, a third mutation in HESX1, Asn125Ser (N125S), occurs at a high frequency in the Afro-Caribbean population and may therefore reflect a population-specific polymorphism. To investigate the molecular basis for these clinical phenotypes, we have examined the impact of these mutations on the regulatory functions of HESX1. We show that Hesx1 is a promoter-specific transcriptional repressor with a minimal 36 amino acid repression domain which can mediate promoter-specific repression by suppressing the activity of homeodomain-containing activator proteins. Mutations in HESX1 associated with pituitary disease appear to modulate the DNA-binding affinity of HESX1 rather than its transcriptional activity. Wild-type HESX1 binds a dimeric homeodomain site with high affinity (K(d) 31 nM) whilst HESX1(S170L) binds with a 5-fold lower activity (K(d) 150 nM) and HESX1(R160C) does not bind at all. Although HESX1(R160C) has only been shown to be associated with the SOD phenotype in children homozygous for the mutation, HESX1(R160C) can inhibit DNA binding by wild-type HESX1 both in vitro and in vivo in cell culture. This dominant negative activity of HESX1(R160C) is mediated by the Hesx1 repression domain, supporting the idea that the repression domain is implicated in interactions between homeodomain proteins. Our data suggest a possible molecular paradigm for the dominant inheritance observed in some pituitary disorders.

Animals↗
PubMed2001

Virulence gene regulation in Salmonella enterica.

In order to infect a host, a microbe must be equipped with special properties known as virulence factors. Bacterial virulence factors are required to facilitate colonization, to survive under host defenses, and to permit multiplication inside the host. However, the possession of genes encoding virulence factors does not guarantee effective infection. There is considerable evidence that tight regulation of a given virulence factor is as important as the possession of the virulence factors themselves. Thus, an understanding of the regulation of virulence expression is fundamental to our comprehension of any infection process and can identify potential targets for disease prevention and therapy. We have summarized the lessons learned from experimental salmonellosis in terms of virulence regulation and hope to illustrate the differing requirements for gene and virulence expression.

Adaptation, Physiological↗
PubMed2000

Domestic fire injuries treated in New Zealand hospitals 1988-1995.

AIM: To describe demographic features of people discharged from New Zealand hospitals following injury caused by fire and flame in domestic locations. METHOD: Review of hospital discharge data for the years 1988-1995. RESULTS: From 1988-1995 there were 1493 discharges from New Zealand hospitals with injury as the result of fire and flame in domestic locations. Age-standardised hospitalisation rates for fire related injury over the period have been stable, with an overall discharge rate of 5.45 hospitalisations per 100000 person years. Male discharges exceeded female in all years (RR 1.97, 95% CI 1.73-2.14). Stratification by age indicated that discharge rates were highest among New Zealanders aged over 75 years and under fifteen years. Maori discharge rates exceeded non-Maori over all age groups (RR 3.3, 95% CI 2.82-3.58). CONCLUSION: Maori discharge rates for fire related injury in the home are substantially higher than non-Maori in all age groups, and highlight the importance of developing culturally appropriate injury prevention strategies. Social and material determinants of injury need to be addressed through public policy, provision of quality housing and community development initiatives.

Accidents, Home↗
PubMed2000

Hex is a transcriptional repressor that contributes to anterior identity and suppresses Spemann organiser function.

One of the earliest markers of anterior asymmetry in vertebrate embryos is the transcription factor Hex. We find that Hex is a transcriptional repressor that can be converted to an activator by fusing full length Hex to two copies of the minimal transcriptional activation domain of VP16 together with the flexible hinge region of the (lambda) repressor (Hex-(lambda)VP2). Retention of the entire Hex open reading frame allows one to examine Hex function without disrupting potential protein-protein interactions. Expression of Hex-(lambda)VP2 in Xenopus inhibits expression of the anterior marker Cerberus and results in anterior truncations. Such embryos have multiple notochords and disorganised muscle tissue. These effects can occur in a cell non-autonomous manner, suggesting that one role of wild-type Hex is to specify anterior structures by suppressing signals that promote dorsal mesoderm formation. In support of this idea, over-expression of wild-type Hex causes cell non-autonomous dorso-anteriorization, as well as cell autonomous suppression of dorsal mesoderm. Suppression of dorsal mesoderm by Hex is accompanied by the down-regulation of Goosecoid and Chordin, while induction of dorsal mesoderm by Hex-(lambda)VP2 results in activation of these genes. Transient transfection experiments in ES cells suggest that Goosecoid is a direct target of Hex. Together, our results support a model in which Hex suppresses organiser activity and defines anterior identity.

Animals↗
PubMed2000

The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation.

The homeobox gene Hex is expressed in the anterior visceral endoderm (AVE) and rostral definitive endoderm of early mouse embryos. Later, Hex transcripts are detected in liver, thyroid and endothelial precursor cells. A null mutation was introduced into the Hex locus by homologous recombination in embryonic stem cells. Hex mutant embryos exhibit varying degrees of anterior truncation as well as liver and thyroid dysplasia. The liver diverticulum is formed but migration of hepatocytes into the septum transversum fails to occur. Development of the thyroid is arrested at the thyroid bud stage at 9.5 dpc. Brain defects are restricted to the rostral forebrain and have a caudal limit at the zona limitans intrathalamica, the boundary between dorsal and ventral thalamus. Analysis of Hex(-/-) mutants at early stages shows that the prospective forebrain ectoderm is correctly induced and patterned at 7.5 days post coitum (dpc), but subsequently fails to develop. AVE markers are expressed and correctly positioned but development of rostral definitive endoderm is greatly disturbed in Hex(-/-) embryos. Chimeric embryos composed of Hex(-/-) cells developing within a wild-type visceral endoderm show forebrain defects indicating that Hex is required in the definitive endoderm. All together, these results demonstrate that Hex function is essential in definitive endoderm for normal development of the forebrain, liver and thyroid gland.

Animals↗
PubMed1999

Seasonal differences in risk factors for sudden infant death syndrome. The New Zealand Cot Death Study Group.

The aim of this study was to explore whether the risk of sudden infant death syndrome (SIDS) associated with prone sleeping position and other risk factors varies with season. The study was a large nation-wide case-control study, which compared 485 cases with 1800 controls. Parents of 393 (81.0%) cases and 1591 (88.4%) controls were interviewed. Obstetric records were also examined. Infants dying in winter were older and had lower birthweights than those dying in summer. The increased risk of SIDS associated with prone sleeping position was greater in winter than in summer. In contrast, the increased risk of SIDS associated with excess thermal insulation and bed sharing was less in winter than in summer. Prone sleeping position accounts for about half of the difference between the mortality rate in summer and that in winter. This suggests that some factor related to season modifies the effect of prone sleeping position.

Age Distribution↗
PubMed1998

Ethnic differences in parent/infant co-sleeping practices in New Zealand.

AIM: This study was designed to monitor changes in the prevalence of risk factors for sudden infant death syndrome (SIDS) in the New Zealand population. The behaviour of interest is parent/infant co-sleeping. This paper reports parent/infant co-sleeping arrangements of different ethnic groups in New Zealand. METHODS: A stratified random sample of 6268 infants attending Plunket clinics for their three and six-month visits was taken over the years 1995-1996. Maori and Pacific infants were oversampled. Parents who shared a bed with their infant were asked how they arranged the babies sleeping place according to pre-coded diagrams. Routine parent/infant co-sleeping was defined as "bed sharing at least four nights over the last two weeks". RESULTS: There were 2693 infants who shared the bed with their sleeping parents during at least one of the previous 14 nights. Of these infants, 1060 routinely shared the parents' bed. At three months, 56% of routinely co-sleeping infants slept directly in the bed, 29% slept in a raised position, 3% slept in a carrycot or basket, and 5% in other positions. At six months, 60% of the routinely co-sleeping infants slept directly in the bed with their parents, 23% slept in a raised position, 1% slept in a carrycot or basket, and 7% in other positions. There were significant differences in the co-sleeping locations by ethnicity. CONCLUSION: There is still some ongoing dispute as to whether parent/infant co-sleeping is a risk factor for SIDS. This study has identified differences in the way infants co-sleep with their parents and this can be used to clarify infant care practices in relation to SIDS.

Bedding and Linens↗
PubMed1996

Do differences in the prevalence of risk factors explain the higher mortality from sudden infant death syndrome in New Zealand compared with the UK?

AIMS: To compare the prevalence of risk factors for the sudden infant death syndrome (SIDS) in New Zealand (SIDS mortality 3.53/1000) with that in the South West Thames (SWT) region of the United Kingdom (SIDS mortality 1.36/1000). METHODS: The methodology of the study was essentially identical in New Zealand and SWT. The subjects in both countries were randomly selected from all births in the study regions. The subjects were randomly allocated an age at which to be interviewed using the same questionnaire in the two study areas. Obstetric records were also examined. Eighteen hundred subjects were selected in New Zealand and 700 subjects in SWT. RESULTS: Younger and unmarried mothers were slightly more common in New Zealand than in SWT. The prevalence of maternal smoking, prone sleeping position and infants' sharing of beds with another person were all higher in New Zealand than SWT, thus increasing the risk of SIDS (maternal smoking in pregnancy: 31.0% vs 23.8% respectively, chi 2 = 11.6, p = 0.001; prone sleeping position: 32.9% vs 25.9%, chi 2 = 18.9, p < 0.001; bed sharing: 10.5% vs 6.8%, chi 2 = 6.0, p = 0.14). However, New Zealand infants were breast fed more frequently and for longer than infants in SWT, which would tend to reduce the risk of SIDS in the New Zealand population. In combination the differences in the prevalences of these four risk factors explain only 20% of the excess risk of SIDS in New Zealand. CONCLUSIONS: The high SIDS mortality rate in New Zealand is not simply explained by a high prevalence of known and modifiable risk factors for SIDS.

Breast Feeding↗
PubMed1996

Soft cot mattresses and the sudden infant death syndrome.

AIMS: To investigate whether soft cot mattresses are a risk factor for the sudden infant death syndrome (SIDS). METHODS: A follow up postal questionnaire was sent to the subjects who were interviewed 3.8 years (range 2.2 to 5.2 years) previously as part of the New Zealand Cot Death Study, a large nationwide case-control study. RESULTS: 105 European SIDS cases were compared with 828 European controls. Soft cot mattresses were associated with an increased risk of SIDS (adjusted OR = 2.36; 95% CI = 1.06, 5,25) compared with average or hard mattresses. The firmness of the mattress did not interact with the sleeping position of infant. CONCLUSIONS: Soft cot mattresses should be avoided.

Beds↗
PubMed1996

Marital status and births after losing a baby from sudden infant death.

UNLABELLED: To describe the change in marital status and subsequent live births of mothers who have lost a baby from sudden infant death (SID or cot death), a postal questionnaire was sent to European mothers who had been interviewed approximately 3.7 years (range 2.2-5.2 years) previously as part of a nationwide case-control study. Mothers of 105 (60.3%) cases and 828 (76.9%) controls replied. Changes in marital status between the time of interview and the time of the postal questionnaire did not differ between mothers of cases and that of controls when adjusted for marital status at the time of death/nominated date for controls. Cases were more likely to have further children than controls (P < 0.001) and had them sooner after the death than after the nominated date for control babies (P < 0.001). Case mothers were more likely than controls to have a second child after the death/nominated date, however the interval between the first and second child after the death/nominated date was the same as that for controls. CONCLUSIONS: Although the death of an infant is a major stress on marital relationships, at approximately 3.7 years marital breakdown is no higher than in the control population. After the death of her baby the mother "replaces" the child by having more children than control mothers and having the first one earlier than control mothers. Mothers who lose a baby from SID are more fertile than the control population both before and after the death.

Adult↗
PubMed1995

Immunisation and the sudden infant death syndrome. New Zealand Cot Death Study Group.

AIMS: To examine the relation between immunisation and the risk of sudden infant death syndrome (SIDS). METHODS: A large nationwide case-control study. Parental held records were used to measure immunisation status. RESULTS: Infants were at increased risk of SIDS if they had not received the 6 week, 3 month, and 5 month immunisations. After controlling for potential confounding variables, including those which measured health care use and infant illness, the relative risk of SIDS for infants not being immunised at 6 weeks was 2.1 (95% confidence interval = 1.2, 3.5). Four percent of cases died within four days of immunisation and 7.6% of control infants had been immunised within four days of the nominated date. There was a reduced chance of SIDS in the four days immediately following immunisation (OR = 0.5; 95% CI = 0.2 to 0.9). CONCLUSIONS: Immunisation does not increase the risk of SIDS and may even lower the risk.

Case-Control Studies↗