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1.  Glucagon-like peptide-2 (GLP-2) increases net amino acid utilization by the portal-drained viscera of ruminating calves 
Glucagon-like peptide-2 (GLP-2) increases small intestinal mass and blood flow in ruminant calves, but its impact on nutrient metabolism across the portal-drained viscera (PDV) and liver is unknown. Eight Holstein calves with catheters in the carotid artery, mesenteric vein, portal vein and hepatic vein were paired by age and randomly assigned to control (0.5% bovine serum albumin in saline; n =4) or GLP-2 (100 μg/kg BW per day bovine GLP-2 in bovine serum albumin; n =4). Treatments were administered subcutaneously every 12 h for 10 days. Blood flow was measured on days 0 and 10 and included 3 periods: baseline (saline infusion), treatment (infusion of bovine serum albumin or 3.76 μg/kg BW per h GLP-2) and recovery (saline infusion). Arterial concentrations and net PDV, hepatic and total splanchnic fluxes of glucose, lactate, glutamate, glutamine, β-hydroxybutyrate and urea-N were measured on days 0 and 10. Arterial concentrations and net fluxes of all amino acids and glucose metabolism using continuous intravenous infusion of [U13-C]glucose were measured on day 10 only. A 1-h infusion of GLP-2 increased blood flow in the portal and hepatic veins when administered to calves not previously exposed to exogenous GLP-2, but after a 10-day administration of GLP-2 the blood flow response to the 1-h GLP-2 infusion was substantially attenuated. The 1-h GLP-2 infusion also did not appreciably alter nutrient fluxes on either day 0 or 10. In contrast, long-term GLP-2 administration reduced arterial concentrations and net PDV flux of many essential and non-essential amino acids. Despite the significant alterations in amino acid metabolism, glucose irreversible loss and utilization by PDV and non-PDV tissues were not affected by GLP-2. Fluxes of amino acids across the PDV were generally reduced by GLP-2, potentially by increased small intestinal epithelial growth and thus energy and amino acid requirements of this tissue. Increased PDV extraction of glutamine and alterations in PDV metabolism of arginine, ornithine and citrulline support the concept that GLP-2 influences intestine-specific amino acid metabolism. Alterations in amino acid metabolism but unchanged glucose metabolism suggests that the growth effects induced by GLP-2 in ruminants increase reliance on amino acids preferentially over glucose. Thus, GLP-2 increases PDV utilization of amino acids, but not glucose, concurrent with stimulated growth of the small intestinal epithelium in post-absorptive ruminant calves.
doi:10.1017/S175173111200095X
PMCID: PMC3973745  PMID: 23031436
blood flow; glucose; amino acid; flux; ruminant
2.  Alcohol consumption in men is influenced by qualitatively different genetic factors in adolescence and adulthood 
Psychological medicine  2013;43(9):1857-1868.
Background
Alcohol consumption is influenced by genetic factors. Previous studies have examined the heritability of alcohol consumption, or related phenotypes, from adolescence into adulthood, frequently finding that total heritability changes over time. However, it remains unclear whether the same genes underlie liability to alcohol consumption across development versus whether novel risk genes become important over time.
Method
A population-based study of adult male twins (n=1790) born in Virginia, USA, retrospectively reported on their average monthly alcohol consumption from early adolescence through adulthood. We used twin modeling methods to explore genetic and environmental influences on alcohol consumption over time.
Results
One latent genetic factor accounted for the majority of the heritability in alcohol consumption during mid-to late adolescence, but its influence declined thereafter ; from young adulthood forward, heritability was largely attributable to a second genetic factor. The total heritability of alcohol consumption increased from 0 at ages 12–14 years to 0.40 by ages 18–21 years. Shared environmental factors declined in influence over time.
Conclusions
The heritability of alcohol consumption over time is dynamic both quantitatively and qualitatively. These results have important implications for gene identification endeavors. Furthermore, these findings could inform efforts to elucidate developmentally dynamic behaviors, such as antisocial behavior.
doi:10.1017/S0033291712002917
PMCID: PMC3670965  PMID: 23282961
Adolescent-limited genetic factors; alcohol consumption; gene identification; genetic influences; genetic innovation; twin modeling
3.  Mode of Communication, Perceived Level of Understanding, and Perceived Quality of Life in Youth Who Are Deaf or Hard of Hearing 
Given the important role of parent–youth communication in adolescent well-being and quality of life, we sought to examine the relationship between specific communication variables and youth perceived quality of life in general and as a deaf or hard-of-hearing (DHH) individual. A convenience sample of 230 youth (mean age = 14.1, standard deviation = 2.2; 24% used sign only, 40% speech only, and 36% sign + speech) was surveyed on communication-related issues, generic and DHH-specific quality of life, and depression symptoms. Higher youth perception of their ability to understand parents’ communication was significantly correlated with perceived quality of life as well as lower reported depressive symptoms and lower perceived stigma. Youth who use speech as their single mode of communication were more likely to report greater stigma associated with being DHH than youth who used both speech and sign. These findings demonstrate the importance of youths’ perceptions of communication with their parents on generic and DHH-specific youth quality of life.
doi:10.1093/deafed/enr015
PMCID: PMC3202327  PMID: 21536686
4.  The quantitative-genetic and QTL architecture of trait integration and modularity in Brassica rapa across simulated seasonal settings 
Heredity  2010;106(4):661-677.
Within organisms, groups of traits with different functions are frequently modular, such that variation among modules is independent and variation within modules is tightly integrated, or correlated. Here, we investigated patterns of trait integration and modularity in Brassica rapa in response to three simulated seasonal temperature/photoperiod conditions. The goals of this research were to use trait correlations to understand patterns of trait integration and modularity within and among floral, vegetative and phenological traits of B. rapa in each of three treatments, to examine the QTL architecture underlying patterns of trait integration and modularity, and to quantify how variation in temperature and photoperiod affects the correlation structure and QTL architecture of traits. All floral organs of B. rapa were strongly correlated, and contrary to expectations, floral and vegetative traits were also correlated. Extensive QTL co-localization suggests that covariation of these traits is likely due to pleiotropy, although physically linked loci that independently affect individual traits cannot be ruled out. Across treatments, the structure of genotypic and QTL correlations was generally conserved. Any observed variation in genetic architecture arose from genotype × environment interactions (GEIs) and attendant QTL × E in response to temperature but not photoperiod.
doi:10.1038/hdy.2010.103
PMCID: PMC3183896  PMID: 20736971
Brassica rapa; flowers; modularity; photoperiod; temperature; trait integration
5.  A population-based twin study of the genetic and environmental relationship of major depression, regular tobacco use and nicotine dependence 
Psychological medicine  2010;41(2):395-405.
Background
Numerous epidemiological studies have reported a positive association between major depression (MD) and regular tobacco use (RU) or nicotine dependence (ND). However, few have used a genetically informative design to assess whether these traits share a common genetic and/or environmental liability.
Method
We assessed MD, RU and ND in same-sex twins from the population-based Swedish Twin Registry. In males, we examined both cigarette use and snus (smokeless tobacco) use. We used structural equation modeling to examine the relationship between MD, RU, and ND given RU.
Results
The results suggest modest correlations between MD and RU, and between MD and ND. In males, the liability shared between MD and RU is solely genetic for both cigarettes and snus, while MD and ND share both genetic and unique environmental influences. The continuation to ND given RU differed considerably between cigarette and snus users. In females, both MD–RU and MD–ND relationships are partially attributable to genetic and unique environmental correlations.
Conclusions
The relationship among MD, RU and ND is at least partially attributable to shared genetic and environmental risk factors. The genetic and environmental correlations between traits are modest. The nature of the shared liability differs by sex, and in males, by the type of tobacco product used. Differences between previous reports and results presented in the current study are suggestive of population differences in how MD and tobacco use inter-relate.
doi:10.1017/S0033291710000589
PMCID: PMC3016459  PMID: 20406522
Genetic risk; shared liability; twin modeling
6.  Audit-induced change reduces complications of the Ganz trochanteric flip approach 
INTRODUCTION
The Ganz trochanteric flip approach aims to avoid the potential risk of avascular necrosis in hip conserving surgery and may reduce the risk of femoral neck fractures, neck thinning and femoral head implant migration in hip resurfacing. Our initial audit revealed the complications of non-union and trochanteric screw irritation to be associated with this approach. We, therefore, modified our selection criteria and re-audited our results.
SUBJECTS AND METHODS
The initial audit (IA) ran between January 2003 and November 2007 after which an age limit of 50 years was recommended. The re-audit (RA) ran between November 2007 and December 2008 where one of the senior authors stopped using the approach in the over 50 year age group whilst the other senior author continued on selected patients over 50 years.
RESULTS
There were 545 hips in the IA and 152 hips in the RA group. The incidence of non-union decreased in the RA after the change of selection criteria (6.2% [IA] vs 1.3% [RA]). In both audit groups, the incidence of non-union increased with age, and in the RA no non-unions were observed under the age of 50 years. The incidence of screw irritation and the necessity for removal remained relatively unchanged (20.7% [IA] vs 28.3% [RA]) with a combined incidence of 22.4%.
CONCLUSIONS
The trochanteric flip approach to the hip can be used safely with an acceptable complication rate in young adult impingement and resurfacing surgery. Caution must, however, be exercised in patients over 50 years of age as they have a higher incidence of trochanteric non-union. In addition, all patients should be consented for the possibility of screw removal as a second procedure.
doi:10.1308/003588410X12699663904637
PMCID: PMC3229358  PMID: 20615300
Ganz trochanteric flip; Audit; Complications; Non-union; Screw irritation
7.  Visualizing CD4 T-cell migration into inflamed skin and its inhibition by CCR4/CCR10 blockades using in vivo imaging model 
The British journal of dermatology  2009;162(3):487-496.
Summary
Background
Chemokines are critical mediators of T-cell homing into inflamed skin. The complex nature of this multicellular response makes it difficult to analyse mechanisms mediating the early responses in vivo.
Objectives
To directly visualize T-cell homing into inflamed skin and its inhibition by blockades using a unique noninvasive confocal microscopy.
Materials and methods
A mouse model of allergic contact dermatitis was used. T cells from oxazolone-sensitized and -challenged Balb/c mice were first analysed phenotypically in vitro. CD4 T cells were then labelled with a tracker dye and transferred into Balb/c-SCID mice. The recipient mice were challenged with oxazolone and CD4 T-cell homing into inflamed skin was visualized.
Results
T cells with the skin homing receptors CCR4 and CCR10 were increased in the affected skin and draining lymph nodes, and effectively attracted by their specific chemokines CCL17, CCL22 and CCL27 in vitro. Using in vivo imaging, T-cell migration into the inflamed skin was observed at 2 h after application, peaking at 12 h and continuing for 48 h. Simultaneous systemic administration of neutralizing antibodies against CCR4 ligands (CCL17 and CCL 22) and CCR10 ligand (CCL27) led to a significant suppression of T-cell migration and skin inflammation.
Conclusions
Our data indicate that these tissue-selective adhesion molecules and chemokine/receptor pathways act in concert to attract specialized T-cell populations to mediate cutaneous inflammation. The in vivo imaging technique can be applicable to other models of cutaneous diseases to help with better understanding of the pathogenesis and monitoring the therapeutic effects.
doi:10.1111/j.1365-2133.2009.09552.x
PMCID: PMC3037861  PMID: 19832835
cell trafficking; chemokines; skin homing; T cells
8.  The cosmopolitan maternal heritage of the Thoroughbred racehorse breed shows a significant contribution from British and Irish native mares 
Biology Letters  2010;7(2):316-320.
The paternal origins of Thoroughbred racehorses trace back to a handful of Middle Eastern stallions, imported to the British Isles during the seventeenth century. Yet, few details of the foundation mares were recorded, in many cases not even their names (several different maternal lineages trace back to ‘A Royal Mare’). This has fuelled intense speculation over their origins. We examined mitochondrial DNA from 1929 horses to determine the origin of Thoroughbred foundation mares. There is no evidence to support exclusive Arab maternal origins as some historical records have suggested, or a significant importation of Oriental mares (the term used in historic records to refer to Middle East and western Asian breeds including Arab, Akhal-Teke, Barb and Caspian). Instead, we show that Thoroughbred foundation mares had a cosmopolitan European heritage with a far greater contribution from British and Irish Native mares than previously recognized.
doi:10.1098/rsbl.2010.0800
PMCID: PMC3061175  PMID: 20926431
Thoroughbred horse; foundation of breed; maternal origins; phylogenetics; mitochondrial DNA
9.  The autoantibody rheumatoid factor may be an independent risk factor for ischaemic heart disease in men 
Heart  2007;93(10):1263-1267.
Background
Subjects with rheumatoid arthritis have an increased prevalence of ischaemic heart disease (IHD). This is most likely in those people with the autoantibody rheumatoid factor (RF). RF is strongly associated with rheumatoid arthritis (RA) but is also present in up to 15% of all adults.
Objective
To determine whether RF might identify people in a general population who also share an increased likelihood of developing IHD.
Methods
Subjects from the Hertfordshire Cohort Study were investigated for the presence of RF. Subjects completed a questionnaire and attended a clinic where a history of IHD was recorded (ECG, coronary artery bypass grafting, Rose chest pain). Associations between the presence of RF, antinuclear antibodies (ANA), anticardiolipin antibodies (ACA) and IHD in 567 men and 589 women were investigated and compared with traditional risk factors for IHD.
Results
RF was associated with an increased likelihood of IHD in men (odds ratio (OR) = 3.1, 95% CI 1.7 to 5.4, p<0.001). This increased risk could not be explained by traditional risk factors for IHD (mutually adjusted OR for RF 2.9 (95% CI 1.6 to 5.3), p<0.001). There was no significant association between RF in women or between ANA or ACA with IHD in men or women.
Conclusion
This work suggests that RF is an independent risk factor for IHD in the general population. It lends support to the importance of inflammation in atherosclerosis and suggests that autoimmune processes may be involved. In addition, it raises the intriguing possibility that RF may have a direct role in the pathogenesis of IHD in some subjects.
doi:10.1136/hrt.2006.097816
PMCID: PMC2000921  PMID: 17550930
10.  Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative 
Objective
To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA).
Methods
697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008–9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007–2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.
Results
A total of 39 756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA.
Conclusions
Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.
doi:10.1136/ard.2010.130625
PMCID: PMC3002765  PMID: 20724311
12.  Case of the month: Cutaneous myiasis in a returning traveller from the Algarve: first report of tumbu maggots, Cordylobia anthropophaga, acquired in Portugal 
Emergency Medicine Journal : EMJ  2006;23(3):236-237.
A 61 year old woman returning to the UK from the Algarve and complaining of boil‐like lesions was found to have cutaneous myiasis caused by tumbu maggots, Cordylobia anthropophaga. This is apparently the first report of acquisition of this form of myiasis in Portugal.
doi:10.1136/emj.2005.028365
PMCID: PMC2464429  PMID: 16498169
myiasis; tumbu; Cordylobia anthropophaga; Portugal
13.  Growth and infectious exposure during infancy and the risk of rheumatoid factor in adult life 
Annals of the Rheumatic Diseases  2005;65(3):401-404.
Background
The contribution of the environment to rheumatoid arthritis (RA) remains uncertain. Intrauterine and early postnatal life may be important. Rheumatoid factor (RF) found in around 10% of the normal population confers a risk of developing RA and may be present years before onset of clinical disease. The immune pathology leading to RA and RF may have similar genetic and environmental influences.
Objective
To measure RF in people for whom data on birth weight, infant growth, and markers of infectious exposure during infancy and childhood, had been previously recorded.
Methods
675 men and 668 women aged 59–67 years, born and still resident in Hertfordshire, UK, were studied. RF was measured with an ELISA. Associations between presence of RF, early growth, and markers of hygiene in infancy, were investigated.
Results
RF was detected in 112/675 (16.6%) men and 79/668 (11.8%) women. No significant relationships existed between early growth and presence of RF in men or women. Among women, sharing a bedroom during childhood was associated with a lower risk of RF positivity (OR = 0.48, 95% CI 0.30 to 0.78, p = 0.003).
Conclusions
A developing immune system exposed to increased infectious exposure is less likely to produce RF in adult life; this may reduce the pathological process which leads to RA.
doi:10.1136/ard.2005.036301
PMCID: PMC1798049  PMID: 16079171
rheumatoid factor; rheumatoid arthritis; environment; infection; hygiene
14.  Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative 
Annals of the Rheumatic Diseases  2008;68(7):1086-1093.
Objectives:
To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders.
Methods:
751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.
Results:
A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases.
Conclusions:
Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.
doi:10.1136/ard.2008.094474
PMCID: PMC2689523  PMID: 19033291
15.  An unusual cause of an acutely locked knee 
Emergency Medicine Journal : EMJ  2005;22(8):588-589.
doi:10.1136/emj.2003.012567
PMCID: PMC1726871  PMID: 16046768
16.  Remote sensing-based predictors improve distribution models of rare, early successional and broadleaf tree species in Utah 
The Journal of Applied Ecology  2007;44(5):1057-1067.
Compared to bioclimatic variables, remote sensing predictors are rarely used for predictive species modelling. When used, the predictors represent typically habitat classifications or filters rather than gradual spectral, surface or biophysical properties. Consequently, the full potential of remotely sensed predictors for modelling the spatial distribution of species remains unexplored. Here we analysed the partial contributions of remotely sensed and climatic predictor sets to explain and predict the distribution of 19 tree species in Utah. We also tested how these partial contributions were related to characteristics such as successional types or species traits.We developed two spatial predictor sets of remotely sensed and topo-climatic variables to explain the distribution of tree species. We used variation partitioning techniques applied to generalized linear models to explore the combined and partial predictive powers of the two predictor sets. Non-parametric tests were used to explore the relationships between the partial model contributions of both predictor sets and species characteristics.More than 60% of the variation explained by the models represented contributions by one of the two partial predictor sets alone, with topo-climatic variables outperforming the remotely sensed predictors. However, the partial models derived from only remotely sensed predictors still provided high model accuracies, indicating a significant correlation between climate and remote sensing variables. The overall accuracy of the models was high, but small sample sizes had a strong effect on cross-validated accuracies for rare species.Models of early successional and broadleaf species benefited significantly more from adding remotely sensed predictors than did late seral and needleleaf species. The core-satellite species types differed significantly with respect to overall model accuracies. Models of satellite and urban species, both with low prevalence, benefited more from use of remotely sensed predictors than did the more frequent core species.Synthesis and applications. If carefully prepared, remotely sensed variables are useful additional predictors for the spatial distribution of trees. Major improvements resulted for deciduous, early successional, satellite and rare species. The ability to improve model accuracy for species having markedly different life history strategies is a crucial step for assessing effects of global change.
doi:10.1111/j.1365-2664.2007.01348.x
PMCID: PMC2368764  PMID: 18642470
core-satellite species hypothesis; K-fold cross-validation; Landsat TM; partial regression; predictive habitat distribution models; species traits; variation partitioning
17.  Out of the Smokescreen: does an anti-smoking advertisement affect young women's perception of smoking in movies and their intention to smoke? 
Tobacco Control  2004;13(3):277-282.
Objective: To evaluate the effect of an anti-smoking advertisement on young women's perceptions of smoking in movies and their intention to smoke.
Subjects/setting: 2038 females aged 12–17 years attending cinemas in New South Wales, Australia.
Design/intervention: Quasi-experimental study of patrons, who were surveyed after having viewed a movie at their local cinema. The control group was surveyed during week 1 and the intervention group, during week 2. Before seeing the movie in week 2, a 30 second anti-smoking advertisement was shown, which featured a well known female actor drawing attention to the prevalence of smoking in movies.
Outcomes: Attitude of current smokers and non-smokers to smoking in the movies; intention of current smokers and non-smokers to be smoking in 12 months time.
Results: Among non-smokers, 48.2% of the intervention subjects thought that the smoking in the movie they viewed was "not OK" compared with 28.3% of the control subjects (p < 0.0001). However, there was no difference among smokers in the intervention (26.4%) and control (16.9%) groups (p = 0.28). A higher percentage of current smokers in the intervention group indicated they were unlikely to smoke in 12 months time (47.8%) than smokers in the control condition (31.9%) (p = 0.03). For non-smokers, there was no difference in smoking intentions between conditions, with 95% saying they would be unlikely to be smoking in 12 months time.
Conclusions: This "real world" study suggests that placing an anti-smoking advertisement before movies containing smoking scenes can help to "immunise" young women against the influences of film stars smoking.
doi:10.1136/tc.2003.005280
PMCID: PMC1747895  PMID: 15333884
18.  High grade heart block in association with SLE 
doi:10.1136/ard.2002.005322
PMCID: PMC1754990  PMID: 15082501
19.  Early history of European domestic cattle as revealed by ancient DNA 
Biology Letters  2005;2(1):155-159.
We present an extensive ancient DNA analysis of mainly Neolithic cattle bones sampled from archaeological sites along the route of Neolithic expansion, from Turkey to North-Central Europe and Britain. We place this first reasonable population sample of Neolithic cattle mitochondrial DNA sequence diversity in context to illustrate the continuity of haplotype variation patterns from the first European domestic cattle to the present. Interestingly, the dominant Central European pattern, a starburst phylogeny around the modal sequence, T3, has a Neolithic origin, and the reduced diversity within this cluster in the ancient samples accords with their shorter history of post-domestic accumulation of mutation.
doi:10.1098/rsbl.2005.0404
PMCID: PMC1617209  PMID: 17148352
ancient DNA; Bos taurus; Neolithic; domestication; mitochondrial haplotypes; starburst network
20.  Intervention to reduce environmental tobacco smoke exposure in Latino children: null effects on hair biomarkers and parent reports 
Tobacco Control  2004;13(1):90-92.
Design: A two group, randomised control trial was conducted.
Setting: Areas of San Diego county with a large Latino population.
Participants: 143 Latino parent–child pairs.
Intervention: Trained bicultural and bilingual Latina lay community health advisors, or promotoras, conducted problem solving aimed at lowering the target child's exposure to ETS in the household. Six home and telephone sessions were delivered by the promotoras over a four month period.
Main outcome measures: Outcome measures were collected at baseline, immediately post-intervention, three months post-intervention, and 12 months post-intervention. Four outcomes were considered: (1) parent's paper-and-pencil reports of the child's past month exposure; (2) hair samples from the child analysed for past month nicotine; (3) hair samples from the child analysed for past month cotinine; and (4) per cent confirmed reducers.
Results: There were no significant condition-by-time interactions, the term indicative of a differential intervention effect. Significant or near significant time main effects were seen for children's hair cotinine, per cent confirmed reducers, and, in particular, parent reports of exposure.
Conclusions: Applying a lay promotora model to deliver the behavioural problem solving intervention unfortunately was not effective. A likely explanation relates to the difficulty of delivering a relatively complex intervention by lay women untrained in behaviour change theory and research methods.
doi:10.1136/tc.2003.004440
PMCID: PMC1747828  PMID: 14985605
21.  Relationship between birth weight and adult lung function: controlling for maternal factors 
Thorax  2003;58(12):1061-1065.
Methods: In 2001 the cohort was assessed for current lung function, smoking status, and respiratory symptoms. Birth details obtained from the Aberdeen Maternity and Neonatal Databank recorded birth weight, gestation, parity, and mother's age and height.
Results: 381 subjects aged 45–50 years were traced and tested for lung function; 323 (85%) had birth details available. A significant linear trend (p<0.01) was observed between birth weight and current forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) values (adjusted for height, age, sex, weight, deprivation category (Depcat), childhood group, and smoking status). This trend remained significant after adjusting birth weight for gestation, parity, sex, mother's height and weight (p = 0.01). The relationship between birth weight and FEV1 and FVC remained significant when adjusted for smoking history. There was no association between birth weight and current wheezing symptoms.
Conclusion: There is a positive linear trend between birth weight, adjusted for maternal factors, and lung function in adulthood. The strength of this association supports the "fetal origins hypothesis" that impairment of fetal growth is a significant influence on adult lung function.
doi:10.1136/thorax.58.12.1061
PMCID: PMC1746540  PMID: 14645976
22.  Passive Sexual Transmission of Human Immunodeficiency Virus Type 1 Variants and Adaptation in New Hosts†  
Journal of Virology  2006;80(14):7226-7234.
Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.
doi:10.1128/JVI.02014-05
PMCID: PMC1489048  PMID: 16809328
23.  Evaluation of a Commercial Latex Agglutination Assay for Serological Diagnosis of Leptospirosis 
Journal of Clinical Microbiology  2006;44(5):1853-1855.
Leptospirosis is a febrile zoonosis of worldwide distribution. A latex agglutination assay was evaluated in two studies, the first using a panel of well-characterized sera from patients with leptospirosis and from patients with other disease states and the second, a prospective hospital-based study, evaluating sera from 186 consecutive patients admitted to hospital with acute febrile illness. The confirmed leptospirosis serum panel included paired acute- and convalescent-phase specimens from 40 cases, of which 34 gave positive latex tests (case sensitivity, 85%; 95% confidence interval [95% CI], 70 to 94%). The other diseases represented in the panel of 112 specimens from nonleptospirosis patients included autoimmune diseases, brucellosis, dengue, melioidosis, malaria, syphilis, toxoplasmosis, viral hepatitis, and a number of other viral infections. The specificity of latex agglutination using this panel was 81% (95% CI, 73 to 87%). Among the patients with acute febrile illness, there were 25 cases of leptospirosis and 161 patients with other diagnoses. The sensitivity and specificity of latex agglutination in this group were 88% (95% CI, 72 to 97%) and 98% (95% CI, 95 to 100%), respectively. In this evaluation, the two distinct groups of specimens gave similar results for sensitivity, but specificity was different in each study. The sensitivity and specificity observed for the hospital study were similar to those obtained in evaluations of other rapid tests in the same population. The results of this study suggest that multiple evaluations of new diagnostic assays should be performed, because performance characteristics may vary in different populations.
doi:10.1128/JCM.44.5.1853-1855.2006
PMCID: PMC1479163  PMID: 16672421
24.  Associations between ST depression, four year mortality, and in-hospital revascularisation in unselected patients with non-ST elevation acute coronary syndromes 
Heart  2003;89(5):490-495.
Objective: To determine the associations between changes on the presenting ECG, in-hospital revascularisation, and four year mortality in patients with non-ST elevation acute coronary syndromes.
Design: Prospective evaluation of all consecutive patients admitted in 1993 to the Green Lane Hospital coronary care unit, Auckland, New Zealand. Late follow up was undertaken at a median of 52 months. The ECGs were analysed after the hospital admission.
Setting: Tertiary referral centre with direct local coronary care unit admissions.
Interventions: Patients underwent physician recommended in-hospital revascularisation or initial conservative management.
Results: The four year survival was 88% in the 115 patients who underwent revascularisation (65 (19%) percutaneous and 53 (16%) surgical revascularisation), compared with 75% in 316 patients managed conservatively (p = 0.024). Four year survival for patients undergoing revascularisation versus initial conservative management with respect to ECG groups was: no ECG changes (n = 101), 97% v 92% (p = 0.35); T wave inversion or 0.5 mm ST depression (n = 108), 89% v 78% (p = 0.18); ST depression ≥ 1 mm (n = 122), 80% v 58% (p = 0.014); χ2 = 29, p < 0.001 for the linear trend across the groups. On multivariate analysis, independent predictors of four year mortality were: age (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.08; p = 0.0046); ECG group (OR 1.88, 95% CI 1.21 to 2.95; p = 0.043); radiological pulmonary oedema (OR 2.81, 95% CI 1.18 to 7.05; p = 0.025); and revascularisation (OR 0.43, 95% CI 0.20 to 0.90; p = 0.023).
Conclusions: Among unselected patients with non-ST elevation acute coronary syndromes, in-hospital revascularisation is associated with decreased mortality at up to four years after admission. This association appears greater in patients with ST depression of ≥ 1 mm on the presenting ECG.
PMCID: PMC1767628  PMID: 12695448
mortality; revascularisation; acute coronary syndrome
25.  The effect of gel burns dressings on skin temperature 
Emergency Medicine Journal : EMJ  2002;19(3):224-225.
Objectives: This study was designed to investigate the effect on skin temperature of different methods of use of a hydrogel dressing.
Methods: Twelve volunteers had temperature measured under a hydrogel dressing with different combinations of air movement and bandaging.
Results: A large drop in skin temperature was only achieved when the dressing was left exposed with air movement over the surface of the dressing.
Conclusions: A temperature that gives effective analgesia is not reached if the dressing is used in accordance with the manufacturer's instructions (covered with an insulating layer). This explains the authors' observation that paramedics and patients often leave these dressings uncovered.
doi:10.1136/emj.19.3.224
PMCID: PMC1725847  PMID: 11971832

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