Search tips
Search criteria

Results 1-14 (14)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
1.  Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study 
BMJ Open  2015;5(1):e006474.
To estimate the efficacy of a probiotic yogurt compared to a pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in children.
Design and setting
This was a multisite, randomised, double-blind, placebo-controlled clinical trial conducted between September 2009 and 2012. The study was conducted through general practices and pharmacies in Launceston, Tasmania, Australia.
Participants and interventions
Children (aged 1–12 years) prescribed antibiotics, were randomised to receive 200 g/day of either yogurt (probiotic) containing Lactobacillus rhamnosus GG (LGG), Bifidobacterium lactis (Bb-12) and Lactobacillus acidophilus (La-5) or a pasteurised yogurt (placebo) for the same duration as their antibiotic treatment.
Stool frequency and consistency were recorded for the duration of treatment plus 1 week. Primary outcome was stool frequency and consistency, classified at different levels of diarrhoea severity. Due to the small number of cases of diarrhoea, comparisons between groups were made using Fisher's exact analysis.
72 children commenced and 70 children (36 placebo and 34 probiotic) completed the trial. There were no incidents of severe diarrhoea (stool consistency ≥6, ≥3 stools/day for ≥2 consecutive days) in the probiotic group and six in the placebo group (Fisher's exact p=0.025). There was also only one episode of minor diarrhoea (stool consistency ≥5, ≥2 stools/day for ≥2 days in the probiotic group compared to 21 in the placebo group (Fisher's exact p<0.001). The probiotic group reported fewer adverse events (1 had abdominal pain, 1 vomited and 1 had headache) than the placebo group (6 had abdominal pain, 4 had loss of appetite and 1 had nausea).
A yogurt combination of LGG, La-5 and Bb-12 is an effective method for reducing the incidence of antibiotic-associated diarrhoea in children.
Trial registration number
Australian New Zealand Clinical Trials Registry ACTRN12609000281291
PMCID: PMC4298112  PMID: 25588782
2.  Zinc status of northern Tasmanian adults 
Information regarding Zn status in the Australian population is very limited. Mild deficiencies in Zn have been associated with CVD, impaired immune function and poor healing. A cross-sectional study of 497 northern Tasmanian adults (24–82 years of age) was conducted to assess Zn status. Dietary intakes were assessed by FFQ and serum concentrations of Zn were evaluated using International Zinc Nutrition Consultative Group methodology. Mean Zn intakes were 12·6 (sd 4·4) mg/d for men and 10·9 (sd 3·6) mg/d for women. It was found that 52 % of men but only 9 % of women consumed less than the Australia/New Zealand estimated average requirement for Zn. Mean serum Zn was 13·0 (sd 2·4) µmol/l in men and 13·0 (sd 2·5) µmol/l in women. Overall, 15 % of men and 7 % of women had low serum Zn levels. Furthermore, low serum Zn was observed in 18 % of men 50 years or older and 30 % of men 70 years or older. The present results suggest that mild Zn deficiency may be prevalent in older Tasmanian adults, particularly men; and due to the importance of Zn in many areas of health, this could be of public health concern.
PMCID: PMC4463943  PMID: 26090095
Zinc status; Population studies; Australia; AGP, α-1 acid glycoprotein ; EAR, estimated average requirement ; IZiNCG, International Zinc Nutrition Consultative Group
3.  Development and Experimental Application of an HPLC Procedure for the Determination of Capsaicin and Dihydrocapsaicin in Serum Samples from Human Subjects 
Total capsaicins are extracted from 2 mL aliquots of serum or plasma using methyl-isobutyl ketone, evaporation of the extract to dryness and reconstitution with 200 μL of acetonitrile. The HPLC mobile phase is 40:60 water:acetonitrile. The absorbance of the eluent is monitored at 205 nm. Standardisation uses a known mixture of pure capsaicin and dihydrocapsaicin. Accuracies are 98.9 and 100.6 % for capsaicin and dihydrocapsaicin respectively. Inter batch reproducibility for both is 15 %. The limits of detection are 2.6 and 3.8 ng/mL for capsaicin and dihydrocapsaicin respectively. Analyses of sera obtained previously from human subjects who had eaten chilli containing meals showed that in those that absorbed capsaicins (N = 30) then the median, mean and SD of their serum capsaicin were: 13.4, 18.9 and 16.3 ng/mL. The corresponding data for those sera (N = 13) that had measurable levels of dihydrocapsaicin were: 6.9, 7.5 and 3.6 ng/mL. This procedure is suitable for use in prospective studies of the metabolism of orally ingested chilli.
PMCID: PMC3783918  PMID: 24426233
HPLC; Capsaicin; Dihydrocapsaicin; Serum levels; Post oral dose
4.  Harvard Personal Genome Project: lessons from participatory public research 
Genome Medicine  2014;6(2):10.
Since its initiation in 2005, the Harvard Personal Genome Project has enrolled thousands of volunteers interested in publicly sharing their genome, health and trait data. Because these data are highly identifiable, we use an ‘open consent’ framework that purposefully excludes promises about privacy and requires participants to demonstrate comprehension prior to enrollment.
Our model of non-anonymous, public genomes has led us to a highly participatory model of researcher-participant communication and interaction. The participants, who are highly committed volunteers, self-pursue and donate research-relevant datasets, and are actively engaged in conversations with both our staff and other Personal Genome Project participants. We have quantitatively assessed these communications and donations, and report our experiences with returning research-grade whole genome data to participants. We also observe some of the community growth and discussion that has occurred related to our project.
We find that public non-anonymous data is valuable and leads to a participatory research model, which we encourage others to consider. The implementation of this model is greatly facilitated by web-based tools and methods and participant education. Project results are long-term proactive participant involvement and the growth of a community that benefits both researchers and participants.
PMCID: PMC3978420  PMID: 24713084
5.  Meeting report for the 1st skin microbiota workshop, boulder, CO October 15-16 2012 
This report details the outcome of the 1st Skin Microbiota Workshop, Boulder, CO, held on October 15th-16th 2012. The workshop was arranged to bring Department of Defense personnel together with experts in microbial ecology, human skin physiology and anatomy, and computational techniques for interrogating the microbiome to define research frontiers at the intersection of these important areas. The workshop outlined a series of questions and created several working groups to address those questions, specifically to promote interdisciplinary activity and potential future collaboration. The US Army provided generous grant support and the meeting was organized and hosted by the University of Colorado at Boulder. A primary forward vision of the meeting was the importance of understanding skin microbial communities to improve the health and stealth of US Army warfighters.
PMCID: PMC4334105
Skin microbiome; Army; Bioinformatics
6.  The Association between Seasonal Variation in Vitamin D, Postural Sway, and Falls Risk: An Observational Cohort Study 
Journal of Aging Research  2013;2013:751310.
Introduction. Low serum vitamin D levels are associated with increased postural sway. Vitamin D varies seasonally. This study investigates whether postural sway varies seasonally and is associated with serum vitamin D and falls. Methods. In a longitudinal observational study, eighty-eight independently mobile community-dwelling older adults (69.7 ± 7.6 years) were evaluated on five occasions over one year, measuring postural sway (force platform), vitamin D levels, fall incidence, and causes and adverse outcomes. Mixed-methods Poisson regression was used to determine associations between measures. Results. Postural sway did not vary over the year. Vitamin D levels varied seasonally (P < 0.001), peaking in summer. Incidence of falls (P = 0.01) and injurious falls (P = 0.02) were lower in spring, with the highest fall rate at the end of autumn. Postural sway was not related to vitamin D (P = 0.87) or fall rates, but it was associated with fall injuries (IRR 1.59 (CI 1.14 to 2.24, P = 0.007). Conclusions. Postural sway remained stable across the year while vitamin D varied seasonally. Participants with high values for postural sway demonstrated higher rates of injurious falls. This study provides important evidence for clinicians and researchers providing interventions measuring balance outcomes across seasons.
PMCID: PMC3816055  PMID: 24223307
7.  Our genomes today: time to be clear 
Genome Medicine  2013;5(6):52.
PMCID: PMC3706891  PMID: 23806003
8.  Make Vitamin D While the Sun Shines, Take Supplements When It Doesn′t: A Longitudinal, Observational Study of Older Adults in Tasmania, Australia 
PLoS ONE  2013;8(3):e59063.
Low vitamin D status has been associated with a number of chronic conditions, particularly in older adults. The aim of this study was to identify how best to maintain optimum vitamin D status throughout the year in this high-risk population. The main objectives of the study were to assess seasonal vitamin D status; identify the main determinants of vitamin D status; determine if taking part in the study led to alterations in participant behaviour and vitamin D status. A longitudinal design across four consecutive seasons observed ninety-one 60–85 year old community-dwelling adults in Tasmania (41π S) over 13 consecutive months, with a follow-up assessment at next winter's end. Associations between solar UVB exposure, sun protection behaviours, dietary and supplemental vitamin D with serum 25(OH)D concentrations were assessed. Variation in serum 25(OH)D demonstrated an identical pattern to solar UVB, lagging 8–10 weeks. Serum 25(OH)D was positively associated with summer UVB (mean 15.9 nmol/L; 95%CI 11.8–19.9 nmol/L, p<0.001) and vitamin D supplementation (100–600 IU/day: 95%CI 10.2 nmol/L; 0.8–19.6 nmol/L; p = 0.03; 800 IU/day: 21.0 nmol/L; 95%CI 8.1–34.0 nmol/L; p = 0.001). Seasonal variation in serum 25(OH)D was greatly diminished in supplement users. The most common alteration in participant behaviour after the study was ingesting vitamin D supplements. Post-study vitamin D supplementation ℘800 IU/day was seven times more likely than during the study resulting in mean difference in serum 25(OH)D between supplement and non-supplement users of 30.1 nmol/L (95%CI 19.4–40.8 nmol/L; p<0.001). The main limitation was homogeneity of participant ethnicity. Solar exposure in summer and ingestion of vitamin D supplements in other seasons are the most effective ways of achieving and maintaining year-round vitamin D sufficiency in older adults in the Southern hemisphere. Vitamin D supplementation has greatest effect on vitamin D status if ingested during and after winter, i.e. between the autumn and spring equinoxes.
PMCID: PMC3601102  PMID: 23527088
9.  Targeted and genome-scale methylomics reveals gene body signatures in human cell lines 
Nature biotechnology  2009;27(4):361-368.
Cytosine methylation, an epigenetic modification of DNA, is a target of growing interest for developing high throughput profiling technologies. Here we introduce two new, complementary techniques for cytosine methylation profiling utilizing next generation sequencing technology: bisulfite padlock probes (BSPPs) and methyl sensitive cut counting (MSCC). In the first method, we designed a set of ~10,000 BSPPs distributed over the ENCODE pilot project regions to take advantage of existing expression and chromatin immunoprecipitation data. We observed a pattern of low promoter methylation coupled with high gene body methylation in highly expressed genes. Using the second method, MSCC, we gathered genome-scale data for 1.4 million HpaII sites and confirmed that gene body methylation in highly expressed genes is a consistent phenomenon over the entire genome. Our observations highlight the usefulness of techniques which are not inherently or intentionally biased in favor of only profiling particular subsets like CpG islands or promoter regions.
PMCID: PMC3566772  PMID: 19329998
10.  Accurate whole genome sequencing and haplotyping from10-20 human cells 
Nature  2012;487(7406):190-195.
Recent advances in whole genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, Long Fragment Read (LFR) technology, similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100 pg of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants (SNVs) were assembled into long haplotype contigs. Removal of false positive SNVs not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 Mb. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications.
PMCID: PMC3397394  PMID: 22785314
11.  Three-year follow-up of a randomised clinical trial of intravenous versus oral iron for anaemia in pregnancy 
BMJ Open  2012;2(5):e000998.
To date, there are no data available concerning the impact of iron therapy on the long-term well-being and health-related quality of life (HRQoL) in pregnancy.
To assess the long-term effect of iron therapy on HRQoL in pregnancy.
This is a follow-up study conducted between January 2010 and January 2011 of an earlier randomised open-label clinical trial of intravenous and oral iron versus oral iron for pregnancy-related iron deficiency anaemia. We used a modified version of the SF-36 questionnaire together with the original prospective HRQoL data collected during and after pregnancy.
Participants and interventions
Of the original evaluable 183 pregnant Caucasian women randomised to receive oral iron or a single intravenous iron polymaltose infusion followed by oral iron maintenance, 126 women completed the follow-up HRQoL study.
The participants were followed up 4 weeks after treatment, predelivery and postdelivery for a median period of 32 months (range, 26–42) with a well-being and HRQoL questionnaire using a modified SF-36 QoL-survey and child growth charts as set by the Australasian Paediatric Endocrine Group (APEG).
Patients who received intravenous iron demonstrated significantly higher haemoglobin and serum ferritin levels (p<0.001). There were strong associations between iron status and a number of the HRQoL parameters, with improved general health (p<0.001), improved vitality (physical energy) (p<0.001), less psychological downheartedness (p=0.005), less clinical depression (p=0.003) and overall improved mental health (p<0.001). The duration of breastfeeding was longer (p=0.046) in the intravenous iron group. The babies born in both groups recorded similarly on APEG growth chart assessments.
Our data suggest that HRQoL is improved until after pregnancy in anaemic pregnant women by repletion of their iron stores during pregnancy. About 80% of the intravenous iron group showed a maintained normal ferritin until delivery with long-term benefits. Further studies to confirm these findings are warranted.
PMCID: PMC3488743  PMID: 23087011
Qualitative Research
12.  Neuronal activity modifies DNA methylation landscape in the adult brain 
Nature neuroscience  2011;14(10):1345-1351.
DNA methylation has been traditionally viewed as a highly stable epigenetic mark in post-mitotic cells, however, postnatal brains appear to exhibit stimulus-induced methylation changes, at least in a few identified CpG dinucleotides. How extensively the neuronal DNA methylome is regulated by neuronal activity is unknown. Using a next-generation sequencing-based method for genome-wide analysis at a single-nucleotide resolution, we quantitatively compared the CpG methylation landscape of adult mouse dentate granule neurons in vivo before and after synchronous neuronal activation. About 1.4% of 219,991 CpGs measured show rapid active demethylation or de novo methylation. Some modifications remain stable for at least 24 hours. These activity-modified CpGs exhibit a broad genomic distribution with significant enrichment in low-CpG density regions, and are associated with brain-specific genes related to neuronal plasticity. Our study implicates modification of the neuronal DNA methylome as a previously under-appreciated mechanism for activity-dependent epigenetic regulation in the adult nervous system.
PMCID: PMC3183401  PMID: 21874013
13.  Phased Whole-Genome Genetic Risk in a Family Quartet Using a Major Allele Reference Sequence 
PLoS Genetics  2011;7(9):e1002280.
Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (<1,000 base pairs). We use family inheritance state analysis to control sequencing error and inform family-wide haplotype phasing, allowing quantification of genome-wide compound heterozygosity. We develop a sequence-based methodology for Human Leukocyte Antigen typing that contributes to disease risk prediction. Finally, we advance methods for analysis of disease and pharmacogenomic risk across the coding and non-coding genome that incorporate phased variant data. We show these methods are capable of identifying multigenic risk for inherited thrombophilia and informing the appropriate pharmacological therapy. These ethnicity-specific, family-based approaches to interpretation of genetic variation are emblematic of the next generation of genetic risk assessment using whole-genome sequencing.
Author Summary
An individual's genetic profile plays an important role in determining risk for disease and response to medical therapy. The development of technologies that facilitate rapid whole-genome sequencing will provide unprecedented power in the estimation of disease risk. Here we develop methods to characterize genetic determinants of disease risk and response to medical therapy in a nuclear family of four, leveraging population genetic profiles from recent large scale sequencing projects. We identify the way in which genetic information flows through the family to identify sequencing errors and inheritance patterns of genes contributing to disease risk. In doing so we identify genetic risk factors associated with an inherited predisposition to blood clot formation and response to blood thinning medications. We find that this aligns precisely with the most significant disease to occur to date in the family, namely pulmonary embolism, a blood clot in the lung. These ethnicity-specific, family-based approaches to interpretation of individual genetic profiles are emblematic of the next generation of genetic risk assessment using whole-genome sequencing.
PMCID: PMC3174201  PMID: 21935354
14.  The Lipid lowering and Onset of Renal Disease (LORD) Trial: A randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease 
BMC Nephrology  2008;9:4.
There is evidence that dyslipidemia is associated with chronic kidney disease (CKD). Experimental studies have established that lipids are damaging to the kidney and animal intervention studies show statins attenuate this damage. Small clinical trials, meta-analyses, observational studies and post-hoc analyses of cardiovascular intervention studies all support the concept that statins can reduce kidney damage in humans. Based on this background, a double blind randomized placebo controlled trial was designed to assess the effectiveness of atorvastatin 10 mg on slowing the progression of kidney disease in a population of patients with CKD.
The Lipid lowering and Onset of Renal Disease (LORD) trial is a three-year, single center, multi-site, double blind, randomized, placebo controlled trial. The primary outcome measure is kidney function measured by eGFR calculated by both Modification of Diet in Renal Disease (MDRD) and Cockcroft and Gault equations. Secondary outcome measures include kidney function measured by 24-hour urine creatinine clearance and also 24-hour urinary protein excretion, markers of oxidative stress, inflammation and drug safety and tolerability.
The results of this study will help determine the effectiveness and safety of atorvastatin and establish its effects on oxidative stress and inflammation in patients with CKD.
Trial Registration
PMCID: PMC2276485  PMID: 18366658

Results 1-14 (14)