The health professional behind the syringe: Benefits of a pharmacist vaccination program

Background: The Queensland Pharmacist Immunisation Pilot (QPIP) which ran in 2014 was Australia’s first to allow pharmacists to administer vaccinations. An aim of QPIP was to investigate the benefits of trained pharmacists administering vaccinations in a community pharmacy setting. Methods: Participant demographics and previous influenza vaccination experiences were recorded using GuildCare software. Participants also completed a ‘post-vaccination satisfaction survey’ following their influenza vaccination. Results: A total of 10,889 participant records and 8,737 satisfaction surveys were analysed. Overall, 1.9% of the participants reported living with a chronic illness, and 22.5% were taking concomitant medications. As part of the consultation before receiving the vaccine, participants acknowledged the opportunity to discuss other aspects of their health with the pharmacist, including concerns about their general health, allergies, and other medications they were taking. It was worth noting that 17.5% of people would not have received an influenza vaccination if the QPIP service was unavailable. Additionally, approximately 10% of all participants were eligible to receive a free vaccination from the National Immunisation Program, but still opted to receive their vaccine from a pharmacist. Conclusion: The findings from this pilot demonstrate the benefit of a pharmacist vaccination program in increasing vaccination rates, and have helped pave the way for expanding the scope of practice for pharmacists.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and approximately 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-)(8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure

The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 x 10(-8)) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 x 10(-6)). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Common variants in the trichohyalin gene are associated with straight hair in Europeans

Hair morphology is highly differentiated between populations and among people of European ancestry. Whereas hair morphology in East Asian populations has been studied extensively, relatively little is known about the genetics of this trait in Europeans. We performed a genome-wide association scan for hair morphology (straight, wavy, curly) in three Australian samples of European descent. All three samples showed evidence of association implicating the Trichohyalin gene (TCHH), which is expressed in the developing inner root sheath of the hair follicle, and explaining approximately 6% of variance (p=1.5x10(-31)). These variants are at their highest frequency in Northern Europeans, paralleling the distribution of the straight-hair EDAR variant in Asian populations.

Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2x10(-201)), ABCG2 (p = 3.1x10(-26)), SLC17A1 (p = 3.0x10(-14)), SLC22A11 (p = 6.7x10(-14)), SLC22A12 (p = 2.0x10(-9)), SLC16A9 (p = 1.1x10(-8)), GCKR (p = 1.4x10(-9)), LRRC16A (p = 8.5x10(-9)), and near PDZK1 (p = 2.7x10(-9)). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0x10(-26)) and propionyl-L-carnitine (p = 5.0x10(-8)) concentrations, which in turn were associated with serum UA levels (p = 1.4x10(-57) and p = 8.1x10(-54), respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.

Sequence variants in three loci influence monocyte counts and erythrocyte volume

Blood cells participate in vital physiological processes, and their numbers are tightly regulated so that homeostasis is maintained. Disruption of key regulatory mechanisms underlies many blood-related Mendelian diseases but also contributes to more common disorders, including atherosclerosis. We searched for quantitative trait loci (QTL) for hematology traits through a whole-genome association study, because these could provide new insights into both hemopoeitic and disease mechanisms. We tested 1.8 million variants for association with 13 hematology traits measured in 6015 individuals from the Australian and Dutch populations. These traits included hemoglobin composition, platelet counts, and red blood cell and white blood cell indices. We identified three regions of strong association that, to our knowledge, have not been previously reported in the literature. The first was located in an intergenic region of chromosome 9q31 near LPAR1, explaining 1.5% of the variation in monocyte counts (best SNP rs7023923, p=8.9x10(-14)). The second locus was located on chromosome 6p21 and associated with mean cell erythrocyte volume (rs12661667, p=1.2x10(-9), 0.7% variance explained) in a region that spanned five genes, including CCND3, a member of the D-cyclin gene family that is involved in hematopoietic stem cell expansion. The third region was also associated with erythrocyte volume and was located in an intergenic region on chromosome 6q24 (rs592423, p=5.3x10(-9), 0.6% variance explained). All three loci replicated in an independent panel of 1543 individuals (p values=0.001, 9.9x10(-5), and 7x10(-5), respectively). The identification of these QTL provides new opportunities for furthering our understanding of the mechanisms regulating hemopoietic cell fate.

Reducing uncertainty in the assessment of the Australian spanner crab fishery

In collaboration with the New South Wales Department of Primary Industries we compared the effectiveness of the spanner crab monitoring systems used by New South Wales and Queensland and developed a fishery-independent survey protocol acceptable to both states. The objectives of this project were to: 1. Determine the age at which spanner crabs (Ranina ranina) recruit to the fishery 2. Develop a common methodology for monitoring and assessing the Australian spanner crab stock 3. Investigate sources of variability in apparent population density.

Harvest strategy evaluation to optimise the sustainability and value of the Queensland scallop fishery. Queensland scallop fishery - FRDC Project No 2006/024 Final Report

Objective 1. Measure spatial and temporal trawl frequency of scallop grounds using VMS data. This will provide a relative measure of how often individual undersized scallops are caught and put through a tumbler 2. Estimate discard mortality and growth rates for saucer scallops using cage experiments. 3. Evaluate the current management measures, in particular the seasonal closure, rotational closure and seasonally varying minimum legal sizes using stock assessment and management modeling models. Recommend optimal range of management measures to ensure long-term viability and value of the Scallop fishery based on a formal management strategy evaluation. Outcomes acheived to date: 1. Improved understanding of the survival rates of discarded sub-legal scallops; 2. Preliminary von Bertalanffy growth parameters using data from tagged-and-released scallops; 3. Changing trends in vessels and fishing gear used in the Queensland scallop fishery and their effect on scallop catch rates over time using standardised catch rates quantified; 4. Increases in fishing power of vessels operating in the Queensland scallop fishery quantified; 5. Trawl intensity mapped and quantified for all Scallop Replenishment Areas; 6. Harvest Strategy Evaluations completed.

Fishing power and standardised catch rates: Implications of missing vessel-characteristic data from the Australian eastern king prawn fishery

Standardised time series of fishery catch rates require collations of fishing power data on vessel characteristics. Linear mixed models were used to quantify fishing power trends and study the effect of missing data encountered when relying on commercial logbooks. For this, Australian eastern king prawn (Melicertus plebejus) harvests were analysed with historical (from vessel surveys) and current (from commercial logbooks) vessel data. Between 1989 and 2010, fishing power increased up to 76%. To date, both forward-filling and, alternatively, omitting records with missing vessel information from commercial logbooks produce broadly similar fishing power increases and standardised catch rates, due to the strong influence of years with complete vessel data (16 out of 23 years of data). However, if gaps in vessel information had not originated randomly and skippers from the most efficient vessels were the most diligent at filling in logbooks, considerable errors would be introduced. Also, the buffering effect of complete years would be short lived as years with missing data accumulate. Given ongoing changes in fleet profile with high-catching vessels fishing proportionately more of the fleet’s effort, compliance with logbook completion, or alternatively ongoing vessel gear surveys, is required for generating accurate estimates of fishing power and standardised catch rates.

Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)) and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Quantitative Trait Loci for CD4:CD8 Lymphocyte Ratio Are Associated with Risk of Type 1 Diabetes and HIV-1 Immune Control

Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 × 10−28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 × 10−14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 × 10−9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.

Short- and long-term movement patterns in the freshwater whipray (Himantura dalyensis) determined by the signal processing of passive acoustic telemetry data.

Patterns of movement in aquatic animals reflect ecologically important behaviours. Cyclical changes in the abiotic environment influence these movements, but when multiple processes occur simultaneously, identifying which is responsible for the observed movement can be complex. Here we used acoustic telemetry and signal processing to define the abiotic processes responsible for movement patterns in freshwater whiprays (Himantura dalyensis). Acoustic transmitters were implanted into the whiprays and their movements detected over 12 months by an array of passive acoustic receivers, deployed throughout 64 km of the Wenlock River, Qld, Australia. The time of an individual's arrival and departure from each receiver detection field was used to estimate whipray location continuously throughout the study. This created a linear-movement-waveform for each whipray and signal processing revealed periodic components within the waveform. Correlation of movement periodograms with those from abiotic processes categorically illustrated that the diel cycle dominated the pattern of whipray movement during the wet season, whereas tidal and lunar cycles dominated during the dry season. The study methodology represents a valuable tool for objectively defining the relationship between abiotic processes and the movement patterns of free-ranging aquatic animals and is particularly expedient when periods of no detection exist within the animal location data.

Testing the efficacy of low volume herbicide applications on Chromolaena odorata

Siam Weed (Chromoleana odorata) is the target of an eradication program in north Queensland; however some infestations occur on ground inaccessible to high volume, ground based herbicide spray equipment. Four foliar herbicides were applied to dense infestations of mature Siam Weed in March 2009, near Townsville, north Queensland. Low volume, high concentration solutions containing 40 g L-1 a.i. glyphosate, 1.2 g L-1 a.i metsulfuron-methyl, 10 g L-1 a.i. fluroxypyr + 0.7 g L-1 a.i. aminopyralid and 15 g L-1 a.i. triclopyr + 5 g L-1 a.i. picloram + 0.4 g L-1 a.i. aminopyralid were applied using a 5 L backpack and hand gun (or splatter gun). Relatively small amounts (approximately 24-28 mL) of the high concentration solutions were applied to each bush and assessments of the replicated treated and untreated control plots were conducted 76, 207 and 356 days after treatment. These assessments demonstrated that the fluroxypyr and triclopyr based herbicides controlled 96 to 100% of plants. The metsulfuron-methyl and glyphosate based herbicides controlled 40 and 57% of plants respectively 12 months after treatment, when 3% of untreated control plants were dead. The trial demonstrated that this application method and either of two herbicides provides an additional tool for controlling Siam weed in remote areas, which are inaccessible to traditional higher volume foliar herbicide applications. Lower volume herbicide solutions reduce the volume of water and thus the effort needed to effectively treat less accessible infestations.