Johnny Lo

Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma

Repeat tumor biopsies to study genomic changes during therapy are difficult, invasive and data are confounded by tumoral heterogeneity. The analysis of circulating tumor DNA (ctDNA) can provide a non-invasive approach to assess prognosis and the genetic evolution of tumors in response to therapy. Mutation-specific droplet digital PCR was used to measure plasma concentrations of oncogenic BRAF and NRAS variants in 48 patients with advanced metastatic melanoma prior to treatment with targeted therapies (vemurafenib, dabrafenib or dabrafenib/trametinib combination) or immunotherapies (ipilimumab, nivolumab or pembrolizumab). Baseline ctDNA levels were evaluated relative to treatment response and progression-free survival (PFS). Tumor-associated ctDNA was detected in the plasma of 35/48 (73%) patients prior to treatment and lower ctDNA levels at this time point were significantly associated with response to treatment and prolonged PFS, irrespective of therapy type. Levels of ctDNA decreased significantly in patients treated with MAPK inhibitors (p < 0.001) in accordance with response to therapy, but this was not apparent in patients receiving immunotherapies. We show that circulating NRAS mutations, known to confer resistance to BRAF inhibitors, were detected in 3 of 7 (43%) patients progressing on kinase inhibitor therapy. Significantly, ctDNA rebound and circulating mutant NRAS preceded radiological detection of progressive disease. Our data demonstrate that ctDNA is a useful biomarker of response to kinase inhibitor therapy and can be used to monitor tumor evolution and detect the early appearance of resistance effectors.

Cardiovascular, Metabolic Effects and Dietary Composition of Ad-Libitum Paleolithic vs. Australian Guide to Healthy Eating Diets: A 4-Week Randomised Trial.

(1) Background: The Paleolithic diet is popular in Australia, however, limited literature surrounds the dietary pattern. Our primary aim was to compare the Paleolithic diet with the Australian Guide to Healthy Eating (AGHE) in terms of anthropometric, metabolic and cardiovascular risk factors, with a secondary aim to examine the macro and micronutrient composition of both dietary patterns; (2) Methods: 39 healthy women (mean ± SD age 47 ± 13 years, BMI 27 ± 4 kg/m2) were randomised to either the Paleolithic (n = 22) or AGHE diet (n = 17) for four weeks. Three-day weighed food records, body composition and biochemistry data were collected pre and post intervention; (3) Results: Significantly greater weight loss occurred in the Paleolithic group (−1.99 kg, 95% CI −2.9, −1.0), p < 0.001). There were no differences in cardiovascular and metabolic markers between groups. The Paleolithic group had lower intakes of carbohydrate (−14.63% of energy (E), 95% CI −19.5, −9.7), sodium (−1055 mg/day, 95% CI −1593, −518), calcium (−292 mg/day 95% CI −486.0, −99.0) and iodine (−47.9 μg/day, 95% CI −79.2, −16.5) and higher intakes of fat (9.39% of E, 95% CI 3.7, 15.1) and β-carotene (6777 μg/day 95% CI 2144, 11410) (all p < 0.01); (4) Conclusions: The Paleolithic diet induced greater changes in body composition over the short-term intervention, however, larger studies are recommended to assess the impact of the Paleolithic vs. AGHE diets on metabolic and cardiovascular risk factors in healthy populations.

Compliance, Palatability and Feasibility of PALEOLITHIC and Australian Guide to Healthy Eating Diets in Healthy Women: A 4-Week Dietary Intervention

(1) Background/Objectives: The Paleolithic diet has been receiving media coverage in Australia and claims to improve overall health. The diet removes grains and dairy, whilst encouraging consumption of fruits, vegetables, meat, eggs and nuts. Our aim was to compare the diet to the Australian Guide to Healthy Eating (AGHE) in terms of compliance, palatability and feasibility; (2) Subjects/Methods: 39 healthy women (age 47 ± 13 years, BMI 27 ± 4 kg/m2) were randomised to an ad-libitum Paleolithic (n = 22) or AGHE diet (n = 17) for 4-weeks. A food checklist was completed daily, with mean discretionary consumption (serves/day) calculated to assess compliance. A 12-item questionnaire was administered post intervention to assess palatability and feasibility; (3) Results: The AGHE group reported greater daily consumption of discretionary items (1.0 + 0.6 vs. 0.57 + 0.6 serves/day, p = 0.03). Compared to the AGHE group, the Paleolithic group reported a significantly greater number of events of diarrhoea (23%, 0%, p = 0.046), costs associated with grocery shopping (69%, 6% p < 0.01) and belief that the diet was not healthy (43%, 0% p < 0.01); (4) Conclusions: Compliance to both diets was high but the potential side effects and increased cost suggest that the Paleolithic diet may not be practical in clinical/public health settings. Further studies are required to assess longer term feasibility.

Structural Analysis of the National Geochemical Survey of Australia Data

The National Geochemical Survey of Australia is a low density geochemical survey that collected catchment sediment samples covering most of Australia. Concentrations of 60 elements from both bottom and top soil as well as two grain size fractions were obtained, of which 51 were used in the analysis presented here. As the data are compositional, a centered logratio (clr) transform was applied to enable the use of standard geostatistical techniques. The method of minimum/maximum autocorrelation factors (MAF), a multivariate spatial decorrelation method, was applied to the clr-transformed data by soil horizon and grain-size fraction to assess its suitability for structure identification in a compositional setting. The results show MAF to be effective for the delineation of geochemical regions. A structural analysis of the factors indicates slight differences in continuity across soil layers and grain fraction which lead to differences in the strength with which regional features appear on interpolated maps.

Utilising a multi-item questionnaire to assess household food security in Australia

Abstract Issue addressed Currently, two food sufficiency questions are utilised as a proxy measure of national food security status in Australia. These questions do not capture all dimensions of food security and have been attributed to underreporting of the problem. The purpose of this study was to investigate food security using the short form of the US Household Food Security Survey Module (HFSSM) within an Australian context; and explore the relationship between food security status and multiple socio‐demographic variables. Methods Two online surveys were completed by 2334 Australian participants from November 2014 to February 2015. Surveys contained the short form of the HFSSM and twelve socio‐demographic questions. Cross‐tabulations chi‐square tests and a multinomial logistic regression model were employed to analyse the survey data. Results Food security status of the respondents was classified accordingly: High or Marginal (64%, n = 1495), Low (20%, n = 460) or Very Low (16%, n = 379). Significant independent predictors of food security were age (P < 0.001), marital status (P = 0.005), household income (P < 0.001) and education (P < 0.001). Conclusion Findings suggest food insecurity is an important issue across Australia and that certain groups, regardless of income, are particularly vulnerable. So what? Government policy and health promotion interventions that specifically target “at risk” groups may assist to more effectively address the problem. Additionally, the use of a multi‐item measure is worth considering as a national indicator of food security in Australia.

Prescribing or dispensing medication represents the best opportunity for GPs and pharmacists to engage older people in alcohol-related clinical conversations

This research aimed to identify older Australian drinkers’ knowledge about Australian Alcohol Guidelines and their beliefs about the risks and benefits of alcohol; their recall of alcohol‐related issues being raised with them by their community pharmacist and General Practitioner (GP); and their receptiveness to alcohol‐related information being provided by either health professional.

Dynamic modeling of GNSS troposphere wet delay for estimation of precipitable water vapour

Abstract Proper dynamic modelling of the troposphere wet delay using the Global Navigation Satellite Systems (GNSS) measurements is important in precise point positioning and in estimation of the PrecipitableWater Vapour (PWV) for weather forecast. The random walk (RW) and the first-order Gauss-Markov (GM) autocorrelation models are commonly used for this purpose. However, it was found that these models consistently underestimate the temporal correlations that exist among the troposphere wet delay. Therefore, a new dynamic model is proposed. The performance of the proposed model in following the autocorrelation of actual data is demonstrated and its impact on the near-real time estimation of the wet delay was tested and compared to that of the GMand RWmodels. Results showed that the proposed model outperformed these models. When the computed wet delays were used to compute PWV, their estimated valueswere very close to actual PWV data measured by radiosonde with differences less than 1 mm.

A hybrid model for joint simulation of high-dimensional continuous and categorical variables

It is a common challenge for the geosciences to jointly model the uncertainty in continuous and categorical regionalised variables and to reproduce observed spatial correlation and complex relationships in realisations. The demand for computational efficiency in the case of high-dimensional data and large simulation domains has led practitioners to utilise approaches based on decorrelation/recorrelation and independent simulation. Among such approaches the method of min/max autocorrelation factors (MAF) has proven to be a practical technique for industrial purposes. This study presents a hybrid model for joint simulation of high-dimensional continuous and categorical variables. Continuous variables are transformed to Gaussian random functions (GRFs) via anamorphosis functions and categorical variables are obtained by truncating one or more GRFs based on the plurigaussian model. MAF factors are then derived from all GRFs. After independent simulation of MAF factors, different realisations of continuous and categorical variables are obtained via back-transformation of MAF factors followed by back-transformation for continuous and truncation for categorical variables, respectively. The proposed algorithm is illustrated through a case study.

Community pharmacists require additional support to develop capacity in delivering alcohol-related health information to older adults.

This qualitative study explored the barriers and enablers influencing Western Australian (WA) community pharmacists’ knowledge, confidence, willingness and practice in engaging older clients (>60 years) in alcohol‐related health discussions.

Which Food Security Determinants Predict Adequate Vegetable Consumption among Rural Western Australian Children

Improving the suboptimal vegetable consumption among the majority of Australian children is imperative in reducing chronic disease risk. The objective of this research was to determine whether there was a relationship between food security determinants (FSD) (i.e., food availability, access, and utilisation dimensions) and adequate vegetable consumption among children living in regional and remote Western Australia (WA). Caregiver-child dyads (n = 256) living in non-metropolitan/rural WA completed cross-sectional surveys that included questions on FSD, demographics and usual vegetable intake. A total of 187 dyads were included in analyses, which included descriptive and logistic regression analyses via IBM SPSS (version 23). A total of 13.4% of children in this sample had adequate vegetable intake. FSD that met inclusion criteria (p ≤ 0.20) for multivariable regression analyses included price; promotion; quality; location of food outlets; variety of vegetable types; financial resources; and transport to outlets. After adjustment for potential demographic confounders, the FSD that predicted adequate vegetable consumption were, variety of vegetable types consumed (p = 0.007), promotion (p = 0.017), location of food outlets (p = 0.027), and price (p = 0.043). Food retail outlets should ensure that adequate varieties of vegetable types (i.e., fresh, frozen, tinned) are available, vegetable messages should be promoted through food retail outlets and in community settings, towns should include a range of vegetable purchasing options, increase their reliance on a local food supply and increase transport options to enable affordable vegetable purchasing.