Whole exome sequencing is an efficient and sensitive method for detection of germline mutations in patients with phaeochromcytomas and paragangliomas

Background Genetic testing is recommended when the probability of a disease-associated germline mutation exceeds 10%. Germline mutations are found in approximately 25% of individuals with phaeochromcytoma (PCC) or paraganglioma (PGL); however, genetic heterogeneity for PCC/PGL means many genes may require sequencing. A phenotype-directed iterative approach may limit costs but may also delay diagnosis, and will not detect mutations in genes not previously associated with PCC/PGL. Objective To assess whether whole exome sequencing (WES) was efficient and sensitive for mutation detection in PCC/PGL. Methods Whole exome sequencing was performed on blinded samples from eleven individuals with PCC/PGL and known mutations. Illumina TruSeq™ (Illumina Inc, San Diego, CA, USA) was used for exome capture of seven samples, and NimbleGen SeqCap EZ v3.0 (Roche NimbleGen Inc, Basel, Switzerland) for five samples (one sample was repeated). Massive parallel sequencing was performed on multiplexed samples. Sequencing data were called using Genome Analysis Toolkit and annotated using annovar. Data were assessed for coding variants in RET, NF1, VHL, SDHD, SDHB, SDHC, SDHA, SDHAF2, KIF1B, TMEM127, EGLN1 and MAX. Target capture of five exome capture platforms was compared. Results Six of seven mutations were detected using Illumina TruSeq™ exome capture. All five mutations were detected using NimbleGen SeqCap EZ v3.0 platform, including the mutation missed using Illumina TruSeq™ capture. Target capture for exons in known PCC/PGL genes differs substantially between platforms. Exome sequencing was inexpensive (<$A800 per sample for reagents) and rapid (results <5 weeks from sample reception). Conclusion Whole exome sequencing is sensitive, rapid and efficient for detection of PCC/PGL germline mutations. However, capture platform selection is critical to maximize sensitivity.

Using Bourdieu in education research: Theory and methods

This workshop will snapshot Bourdieu's sociology. In recognition of Bourdieu's work as a powerful theoretical instrument to speculate the reproduction of social orders and cultural values, the workshop will firstly discuss the core concepts of habitus, capital, and field – the foundational triad of Bourdieu's sociology. Although Bourdieu's original work was built on some quantitative studies, his sociology has been largely qualitatively used in education research. Different from the bulk of extant research, the workshop will secondly showcase some quantitative and mixed methods research that uses a Bourdieusian framework. Mindful of such a framework helping understand social practice at a macro level, the workshop will then make an attempt to think through the macro and the micro by weaving together Bourdieu's sociology with Garfinkel's ethnomethodology. The workshop will conclude with some reflections and communications in terms of how to better realise the full value of Bourdieu in education research.

Defining a developmental subtype of bipolar disorder in a sample of nonreferred adults by age at onset

Objective To test the hypothesis that the age at onset of bipolar disorder would identify a developmental subtype of bipolar disorder in adults characterized by increased levels of irritability, chronic course, rapid cycling, and comorbidity with attention deficit hyperactivity disorder. Methods Forty-four adult subjects diagnosed with bipolar disorder were selected from large family studies of youth with and without attention deficit hyperactivity disorder. These subjects were stratified by the age at onset in childhood (younger than 13 years; n = 8, 18%), adolescence (13–18 years; n = 12, 27%, or adulthood (older than 19 years; n = 24, 55%). All subjects were administered structure diagnostic interviews and a brief cognitive battery. Results In contrast with adult-onset bipolar disorder, child-onset bipolar disorder was associated with a longer duration of illness, more irritability than euphoria, a mixed presentation, a more chronic or rapid-cycling course, and increased comorbidity with childhood disruptive behavior disorders and anxiety disorders. Conclusion Stratification by age at onset of bipolar disorder identified subgroups of adult subjects with differing clinical correlates. This pattern of correlates is consistent with findings documented in children with pediatric bipolar disorder and supports the hypothesis that child-onset bipolar disorder may represent a developmental subtype of the disorder.

Fourier spectral methods for fractional-in-space reaction-diffusion equations

Fractional differential equations are becoming increasingly used as a powerful modelling approach for understanding the many aspects of nonlocality and spatial heterogeneity. However, the numerical approximation of these models is demanding and imposes a number of computational constraints. In this paper, we introduce Fourier spectral methods as an attractive and easy-to-code alternative for the integration of fractional-in-space reaction-diffusion equations described by the fractional Laplacian in bounded rectangular domains ofRn. The main advantages of the proposed schemes is that they yield a fully diagonal representation of the fractional operator, with increased accuracy and efficiency when compared to low-order counterparts, and a completely straightforward extension to two and three spatial dimensions. Our approach is illustrated by solving several problems of practical interest, including the fractional Allen–Cahn, FitzHugh–Nagumo and Gray–Scott models, together with an analysis of the properties of these systems in terms of the fractional power of the underlying Laplacian operator.

A rapid and label-free dual detection of Hg (II) and cysteine with the use of fluorescence switching of graphene quantum dots

A simple and rapid method of analysis for mercury ions (Hg2+) and cysteine (Cys) was developed with the use of graphene quantum dots (GQDs) as a fluorescent probe. In the presence of GQDs, Hg2+ cations are absorbed on their negatively charged surface by means of electrostatic interactions. Thus, the fluorescence (FL) of the GQDs would be significantly quenched as a result of the FL charge transfer, e.g. 92% quenching at 450 nm occurs for a 5 μmol L−1 Hg2+ solution. However, when Cys was added, a significant FL enhancement was observed (510% at 450 nm for a 8.0 μmol L−1 Cys solution), and Hg2+ combined with Cys rather than with the GQDs in an aqueous solution. This occurred because a strong metalsingle bondthiol bond formed, displacing the weak electrostatic interactions, and this resulted in an FL enhancement of the GQDs. The limits of detection (LOD) for Hg2+ and Cys were 0.439 nmol L−1 and 4.5 nmol L−1, respectively. Also, this method was used successfully to analyze Hg2+ and Cys in spiked water samples.

Dissimilarities in alignment-free methods for phylogenetic analysis based on genomes

Whole genome sequences are generally accepted as excellent tools for studying evolutionary relationships. Due to the problems caused by the uncertainty in alignment, existing tools for phylogenetic analysis based on multiple alignments could not be directly applied to the whole-genome comparison and phylogenomic studies. There has been a growing interest in alignment-free methods for phylogenetic analysis using complete genome data. The “distances” used in these alignment-free methods are not proper distance metrics in the strict mathematical sense. In this study, we first review them in a more general frame — dissimilarity. Then we propose some new dissimilarities for phylogenetic analysis. Last three genome datasets are employed to evaluate these dissimilarities from a biological point of view.

Graphene quantum dots and the resonance light scattering technique for trace analysis of phenol in different water samples

A novel, highly selective resonance light scattering (RLS) method was researched and developed for the analysis of phenol in different types of industrial water. An important aspect of the method involved the use of graphene quantum dots (GQDs), which were initially obtained from the pyrolysis of citric acid dissolved in aqueous solutions. The GQDs in the presence of horseradish peroxidase (HRP) and H2O2 were found to react quantitatively with phenol such that the RLS spectral band (310 nm) was quantitatively enhanced as a consequence of the interaction between the GQDs and the quinone formed in the above reaction. It was demonstrated that the novel analytical method had better selectivity and sensitivity for the determination of phenol in water as compared to other analytical methods found in the literature. Thus, trace amounts of phenol were detected over the linear ranges of 6.00×10−8–2.16×10−6 M and 2.40×10−6–2.88×10−5 M with a detection limit of 2.20×10−8 M. In addition, three different spiked waste water samples and two untreated lake water samples were analysed for phenol. Satisfactory results were obtained with the use of the novel, sensitive and rapid RLS method.

Incidence and mortality of female breast cancer in the Asia-Pacific region

Objective: To provide an overview of the incidence and mortality of female breast cancer for countries in the Asia-Pacific region. Methods: Statistical information about breast cancer was obtained from publicly available cancer registry and mortality databases (such as GLOBOCAN), and supplemented with data requested from individual cancer registries. Rates were directly age-standardised to the Segi World Standard population and trends were analysed using joinpoint models. Results: Breast cancer was the most common type of cancer among females in the region, accounting for 18% of all cases in 2012, and was the fourth most common cause of cancer-related deaths (9%). Although incidence rates remain much higher in New Zealand and Australia, rapid rises in recent years were observed in several Asian countries. Large increases in breast cancer mortality rates also occurred in many areas, particularly Malaysia and Thailand, in contrast to stabilising trends in Hong Kong and Singapore, while decreases have been recorded in Australia and New Zealand. Mortality trends tended to be more favourable for women aged under 50 compared to those who were 50 years or older. Conclusion: It is anticipated that incidence rates of breast cancer in developing countries throughout the Asia-Pacific region will continue to increase. Early detection and access to optimal treatment are the keys to reducing breast cancer-related mortality, but cultural and economic obstacles persist. Consequently, the challenge is to customise breast cancer control initiatives to the particular needs of each country to ensure the best possible outcomes.

Methods for constructing uncertainty intervals for queries of Bayesian nets

In this paper the issue of finding uncertainty intervals for queries in a Bayesian Network is reconsidered. The investigation focuses on Bayesian Nets with discrete nodes and finite populations. An earlier asymptotic approach is compared with a simulation-based approach, together with further alternatives, one based on a single sample of the Bayesian Net of a particular finite population size, and another which uses expected population sizes together with exact probabilities. We conclude that a query of a Bayesian Net should be expressed as a probability embedded in an uncertainty interval. Based on an investigation of two Bayesian Net structures, the preferred method is the simulation method. However, both the single sample method and the expected sample size methods may be useful and are simpler to compute. Any method at all is more useful than none, when assessing a Bayesian Net under development, or when drawing conclusions from an ‘expert’ system.

Missing in space: An evaluation of imputation methods for missing data in spatial analysis of risk factors for type II diabetes

Background Spatial analysis is increasingly important for identifying modifiable geographic risk factors for disease. However, spatial health data from surveys are often incomplete, ranging from missing data for only a few variables, to missing data for many variables. For spatial analyses of health outcomes, selection of an appropriate imputation method is critical in order to produce the most accurate inferences. Methods We present a cross-validation approach to select between three imputation methods for health survey data with correlated lifestyle covariates, using as a case study, type II diabetes mellitus (DM II) risk across 71 Queensland Local Government Areas (LGAs). We compare the accuracy of mean imputation to imputation using multivariate normal and conditional autoregressive prior distributions. Results Choice of imputation method depends upon the application and is not necessarily the most complex method. Mean imputation was selected as the most accurate method in this application. Conclusions Selecting an appropriate imputation method for health survey data, after accounting for spatial correlation and correlation between covariates, allows more complete analysis of geographic risk factors for disease with more confidence in the results to inform public policy decision-making.

Customised osteotomy guides and endoprosthetic reconstruction for periacetabular tumours

Purpose We sought to analyse clinical and oncological outcomes of patients after guided resection of periacetabular tumours and endoprosthetic reconstruction of the remaining defect. Methods From 1988 to 2008, we treated 56 consecutive patients (mean age 52.5 years, 41.1 % women). Patients were followed up either until death or February 2011 (mean follow up 5.5 years, range 0.1–22.5, standard deviation ± 5.3). Kaplan–Meier analysis was used to estimate survival rates. Results Disease-specific survival was 59.9 % at five years and 49.7 % at ten and 20 years, respectively. Wide resection margins were achieved in 38 patients, whereas 11 patients underwent marginal and seven intralesional resection. Survival was significantly better in patients with wide or marginal resection than in patients with intralesional resection (p = 0.022). Survival for patients with secondary tumours was significantly worse than for patients with primary tumours (p = 0.003). In 29 patients (51.8 %), at least one reoperation was necessary, resulting in a revision-free survival of 50.5 % at five years, 41.1 % at ten years and 30.6 % at 20 years. Implant survival was 77.0 % at five years, 68.6 % at ten years and 51.8 % at 20 years. A total of 35 patients (62.5 %) experienced one or more complications after surgery. Ten of 56 patients (17.9 %) experienced local recurrence after a mean of 8.9 months. The mean postoperative Musculoskeletal Tumor Society (MSTS) score was 18.1 (60.1 %). Conclusion The surgical approach assessed in this study simplifies the process of tumour resection and prosthesis implantation and leads to acceptable clinical and oncological outcomes.

Measuring load of phosphate in the environment by passive sampling techniques: An introduction

Phosphorus has a number of indispensable biochemical roles, but its natural deposition and the low solubility of phosphates as well as their rapid transformation to insoluble forms make the element commonly the growth-limiting nutrient, particularly in aquatic ecosystems. Famously, phosphorus that reaches water bodies is commonly the main cause of eutrophication. This undesirable process can severely affect many aquatic biotas in the world. More management practices are proposed but long-term monitoring of phosphorus level is necessary to ensure that the eutrophication won't occur. Passive sampling techniques, which have been developed over the last decades, could provide several advantages to the conventional sampling methods including simpler sampling devices, more cost-effective sampling campaign, providing flow proportional load as well as representative average of concentrations of phosphorus in the environment. Although some types of passive samplers are commercially available, their uses are still scarcely reported in the literature. In Japan, there is limited application of passive sampling technique to monitor phosphorus even in the field of agricultural environment. This paper aims to introduce the relatively new P-sampling techniques and their potential to use in environmental monitoring studies.

Towards development of a rapid and effective non-destructive testing strategy to identify brominated flame retardants in the plastics of consumer products

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants (BFRs) once extensively used in the plastics of a wide range of consumer products. The listing of certain congeners that are constituents of commercial PBDE mixtures (including c-octaBDE) in the Stockholm Convention and tightening regulation of many other BFRs in recent years have created the need for a rapid and effective method of identifying BFR-containing plastics. A three-tiered testing strategy comparing results from non-destructive testing (X-ray fluorescence (XRF)) (n = 1714), a surface wipe test (n = 137) and destructive chemical analysis (n = 48) was undertaken to systematically identify BFRs in a wide range of consumer products. XRF rapidly identified bromine in 92% of products later confirmed to contain BFRs. Surface wipes of products identified tetrabromobisphenol A (TBBPA), c-octaBDE congeners and BDE-209 with relatively high accuracy (> 75%) when confirmed by destructive chemical analysis. A relationship between the amounts of BFRs detected in surface wipes and subsequent destructive testing shows promise in predicting not only the types of BFRs present but also estimating the concentrations present. Information about the types of products that may contain persistent BFRs will assist regulators in implementing policies to further reduce the occurrence of these chemicals in consumer products.

Impacts of tillage and application methods on atrazine and alachlor losses from upland fields: Research paper

The effects of tillage practises and the methods of chemical application on atrazine and alachlor losses through run-off were evaluated for five treatments: conservation (untilled) and surface (US), disk and surface, plow and surface, disk and preplant-incorporated, and plow and preplant-incorporated treatments. A rainfall simulator was used to create 63.5 mm h^-1 of rainfall for 60 min and 127 mm h^-1 for 15 min. Rainfall simulation occurred 24-36 h after chemical application. There was no significant difference in the run-off volume among the treatments but the untilled treatment significantly reduced erosion loss. The untilled treatments had the highest herbicide concentration and the disk treatments were higher than the plow treatments. The surface treatments showed a higher concentration than the incorporated treatments. The concentration of herbicides in the water decreased with time. Among the experimental sites, the one with sandy loam soil produced the greatest losses, both in terms of the run-off volume and herbicide loss. The US treatments had the highest loss and the herbicide incorporation treatments had smaller losses through run-off as the residue cover was effective in preventing herbicide losses. Incorporation might be a favorable method of herbicide application to reduce the herbicide losses by run-off.

Raman spectroscopy techniques for detection of energetic materials at high and low concentration

This thesis presents the development of a rapid, sensitive and reproducible spectroscopic method for the detection of TNT in forensic and environmental applications. Simple nano sensors prepared by cost effective methods were utilized as sensitive platforms for the detection of TNT by surface enhanced Raman spectroscopy. The optimization of the substrate and the careful selection of a suitable recognition molecule contributed to the significant improvements of sensitive and selective targeting over current detection methods. The work presented in this thesis paves the way for effective detection and monitoring of explosives residues in law enforcement and environmental health applications.