Prostate radiotherapy treatment plan quality : effects of hip prostheses

Introduction This study aimed to examine the geometric and dosimetric results when radiotherapy treatment plans are designed for prostate cancer patients with hip prostheses. Methods Ten EBRT treatment plans for localised prostate cancer, in the presence of hip prostheses, were analysed and compared with a reference set of 196 treatment plans for localised prostate cancer in patients without prostheses. Crowe et al.’s TADA code [1] was used to extract treatment plan parameters and evaluate doses to target volumes and critical structures against recommended goals [2] and constraints [3, 4]. Results The need to avoid transmitting the radiation beam through the hip prostheses limited the range of gantry angles available for use in both the rotational (VMAT) and the non-rotational (3DCRT and IMRT) radiotherapy treatments. This geometric limitation (exemplified in the VMAT data shown in Fig. 1) reduced the overall quality of the treatment plans for patients with prostheses compared to the reference plans. All plans with prostheses failed the PTV dose homogeneity requirement [2], whereas only 4 % of the plans without prostheses failed this test. Several treatment plans for patients with hip prostheses also failed the QUANTEC requirements that less than 50 % of the rectum receive 50 Gy and less than 35 % of the rectum receive 60 Gy to keep the grade 3 toxicity rate below 10 % [3], or the Hansen and Roach requirement that less than 25 % of the bladder receive 75 Gy [4]. Discussion and conclusions The results of this study exemplify the difficulty of designing prostate radiotherapy treatment plans, where beams provide adequate doses to targeted tissues while avoiding nearby organs at risk, when the presence of hip prostheses limits the available treatment geometries. This work provides qualitative evidence of the compromised dose distributions that can result, in such cases.

Images inside a reflecting spherical surface with possible application in astronomy

This report studies an algebraic equation whose solution gives the image system of a source of light as seen by an observer inside a reflecting spherical surface. The equation is looked at numerically using GeoGebra. Under the hypothesis that our galaxy is enveloped by a reflecting interface this becomes a possible model for many mysterious extra galactic observations.

Chemical and bioanalytical assessment of coal seam gas associated water

A comprehensive study was undertaken involving chemical (inorganic and organic) and bioanalytical (a suite of 14 in vitro bioassays) assessments of coal seam gas (coal bed methane) associated water (CSGW) in Queensland, Australia. CSGW is a by-product of the gas extraction process and is generally considered as water of poor quality. This was done to better understand what is known about the potential biological and environmental effects associated with the organic constituents of CSGW in Australia. In Queensland, large amounts of associated water must be withdrawn from coal seams to allow extraction of the gas. CSGW is disposed of via release to surface water, reinjected to groundwater or reused for irrigation of crops or pasture, supplied for power station cooling and or reinjected specifically to augment drinking water aquifers. Groundwater samples were collected from private wells tapping into the Walloon Coal Measures, the same coal aquifer exploited for coal seam gas production in the Surat Basin, Australia. The inorganic characteristics of these water samples were almost identical to the CSGW entering the nearby gas company operated Talinga-Condabri Water Treatment Facility. The water is brackish with a pH of 8 to 9, high sodium, bicarbonate and chloride concentrations but low calcium, magnesium and negligible sulphate concentrations. Only low levels of polyaromatic hydrocarbons (PAHs) were detected in the water samples, and neither phenols nor volatile organic compounds were found. Results from the bioassays showed no genotoxicity, protein damage, or activation of hormone receptors (with the exception of the estrogen receptor). However, five of the 14 bioassays gave positive responses: an arylhydrocarbon-receptor gene activation assay (AhR-CAFLUX), estrogenic endocrine activity (ERα-CALUX), oxidative stress response (AREc32), interference with cytokine production (THP1-CPA) and non-specific toxicity (Microtox). The observed effects were benchmarked against known water sources and were similar to secondary treated wastewater effluent, stormwater and surface water. As mixture toxicity modelling demonstrated, the detected PAHs explained less than 5% of the observed biological effects.

BDNF SNPs are implicated in comorbid alcohol dependence in schizophrenia but not in alcohol-dependent patients without schizophrenia

Aims The functional BDNF single nucleotide polymorphism (SNP) rs6265 has been associated with many disorders including schizophrenia and alcohol dependence. However, studies have been inconsistent, reporting both positive and negative associations. Comorbid alcohol dependence has a high prevalence in schizophrenia so we investigated the role of rs6265 in alcohol dependence in Australian populations of schizophrenia and alcohol dependent patients. Methods Two BDNF SNPs rs6265 and a nearby SNP rs7103411 were genotyped in a total of 848 individuals. These included a schizophrenia group (n = 157) and a second schizophrenia replication group (n = 235), an alcohol dependent group (n = 231) that had no schizophrenia diagnosis and a group of healthy controls (n = 225). Results Allelic association between rs7103411 and comorbid alcohol dependence was identified (P = 0.044) in the primary schizophrenia sample. In the replication study, we were able to detect allelic associations between both BDNF SNPs and comorbid alcohol dependence (rs6265, P = 0.006; rs7103411, P = 0.014). Moreover, we detected association between both SNPs and risk-taking behaviour after drinking (rs6265, P = 0.005; rs7103411, P = 0.009) and we detected strong association between both SNPs and alcohol dependence in males (rs6265, P = 0.009; rs7103411, P = 0.013) while females showed association with multiple behavioural measures reflecting repetitive alcohol consumption. Haplotype analysis revealed the rs6265-rs7103411 A/C haplotype is associated with comorbid alcohol dependence (P = 0.002). When these SNPs were tested in the non-schizophrenia alcohol dependent group we were unable to detect association. Conclusion We conclude that these BDNF SNPs play a role in development of comorbid alcohol dependence in schizophrenia while our data does not indicate that they play a role in alcohol dependent patients who do not have schizophrenia.

Digital culture : blurred boundaries and ethical considerations

The Weberian sense of work and life suggests that working is something around which the rest of life flows. Moreover, work life and domestic life have been defined as separate for most people based on physical structures. That is, being physically in a building at work limited your ability to interact with those who are not nearby – not part of work. As such, social conventions regarding the uses of media at work have become part of our cultural sensibilities – we “know” it is not proper to have romantic discourse over the office phone, much less romance during work! Doing so becomes news. Yet, despite the construction of such distinctions, these workspaces and places have always been difficult to render as such. For example, one might consider the relatively recent development of teleworking from the 1980s or the “putting out system”[1] which dates back to the 1400s – both requiring work in the home. The papers in this special issue draw our attention to some of the ethical issues raised by the growing pervasiveness of information and communications technologies (ICTs) in our everyday lives and the fact that it is becoming increasingly difficult to make distinctions between being somewhere (like work) and being away from some things (like one’s friends, social interests and other parts of life that are not integrated into this space or place [2] )...

Approximate Bayesian Computation for astronomical model analysis : a case study in galaxy demographics and morphological transformation at high redshift

Approximate Bayesian Computation’ (ABC) represents a powerful methodology for the analysis of complex stochastic systems for which the likelihood of the observed data under an arbitrary set of input parameters may be entirely intractable – the latter condition rendering useless the standard machinery of tractable likelihood-based, Bayesian statistical inference [e.g. conventional Markov chain Monte Carlo (MCMC) simulation]. In this paper, we demonstrate the potential of ABC for astronomical model analysis by application to a case study in the morphological transformation of high-redshift galaxies. To this end, we develop, first, a stochastic model for the competing processes of merging and secular evolution in the early Universe, and secondly, through an ABC-based comparison against the observed demographics of massive (Mgal > 1011 M⊙) galaxies (at 1.5 < z < 3) in the Cosmic Assembly Near-IR Deep Extragalatic Legacy Survey (CANDELS)/Extended Groth Strip (EGS) data set we derive posterior probability densities for the key parameters of this model. The ‘Sequential Monte Carlo’ implementation of ABC exhibited herein, featuring both a self-generating target sequence and self-refining MCMC kernel, is amongst the most efficient of contemporary approaches to this important statistical algorithm. We highlight as well through our chosen case study the value of careful summary statistic selection, and demonstrate two modern strategies for assessment and optimization in this regard. Ultimately, our ABC analysis of the high-redshift morphological mix returns tight constraints on the evolving merger rate in the early Universe and favours major merging (with disc survival or rapid reformation) over secular evolution as the mechanism most responsible for building up the first generation of bulges in early-type discs.

Multi-agent systems for modeling high penetration photovoltaic system impacts in distribution networks

This paper reviews the use of multi-agent systems to model the impacts of high levels of photovoltaic (PV) system penetration in distribution networks and presents some preliminary data obtained from the Perth Solar City high penetration PV trial. The Perth Solar City trial consists of a low voltage distribution feeder supplying 75 customers where 29 consumers have roof top photovoltaic systems. Data is collected from smart meters at each consumer premises, from data loggers at the transformer low voltage (LV) side and from a nearby distribution network SCADA measurement point on the high voltage side (HV) side of the transformer. The data will be used to progressively develop MAS models.

Female greater wax moths reduce sexual display behavior in relation to the potential risk of predation by echolocating bats

Female greater wax moths Galleria mellonella display by wing fanning in response to bursts of ultrasonic calls produced by males. The temporal and spectral characteristics of these calls show some similarities with the echolocation calls of bats that emit frequency-modulated (FM) signals. Female G. mellonella therefore need to distinguish between the attractive signals of male conspecifics, which may lead to mating opportunities, and similar sounds made by predatory bats. We therefore predicted that (1) females would display in response to playbacks of male calls; (2) females would not display in response to playbacks of the calls of echolocating bats (we used the calls of Daubenton's bat Myotis daubentonii as representative of a typical FM echolocating bat); and (3) when presented with male calls and bat calls during the same time block, females would display more when perceived predation risk was lower. We manipulated predation risk in two ways. First, we varied the intensity of bat calls to represent a nearby (high risk) or distant (low risk) bat. Second, we played back calls of bats searching for prey (low risk) and attacking prey (high risk). All predictions were supported, suggesting that female G. mellonella are able to distinguish conspecific male mating calls from bat calls, and that they modify display rate in relation to predation risk. The mechanism (s) by which the moths separate the calls of bat and moth must involve temporal cues. Bat and moth signals differ considerably in duration, and differences in duration could be encoded by the moth's nervous system and used in discrimination.

Copula-based spatial modelling of geometallurgical variables

The most important aspect of modelling a geological variable, such as metal grade, is the spatial correlation. Spatial correlation describes the relationship between realisations of a geological variable sampled at different locations. Any method for spatially modelling such a variable should be capable of accurately estimating the true spatial correlation. Conventional kriged models are the most commonly used in mining for estimating grade or other variables at unsampled locations, and these models use the variogram or covariance function to model the spatial correlations in the process of estimation. However, this usage assumes the relationships of the observations of the variable of interest at nearby locations are only influenced by the vector distance between the locations. This means that these models assume linear spatial correlation of grade. In reality, the relationship with an observation of grade at a nearby location may be influenced by both distance between the locations and the value of the observations (ie non-linear spatial correlation, such as may exist for variables of interest in geometallurgy). Hence this may lead to inaccurate estimation of the ore reserve if a kriged model is used for estimating grade of unsampled locations when nonlinear spatial correlation is present. Copula-based methods, which are widely used in financial and actuarial modelling to quantify the non-linear dependence structures, may offer a solution. This method was introduced by Bárdossy and Li (2008) to geostatistical modelling to quantify the non-linear spatial dependence structure in a groundwater quality measurement network. Their copula-based spatial modelling is applied in this research paper to estimate the grade of 3D blocks. Furthermore, real-world mining data is used to validate this model. These copula-based grade estimates are compared with the results of conventional ordinary and lognormal kriging to present the reliability of this method.

Some major problems with existing models and terminology associated with kimberlite pipes from a volcanological perspective, and some suggestions

Five significant problems hinder advances in understanding of the volcanology of kimberlites: (1) kimberlite geology is very model driven; (2) a highly genetic terminology drives deposit or facies interpretation; (3) the effects of alteration on preserved depositional textures have been grossly underestimated; (4) the level of understanding of the physical process significance of preserved textures is limited; and, (5) some inferred processes and deposits are not based on actual, modern volcanological processes. These issues need to be addressed in order to advance understanding of kimberlite volcanological pipe forming processes and deposits. The traditional, steep-sided southern African pipe model (Class I) consists of a steep tapering pipe with a deep root zone, a middle diatreme zone and an upper crater zone (if preserved). Each zone is thought to be dominated by distinctive facies, respectively: hypabyssal kimberlite (HK, descriptively called here massive coherent porphyritic kimberlite), tuffisitic kimberlite breccia (TKB, descriptively here called massive, poorly sorted lapilli tuff) and crater zone facies, which include variably bedded pyroclastic kimberlite and resedimented and reworked volcaniclastic kimberlite (RVK). Porphyritic coherent kimberlite may, however, also be emplaced at different levels in the pipe, as later stage intrusions, as well as dykes in the surrounding country rock. The relationship between HK and TKB is not always clear. Sub-terranean fluidisation as an emplacement process is a largely unsubstantiated hypothesis; modern in-vent volcanological processes should initially be considered to explain observed deposits. Crater zone volcaniclastic deposits can occur within the diatreme zone of some pipes, indicating that the pipe was largely empty at the end of the eruption, and subsequently began to fill-in largely through resedimentation and sourcing of pyroclastic deposits from nearby vents. Classes II and III Canadian kimberlite models have a more factual, descriptive basis, but are still inadequately documented given the recency of their discovery. The diversity amongst kimberlite bodies suggests that a three-model classification is an over-simplification. Every kimberlite is altered to varying degrees, which is an intrinsic consequence of the ultrabasic composition of kimberlite and the in-vent context; few preserve original textures. The effects of syn- to post-emplacement alteration on original textures have not been adequately considered to date, and should be back-stripped to identify original textural elements and configurations. Applying sedimentological textural configurations as a guide to emplacement processes would be useful. The traditional terminology has many connotations about spatial position in pipe and of process. Perhaps the traditional terminology can be retained in the industrial situation as a general lithofacies-mining terminological scheme because it is so entrenched. However, for research purposes a more descriptive lithofacies terminology should be adopted to facilitate detailed understanding of deposit characteristics, important variations in these, and the process origins. For example every deposit of TKB is different in componentry, texture, or depositional structure. However, because so many deposits in many different pipes are called TKB, there is an implication that they are all similar and that similar processes were involved, which is far from clear.

Using quantitative wastewater analysis to measure daily usage of conventional and emerging illicit drugs at an annual music festival

Introduction and Aims Wastewater analysis provides a non-intrusive way of measuring drug use within a population. We used this approach to determine daily use of conventional illicit drugs [cannabis, cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA)] and emerging illicit psychostimulants (benzylpiperazine, mephedrone and methylone) in two consecutive years (2010 and 2011) at an annual music festival. Design and Methods Daily composite wastewater samples, representative of the festival, were collected from the on-site wastewater treatment plant and analysed for drug metabolites. Data over 2 years were compared using Wilcoxon matched-pair test. Data from 2010 festival were compared with data collected at the same time from a nearby urban community using equivalent methods. Results Conventional illicit drugs were detected in all samples whereas emerging illicit psychostimulants were found only on specific days. The estimated per capita consumption of MDMA, cocaine and cannabis was similar between the two festival years. Statistically significant (P < 0.05; Z = −2.0–2.2) decreases were observed in use of methamphetamine and one emerging illicit psychostimulant (benzyl piperazine). Only consumption of MDMA was elevated at the festival compared with the nearby urban community. Discussion and Conclusions Rates of substance use at this festival remained relatively consistent over two monitoring years. Compared with the urban community, drug use among festival goers was only elevated for MDMA, confirming its popularity in music settings. Our study demonstrated that wastewater analysis can objectively capture changes in substance use at a music setting without raising major ethical issues. It would potentially allow effective assessments of drug prevention strategies in such settings in the future.

Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene

Aims/hypothesis Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study. Methods Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot. Results The top ranked variant was rs3805931 with p = 2.66 × 10−7, but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10−5) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10−8). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina. Conclusions/interpretation Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

Background To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10−9) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10−8). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10−7) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10−6). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency.

Pull factors attracting residents to Finnish senior houses

Most elderly Finnish residents prefer to age in place, but some relocate because of push factors that create stress in their current homes and pull factors that attract them to a new dwelling. This survey examines the important pull factors that attract seniors to senior houses. Grocery nearby is the strongest pull factor followed by hospital or medical center and public transportation. A factor analysis reveals that attributes can be grouped into three factors: onsite services that allow the residents to maintain an active lifestyle with some luxury, everyday services and facilities that would enable aging in place, and physical activity facilities. Residents have chosen the type of senior housing that supports their lifestyle. Meanwhile, socioeconomic characteristics do not explain the differences in the types of features that attract residents.

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.