Evaluation of volumetric modulated arc therapy (VMAT) with Oncentra MasterPlan® for the treatment of head and neck cancer

Background Several comparison studies have shown the capability of VMAT to achieve similar or better plan quality as IMRT, while reducing the treatment time. The experience of VMAT in a multi vendor environment is limited. We compared the plan quality and performance of VMAT to IMRT and we investigate the effects of varying various user-selectable parameters. Methods IMRT, single arc VMAT and dual arc VMAT were compared for four different head-and-neck tumors. For VMAT, the effect of varying gantry angle spacing and treatment time on the plan quality was investigated. A comparison of monitor units and treatment time was performed. Results IMRT and dual arc VMAT achieved a similar plan quality, while single arc could not provide an acceptable plan quality. Increasing the number of control points does not improve the plan quality. Dual arc VMAT delivery time is about 30% of IMRT delivery time. Conclusions Dual arc VMAT is a fast and accurate technique for the treatment of head and neck cancer. It applies similar number of MUs as IMRT, but the treatment time is strongly reduced, maintaining similar or better dose conformity to the PTV and OAR sparing

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations withP <5 x 10(-8)in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P <5 x 10(-8)) in the discovery samples. Ten novel SNVs, including rs12616219 nearTMEM182, were followed-up and five of them (rs462779 inREV3L, rs12780116 inCNNM2, rs1190736 inGPR101, rs11539157 inPJA1, and rs12616219 nearTMEM182) replicated at a Bonferroni significance threshold (P <4.5 x 10(-3)) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, inCCDC141and two low-frequency SNVs inCEP350andHDGFRP2. Functional follow-up implied that decreased expression ofREV3Lmay lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.Peer reviewe

Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. METHODS: We analyzed similar to 250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.Peer reviewe

Prevention and treatment of long-term social disability amongst young people with emerging severe mental illness with social recovery therapy (The PRODIGY Trial): Study protocol for a randomised controlled trial

© 2017 The Author(s). Background: Young people who have social disability associated with severe and complex mental health problems are an important group in need of early intervention. Their problems often date back to childhood and become chronic at an early age. Without intervention, the long-term prognosis is often poor and the economic costs very large. There is a major gap in the provision of evidence-based interventions for this group, and therefore new approaches to detection and intervention are needed. This trial provides a definitive evaluation of a new approach to early intervention with young people with social disability and severe and complex mental health problems using social recovery therapy (SRT) over a period of 9 months to improve mental health and social recovery outcomes. Methods: This is a pragmatic, multi-centre, single blind, superiority randomised controlled trial. It is conducted in three sites in the UK: Sussex, Manchester and East Anglia. Participants are aged 16 to 25 and have both persistent and severe social disability (defined as engaged in less than 30 hours per week of structured activity) and severe and complex mental health problems. The target sample size is 270 participants, providing 135 participants in each trial arm. Participants are randomised 1:1 using a web-based randomisation system and allocated to either SRT plus optimised treatment as usual (enhanced standard care) or enhanced standard care alone. The primary outcome is time use, namely hours spent in structured activity per week at 15 months post-randomisation. Secondary outcomes assess typical mental health problems of the group, including subthreshold psychotic symptoms, negative symptoms, depression and anxiety. Time use, secondary outcomes and health economic measures are assessed at 9, 15 and 24 months post-randomisation. Discussion: This definitive trial will be the first to evaluate a novel psychological treatment for social disability and mental health problems in young people presenting with social disability and severe and complex non-psychotic mental health problems. The results will have important implications for policy and practice in the detection and early intervention for this group in mental health services. Trial registration: Trial Registry: International Standard Randomised Controlled Trial Number (ISRCTN) Registry. Trial Registration Number: ISRCTN47998710(registered 29/11/2012)

See, feel, taste: The influence of receptacle colour and weight on the evaluation of flavoured carbonated beverages

A study was designed to assess whether the individual and combined effects of product-intrinsic and product-extrinsic factors influence the perception of, and liking for, carbonated beverages. Four hundred and one participants tasted samples of one of three flavours (grapefruit, lemon, or raspberry) of carbonated aromatised non-alcoholic beer. The beverages were served in receptacles that differed in terms of their colour (red or black) and weight (lighter—no added weight, or heavier—20 g weight added). Each participant received the same beverage in each of the four different receptacles, and rated how much they liked the drink. They also evaluated the intensity of each beverage’s sweetness, bitterness, sourness, and carbonation. The results revealed a significant influence of the colour of the receptacle on perceived carbonation, with the beverages tasted from the red receptacles being rated as tasting more carbonated than when served in black receptacles. In terms of flavour, the participants liked the raspberry beverage significantly more than the others, while also rating it as tasting sweeter and less bitter than either of the other flavours. Furthermore, there was a more complex interaction effect involving the weight of the receptacle: Specifically, the perceived bitterness of the beverage moderated the relationship between the receptacle weight and the perceived carbonation. At high levels of bitterness, the drinks were perceived to be more carbonated when served from the heavier receptacle as compared to the lighter one. These findings highlight the complex interplay of product extrinsic and intrinsic factors on the flavour/mouthfeel perception and preference for beverages, and stress the importance of taking both internal product development and external packaging into account in the design of health-oriented beverages

The role of intrinsic and extrinsic sensory factors in sweetness perception of food and beverages: A review

When it comes to eating and drinking, multiple factors from diverse sensory modalities have been shown to influence multisensory flavour perception and liking. These factors have heretofore been strictly divided into either those that are intrinsic to the food itself (e.g., food colour, aroma, texture), or those that are extrinsic to it (e.g., related to the packaging, receptacle or external environment). Given the obvious public health need for sugar reduction, the present review aims to compare the relative influences of product-intrinsic and product-extrinsic factors on the perception of sweetness. Evidence of intrinsic and extrinsic sensory influences on sweetness are reviewed. Thereafter, we take a cognitive neuroscience perspective and evaluate how differences may occur in the way that food-intrinsic and extrinsic information become integrated with sweetness perception. Based on recent neuroscientific evidence, we propose a new framework of multisensory flavour integration focusing not on the food-intrinsic/extrinsic divide, but rather on whether the sensory information is perceived to originate from within or outside the body. This framework leads to a discussion on the combinability of intrinsic and extrinsic influences, where we refer to some existing examples and address potential theoretical limitations. To conclude, we provide recommendations to those in the food industry and propose directions for future research relating to the need for long-term studies and understanding of individual differences

See, feel, taste: The influence of receptacle colour and weight on the evaluation of flavoured carbonated beverages

A study was designed to assess whether the individual and combined effects of product-intrinsic and product-extrinsic factors influence the perception of, and liking for, carbonated beverages. Four hundred and one participants tasted samples of one of three flavours (grapefruit, lemon, or raspberry) of carbonated aromatised non-alcoholic beer. The beverages were served in receptacles that differed in terms of their colour (red or black) and weight (lighter—no added weight, or heavier—20 g weight added). Each participant received the same beverage in each of the four different receptacles, and rated how much they liked the drink. They also evaluated the intensity of each beverage’s sweetness, bitterness, sourness, and carbonation. The results revealed a significant influence of the colour of the receptacle on perceived carbonation, with the beverages tasted from the red receptacles being rated as tasting more carbonated than when served in black receptacles. In terms of flavour, the participants liked the raspberry beverage significantly more than the others, while also rating it as tasting sweeter and less bitter than either of the other flavours. Furthermore, there was a more complex interaction effect involving the weight of the receptacle: Specifically, the perceived bitterness of the beverage moderated the relationship between the receptacle weight and the perceived carbonation. At high levels of bitterness, the drinks were perceived to be more carbonated when served from the heavier receptacle as compared to the lighter one. These findings highlight the complex interplay of product extrinsic and intrinsic factors on the flavour/mouthfeel perception and preference for beverages, and stress the importance of taking both internal product development and external packaging into account in the design of health-oriented beverages

The role of intrinsic and extrinsic sensory factors in sweetness perception of food and beverages: A review

When it comes to eating and drinking, multiple factors from diverse sensory modalities have been shown to influence multisensory flavour perception and liking. These factors have heretofore been strictly divided into either those that are intrinsic to the food itself (e.g., food colour, aroma, texture), or those that are extrinsic to it (e.g., related to the packaging, receptacle or external environment). Given the obvious public health need for sugar reduction, the present review aims to compare the relative influences of product-intrinsic and product-extrinsic factors on the perception of sweetness. Evidence of intrinsic and extrinsic sensory influences on sweetness are reviewed. Thereafter, we take a cognitive neuroscience perspective and evaluate how differences may occur in the way that food-intrinsic and extrinsic information become integrated with sweetness perception. Based on recent neuroscientific evidence, we propose a new framework of multisensory flavour integration focusing not on the food-intrinsic/extrinsic divide, but rather on whether the sensory information is perceived to originate from within or outside the body. This framework leads to a discussion on the combinability of intrinsic and extrinsic influences, where we refer to some existing examples and address potential theoretical limitations. To conclude, we provide recommendations to those in the food industry and propose directions for future research relating to the need for long-term studies and understanding of individual differences