CBCT-to-CT synthesis with a single neural network for head-and-neck, lung and breast cancer adaptive radiotherapy

Purpose: CBCT-based adaptive radiotherapy requires daily images for accurate dose calculations. This study investigates the feasibility of applying a single convolutional network to facilitate CBCT-to-CT synthesis for head-and-neck, lung, and breast cancer patients. Methods: Ninety-nine patients diagnosed with head-and-neck, lung or breast cancer undergoing radiotherapy with CBCT-based position verification were included in this study. CBCTs were registered to planning CTs according to clinical procedures. Three cycle-consistent generative adversarial networks (cycle-GANs) were trained in an unpaired manner on 15 patients per anatomical site generating synthetic-CTs (sCTs). Another network was trained with all the anatomical sites together. Performances of all four networks were compared and evaluated for image similarity against rescan CT (rCT). Clinical plans were recalculated on CT and sCT and analysed through voxel-based dose differences and {\gamma}-analysis. Results: A sCT was generated in 10 seconds. Image similarity was comparable between models trained on different anatomical sites and a single model for all sites. Mean dose differences < 0.5% were obtained in high-dose regions. Mean gamma (2%,2mm) pass-rates > 95% were achieved for all sites. Conclusions: Cycle-GAN reduced CBCT artefacts and increased HU similarity to CT, enabling sCT-based dose calculations. The speed of the network can facilitate on-line adaptive radiotherapy using a single network for head-and-neck, lung and breast cancer patients.Comment: Submitted to Medical Physics; 2019-12-2

Utility of Parental Mediation Model on Youth’s Problematic Online Gaming

The Parental Mediation Model PMM) was initially designed to regulate children’s attitudes towards the traditional media. In the present era, because of prevalent online media there is a need for similar regulative measures. Spending long hours on social media and playing online games increase the risks of exposure to the negative outcomes of online gaming. This paper initially applied the PMM developed by European Kids Online to (i) test the reliability and validity of this model and (ii) identify the effectiveness of this model in controlling problematic online gaming (POG). The data were collected from 592 participants comprising 296 parents and 296 students of four foreign universities, aged 16 to 22 years in Kuala Lumpur (Malaysia). The study found that the modified model of the five-factor PMM (Technical mediation, Monitoring mediation, Restrictive mediation, Active Mediation of Internet Safety, and Active mediation of Internet Use) functions as a predictor for mitigating POG. The findings suggest the existence of a positive relation between ‘monitoring’ and ‘restrictive’ mediation strategies and exposure to POG while Active Mediation of Internet Safety and Active mediation of Internet use were insignificant predictors. Results showed a higher utility of ‘technical’ strategies by the parents led to less POG. The findings of this study do not support the literature suggesting active mediation is more effective for reducing youth’s risky behaviour. Instead, parents need to apply more technical mediations with their children and adolescents’ Internet use to minimize the negative effects of online gaming

The hw-rank: an h-index variant for ranking web pages

We introduce a novel ranking of search results based on a variant of the h-index for directed information networks such as the Web. The h-index was originally introduced to measure an individual researcher’s scientific output and influence, but here a variant of it is applied to assess the ‘‘importance’’ of web pages. Like PageRank, the‘‘importance’’ of a page is defined by the ‘‘importance’’ of the pages linking to it. However, unlike the computation of PageRank which involves the whole web graph, computing the h-index for web pages (the hw-rank) is based on a local computation and only the neighbors of the neighbors of the given node are considered. Preliminary results show a strong correlation between ranking with the hw-rank and PageRank, and moreover its computation is simpler and less complex than computation of the PageRank. Further, larger scale experiments are needed in order to assess the applicability of the method

Variation, variability, and the origin of the avian endocranium:Insights from the anatomy of alioramus altai (theropoda: Tyrannosauroidea)

The internal braincase anatomy of the holotype of Alioramus altai, a relatively small-bodied tyrannosauroid from the Late Cretaceous of Mongolia, was studied using high-resolution computed tomography. A number of derived characters strengthen the diagnosis of this taxon as both a tyrannosauroid and a unique, new species (e.g., endocranial position of the gasserian ganglion, internal ramification of the facial nerve). Also present are features intermediate between the basal theropod and avialan conditions that optimize as the ancestral condition for Coelurosauria--a diverse group of derived theropods that includes modern birds. The expression of several primitive theropod features as derived character states within Tyrannosauroidea establishes previously unrecognized evolutionary complexity and morphological plasticity at the base of Coelurosauria. It also demonstrates the critical role heterochrony may have played in driving patterns of endocranial variability within the group and potentially reveals stages in the evolution of neuroanatomical development that could not be inferred based solely on developmental observations of the major archosaurian crown clades. We discuss the integration of paleontology with variability studies, especially as applied to the nature of morphological transformations along the phylogenetically long branches that tend to separate the crown clades of major vertebrate groups

The vanishing atrial mass.

HEFCEThis is the final version of the article. It first appeared from Oxford University Press via https://doi.org10.1093/ehjci/jew12

Side Chain Hydrophobicity Modulates Therapeutic Activity and Membrane Selectivity of Antimicrobial Peptide Mastoparan-X

The discovery of new anti-infective compounds is stagnating and multi-resistant bacteria continue to emerge, threatening to end the "antibiotic era". Antimicrobial peptides (AMPs) and lipo-peptides such as daptomycin offer themselves as a new potential class of antibiotics; however, further optimization is needed if AMPs are to find broad use as antibiotics. In the present work, eight analogues of mastoparan-X (MPX) were investigated, having side chain modifications in position 1, 8 and 14 to modulate peptide hydrophobicity. The self-association properties of the peptides were characterized, and the peptide-membrane interactions in model membranes were compared with the bactericidal and haemolytic properties. Alanine substitution at position 1 and 14 resulted in higher target selectivity (red blood cells versus bacteria), but also decreased bactericidal potency. For these analogues, the gain in target selectivity correlated to biophysical parameters showing an increased effective charge and reduction in the partitioning coefficient for membrane insertion. Introduction of an unnatural amino acid, with an octyl side chain by amino acid substitution, at positions 1, 8 and 14 resulted in increased bactericidal potency at the expense of radically reduced membrane target selectivity. Overall, optimized membrane selectivity or bactericidal potency was achieved by changes in side chain hydrophobicity of MPX. However, enhanced potency was achieved at the expense of selectivity and vice versa in all cases

The LRRK2 signalling system

The LRRK2 gene is a major contributor to genetic risk for Parkinson's disease and understanding the biology of the leucine-rich repeat kinase 2 (LRRK2, the protein product of this gene) is an important goal in Parkinson's research. LRRK2 is a multi-domain, multi-activity enzyme and has been implicated in a wide range of signalling events within the cell. Because of the complexities of the signal transduction pathways in which LRRK2 is involved, it has been challenging to generate a clear idea as to how mutations and disease associated variants in this gene are altered in disease. Understanding the events in which LRRK2 is involved at a systems level is therefore critical to fully understand the biology and pathobiology of this protein and is the subject of this review

Validation of the surgical fear questionnaire in adult patients waiting for elective surgery

Objectives: Because existing instruments for assessing surgical fear seem either too general or too limited, the Surgical Fear Questionnaire (SFQ) was developed. The aim of this study is to assess the validity and reliability of the SFQ. Methods: Based on existing literature and expert consultation the ten-item SFQ was composed. Data on the SFQ were obtained from 5 prospective studies (N = 3233) in inpatient or day surgery patients. These data were used for exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability analysis and validity analysis. Results: EFA in Study 1 and 2 revealed a two-factor structure with one factor associated with fear of the short-term consequences of surgery (SFQ-s, item 1-4) and the other factor with fear of the long-term consequences of surgery (SFQ-l, item 5-10). However, in both studies two items of the SFQ-l had low factor loadings. Therefore in Study 3 and 4 the 2-factor structure was tested and confirmed by CFA in an eight-item version of the SFQ. Across all studies significant correlations of the SFQ with pain catastrophizing, state anxiety, and preoperative pain intensity indicated good convergent validity. Internal consistency (Cronbach's alpha) was between 0.765-0.920 (SFQ-total), 0.766-0.877 (SFQ-s), and 0.628-0.899 (SFQ-l). The SFQ proved to be sensitive to detect differences based on age, sex, education level, employment status and preoperative pain intensity. Discussion: The SFQ is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences.This study was conducted with departmental funding and supported by a grant from The Netherlands Organisation for Scientific Research (Zon-MW, http://www.zonmw.nl/en/), grant no. 110000007. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Dreams and nightmares of liberal international law: capitalist accumulation, natural rights and state hegemony

This article develops a line of theorising the relationship between peace, war and commerce and does so via conceptualising global juridical relations as a site of contestation over questions of economic and social justice. By sketching aspects of a historical interaction between capitalist accumulation, natural rights and state hegemony, the article offers a critical account of the limits of liberal international law, and attempts to recover some ground for thinking about the emancipatory potential of international law more generally

Analysis of the putative role of CR1 in Alzheimer’s disease: Genetic association, expression and function

Chronic activation of the complement system and induced inflammation are associated with neuropathology in Alzheimer's disease (AD). Recent large genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the C3b/C4b receptor (CR1 or CD35) that are associated with late onset AD. Here, anti-CR1 antibodies (Abs) directed against different epitopes of the receptor, were used to localize CR1 in brain, and relative binding affinities of the CR1 ligands, C1q and C3b, were assessed by ELISA. Most Abs tested stained red blood cells in blood vessels but showed no staining in brain parenchyma. However, two monoclonal anti-CR1 Abs labeled astrocytes in all of the cases tested, and this reactivity was preabsorbed by purified recombinant human CR1. Human brain-derived astrocyte cultures were also reactive with both mAbs. The amount of astrocyte staining varied among the samples, but no consistent difference was conferred by diagnosis or the GWAS-identified SNPs rs4844609 or rs6656401. Plasma levels of soluble CR1 did not correlate with diagnosis but a slight increase was observed with rs4844609 and rs6656401 SNP. There was also a modest but statistically significant increase in relative binding activity of C1q to CR1 with the rs4844609 SNP compared to CR1 without the SNP, and of C3b to CR1 in the CR1 genotypes containing the rs6656401 SNP (also associated with the larger isoform of CR1) regardless of clinical diagnosis. These results suggest that it is unlikely that astrocyte CR1 expression levels or C1q or C3b binding activity are the cause of the GWAS identified association of CR1 variants with AD. Further careful functional studies are needed to determine if the variant-dictated number of CR1 expressed on red blood cells contributes to the role of this receptor in the progression of AD, or if another mechanism is involved