The potential impact of CT-MRI matching on tumor volume delineation in advanced head and neck cancer

To study the potential impact of the combined use of CT and MRI scans on the Gross Tumor Volume (GTV) estimation and interobserver variation. Four observers outlined the GTV in six patients with advanced head and neck cancer on CT, axial MRI, and coronal or sagittal MRI. The MRI scans were subsequently matched to the CT scan. The interobserver and interscan set variation were assessed in three dimensions. The mean CT derived volume was a factor of 1.3 larger than the mean axial MRI volume. The range in volumes was larger for the CT than for the axial MRI volumes in five of the six cases. The ratio of the scan set common (i.e., the volume common to all GTVs) and the scan set encompassing volume (i.e., the smallest volume encompassing all GTVs) was closer to one in MRI (0.3-0.6) than in CT (0.1-0.5). The rest volumes (i.e., the volume defined by one observer as GTV in one data set but not in the other data set) were never zero for CT vs. MRI nor for MRI vs. CT. In two cases the craniocaudal border was poorly recognized on the axial MRI but could be delineated with a good agreement between the observers in the coronal/sagittal MRI. MRI-derived GTVs are smaller and have less interobserver variation than CT-derived GTVs. CT and MRI are complementary in delineating the GTV. A coronal or sagittal MRI adds to a better GTV definition in the craniocaudal directio

Intelligent pressure-based typing biometrics system

The design and development of a real-time enhanced password security system, based on the analysis of habitual typing rhythms of individuals, is discussed in this paper. The paper examines the use of force exerted on the keyboard and time latency between keystrokes to create typing patterns for individual users. Pressure signals which are taken from the sensors underneath the keypad are extracted accordingly. These are then used to recognize authentic users and reject imposters. An experimental setup has been developed to capture the pressure signal information of the users’ typing rhythm. Neuro-fuzzy system is employed as the classifier to measure the user’s typing pattern using the Adaptive Neural Fuzzy Inference System toolbox (ANFIS) in MATLAB

Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated

Elevated level of anterior gradient-2 in pancreatic juice from patients with pre-malignant pancreatic neoplasia

<p>Abstract</p> <p>Background</p> <p>Pancreatic intraepithelial neoplasias (PanINs) are precursors of malignant pancreatic cancer, an ideal stage for early cancer detection. We applied quantitative proteomics to identify aberrantly elevated proteins in pancreatic juice samples derived from patients with PanIN3.</p> <p>Results</p> <p>Twenty proteins were found elevated in all three PanIN juices by at least two-fold. Among these proteins, anterior gradient-2 (AGR2) was found to be 2-10 fold elevated in PanIN3 juice samples analyzed by quantitative proteomics. An ELISA assay was developed to evaluate AGR2 levels in 51 pancreatic juice samples and 23 serum samples from patients with pancreatic cancer, pre-malignant lesions (including PanIN3, PanIN2, Intraductal Papillary Mucinous Neoplasms (IPMNs)) and benign disease controls (including chronic pancreatitis). AGR2 levels in the pancreatic juice samples were found significantly elevated in patients with pre-malignant conditions (PanINs and IPMNs) as well as pancreatic cancer compared to control samples (p ≤ 0.03). By ROC analysis, the AGR2 ELISA achieved 67% sensitivity at 90% specificity in predicting PanIN3 juice samples from the benign disease controls.</p> <p>Conclusions</p> <p>These results suggest that elevation of AGR2 levels in pancreatic juice occurs in early pancreatic cancer progression and could be further investigated as a potential candidate juice biomarker for early detection of pancreatic cancer.</p

Ensemble Place Codes in Hippocampus: CA1, CA3, and Dentate Gyrus Place Cells Have Multiple Place Fields in Large Environments

Previously we reported that the hippocampus place code must be an ensemble code because place cells in the CA1 region of hippocampus have multiple place fields in a more natural, larger-than-standard enclosure with stairs that permitted movements in 3-D. Here, we further investigated the nature of hippocampal place codes by characterizing the spatial firing properties of place cells in the CA1, CA3, and dentate gyrus (DG) hippocampal subdivisions as rats foraged in a standard 76-cm cylinder as well as a larger-than-standard box (1.8 m×1.4 m) that did not have stairs or any internal structure to permit movements in 3-D. The rats were trained to forage continuously for 1 hour using computer-controlled food delivery. We confirmed that most place cells have single place fields in the standard cylinder and that the positional firing pattern remapped between the cylinder and the large enclosure. Importantly, place cells in the CA1, CA3 and DG areas all characteristically had multiple place fields that were irregularly spaced, as we had reported previously for CA1. We conclude that multiple place fields are a fundamental characteristic of hippocampal place cells that simplifies to a single field in sufficiently small spaces. An ensemble place code is compatible with these observations, which contradict any dedicated coding scheme

Maximising data to optimise animal disease early warning systems and risk assessment tools within Europe

Timely and reliable data and information availability and sharing is essential for early warning, prevention and control of transboundary diseases. While there are a growing number of global datasets capable of providing information for use in early warning systems and risk assessment (RA) tools, there are currently time-consuming data cleansing and harmonisation activities which need to be carried out before they can be reliably used and combined. Thus, using global datasets as they stand can lead to errors in RA parameterisation and results due to inherent biases in the data, e.g. missing disease prevalence data treated as a zero may inadvertently penalise those countries which do report disease outbreaks as opposed to those countries which are affected by a pathogen but do not report outbreak data. It is therefore of great importance that data are clearly provided and easy to understand and that data providers strive for greater harmonisation of database standards. In this paper the datasets utilised in the SPARE (’Spatial risk assessment framework for assessing exotic disease incursion and spread through Europe’) project are described and discussed in terms of key criteria: accessibility, availability, completeness, consistency and quality. It is evident that most databases exist as information portals and not exclusively for RA purposes. Another striking issue from this assessment is the need for enhanced data sharing specifically with regards to data on illegal seizures, arthropod vector/wildlife abundance, intra-country livestock movement and national animal disease surveillance. It is hoped that the outcomes of this work will promote discussion and exchange between data providers, including the development of standardised data exchange protocols. The transformation of datasets to a common format is a considerable challenge but recommendations could and should be made on the standardisation of datasets and reporting in order to achieve a unified approach across Europe

Using multi-criteria risk ranking methodology to select case studies for a generic risk assessment framework for exotic disease incursion and spread through Europe

We present a novel approach of using the multi-criteria pathogen prioritisation methodology as a basis for selecting the most appropriate case studies for a generic risk assessment framework. The approach uses selective criteria to rank exotic animal health pathogens according to the likelihood of introduction and the impact of an outbreak if it occurred in the European Union (EU). Pathogens were evaluated based on their impact on production at the EU level and international trade. A subsequent analysis included criteria of relevance to quantitative risk assessment case study selection, such as the availability of data for parameterisation, the need for further research and the desire for the case studies to cover different routes of transmission. The framework demonstrated is flexible with the ability to adjust both the criteria and their weightings to the user's requirements. A web based tool has been developed using the RStudio shiny apps software, to facilitate this

Cellular and clinical impact of Haploinsufficiency for genes involved in ATR signaling

Ataxia telangiectasia and Rad3-related (ATR) protein, a kinase that regulates a DNA damage-response pathway, is mutated in ATR-Seckel syndrome (ATR-SS), a disorder characterized by severe microcephaly and growth delay. Impaired ATR signaling is also observed in cell lines from additional disorders characterized by microcephaly and growth delay, including non-ATR-SS, Nijmegen breakage syndrome, and MCPH1 (microcephaly, primary autosomal recessive, 1)-dependent primary microcephaly. Here, we examined ATR-pathway function in cell lines from three haploinsufficient contiguous gene-deletion disorders--a subset of blepharophimosis-ptosis-epicanthus inversus syndrome, Miller-Dieker lissencephaly syndrome, and Williams-Beuren syndrome--in which the deleted region encompasses ATR, RPA1, and RFC2, respectively. These three genes function in ATR signaling. Cell lines from these disorders displayed an impaired ATR-dependent DNA damage response. Thus, we describe ATR signaling as a pathway unusually sensitive to haploinsufficiency and identify three further human disorders displaying a defective ATR-dependent DNA damage response. The striking correlation of ATR-pathway dysfunction with the presence of microcephaly and growth delay strongly suggests a causal relationship

The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen-processing defects

The nonclassical major histocompatibility complex (MHC) Qa-1b accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, which are expressed by natural killer cells and CD8+ T cells. We here describe that the conserved peptides are replaced by a novel peptide repertoire of surprising diversity as a result of impairments in the antigen-processing pathway. This novel peptide repertoire represents immunogenic neoantigens for CD8+ T cells, as we found that these Qa-1b–restricted T cells dominantly participated in the response to tumors with processing deficiencies. A surprisingly wide spectrum of target cells, irrespective of transformation status, MHC background, or type of processing deficiency, was recognized by this T cell subset, complying with the conserved nature of Qa-1b. Target cell recognition depended on T cell receptor and Qa-1b interaction, and immunization with identified peptide epitopes demonstrated in vivo priming of CD8+ T cells. Our data reveal that Qa-1b, and most likely its human homologue human leukocyte antigen-E, is important for the defense against processing-deficient cells by displacing the monomorphic leader peptides, which relieves the inhibition through CD94/NKG2A on lymphocytes, and by presenting a novel repertoire of immunogenic peptides, which recruits a subset of cytotoxic CD8+ T cells