A Morphing Technique Applied to Lung Motions in Radiotherapy: Preliminary Results

Organ motion leads to dosimetric uncertainties during a patient’s treatment. Much work has been done to quantify the dosimetric effects of lung movement during radiation treatment. There is a particular need for a good description and prediction of organ motion. To describe lung motion more precisely, we have examined the possibility of using a computer technique: a morphing algorithm. Morphing is an iterative method which consists of blending one image into another image. To evaluate the use of morphing, Four Dimensions Computed Tomography (4DCT) acquisition of a patient was performed. The lungs were automatically segmented for different phases, and morphing was performed using the end-inspiration and the end-expiration phase scans only. Intermediate morphing files were compared with 4DCT intermediate images. The results showed good agreement between morphing images and 4DCT images: fewer than 2 % of the 512 by 256 voxels were wrongly classified as belonging/not belonging to a lung section. This paper presents preliminary results, and our morphing algorithm needs improvement. We can infer that morphing offers considerable advantages in terms of radiation protection of the patient during the diagnosis phase, handling of artifacts, definition of organ contours and description of organ motion

Identification and weighting of the most critical "real-life” drug-drug interactions with acenocoumarol in a tertiary care hospital

Purpose: The objective of this study was to identify the most clinically relevant drug-drug interactions (DDIs) at risk of affecting acenocoumarol safety in our tertiary care university hospital, a 2,000 bed institution. Methods: We identified DDIs occurring with acenocoumarol by combining two different sources of information: a 1-year retrospective analysis of acenocoumarol prescriptions and comedications from our Computerized Physician Order Entry (CPOE) system (n = 2,439 hospitalizations) and a retrospective study of clinical pharmacology consultations involving acenocoumarol over the past 14 years (1994-2007) (n = 407). We classified these DDIs using an original risk-analysis method. A criticality index was calculated for each associated drug by multiplying three scores based on mechanism of interaction, involvement in a supratherapeutic international normalized ratio (INR) (≥ 6) and involvement in a severe bleeding. Results: One hundred and twenty-six DDIs were identified and weighted. Twenty-eight drugs had a criticality index ≥ 20 and were therefore considered at high risk for interacting with acenocoumarol by increasing its effect: 75% of these drugs involved a pharmacokinetic mechanism and 14 % a pharmacodynamic mechanism. An unknown mechanism of interaction was involved in 11 % of drugs. Conclusion: Twenty-eight specific drugs were identified as being at high risk for interacting with acenocoumarol in our hospital using an original risk-analysis method. Most analyzed drugs interact with acenocoumarol via a pharmacokinetic mechanism. Actions such as the implementation of alerts in our CPOE system should be specifically developed for these drug

Identification and weighting of the most critical "real-life” drug-drug interactions with acenocoumarol in a tertiary care hospital

Purpose: The objective of this study was to identify the most clinically relevant drug-drug interactions (DDIs) at risk of affecting acenocoumarol safety in our tertiary care university hospital, a 2,000 bed institution. Methods: We identified DDIs occurring with acenocoumarol by combining two different sources of information: a 1-year retrospective analysis of acenocoumarol prescriptions and comedications from our Computerized Physician Order Entry (CPOE) system (n = 2,439 hospitalizations) and a retrospective study of clinical pharmacology consultations involving acenocoumarol over the past 14 years (1994-2007) (n = 407). We classified these DDIs using an original risk-analysis method. A criticality index was calculated for each associated drug by multiplying three scores based on mechanism of interaction, involvement in a supratherapeutic international normalized ratio (INR) (≥ 6) and involvement in a severe bleeding. Results: One hundred and twenty-six DDIs were identified and weighted. Twenty-eight drugs had a criticality index ≥ 20 and were therefore considered at high risk for interacting with acenocoumarol by increasing its effect: 75% of these drugs involved a pharmacokinetic mechanism and 14 % a pharmacodynamic mechanism. An unknown mechanism of interaction was involved in 11 % of drugs. Conclusion: Twenty-eight specific drugs were identified as being at high risk for interacting with acenocoumarol in our hospital using an original risk-analysis method. Most analyzed drugs interact with acenocoumarol via a pharmacokinetic mechanism. Actions such as the implementation of alerts in our CPOE system should be specifically developed for these drug

Using ERA-Interim reanalysis for creating datasets of energy-relevant climate variables

The construction of a bias-adjusted dataset of climate variables at the near surface using ERA-Interim reanalysis is presented. A number of different, variable-dependent, bias-adjustment approaches have been proposed. Here we modify the parameters of different distributions (depending on the variable), adjusting ERA-Interim based on gridded station or direct station observations. The variables are air temperature, dewpoint temperature, precipitation (daily only), solar radiation, wind speed, and relative humidity. These are available on either 3 or 6 h timescales over the period 1979–2016. The resulting bias-adjusted dataset is available through the Climate Data Store (CDS) of the Copernicus Climate Change Data Store (C3S) and can be accessed at present from ftp://ecem.climate.copernicus.eu. The benefit of performing bias adjustment is demonstrated by comparinginitial and bias-adjusted ERA-Interim data against gridded observational fields

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

The design of a purpose-built exergame for fall prediction and prevention for older people

Background Falls in older people represent a major age-related health challenge facing our society. Novel methods for delivery of falls prevention programs are required to increase effectiveness and adherence to these programs while containing costs. The primary aim of the Information and Communications Technology-based System to Predict and Prevent Falls (iStoppFalls) project was to develop innovative home-based technologies for continuous monitoring and exercise-based prevention of falls in community-dwelling older people. The aim of this paper is to describe the components of the iStoppFalls system. Methods The system comprised of 1) a TV, 2) a PC, 3) the Microsoft Kinect, 4) a wearable sensor and 5) an assessment and training software as the main components. Results The iStoppFalls system implements existing technologies to deliver a tailored home-based exercise and education program aimed at reducing fall risk in older people. A risk assessment tool was designed to identify fall risk factors. The content and progression rules of the iStoppFalls exergames were developed from evidence-based fall prevention interventions targeting muscle strength and balance in older people. Conclusions The iStoppFalls fall prevention program, used in conjunction with the multifactorial fall risk assessment tool, aims to provide a comprehensive and individualised, yet novel fall risk assessment and prevention program that is feasible for widespread use to prevent falls and fall-related injuries. This work provides a new approach to engage older people in home-based exercise programs to complement or provide a potentially motivational alternative to traditional exercise to reduce the risk of falling

Crowd-Based Mining of Reusable Process Model Patterns

Process mining is a domain where computers undoubtedly outperform humans. It is a mathematically complex and computationally demanding problem, and event logs are at too low a level of abstraction to be intelligible in large scale to humans. We demonstrate that if instead the data to mine from are models (not logs), datasets are small (in the order of dozens rather than thousands or millions), and the knowledge to be discovered is complex (reusable model patterns), humans outperform computers. We design, implement, run, and test a crowd-based pattern mining approach and demonstrate its viability compared to automated mining. We specifically mine mashup model patterns (we use them to provide interactive recommendations inside a mashup tool) and explain the analogies with mining business process models. The problem is relevant in that reusable model patterns encode valuable modeling and domain knowledge, such as best practices or organizational conventions, from which modelers can learn and benefit when designing own models. © 2014 Springer International Publishing Switzerland

Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event

Removal of cell surface heparan sulfate increases TACE activity and cleavage of ErbB4 receptor

<p>Abstract</p> <p>Background</p> <p>Nuclear localization of proteolytically formed intracellular fragment of ErbB4 receptor tyrosine kinase has been shown to promote cell survival, and nuclear localization of ErbB4 receptor has been described in human breast cancer. Tumor necrosis factor alpha converting enzyme (TACE) initiates the proteolytic cascade leading to ErbB4 intracellular domain formation. Interactions between matrix metalloproteases and heparan sulfate have been described, but the effect of cell surface heparan sulfate on TACE activity has not been previously described.</p> <p>Results</p> <p>As indicated by immunodetection of increased ErbB4 intracellular domain formation and direct enzyme activity analysis, TACE activity was substantially amplified by enzymatic removal of cell surface heparan sulfate but not chondroitin sulfate.</p> <p>Conclusion</p> <p>In this communication, we suggest a novel role for cell surface heparan sulfate. Removal of cell surface heparan sulfate led to increased formation of ErbB4 intracellular domain. As ErbB4 intracellular domain has previously been shown to promote cell survival this finding may indicate a novel mechanism how HS degradation active in tumor tissue may favor cell survival.</p