60 research outputs found

    X-Tream: a novel dosimetry system for Synchrotron Microbeam Radiation Therapy

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    Microbeam Radiation Therapy (MRT) is a radiation treatment technique under development for inoperable brain tumors. MRT is based on the use of a synchrotron generated X-ray beam with an extremely high dose rate ( ~ 20 kGy/sec), striated into an array of X-ray micro-blades. In order to advance to clinical trials, a real-time dosimeter with excellent spatial resolution must be developed for absolute dosimetry. The design of a real-time dosimeter for such a radiation scenario represents a significant challenge due to the high photon flux and vertically striated radiation field, leading to very steep lateral dose gradients. This article analyses the striated radiation field in the context of the requirements for temporal dosimetric measurements and presents the architecture of a new dosimetry system based on the use of silicon detectors and fast data acquisition electronic interface. The combined system demonstrates micrometer spatial resolution and microsecond real time readout with accurate sensitivity and linearity over five orders of magnitude of input signal. The system will therefore be suitable patient treatment plan verification and may also be expanded for in-vivo beam monitoring for patient safety during the treatment

    Automated echocardiographic detection of heart failure with preserved ejection fraction using artificial intelligence

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    Background: Detection of heart failure with preserved ejection fraction (HFpEF) involves integration of multiple imaging and clinical features which are often discordant or indeterminate. Objectives: We applied artificial intelligence (AI) to analyze a single apical four-chamber (A4C) transthoracic echocardiogram videoclip to detect HFpEF. Methods: A three-dimensional convolutional neural network was developed and trained on A4C videoclips to classify patients with HFpEF (diagnosis of HF, EF≄50%, and echocardiographic evidence of increased filling pressure; cases) versus without HFpEF (EF≄50%, no diagnosis of HF, normal filling pressure; controls). Model outputs were classified as HFpEF, no HFpEF, or non-diagnostic (high uncertainty). Performance was assessed in an independent multi-site dataset and compared to previously validated clinical scores. Results: Training and validation included 2971 cases and 3785 controls (validation holdout, 16.8% patients), and demonstrated excellent discrimination (AUROC:0.97 [95%CI:0.96-0.97] and 0.95 [0.93-0.96] in training and validation, respectively). In independent testing (646 cases, 638 controls), 94 (7.3%) were non-diagnostic; sensitivity (87.8%; 84.5-90.9%) and specificity (81.9%; 78.2-85.6%) were maintained in clinically relevant subgroups, with high repeatability and reproducibility. Of 701 and 776 indeterminate outputs from the HFA-PEFF and H2FPEF scores, the AI HFpEF model correctly reclassified 73.5 and 73.6%, respectively. During follow-up (median [IQR]:2.3 [0.5-5.6] years), 444 (34.6%) patients died; mortality was higher in patients classified as HFpEF by AI (hazard ratio [95%CI]:1.9 [1.5-2.4]). Conclusion: An AI HFpEF model based on a single, routinely acquired echocardiographic video demonstrated excellent discrimination of patients with versus without HFpEF, more often than clinical scores, and identified patients with higher mortality

    A Cell Motility Screen Reveals Role for MARCKS-Related Protein in Adherens Junction Formation and Tumorigenesis

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    Invasion through the extracellular matrix (ECM) is important for wound healing, immunological responses and metastasis. We established an invasion-based cell motility screen using Boyden chambers overlaid with Matrigel to select for pro-invasive genes. By this method we identified antisense to MARCKS related protein (MRP), whose family member MARCKS is a target of miR-21, a microRNA involved in tumor growth, invasion and metastasis in multiple human cancers. We confirmed that targeted knockdown of MRP, in both EpRas mammary epithelial cells and PC3 prostate cancer cells, promoted in vitro cell migration that was blocked by trifluoperazine. Additionally, we observed increased immunofluoresence of E-cadherin, ÎČ-catenin and APC at sites of cell-cell contact in EpRas cells with MRP knockdown suggesting formation of adherens junctions. By wound healing assay we observed that reduced MRP supported collective cell migration, a type of cell movement where adherens junctions are maintained. However, destabilized adherens junctions, like those seen in EpRas cells, are frequently important for oncogenic signaling. Consequently, knockdown of MRP in EpRas caused loss of tumorigenesis in vivo, and reduced Wnt3a induced TCF reporter signaling in vitro. Together our data suggest that reducing MRP expression promotes formation of adherens junctions in EpRas cells, allowing collective cell migration, but interferes with oncogenic ÎČ-catenin signaling and tumorigenesis

    The clinical utility of the continuous performance test and objective measures of activity for diagnosing and monitoring ADHD in children: a systematic review

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    Attention deficit hyperactivity disorder (ADHD) is typically diagnosed using clinical observation and subjective informant reports. Once children commence ADHD medication, robust monitoring is required to detect partial or non-responses. The extent to which neuropsychological continuous performance tests (CPTs) and objective measures of activity can clinically aid the assessment and titration process in ADHD is not fully understood. This review describes the current evidence base for the use of CPTs and objectively measured activity to support the diagnostic procedure and medication management for children with ADHD. Four databases (PsycINFO, Medline, Allied and Complementary Medicine (AMED) and PsycARTICLES) were systematically searched to understand the current evidence base for: (1) the use of CPTs to aid clinical assessment of ADHD; (2) the use of CPTs to aid medication management; (3) the clinical utility of objective measures of activity in ADHD. Sixty relevant articles were identified. The search revealed six commercially available CPTs that had been reported on for their clinical use. There were mixed findings with regard to the use of CPTs to assess and manage medication, with contrasting evidence on their ability to support clinical decision making. There was a strong evidence base for the use of objective measures of activity to aid ADHD/non-ADHD group differentiation, which appears sensitive to medication effects and would also benefit from further research on their clinical utility. The findings suggest that combining CPTs and an objective measure of activity may be particularly useful as a clinical tool and worthy of further pursuit

    Cross-border trafficking in human beings: prevention and intervention strategies for reducing sexual exploitation

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    Over the years, growing attention has been given to the phenomenon of trafficking in human beings (THB). Sexual exploitation was until recently by far the most commonly identified feature of THB, followed by forced labour. Many activities to combat trafficking for the purpose of sexual exploitation have been initiated by numerous supranational, international as well as national organizations. Much is written about these initiatives, but some areas have been neglected. Knowledge on ‘what works’ is in particular limited. The growing attention to THB entails a demand for more information. The severity of the crime and the impact on its victims makes it of utmost importance to gain more insight into the working and effectiveness of anti-trafficking strategies and interventions. The main objective of this review was to assess the presently available evidence on the effects of interventions that aim to prevent and suppress trafficking in human beings

    Experimental Indicators of Current Unbalance in Building Integrated Photovoltaic Systems

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    Unbalance of the three-phase currents in photovoltaic (PV) systems may depend on structural aspects of the installation, the effect of partial shading, or both. In this paper, a number of unbalance indicators are calculated starting from data measured during experimental analyses on a real building-integrated PV system representing different types of unbalance. Detailed information is obtained from indices identifying the balance and unbalance components also in the presence of waveform distortion. These indices extend the current definitions of unbalance given in the power quality standards. The results show that the unbalance cannot be considered negligible even without single-phase inverters and is more significant if non-linear loads add a contribution to both harmonic distortion and unbalance seen from the distribution transformer

    Knowledge Discovery from the Statistical Analysis of On-Site Photovoltaic System Data

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    This paper presents some novel ideas and findings to assist data analysts and operators in discovering specific situations from the analysis of photovoltaic data collected in the field. The daily time series of solar irradiance and active power production are transformed into probability distribution functions (PDFs), then the skewness of the PDF is assessed as a potential indicator of orientation of the PV system in directions different from South. The relevant PDFs corresponding to bright days are identified by applying a clustering procedure. The combined calculation of skewness and correlation between solar irradiance and active power data is also used to discover specific cases in which high shadowing occurs in particular days of the year and at particular times. The analyses are carried out by using data collected on-site in PV systems installed at different locations
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