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Showing papers by "Philips published in 2018"


Journal ArticleDOI
TL;DR: A reinforcement learning agent, the AI Clinician, can assist physicians by providing individualized and clinically interpretable treatment decisions to improve patient outcomes by extracting implicit knowledge from an amount of patient data that exceeds by many-fold the life-time experience of human clinicians.
Abstract: Sepsis is the third leading cause of death worldwide and the main cause of mortality in hospitals1–3, but the best treatment strategy remains uncertain. In particular, evidence suggests that current practices in the administration of intravenous fluids and vasopressors are suboptimal and likely induce harm in a proportion of patients1,4–6. To tackle this sequential decision-making problem, we developed a reinforcement learning agent, the Artificial Intelligence (AI) Clinician, which extracted implicit knowledge from an amount of patient data that exceeds by many-fold the life-time experience of human clinicians and learned optimal treatment by analyzing a myriad of (mostly suboptimal) treatment decisions. We demonstrate that the value of the AI Clinician’s selected treatment is on average reliably higher than human clinicians. In a large validation cohort independent of the training data, mortality was lowest in patients for whom clinicians’ actual doses matched the AI decisions. Our model provides individualized and clinically interpretable treatment decisions for sepsis that could improve patient outcomes.

678 citations


Journal ArticleDOI
05 Apr 2018-Nature
TL;DR: The observation of a quantized conductance plateau at 2e2/h in the zero-bias conductance measured in indium antimonide semiconductor nanowires covered with an aluminium superconducting shell strongly supports the existence of Majorana zero-modes in the system.
Abstract: Majorana zero-modes - a type of localized quasiparticle - hold great promise for topological quantum computing. Tunnelling spectroscopy in electrical transport is the primary tool for identifying the presence of Majorana zero-modes, for instance as a zero-bias peak in differential conductance. The height of the Majorana zero-bias peak is predicted to be quantized at the universal conductance value of 2e 2 /h at zero temperature (where e is the charge of an electron and h is the Planck constant), as a direct consequence of the famous Majorana symmetry in which a particle is its own antiparticle. The Majorana symmetry protects the quantization against disorder, interactions and variations in the tunnel coupling. Previous experiments, however, have mostly shown zero-bias peaks much smaller than 2e 2 /h, with a recent observation of a peak height close to 2e 2 /h. Here we report a quantized conductance plateau at 2e 2 /h in the zero-bias conductance measured in indium antimonide semiconductor nanowires covered with an aluminium superconducting shell. The height of our zero-bias peak remains constant despite changing parameters such as the magnetic field and tunnel coupling, indicating that it is a quantized conductance plateau. We distinguish this quantized Majorana peak from possible non-Majorana origins by investigating its robustness to electric and magnetic fields as well as its temperature dependence. The observation of a quantized conductance plateau strongly supports the existence of Majorana zero-modes in the system, consequently paving the way for future braiding experiments that could lead to topological quantum computing.

582 citations


Journal ArticleDOI
TL;DR: The eICU Collaborative Research Database as mentioned in this paper is a multi-center intensive care unit (ICU) database with high granularity data for over 200,000 admissions to ICUs monitored by e-ICU Programs across the United States.
Abstract: Critical care patients are monitored closely through the course of their illness. As a result of this monitoring, large amounts of data are routinely collected for these patients. Philips Healthcare has developed a telehealth system, the eICU Program, which leverages these data to support management of critically ill patients. Here we describe the eICU Collaborative Research Database, a multi-center intensive care unit (ICU)database with high granularity data for over 200,000 admissions to ICUs monitored by eICU Programs across the United States. The database is deidentified, and includes vital sign measurements, care plan documentation, severity of illness measures, diagnosis information, treatment information, and more. Data are publicly available after registration, including completion of a training course in research with human subjects and signing of a data use agreement mandating responsible handling of the data and adhering to the principle of collaborative research. The freely available nature of the data will support a number of applications including the development of machine learning algorithms, decision support tools, and clinical research.

574 citations


Journal Article
01 Sep 2018-Nature
TL;DR: The e ICU Collaborative Research Database is described, a multi-center intensive care unit (ICU) database with high granularity data for over 200,000 admissions to ICUs monitored by eICU Programs across the United States.
Abstract: Critical care patients are monitored closely through the course of their illness. As a result of this monitoring, large amounts of data are routinely collected for these patients. Philips Healthcare has developed a telehealth system, the eICU Program, which leverages these data to support management of critically ill patients. Here we describe the eICU Collaborative Research Database, a multi-center intensive care unit (ICU)database with high granularity data for over 200,000 admissions to ICUs monitored by eICU Programs across the United States. The database is deidentified, and includes vital sign measurements, care plan documentation, severity of illness measures, diagnosis information, treatment information, and more. Data are publicly available after registration, including completion of a training course in research with human subjects and signing of a data use agreement mandating responsible handling of the data and adhering to the principle of collaborative research. The freely available nature of the data will support a number of applications including the development of machine learning algorithms, decision support tools, and clinical research.

452 citations


Journal ArticleDOI
TL;DR: The results show that increasing the intensity of polychromatic white light has been found to increase subjective ratings of alertness in a majority of studies, though a substantial proportion of studies failed to find significant effects, possibly due to small sample sizes or high baseline light intensities.

189 citations


Journal ArticleDOI
15 Feb 2018-PLOS ONE
TL;DR: The results indicate that CNNs are a valid alternative to existing approaches in patient phenotyping and cohort identification, and should be further investigated, and the deep learning approach presented in this paper can be used to assist clinicians during chart review or support the extraction of billing codes from text by identifying and highlighting relevant phrases for various medical conditions.
Abstract: In secondary analysis of electronic health records, a crucial task consists in correctly identifying the patient cohort under investigation. In many cases, the most valuable and relevant information for an accurate classification of medical conditions exist only in clinical narratives. Therefore, it is necessary to use natural language processing (NLP) techniques to extract and evaluate these narratives. The most commonly used approach to this problem relies on extracting a number of clinician-defined medical concepts from text and using machine learning techniques to identify whether a particular patient has a certain condition. However, recent advances in deep learning and NLP enable models to learn a rich representation of (medical) language. Convolutional neural networks (CNN) for text classification can augment the existing techniques by leveraging the representation of language to learn which phrases in a text are relevant for a given medical condition. In this work, we compare concept extraction based methods with CNNs and other commonly used models in NLP in ten phenotyping tasks using 1,610 discharge summaries from the MIMIC-III database. We show that CNNs outperform concept extraction based methods in almost all of the tasks, with an improvement in F1-score of up to 26 and up to 7 percentage points in area under the ROC curve (AUC). We additionally assess the interpretability of both approaches by presenting and evaluating methods that calculate and extract the most salient phrases for a prediction. The results indicate that CNNs are a valid alternative to existing approaches in patient phenotyping and cohort identification, and should be further investigated. Moreover, the deep learning approach presented in this paper can be used to assist clinicians during chart review or support the extraction of billing codes from text by identifying and highlighting relevant phrases for various medical conditions.

157 citations


Journal ArticleDOI
TL;DR: The aim of the 2016 quantitative susceptibility mapping (QSM) reconstruction challenge was to test the ability of various QSM algorithms to recover the underlying susceptibility from phase data faithfully.
Abstract: Purpose The aim of the 2016 quantitative susceptibility mapping (QSM) reconstruction challenge was to test the ability of various QSM algorithms to recover the underlying susceptibility from phase data faithfully. Methods Gradient-echo images of a healthy volunteer acquired at 3T in a single orientation with 1.06 mm isotropic resolution. A reference susceptibility map was provided, which was computed using the susceptibility tensor imaging algorithm on data acquired at 12 head orientations. Susceptibility maps calculated from the single orientation data were compared against the reference susceptibility map. Deviations were quantified using the following metrics: root mean squared error (RMSE), structure similarity index (SSIM), high-frequency error norm (HFEN), and the error in selected white and gray matter regions. Results Twenty-seven submissions were evaluated. Most of the best scoring approaches estimated the spatial frequency content in the ill-conditioned domain of the dipole kernel using compressed sensing strategies. The top 10 maps in each category had similar error metrics but substantially different visual appearance. Conclusion Because QSM algorithms were optimized to minimize error metrics, the resulting susceptibility maps suffered from over-smoothing and conspicuity loss in fine features such as vessels. As such, the challenge highlighted the need for better numerical image quality criteria. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

152 citations


Journal ArticleDOI
TL;DR: Anti-TNF (tumour necrosis factor) therapy was approved for use in Crohn’s disease in 1998, and has changed the paradigm of treatment, leading to improved rates of response and remission in patients.
Abstract: Crohn’s disease (CD) accounts for a variety of clinical manifestations or phenotypes that stem from chronic inflammation in the gastrointestinal tract. Its worldwide incidence is increasing including younger or childhood-onset of disease. The natural history of Crohn’s disease is characterized by a remitting and relapsing course that progresses to complications and surgery in most patients. The goals of treatment are to achieve clinical and endoscopic remission, to avoid disease progression and minimise surgical resections. Medical treatment usually features antibiotics, corticosteroids, immunomodulators (thiopurines, methotrexate). Anti-TNF (tumour necrosis factor) therapy was approved for use in Crohn’s disease in 1998, and has changed the paradigm of treatment, leading to improved rates of response and remission in patients. There are significant considerations that need to be borne in mind, when treating patients including immunogenicity, safety profile and duration of treatment.

150 citations


Proceedings ArticleDOI
02 Sep 2018
TL;DR: A phoneme and spectrogram combined CNN model proved to be most accurate in recognizing emotions on IEMOCAP data and achieved more than 4% increase in overall accuracy and average class accuracy as compared to the existing state-of-the-art methods.
Abstract: This paper proposes a speech emotion recognition method based on phoneme sequence and spectrogram. Both phoneme sequence and spectrogram retain emotion contents of speech which is missed if the speech is converted into text. We performed various experiments with different kinds of deep neural networks with phoneme and spectrogram as inputs. Three of those network architectures are presented here that helped to achieve better accuracy when compared to the stateof-the-art methods on benchmark dataset. A phoneme and spectrogram combined CNN model proved to be most accurate in recognizing emotions on IEMOCAP data. We achieved more than 4% increase in overall accuracy and average class accuracy as compared to the existing state-of-the-art methods.

140 citations


Journal ArticleDOI
TL;DR: Magnetic resonance (MR) imaging is now commonly used for liver iron quantification, including assessment of distribution, detection, grading, and monitoring of treatment response in iron overload.
Abstract: This review describes MR imaging techniques for liver iron quantification and provides an overview of common causes, complications, and treatments of liver iron overload, with discussion of pitfalls and future directions in liver iron quantification.

118 citations


Journal ArticleDOI
TL;DR: Intraprocedural CBCT imaging with augmented fluoroscopy is feasible and effective and is associated with high DY during ENB-guided biopsies.
Abstract: Background Electromagnetic navigation bronchoscopy (ENB) has been widely adopted as a guidance technique for biopsy of peripheral lung nodules However, ENB is limited by the lack of real-time confirmation of the biopsy devices Intraprocedural cone-beam computed tomography (CBCT) imaging can be utilized to assess or confirm the location of biopsy devices The aim of this study is to determine the safety and diagnostic yield (DY) of image fusion of intraprocedural CBCT data with live fluoroscopy (augmented fluoroscopy) during ENB-guided biopsy of peripheral lung nodules Methods Data from 75 consecutive patients who underwent biopsy with ENB was collected retrospectively Patients underwent CBCT imaging while temporarily suspending mechanical ventilation CBCT data were acquired and 3-dimensional segmentation of nodules was performed using commercially available software (OncoSuite) During ENB, the segmented lesions were projected and fused with live fluoroscopy enabling real-time 3-dimensional guidance Results A total of 93 lesions with a median size of 160 mm were biopsied in 75 consecutive patients The overall DY by lesion was 837% (95% confidence interval, 748%-899%) Multivariate regression analysis showed no independent correlation between lesion size, lesion location, lesion visibility under standard fluoroscopy, and the presence of a bronchus sign with DY Pneumothorax occurred in 3 patients (4%) Conclusion Intraprocedural CBCT imaging with augmented fluoroscopy is feasible and effective and is associated with high DY during ENB-guided biopsies

Journal ArticleDOI
TL;DR: Using state-of-the-art HARDI tractography algorithm, the subcortical connectivity of the insula is explored by exploring the structural connectivity of insular ROIs with the thalamus, amygdala, hippocampus, putamen, globus pallidus, caudate nucleus and nucleus accumbens.
Abstract: Hidden beneath the Sylvian fissure and sometimes considered as the fifth lobe of the brain, the insula plays a multi-modal role from its strategic location. Previous structural studies have reported cortico-cortical connections with the frontal, temporal, parietal and occipital lobes, but only a few have looked at its connections with subcortical structures. The insular cortex plays a role in a wide range of functions including processing of visceral and somatosensory inputs, olfaction, audition, language, motivation, craving, addiction and emotions such as pain, empathy and disgust. These functions implicate numerous subcortical structures, as suggested by various functional studies. Based on these premises, we explored the structural connectivity of insular ROIs with the thalamus, amygdala, hippocampus, putamen, globus pallidus, caudate nucleus and nucleus accumbens. More precisely, we were interested in unraveling the specific areas of the insula connected to these subcortical structures. By using state-of-the-art HARDI tractography algorithm, we explored here the subcortical connectivity of the insula.

Journal ArticleDOI
TL;DR: Transarterial chemoembolization outcomes in patients with HCC may be predicted before procedures by combining clinical patient data and baseline MR imaging with the use of AI and ML techniques.

Journal ArticleDOI
TL;DR: This investigation supports the volumetric hypothesis with living skin experiments and Monte Carlo simulations ofRemote PPG-amplitude in visible light (VIS) and infrared (IR) and indicates that remote PPG systems indeed probe arterial blood.
Abstract: Remote photoplethysmography (PPG) is an optical measurement technique with established applications in vital signs monitoring. Recently, the consensual understanding of blood volume variations (BVVs) as the origin of PPG signals was challenged, raising validity concerns about the remote SpO2 methodology. Recognizing the imperative for new opto-physiological evidence, this investigation supports the volumetric hypothesis with living skin experiments and Monte Carlo simulations of remote PPG-amplitude in visible light (VIS) and infrared (IR). Multilayered models of the skin were developed to simulate the separate contributions from skin layers containing pulsatile arterioles to the PPG signal in the 450–1000 nm range. The simulated spectra were qualitatively compared with observations of the resting and compressed finger pad, and complemented with videocapillaroscopy. Our results indicate that remote PPG systems indeed probe arterial blood. Green wavelengths probe dermal arterioles while red-IR wavelengths also reach subcutaneous BVVs. Owing to stable penetration depths, the red-IR diagnostic window promotes the invariance of SpO2 measurements to skin non-homogeneities.

Journal ArticleDOI
15 Jul 2018-Spine
TL;DR: MIS screw placement directed by AR with intraoperative 3D imaging in a hybrid OR is accurate and efficient, without any fluoroscopy or x-ray imaging during the procedure.
Abstract: Study design Cadaveric laboratory study. Objective To assess the feasibility and accuracy of minimally invasive thoracolumbar pedicle screw placement using augmented reality (AR) surgical navigation. Summary of background data Minimally invasive spine (MIS) surgery has increasingly become the method of choice for a wide variety of spine pathologies. Navigation technology based on AR has been shown to be feasible, accurate, and safe in open procedures. AR technology may also be used for MIS surgery. Methods The AR surgical navigation was installed in a hybrid operating room (OR). The hybrid OR includes a surgical table, a motorized flat detector C-arm with intraoperative 2D/3D imaging capabilities, integrated optical cameras for AR navigation, and patient motion tracking using optical markers on the skin. Navigation and screw placement was without any x-ray guidance. Two neurosurgeons placed 66 Jamshidi needles (two cadavers) and 18 cannulated pedicle screws (one cadaver) in the thoracolumbar spine. Technical accuracy was evaluated by measuring the distance between the tip of the actual needle position and the corresponding planned path as well as the angles between the needle and the desired path. Time needed for navigation along the virtual planned path was measured. An independent reviewer assessed the postoperative scans for the pedicle screws' clinical accuracy. Results Navigation time per insertion was 90 ± 53 seconds with an accuracy of 2.2 ± 1.3 mm. Accuracy was not dependent on operator. There was no correlation between navigation time and accuracy. The mean error angle between the Jamshidi needles and planned paths was 0.9° ± 0.8°. No screw was misplaced outside the pedicle. Two screws breached 2 to 4 mm yielding an overall accuracy of 89% (16/18). Conclusion MIS screw placement directed by AR with intraoperative 3D imaging in a hybrid OR is accurate and efficient, without any fluoroscopy or x-ray imaging during the procedure. Level of evidence N/A.

Journal ArticleDOI
TL;DR: Elevation of T1 and T2 values and ECV was associated with severity of liver fibrosis and portal hypertension in an experimental animal model.
Abstract: Purpose To evaluate MRI T1 and T2 mapping with calculation of extracellular volume (ECV) for diagnosis and grading of liver fibrosis. Materials and Methods Different grades of fibrosis were induced in 60 male Sprague-Dawley rats by bile duct ligation (BDL) and carbon-tetrachloride (CCl4) intoxication. Portal pressure was measured invasively, whereas hepatic fibrosis was quantified by hydroxyproline content, Sirius red staining, and α smooth muscle actin staining. T1 values, T2 values, and ECV were assessed by using quantitative MRI mapping techniques. Results T1 values in animals 4 weeks after BDL were greater than in control animals (718 msec ± 74 vs 578 msec ± 33, respectively; P < .001). T2 values at 4 weeks were also greater in animals that underwent BDL than in control animals (46 msec ± 6 vs 29 msec ± 2, respectively; P < .001). Similar T1 and T2 findings were observed after CCl4 intoxication. ECV was greater in animals 4 weeks after BDL compared with control animals (31.3% ± 1.3 vs 18.2% ± 3.5, respectively; P < .001), with similar results after CCl4 intoxication. High correlations were found between ECV and hepatic hydroxyproline content (BDL: r = 0.68, P < .001; CCl4: r = 0.65, P < .001), Sirius red staining (BDL: r = 0.88, P < .001; CCl4: r = 0.82, P < .001), α smooth muscle actin staining (BDL: r = 0.70, P < .001; CCl4: r = 0.73, P < .001), and portal pressure (BDL: r = 0.54, P = .003; CCl4: r = 0.39, P = .043). Conclusion Elevation of T1 and T2 values and ECV was associated with severity of liver fibrosis and portal hypertension in an experimental animal model.

Journal ArticleDOI
TL;DR: An analysis of EU and US clinical trial databases has shown that mesh nebulizer are now preferred over jet nebulizers for clinical trials sponsored by pharmaceutical companies, showing a strong preference for the use of mesh neBulizers in trials involving high cost and niche therapy areas.
Abstract: In the 24 years since first being marketed, the mesh nebulizer has been developed by five main manufacturers into a viable solution for the delivery of high-value nebulized drugs. Mesh nebulizers provide increased portability, convenience and energy efficiency along with similar lung deposition and increased ease of use compared with jet nebulizers. An analysis of EU and US clinical trial databases has shown that mesh nebulizers are now preferred over jet nebulizers for clinical trials sponsored by pharmaceutical companies. The results show a strong preference for the use of mesh nebulizers in trials involving high cost and niche therapy areas. Built-in capability to optimize the way patients use their mesh nebulizer and manage their disease will further increase uptake. [Formula: see text].

Journal ArticleDOI
TL;DR: A novel role for gene methylation that helped discriminate high BCL-2–expressing SCLCs is uncovered, suggesting that a substantial fraction of patients with SCLC could benefit from venetoclax.
Abstract: Purpose: Small-cell lung cancer (SCLC) is an often-fatal neuroendocrine carcinoma usually presenting as extensive disease, carrying a 3% 5-year survival. Despite notable advances in SCLC genomics, new therapies remain elusive, largely due to a lack of druggable targets.Experimental Design: We used a high-throughput drug screen to identify a venetoclax-sensitive SCLC subpopulation and validated the findings with multiple patient-derived xenografts of SCLC.Results: Our drug screen consisting of a very large collection of cell lines demonstrated that venetoclax, an FDA-approved BCL-2 inhibitor, was found to be active in a substantial fraction of SCLC cell lines. Venetoclax induced BIM-dependent apoptosis in vitro and blocked tumor growth and induced tumor regressions in mice bearing high BCL-2-expressing SCLC tumors in vivo BCL-2 expression was a predictive biomarker for sensitivity in SCLC cell lines and was highly expressed in a subset of SCLC cell lines and tumors, suggesting that a substantial fraction of patients with SCLC could benefit from venetoclax. Mechanistically, we uncover a novel role for gene methylation that helped discriminate high BCL-2-expressing SCLCs.Conclusions: Altogether, our findings identify venetoclax as a promising new therapy for high BCL-2-expressing SCLCs. Clin Cancer Res; 24(2); 360-9. ©2017 AACR.

Journal ArticleDOI
TL;DR: The results obtained demonstrate that the Si-NPs were homogeneously incorporated in the electrospun fibers, resulting in an improvement of the tensile properties of the prepared materials.

Journal ArticleDOI
TL;DR: The out-of-plane oriented films are demonstrated to outperform the in-planeoriented films in the hydrogen evolution reaction for water splitting applications and an extensive study based on high-resolution transmission electron microscopy is presented to unravel the nucleation mechanism of MoS2 on SiO2/Si substrates at 450 °C.
Abstract: Low-temperature controllable synthesis of monolayer-to-multilayer thick MoS2 with tuneable morphology is demonstrated by using plasma enhanced atomic layer deposition (PEALD). The characteristic self-limiting ALD growth with a growth-per-cycle of 0.1 nm per cycle and digital thickness control down to a monolayer are observed with excellent wafer scale uniformity. The as-deposited films are found to be polycrystalline in nature showing the signature Raman and photoluminescence signals for the mono-to-few layered regime. Furthermore, a transformation in film morphology from in-plane to out-of-plane orientation of the 2-dimensional layers as a function of growth temperature is observed. An extensive study based on high-resolution transmission electron microscopy is presented to unravel the nucleation mechanism of MoS2 on SiO2/Si substrates at 450 °C. In addition, a model elucidating the film morphology transformation (at 450 °C) is hypothesized. Finally, the out-of-plane oriented films are demonstrated to outperform the in-plane oriented films in the hydrogen evolution reaction for water splitting applications.

Journal ArticleDOI
TL;DR: To fill the gap between the sensory evaluation and the instrumental measurement of texture, it is necessary to examine the physical change of foods during the oral processing to give the designing principle of palatable and safe foods.
Abstract: There is still a gap between instrumental measurement and sensory evaluation because of the complexity of food texture in spite of many efforts. In sensory evaluation, the terms describing the texture should be well understood by panelists, which poses a problem of establishing lexicons and training panelists. In the instrumental measurement, more efforts are required to understand the large deformation and fracture behavior of foods. The texture profile analysis (TPA) proposed by Alina Szczesniak, Malcolm Bourne, and Sherman has been applied to many foods, and was useful to develop the understanding of textures. But sometimes confusion of the interpretation of TPA parameters appeared. Many new techniques have been introduced to quantify TPA parameters. Recent efforts to fill the gap between sensory evaluation and instrumental measurements, human measurements, or physiological measurements have been introduced. This endeavor is an effort of synthesizing the dentistry and biomedical approach, sensory and psychological approach, and material science approach, and therefore, the collaboration among these disciplines is necessary. This manuscript mainly discusses texture studies for solid foods. Practical applications To fill the gap between the sensory evaluation and the instrumental measurement of texture, it is necessary to examine the physical change of foods during the oral processing. This will give us the designing principle of palatable and safe foods.

Journal ArticleDOI
TL;DR: Netosis is a prominent pro-thromBotic participant in all distinct types of atherothrombosis, which may facilitate the progression of thrombotic or haemorrhagic complications and thus the onset of ensuing clinical coronary ischemic syndromes.
Abstract: Acute coronary syndromes can be initiated by either atherosclerotic fibrous cap ruptures, superficial plaque erosions or intraplaque haemorrhages (IPHs). Since neutrophil extracellular traps (NETs) display pro-inflammatory and pro-thrombotic properties, we investigated the presence, extent and distribution of neutrophils and NETs in different types of plaque complications in relation to the age of overlying thrombus mass or haemorrhage. Sixty-four paraffin-embedded coronary plaque segments of 30 acute myocardial infarction patients were retrieved from the autopsy archives, which contained 44 complicated plaques (17 IPHs, 9 erosions and 18 ruptures) and 20 intact plaques. Complicated plaques were further categorized according to the histological age of thrombus or haemorrhage. Immunohistochemistry was performed to visualize neutrophils (anti-myeloperoxidase, anti-elastase and anti-CD177) and NETs (anti-citrullinated histone-3 and anti-peptidyl-arginine-deiminase-4). The results were scored semi-quantitatively. Neutrophils and NETs were abundantly present in all types of complicated, but not in intact, plaques (p < 0.05). They were found in thrombus, haemorrhages and at the thrombus-plaque interface, with no significant differences in extent between ruptures, erosions and IPHs. Interestingly, adjacent perivascular tissue of complicated, but not of intact plaques, also contained high numbers of neutrophils and NETs (p < 0.05). In thrombus and haemorrhage of different age, neutrophils and NETs were more frequently present in non-organized (fresh) thrombi and in on-going IPHs. In conclusion, netosis is a prominent pro-thrombotic participant in all distinct types of atherothrombosis, which may facilitate the progression of thrombotic or haemorrhagic complications and thus the onset of ensuing clinical coronary ischemic syndromes.

Journal ArticleDOI
TL;DR: Fractional volumes of prostatic lumen, stroma, and epithelium change significantly when cancer is present and have the potential to improve the diagnosis of prostate cancer and determine its aggressiveness.
Abstract: The fractional volumes of three prostate tissue components—stroma, epithelium, and lumen—estimated noninvasively by using hybrid multidimensional MR imaging can be used for detecting prostate cancer and correlate more strongly with Gleason score than conventional T2 values and apparent diffusion coefficients

Journal ArticleDOI
01 Mar 2018-PLOS ONE
TL;DR: A highly versatile clinical-scale field applicator that enables the generation of strong magnetic fields as well as strong field gradients over a large workspace and opens the door for image-guided radiation-free remote magnetic control of devices at the clinical scale, which may be useful in minimally invasive diagnostic and therapeutic medical interventions.
Abstract: Remote magnetic manipulation is a powerful technique for controlling devices inside the human body. It enables actuation and locomotion of tethered and untethered objects without the need for a local power supply. In clinical applications, it is used for active steering of catheters in medical interventions such as cardiac ablation for arrhythmia treatment and for steering of camera pills in the gastro-intestinal tract for diagnostic video acquisition. For these applications, specialized clinical-scale field applicators have been developed, which are rather limited in terms of field strength and flexibility of field application. For a general-purpose field applicator, flexible field generation is required at high field strengths as well as high field gradients to enable the generation of both torques and forces on magnetic devices. To date, this requirement has only been met by small-scale experimental systems. We have built a highly versatile clinical-scale field applicator that enables the generation of strong magnetic fields as well as strong field gradients over a large workspace. We demonstrate the capabilities of this coil-based system by remote steering of magnetic drills through gel and tissue samples with high torques on well-defined curved trajectories. We also give initial proof that, when equipped with high frequency transmit-receive coils, the machine is capable of real-time magnetic particle imaging while retaining a clinical-scale bore size. Our findings open the door for image-guided radiation-free remote magnetic control of devices at the clinical scale, which may be useful in minimally invasive diagnostic and therapeutic medical interventions.

Journal ArticleDOI
27 Sep 2018-PLOS ONE
TL;DR: The first X-ray dark-field images of in-situ human lungs in a deceased body are presented, demonstrating the feasibility of X-raysdark-field chest radiography on a human scale and correlated with findings of computed tomography imaging and autopsy.
Abstract: Disorders of the lungs such as chronic obstructive pulmonary disease (COPD) are a major cause of chronic morbidity and mortality and the third leading cause of death in the world. The absence of sensitive diagnostic tests for early disease stages of COPD results in under-diagnosis of this treatable disease in an estimated 60-85% of the patients. In recent years a grating-based approach to X-ray dark-field contrast imaging has shown to be very sensitive for the detection and quantification of pulmonary emphysema in small animal models. However, translation of this technique to imaging systems suitable for humans remains challenging and has not yet been reported. In this manuscript, we present the first X-ray dark-field images of in-situ human lungs in a deceased body, demonstrating the feasibility of X-ray dark-field chest radiography on a human scale. Results were correlated with findings of computed tomography imaging and autopsy. The performance of the experimental radiography setup allows acquisition of multi-contrast chest X-ray images within clinical boundary conditions, including radiation dose. Upcoming clinical studies will have to demonstrate that this technology has the potential to improve early diagnosis of COPD and pulmonary diseases in general.

Journal ArticleDOI
TL;DR: This work investigated the prognostic value of psychosocial factors for predicting first or recurrent events after discharge following hospitalization for heart failure.
Abstract: Aims: Psychosocial factors are rarely collected in studies investigating the prognosis of patients with heart failure (HF), and only time to first event is commonly reported. We investigated the prognostic value of psychosocial factors for predicting first or recurrent events after discharge following hospitalization for HF. Methods and results: OPERA-HF is an observational study enrolling patients hospitalized for HF. In addition to clinical variables, psychosocial variables are recorded. Patients provide the information through questionnaires that include social information, depression and anxiety scores, and cognitive function. Kaplan–Meier, Cox regression and the Andersen–Gill model were used to identify predictors of first and recurrent events (readmissions or death). Of 671 patients (age 76 ± 15 years, 66% men) with 1-year follow-up, 291 had no subsequent event, 34 died without being readmitted, 346 had one or more unplanned readmissions, and 71 patients died after a first readmission. Increasing age, higher urea and creatinine, and the presence of co-morbidities (diabetes, history of myocardial infarction, chronic obstructive pulmonary disease) were all associated with increasing risk of first or recurrent events. Psychosocial variables independently associated with both the first and recurrent events were: presence of frailty, moderate-to-severe depression, and moderate-to-severe anxiety. Living alone and the presence of cognitive impairment were independently associated only with an increasing risk of recurrent events. Conclusion: Psychosocial factors are strongly associated with unplanned recurrent readmissions or mortality following an admission to hospital for HF. Further research is needed to show whether recognition of these factors and support tailored to individual patients' needs will improve outcomes.

Journal ArticleDOI
TL;DR: This scanner represents the first solid-state DPC PET/CT, a technologic leap beyond photomultipliers tubes and anger logic and leads to promising clinical opportunities with excellent image quality, lesion detectability, and diagnostic confidence.
Abstract: The first solid-state silicon photomultiplier (SiPM) digital photon counting (DPC) clinical PET/CT system was introduced by Philips in recent years. The system differs from other SiPM-based PET/CT systems and uses lutetiumyttrium oxyorthosilicate (LYSO) scintillators directly coupled with their own individual SiPM DPC detectors eliminating the need for Anger-logic positioning decoding. We evaluated the system performance, characteristics, and stability of the next generation DPC clinical PET/CT based on NEMA NU2-2012 tests, NEMA NU2-2018 test (timing resolution) and human studies. An energy resolution of 11.2% was measured. NEMA NU2-2012 tests revealed a spatial resolution (mm in FWHM) from (3.96, 4.01, 4.01) at 1 cm to (5.81, 5.83, 4.95) at 20 cm for (axial, radial, tangential). A 5.7 cps/kBq system sensitivity was measured. Peak noise equivalent count rate (NECR) and peak true count rate could not be determined as each exhibited increasing values up to the maximum activity measured (~ 1100 MBq). The maximum NECR was 171 kcps @ 50.5 kBq/mL, with corresponding scatter fraction of 30.8% and maximum trues of 681 kcps. NEMA hot sphere contrast ranged from 62% (10 mm) to 88% (22 mm), cold sphere contrast of 86% (28 mm) and 89% (37 mm). A timing resolution of 322 ps (22Na point source based) and 332 ps (NEMA NU2-2018) was obtained. It revealed < 1% change in TOF timing and ± 0.4% change in energy resolution during 31-month stability monitoring. CQIE assessment found < 3% axial variance in SUV. 100–60% recovery coefficients of activity concentration at various sphere sizes and contrast levels were measured. This scanner represents the first solid-state DPC PET/CT, a technologic leap beyond photomultipliers tubes and anger logic. It presents considerable improvements in system performance and characteristics with excellent time-of-flight capability compared to conventional photomultiplier tube (PMT) PET/CT systems. The DPC system leads to promising clinical opportunities with excellent image quality, lesion detectability, and diagnostic confidence.

Journal ArticleDOI
TL;DR: Spectral photon-counting CT (SPCCT) in combination with a two-contrast agent injection protocol may provide reliable detection of endoleaks with a single CT acquisition and potentially reduce radiation burden for EVAR patients under post-interventional surveillance.
Abstract: After endovascular aortic repair (EVAR), discrimination of endoleaks and intra-aneurysmatic calcifications within the aneurysm often requires multiphase computed tomography (CT). Spectral photon-counting CT (SPCCT) in combination with a two-contrast agent injection protocol may provide reliable detection of endoleaks with a single CT acquisition. To evaluate the feasibility of SPCCT, the stent-lined compartment of an abdominal aortic aneurysm phantom was filled with a mixture of iodine and gadolinium mimicking enhanced blood. To represent endoleaks of different flow rates, the adjacent compartments contained either one of the contrast agents or calcium chloride to mimic intra-aneurysmatic calcifications. After data acquisition with a SPCCT prototype scanner with multi-energy bins, material decomposition was performed to generate iodine, gadolinium and calcium maps. In a conventional CT slice, Hounsfield units (HU) of the compartments were similar ranging from 147 to 168 HU. Material-specific maps differentiate the distributions within the compartments filled with iodine, gadolinium or calcium. SPCCT may replace multiphase CT to detect endoleaks without sacrificing diagnostic accuracy. It is a unique feature of our method to capture endoleak dynamics and allow reliable distinction from intra-aneurysmatic calcifications in a single scan, thereby enabling a significant reduction of radiation exposure. • SPCCT might enable advanced endoleak detection. • Material maps derived from SPCCT can differentiate iodine, gadolinium and calcium. • SPCCT may potentially reduce radiation burden for EVAR patients under post-interventional surveillance.

Journal ArticleDOI
TL;DR: The accuracy of ED measurement, Zeff determination, and iodine quantitation derived from DL-DECT was demonstrated with phantom measurements, and the accuracies were not sensitive to scan and reconstruction parameters, namely tube potential, dose, rotation time, and spectral reconstruction level.
Abstract: Purpose This study aimed to quantitate the accuracy of the determination of electron density (ED), effective atomic number (Zeff ), and iodine concentration, directed for more accurate radiation therapy planning, with a new dual-layer dual-energy computed tomography (DL-DECT) system. The dependence of the accuracy of these values on the scan and reconstruction parameters, as well as on the phantom size, was also examined. Methods Measurements were performed on a commercial DECT system with a DL detector (IQon Spectral CT, Philips Healthcare), using phantoms with various tissue-equivalent inserts as well as iodine and calcium inserts of different concentrations. The expected values of ED and Zeff for the insert materials were derived from the chemical compositions provided by the vendors. The nominal scan condition for the accuracy measurements was 120 kVp, 20 mGy CTDIvol, 0.812 pitch, 16 × 0.625 mm collimation, and 0.33-second gantry rotation. Results The median deviation of ED ranged from -0.1% to 1.1% for all Gammex tissue inserts. The median deviation of Zeff ranged from -2.3% to 1.7% for soft tissue and bone inserts and was ≤7% for lung inserts. The absolute deviations for ED and Zeff in lung inserts were within 1% of the ED of water and 1 a.u., respectively. For two different phantom sizes, the ED values agreed to within 0.7% and the Zeff values agreed to within 2%, except for the lung inserts. When the scan parameters were changed from 120 kVp/20 mGy to 140 kVp/30 mGy, the ED differed within [-0.51%, 0.65%] and the Zeff differed within [-1.1%, 0.23%] for all materials except lungs, in which Zeff increased by 2.4%. The accuracy of ED and Zeff measurement at 120 kVp was no worse than that at 140 kVp. For iodine quantitation, the median absolute deviations from the nominal values were up to 0.3 mg/mL for iodine concentrations of 2-20 mg/mL, with an overall median deviation of -0.1 mg/mL. Iodine and calcium were well separated on the ED-Zeff scatter plot, even at the lowest concentrations (2 mg/mL for iodine and 50 mg/mL for calcium). Conclusions The accuracy of ED measurement, Zeff determination, and iodine quantitation derived from DL-DECT was demonstrated with phantom measurements. The accuracies were not sensitive to scan and reconstruction parameters, namely tube potential, dose, rotation time, and spectral reconstruction level, especially in the case of electron density.

Posted Content
TL;DR: A novel dependent reading bidirectional LSTM network (DR-BiLSTM) is proposed to efficiently model the relationship between a premise and a hypothesis during encoding and inference in the natural language inference (NLI) task.
Abstract: We present a novel deep learning architecture to address the natural language inference (NLI) task. Existing approaches mostly rely on simple reading mechanisms for independent encoding of the premise and hypothesis. Instead, we propose a novel dependent reading bidirectional LSTM network (DR-BiLSTM) to efficiently model the relationship between a premise and a hypothesis during encoding and inference. We also introduce a sophisticated ensemble strategy to combine our proposed models, which noticeably improves final predictions. Finally, we demonstrate how the results can be improved further with an additional preprocessing step. Our evaluation shows that DR-BiLSTM obtains the best single model and ensemble model results achieving the new state-of-the-art scores on the Stanford NLI dataset.