Simultaneous segmentation and grading of anatomical structures for patient's classification: application to Alzheimer's Disease

Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI).In this paper, we propose an innovative approach to robustly and accurately detect Alzheimer's disease (AD) based on the distinction of specific atrophic patterns of anatomical structures such as hippocampus (HC) and entorhinal cortex (EC). The proposed method simultaneously performs segmentation and grading of structures to efficiently capture the anatomical alterations caused by AD. Known as SNIPE (Scoring by Non-local Image Patch Estimator), the novel proposed grading measure is based on a nonlocal patch-based frame-work and estimates the similarity of the patch surrounding the voxel under study with all the patches present in different training populations. In this study, the training library was composed of two populations: 50 cognitively normal subjects (CN) and 50 patients with AD, randomly selected from the ADNI database. During our experiments, the classification accuracy of patients (CN vs. AD) using several biomarkers was compared: HC and EC volumes, the grade of these structures and finally the combination of their volume and their grade. Tests were completed in a leave-one-out framework using discriminant analysis. First, we showed that biomarkers based on HC provide better classification accuracy than biomarkers based on EC. Second, we demonstrated that structure grading is a more powerful measure than structure volume to distinguish both populations with a classification accuracy of 90%. Finally, by adding the ages of subjects in order to better separate age-related structural changes from disease-related anatomical alterations, SNIPE obtained a classification accuracy of 93%Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Insti- tute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30AG010129, K01 AG030514, and the Dana Foundation.Coupé, P.; Eskildsen, SF.; Manjón Herrera, JV.; Fonov, VS.; Collins, DL.; Alzheimer's Dis Neuroimaging (2012). Simultaneous segmentation and grading of anatomical structures for patient's classification: application to Alzheimer's Disease. NeuroImage. 59(4):3736-3747. https://doi.org/10.1016/j.neuroimage.2011.10.080S3736374759

SoLid : Search for Oscillations with Lithium-6 Detector at the SCK-CEN BR2 reactor

Sterile neutrinos have been considered as a possible explanation for the recent reactor and Gallium anomalies arising from reanalysis of reactor flux and calibration data of previous neutrino experiments. A way to test this hypothesis is to look for distortions of the anti-neutrino energy caused by oscillation from active to sterile neutrino at close stand-off (similar to 6-8m) of a compact reactor core. Due to the low rate of anti-neutrino interactions the main challenge in such measurement is to control the high level of gamma rays and neutron background. The SoLid experiment is a proposal to search for active-to-sterile anti-neutrino oscillation at very short baseline of the SCK center dot CEN BR2 research reactor. This experiment uses a novel approach to detect anti-neutrino with a highly segmented detector based on Lithium-6. With the combination of high granularity, high neutron-gamma discrimination using 6LiF:ZnS(Ag) and precise localization of the Inverse Beta Decay products, a better experimental sensitivity can be achieved compared to other state-of-the-art technology. This compact system requires minimum passive shielding allowing for very close stand off to the reactor. The experimental set up of the SoLid experiment and the BR2 reactor will be presented. The new principle of neutrino detection and the detector design with expected performance will be described. The expected sensitivity to new oscillations of the SoLid detector as well as the first measurements made with the 8 kg prototype detector deployed at the BR2 reactor in 2013-2014 will be reported

Cost-utility analysis of meaning-centered group psychotherapy for cancer survivors

Background: Meaning-centered group psychotherapy for cancer survivors (MCGP-CS) improves meaning, psychological well-being, and mental adjustment to cancer and reduces psychological distress. This randomized controlled trial was conducted to investigate the cost-utility of MCGP-CS compared with supportive group psychotherapy (SGP) and care-as-usual (CAU). Methods: In total, 170 patients were randomized to MCGP-CS, SGP, or CAU. Intervention costs, direct medical and nonmedical costs, productivity losses, and health-related quality of life were measured until 6 months follow-up, using the TIC-P, PRODISQ, data from the hospital information system, and the EQ-5D. The cost-utility was calculated by comparing mean cumulative costs and quality-adjusted life years (QALYs). Results: Mean total costs ranged from €4492 (MCGP-CS) to €5304 (CAU). Mean QALYs ranged.507 (CAU) to.540 (MCGP-CS). MCGP-CS had a probability of 74% to be both less costly and more effective than CAU, and 49% compared with SGP. Sensitivity analyses showed these findings are robust. If society is willing to pay €0 for one gained QALY, MCGP-CS has a 78% probability of being cost-effective compared with CAU. This increases to 85% and 92% at willingness-to-pay thresholds of €10 000 and €30 000, which are commonly accepted thresholds. Conclusions: MCGP-CS is highly likely a cost-effective intervention, meaning that there is a positive balance between the costs and gains of MCGP-CS, in comparison with SGP and CAU

Non-local intracranial cavity extraction

[EN] Automatic and accurate methods to estimate normalized regional brain volumes from MRI data are valuable tools which may help to obtain an objective diagnosis and followup of many neurological diseases. To estimate such regional brain volumes, the intracranial cavity volume (ICV) is often used for normalization. However, the high variability of brain shape and size due to normal intersubject variability, normal changes occurring over the lifespan, and abnormal changes due to disease makes the ICV estimation problem challenging. In this paper, we present a new approach to perform ICV extraction based on the use of a library of prelabeled brain images to capture the large variability of brain shapes. To this end, an improved nonlocal label fusion scheme based on BEaST technique is proposed to increase the accuracy of the ICV estimation. The proposed method is compared with recent state-of-the-art methods and the results demonstrate an improved performance both in terms of accuracy and reproducibility while maintaining a reduced computational burden.The authors want to thank the IXI (EPSRC GR/S21533/02) and OASIS (P50 AG05681, P01 AG03991, R01 AG021910, P50 MH071616, U24 RR021382, and R01 MH56584) dataset promoters for making available this valuable resource to the scientific community which surely will boost the research in brain imaging. This work has been supported by the Spanish Grant TIN2011-26727 from Ministerio de Ciencia e Innovacion. This work was funded in part by operating grants ´ from the Canadian Institutes of Health Research, les Fonds de la recherche sante du Quebec, MINDLab UNIK initiative at ´ Aarhus University, funded by the Danish Ministry of Science, Technology and Innovation, Grant agreement no. 09-065250.Manjón Herrera, JV.; Eskildsen, SF.; Coupé, P.; Romero Gómez, JE.; Collins, L.; Robles Viejo, M. (2014). Non-local intracranial cavity extraction. International Journal of Biomedical Imaging. 2014:1-11. https://doi.org/10.1155/2014/820205S111201

Scoring by nonlocal image patch estimator for early detection of Alzheimer's disease

Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI).Detection of Alzheimer's disease (AD) at the first stages of the pathology is an important task to accelerate the development of new therapies and improve treatment. Compared to AD detection, the prediction of AD using structural MRI at the mild cognitive impairment (MCI) or pre-MCI stage is more complex because the associated anatomical changes are more subtle. In this study, we analyzed the capability of a recently proposed method, SNIPE (Scoring by Nonlocal Image Patch Estimator), to predict AD by analyzing entorhinal cortex (EC) and hippocampus (HC) scoring over the entire ADNI database (834 scans). Detection (AD vs. CN) and prediction (progressive - pMCI vs. stable - sMCI) efficiency of SNIPE were studied using volumetric and grading biomarkers. First, our results indicate that grading-based biomarkers are more relevant for prediction than volume-based biomarkers. Second, we show that HC-based biomarkers are more important than EC-based biomarkers for prediction. Third, we demonstrate that the results obtained by SNIPE are similar to or better than results obtained in an independent study using HC volume, cortical thickness, and tensor-based morphometry, individually and in combination. Fourth, a comparison of new patch-based methods shows that the nonlocal redundancy strategy involved in SNIPE obtained similar results to a new local sparse-based approach. Finally, we present the first results of patch-based morphometry to illustrate the progression of the pathology.We wish to thank Dr. Robin Wolz for providing the list of ADNI subjects used in his study, which allowed us to perform the presented method comparison. We also want to thank the Canadian Institutes of Health Research (MOP-111169) and the Fonds de la recherche en sante du Quebec. Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). The ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics NV, Johnson & Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc., F. Hoffmann-La Roche, Schering-Plough, Synarc Inc., as well as nonprofit partners, the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U. S. Food and Drug Administration. Private sector contributions to the ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study was coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30AG010129, K01 AG030514 and the Dana Foundation and also by the Spanish grant TIN2011-26727 from the Ministerio de Ciencia e Innovacion.Coupé, P.; Eskildsen, SF.; Manjón Herrera, JV.; Fonov, VS.; Pruessner, JC.; Allard, M.; Collins, LD. (2012). Scoring by nonlocal image patch estimator for early detection of Alzheimer's disease. NeuroImage: Clinical. 1(1):141-152. https://doi.org/10.1016/j.nicl.2012.10.002S1411521

Escape probability methods versus "exact" transfer for modelling the X-ray spectrum of Active Galactic Nuclei and X-ray binaries

In the era of XMM-Newton and Chandra missions, it is crucial to use codes able to compute correctly the line spectrum of X-ray irradiated thick media (Thomson thickness of the order of unity) to build models for the structure and the emission of the central regions of AGN or X-ray binaries. In all photoionized codes except in our code Titan, the line intensities are computed with the "escape probability approximation". In its last version, Titan solves the transfer of a thousand lines and of the continuum with the ``Accelerated Lambda Iteration" method, which is one of the most efficient and most secure for line transfer. We find that for conditions typical of the AGN or X-ray binary emission medium, all escape approximations commonly used lead to an overestimation of the soft X-ray lines which can reach one order of magnitude for intense lines.Comment: 19 pages, 14 figures, accepted in A&

Age-dependent prevalence of 14 high-risk HPV types in the Netherlands: implications for prophylactic vaccination and screening

We determined the prevalence of type-specific hrHPV infections in the Netherlands on cervical scrapes of 45 362 women aged 18–65 years. The overall hrHPV prevalence peaked at the age of 22 with peak prevalence of 24%. Each of the 14 hrHPV types decreased significantly with age (P-values between 0.0009 and 0.03). The proportion of HPV16 in hrHPV-positive infections also decreased with age (OR=0.76 (10-year scale), 95% CI=0.67–0.85), and a similar trend was observed for HPV16 when selecting hrHPV-positive women with cervical intraepithelial neoplasia grade 2 or worse (CIN2+) (OR=0.76, 95% CI=0.56–1.01). In women eligible for routine screening (age 29–61 years) with confirmed CIN2+, 65% was infected with HPV16 and/or HPV18. When HPV16/18-positive infections in women eligible for routine screening were discarded, the positive predictive value of cytology for the detection of CIN2+ decreased from 27 to 15%, the positive predictive value of hrHPV testing decreased from 26 to 15%, and the predictive value of a double-positive test (positive HPV test and a positive cytology) decreased from 54 to 41%. In women vaccinated against HPV16/18, screening remains important to detect cervical lesions caused by non-HPV16/18 types. To maintain a high-positive predictive value, screening algorithms must be carefully re-evaluated with regard to the screening modalities and length of the screening interval

On the Link between Gaussian Homotopy Continuation and Convex Envelopes

Abstract. The continuation method is a popular heuristic in computer vision for nonconvex optimization. The idea is to start from a simpli-fied problem and gradually deform it to the actual task while tracking the solution. It was first used in computer vision under the name of graduated nonconvexity. Since then, it has been utilized explicitly or im-plicitly in various applications. In fact, state-of-the-art optical flow and shape estimation rely on a form of continuation. Despite its empirical success, there is little theoretical understanding of this method. This work provides some novel insights into this technique. Specifically, there are many ways to choose the initial problem and many ways to progres-sively deform it to the original task. However, here we show that when this process is constructed by Gaussian smoothing, it is optimal in a specific sense. In fact, we prove that Gaussian smoothing emerges from the best affine approximation to Vese’s nonlinear PDE. The latter PDE evolves any function to its convex envelope, hence providing the optimal convexification

Cost-effectiveness of exercise therapy versus general practitioner care for osteoarthritis of the hip: design of a randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is the most common joint disease, causing pain and functional impairments. According to international guidelines, exercise therapy has a short-term effect in reducing pain/functional impairments in knee OA and is therefore also generally recommended for hip OA. Because of its high prevalence and clinical implications, OA is associated with considerable (healthcare) costs. However, studies evaluating cost-effectiveness of common exercise therapy in hip OA are lacking. Therefore, this randomised controlled trial is designed to investigate the cost-effectiveness of exercise therapy in conjunction with the general practitioner's (GP) care, compared to GP care alone, for patients with hip OA.</p> <p>Methods/Design</p> <p>Patients aged ≥ 45 years with OA of the hip, who consulted the GP during the past year for hip complaints and who comply with the American College of Rheumatology criteria, are included. Patients are randomly assigned to either exercise therapy in addition to GP care, or to GP care alone. Exercise therapy consists of (maximally) 12 treatment sessions with a physiotherapist, and home exercises. These are followed by three additional treatment sessions in the 5th, 7th and 9th month after the first treatment session. GP care consists of usual care for hip OA, such as general advice or prescribing pain medication. Primary outcomes are hip pain and hip-related activity limitations (measured with the Hip disability Osteoarthritis Outcome Score [HOOS]), direct costs, and productivity costs (measured with the PROductivity and DISease Questionnaire). These parameters are measured at baseline, at 6 weeks, and at 3, 6, 9 and 12 months follow-up. To detect a 25% clinical difference in the HOOS pain score, with a power of 80% and an alpha 5%, 210 patients are required. Data are analysed according to the intention-to-treat principle. Effectiveness is evaluated using linear regression models with repeated measurements. An incremental cost-effectiveness analysis and an incremental cost-utility analysis will also be performed.</p> <p>Discussion</p> <p>The results of this trial will provide insight into the cost-effectiveness of adding exercise therapy to GPs' care in the treatment of OA of the hip. This trial is registered in the Dutch trial registry <url>http://www.trialregister.nl</url>: trial number <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1462">NTR1462</a>.</p