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Sample records for robust patient specific

  1. A Robust Specification Theory for Modal Event-Clock Automata

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    Uli Fahrenberg

    2012-07-01

    Full Text Available In a series of recent work, we have introduced a general framework for quantitative reasoning in specification theories. The contribution of this paper is to show how this framework can be applied to yield a robust specification theory for timed specifications.

  2. Contrasting treatment-specific survival using double-robust estimators.

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    Zhang, Min; Schaubel, Douglas E

    2012-12-30

    In settings where a randomized trial is infeasible, observational data are frequently used to compare treatment-specific survival. The average causal effect (ACE) can be used to make inference regarding treatment policies on patient populations, and a valid ACE estimator must account for imbalances with respect to treatment-specific covariate distributions. One method through which the ACE on survival can be estimated involves appropriately averaging over Cox-regression-based fitted survival functions. A second available method balances the treatment-specific covariate distributions through inverse probability of treatment weighting and then contrasts weighted nonparametric survival function estimators. Because both methods have their advantages and disadvantages, we propose methods that essentially combine both estimators. The proposed methods are double robust, in the sense that they are consistent if at least one of the two working regression models (i.e., logistic model for treatment and Cox model for death hazard) is correct. The proposed methods involve estimating the ACE with respect to restricted mean survival time, defined as the area under the survival curve up to some prespecified time point. We derive and evaluate asymptotic results through simulation. We apply the proposed methods to estimate the ACE of donation-after-cardiac-death kidney transplantation with the use of data obtained from multiple centers in the Netherlands. Copyright © 2012 John Wiley & Sons, Ltd.

  3. Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.

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    Heewon Park

    Full Text Available The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc. and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.

  4. A Parametric Counterexample Refinement Approach for Robust Timed Specifications

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    Louis-Marie Traonouez

    2012-07-01

    Full Text Available Robustness analyzes the impact of small perturbations in the semantics of a model. This allows to model hardware imprecision and therefore it has been applied to determine implementability of timed automata. In a recent paper, we extend this problem to a specification theory for real-timed systems based on timed input/output automata, that are interpreted as two-player games. We propose a construction that allows to synthesize an implementation of a specification that is robust under a given timed perturbation, and we study the impact of these perturbations when composing different specifications. To complete this work we present a technique that evaluates the greatest admissible perturbation. It consists in an iterative process that extracts a spoiling strategy when a game is lost, and through a parametric analysis refines the admissible values for the perturbation. We demonstrate this approach with a prototype implementation.

  5. Modelling, Specification and Robustness Issues for Robotic Manipulation Tasks

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    Danica Kragic

    2008-11-01

    Full Text Available In this paper, a system for modeling of service robot tasks is presented. Our work is motivated by the idea that a robotic task may be represented as a set of tractable modules each responsible for a certain part of the task. For general fetch-and-carry robotic applications, there will be varying demands for precision and degrees of freedom involved depending on complexity of the individual module. The particular research problem considered here is the development of a system that supports simple design of complex tasks from a set of basic primitives. The three system levels considered are: i task graph generation which allows the user to easily design or model a task, ii task graph execution which executes the task graph, and iii at the lowest level, the specification and development of primitives required for general fetch-and-carry robotic applications. In terms of robustness, we believe that one way of increasing the robustness of the whole system is by increasing the robustness of individual modules. In particular, we consider a number of different parameters that effect the performance of a model-based tracking system. Parameters such as color channels, feature detection, validation gates, outliers rejection and feature selection are considered here and their affect to the overall system performance is discussed. Experimental evaluation shows how some of these parameters can successfully be evaluated (learned on-line and consequently improve the performance of the system.

  6. Modelling, Specification and Robustness Issues for Robotic Manipulation Tasks

    Directory of Open Access Journals (Sweden)

    Danica Kragic

    2004-06-01

    Full Text Available In this paper, a system for modeling of service robot tasks is presented. Our work is motivated by the idea that a robotic task may be represented as a set of tractable modules each responsible for a certain part of the task. For general fetch-and-carry robotic applications, there will be varying demands for precision and degrees of freedom involved depending on complexity of the individual module. The particular research problem considered here is the development of a system that supports simple design of complex tasks from a set of basic primitives. The three system levels considered are: i task graph generation which allows the user to easily design or model a task, ii task graph execution which executes the task graph, and iii at the lowest level, the specification and development of primitives required for general fetch-and-carry robotic applications. In terms of robustness, we believe that one way of increasing the robustness of the whole system is by increasing the robustness of individual modules. In particular, we consider a number of different parameters that effect the performance of a model-based tracking system. Parameters such as color channels, feature detection, validation gates, outliers rejection and feature selection are considered here and their affect to the overall system performance is discussed. Experimental evaluation shows how some of these parameters can successfully be evaluated (learned on-line and consequently improve the performance of the system.

  7. Robustness

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Narasimhan, Harikrishna

    2012-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of structures...

  8. ColoGuideEx: a robust gene classifier specific for stage II colorectal cancer prognosis.

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    Agesen, Trude H; Sveen, Anita; Merok, Marianne A; Lind, Guro E; Nesbakken, Arild; Skotheim, Rolf I; Lothe, Ragnhild A

    2012-11-01

    Several clinical factors have an impact on prognosis in stage II colorectal cancer (CRC), but as yet they are inadequate for risk assessment. The present study aimed to develop a gene expression classifier for improved risk stratification of patients with stage II CRC. 315 CRC samples were included in the study. Gene expression measurements from 207 CRC samples (stage I-IV) from two independent Norwegian clinical series were obtained using Affymetrix exon-level microarrays. Differentially expressed genes between stage I and stage IV samples from the test series were identified and used as input for L1 (lasso) penalised Cox proportional hazards analyses of patients with stage II CRC from the same series. A second validation was performed in 108 stage II CRC samples from other populations (USA and Australia). An optimal 13-gene expression classifier (PIGR, CXCL13, MMP3, TUBA1B, SESN1, AZGP1, KLK6, EPHA7, SEMA3A, DSC3, CXCL10, ENPP3, BNIP3) for prediction of relapse among patients with stage II CRC was developed using a consecutive Norwegian test series from patients treated according to current standard protocols (n=44, p<0.001, HR=18.2), and its predictive value was successfully validated for patients with stage II CRC in a second Norwegian CRC series collected two decades previously (n=52, p=0.02, HR=3.6). Further validation of the classifier was obtained in a recent external dataset of patients with stage II CRC from other populations (n=108, p=0.001, HR=6.5). Multivariate Cox regression analyses, including all three sample series and various clinicopathological variables, confirmed the independent prognostic value of the classifier (p≤0.004). The classifier was shown to be specific to stage II CRC and does not provide prognostic stratification of patients with stage III CRC. This study presents the development and validation of a 13-gene expression classifier, ColoGuideEx, for prognosis prediction specific to patients with stage II CRC. The robustness was shown

  9. Robust design requirements specification: a quantitative method for requirements development using quality loss functions

    DEFF Research Database (Denmark)

    Pedersen, Søren Nygaard; Christensen, Martin Ebro; Howard, Thomas J.

    2016-01-01

    the requirements are for interpretation. By applying the method and indicator to a case study from the medical device industry, it was found that less than 45% of the potential for quantification had been utilised. Finally, the robust design requirements specification method was successfully applied to three case...

  10. Patient-Specific Computational Modeling

    CERN Document Server

    Peña, Estefanía

    2012-01-01

    This book addresses patient-specific modeling. It integrates computational modeling, experimental procedures, imagine clinical segmentation and mesh generation with the finite element method (FEM) to solve problems in computational biomedicine and bioengineering. Specific areas of interest include cardiovascular problems, ocular and muscular systems and soft tissue modeling. Patient-specific modeling has been the subject of serious research over the last seven years and interest in the area is continually growing and this area is expected to further develop in the near future.

  11. Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8+and CD4+T-cell responses with multiple specificities including a novel DR7-restricted epitope.

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    Baumgaertner, P; Costa Nunes, C; Cachot, A; Maby-El Hajjami, H; Cagnon, L; Braun, M; Derré, L; Rivals, J-P; Rimoldi, D; Gnjatic, S; Abed Maillard, S; Marcos Mondéjar, P; Protti, M P; Romano, E; Michielin, O; Romero, P; Speiser, D E; Jandus, C

    2016-01-01

    Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. In this phase I trial, 19 patients received a mean of 8 (range 1-12) monthly vaccines s.c. composed of the long synthetic NY-ESO-1 79-108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8 + and CD4 + T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patients' HLAs. The most immunogenic regions of the vaccine peptide were NY-ESO-1 89-102 for CD8 + and NY-ESO-1 83-99 for CD4 + T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-1 87-99 ); 7/7 HLA-DR7 + patients generated strong CD4 + T-cell responses, as detected directly ex vivo with fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-1 79-108 peptide combined with the strong immune adjuvant CpG-B induced integrated, robust and functional CD8 + and CD4 + T-cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach.

  12. Latent Patient Cluster Discovery for Robust Future Forecasting and New-Patient Generalization.

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    Ting Qian

    Full Text Available Commonly referred to as predictive modeling, the use of machine learning and statistical methods to improve healthcare outcomes has recently gained traction in biomedical informatics research. Given the vast opportunities enabled by large Electronic Health Records (EHR data and powerful resources for conducting predictive modeling, we argue that it is yet crucial to first carefully examine the prediction task and then choose predictive methods accordingly. Specifically, we argue that there are at least three distinct prediction tasks that are often conflated in biomedical research: 1 data imputation, where a model fills in the missing values in a dataset, 2 future forecasting, where a model projects the development of a medical condition for a known patient based on existing observations, and 3 new-patient generalization, where a model transfers the knowledge learned from previously observed patients to newly encountered ones. Importantly, the latter two tasks-future forecasting and new-patient generalizations-tend to be more difficult than data imputation as they require predictions to be made on potentially out-of-sample data (i.e., data following a different predictable pattern from what has been learned by the model. Using hearing loss progression as an example, we investigate three regression models and show that the modeling of latent clusters is a robust method for addressing the more challenging prediction scenarios. Overall, our findings suggest that there exist significant differences between various kinds of prediction tasks and that it is important to evaluate the merits of a predictive model relative to the specific purpose of a prediction task.

  13. Latent Patient Cluster Discovery for Robust Future Forecasting and New-Patient Generalization.

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    Qian, Ting; Masino, Aaron J

    2016-01-01

    Commonly referred to as predictive modeling, the use of machine learning and statistical methods to improve healthcare outcomes has recently gained traction in biomedical informatics research. Given the vast opportunities enabled by large Electronic Health Records (EHR) data and powerful resources for conducting predictive modeling, we argue that it is yet crucial to first carefully examine the prediction task and then choose predictive methods accordingly. Specifically, we argue that there are at least three distinct prediction tasks that are often conflated in biomedical research: 1) data imputation, where a model fills in the missing values in a dataset, 2) future forecasting, where a model projects the development of a medical condition for a known patient based on existing observations, and 3) new-patient generalization, where a model transfers the knowledge learned from previously observed patients to newly encountered ones. Importantly, the latter two tasks-future forecasting and new-patient generalizations-tend to be more difficult than data imputation as they require predictions to be made on potentially out-of-sample data (i.e., data following a different predictable pattern from what has been learned by the model). Using hearing loss progression as an example, we investigate three regression models and show that the modeling of latent clusters is a robust method for addressing the more challenging prediction scenarios. Overall, our findings suggest that there exist significant differences between various kinds of prediction tasks and that it is important to evaluate the merits of a predictive model relative to the specific purpose of a prediction task.

  14. Challenges and Specifications for Robust Face and Gait Recognition Systems for Surveillance Application

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    BUCIU Ioan

    2014-05-01

    Full Text Available Automated person recognition (APR based on biometric signals addresses the process of automatically recognize a person according to his physiological traits (face, voice, iris, fingerprint, ear shape, body odor, electroencephalogram – EEG, electrocardiogram, or hand geometry, or behavioural patterns (gait, signature, hand-grip, lip movement. The paper aims at briefly presenting the current challenges for two specific non-cooperative biometric approaches, namely face and gait biometrics as well as approaches that consider combination of the two in the attempt of a more robust system for accurate APR, in the context of surveillance application. Open problems from both sides are also pointed out.

  15. Patient-Specific Modeling of Intraventricular Hemodynamics

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    Vedula, Vijay; Marsden, Alison

    2017-11-01

    Heart disease is the one of the leading causes of death in the world. Apart from malfunctions in electrophysiology and myocardial mechanics, abnormal hemodynamics is a major factor attributed to heart disease across all ages. Computer simulations offer an efficient means to accurately reproduce in vivo flow conditions and also make predictions of post-operative outcomes and disease progression. We present an experimentally validated computational framework for performing patient-specific modeling of intraventricular hemodynamics. Our modeling framework employs the SimVascular open source software to build an anatomic model and employs robust image registration methods to extract ventricular motion from the image data. We then employ a stabilized finite element solver to simulate blood flow in the ventricles, solving the Navier-Stokes equations in arbitrary Lagrangian-Eulerian (ALE) coordinates by prescribing the wall motion extracted during registration. We model the fluid-structure interaction effects of the cardiac valves using an immersed boundary method and discuss the potential application of this methodology in single ventricle physiology and trans-catheter aortic valve replacement (TAVR). This research is supported in part by the Stanford Child Health Research Institute and the Stanford NIH-NCATS-CTSA through Grant UL1 TR001085 and partly through NIH NHLBI R01 Grant 5R01HL129727-02.

  16. LMI Based Robust Blood Glucose Regulation in Type-1 Diabetes Patient with Daily Multi-meal Ingestion

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    Mandal, S.; Bhattacharjee, A.; Sutradhar, A.

    2014-04-01

    This paper illustrates the design of a robust output feedback H ∞ controller for the nonlinear glucose-insulin (GI) process in a type-1 diabetes patient to deliver insulin through intravenous infusion device. The H ∞ design specification have been realized using the concept of linear matrix inequality (LMI) and the LMI approach has been used to quadratically stabilize the GI process via output feedback H ∞ controller. The controller has been designed on the basis of full 19th order linearized state-space model generated from the modified Sorensen's nonlinear model of GI process. The resulting controller has been tested with the nonlinear patient model (the modified Sorensen's model) in presence of patient parameter variations and other uncertainty conditions. The performance of the controller was assessed in terms of its ability to track the normoglycemic set point of 81 mg/dl with a typical multi-meal disturbance throughout a day that yields robust performance and noise rejection.

  17. Robust Intensity Modulated Proton Therapy (IMPT Increases Estimated Clinical Benefit in Head and Neck Cancer Patients.

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    Lisanne V van Dijk

    Full Text Available To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT with current photon Intensity Modulated Radiation Therapy (IMRT and PTV-based IMPT for head and neck cancer (HNC patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP and target coverage in the case of setup and range errors.For 10 HNC patients, PTV-based IMRT (7 fields, minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm and range error (±3% combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT.The robustness criterion was met in the IMRT and minimax IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV-based IMPT plans. Seven (out of 10 patients had relatively large NTCP reductions in minimax IMPT plans compared to IMRT. For these patients, xerostomia and dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0-21.1 and 8.1% (95% CI; 4.9-11.2 on average with minimax IMPT. Increasing the number of fields did not contribute to plan robustness, but improved organ sparing.The estimated clinical benefit in terms of NTCP of robust optimized (minimax IMPT is greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the target coverage of minimax IMPT plans in the presence of errors was comparable to IMRT plans.

  18. Patient-Specific Oscillometric Blood Pressure Measurement.

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    Liu, Jiankun; Cheng, Hao-Min; Chen, Chen-Huan; Sung, Shih-Hsien; Moslehpour, Mohsen; Hahn, Jin-Oh; Mukkamala, Ramakrishna

    2016-06-01

    Most automatic cuff blood pressure (BP) measurement devices are based on oscillometry. These devices estimate BP from the envelopes of the cuff pressure oscillations using fixed ratios. The values of the fixed ratios represent population averages, so the devices may only be accurate in subjects with normal BP levels. The objective was to develop and demonstrate the validity of a patient-specific oscillometric BP measurement method. The idea of the developed method was to represent the cuff pressure oscillation envelopes with a physiologic model, and then estimate the patient-specific parameters of the model, which includes BP levels, by optimally fitting it to the envelopes. The method was investigated against gold standard reference BP measurements from 57 patients with widely varying pulse pressures. A portion of the data was used to optimize the patient-specific method and a fixed-ratio method, while the remaining data were used to test these methods and a current office device. The patient-specific method yielded BP root-mean-square-errors ranging from 6.0 to 9.3 mmHg. On an average, these errors were nearly 40% lower than the errors of each existing method. The patient-specific method may improve automatic cuff BP measurement accuracy. A patient-specific oscillometric BP measurement method was proposed and shown to be more accurate than the conventional method and a current device.

  19. Photoinduced carbene generation from diazirine modified task specific phosphonium salts to prepare robust hydrophobic coatings.

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    Ghiassian, Sara; Ismaili, Hossein; Lubbock, Brett D W; Dube, Jonathan W; Ragogna, Paul J; Workentin, Mark S

    2012-08-21

    3-Aryl-3-(trifluormethyl)diazirine functionalized highly fluorinated phosphonium salts (HFPS) were synthesized, characterized, and utilized as photoinduced carbene precursors for covalent attachment of the HFPS onto cotton/paper to impart hydrophobicity to these surfaces. Irradiation of cotton and paper, as proof of concept substrates, treated with the diazirine-HFPS leads to robust hydrophobic cotton and paper surfaces with antiwetting properties, whereas the corresponding control samples absorb water readily. The contact angles of water were determined to be 139° and 137° for cotton and paper, respectively. In contrast, water placed on the untreated or the control samples (those treated with the diazirine-HFPS but not irradiated) is simply absorbed into the surface. Additionaly, the chemically grafted hydrophobic coating showed high durability toward wash cycles and sonication in organic solvents. Because of the mode of activation to covalently tether the hydrophobic coating, it is amenable to photopatterning, which was demonstrated macroscopically.

  20. Cerebral cortex dose sparing for glioblastoma patients: IMRT versus robust treatment planning.

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    Exeli, Ann-Katrin; Kellner, Daniel; Exeli, Lukas; Steininger, Phil; Wolf, Frank; Sedlmayer, Felix; Deutschmann, Heinz

    2018-02-06

    To date, patients with glioblastoma still have a bad median overall survival rate despite radiation dose-escalation and combined modality treatment. Neurocognitive decline is a crucial adverse event which may be linked to high doses to the cortex. In a planning study, we investigated the impact of dose constraints to the cerebral cortex and its relation to the organs at risk for glioblastoma patients. Cortical sparing was implemented into the optimization process for two planning approaches: classical intensity-modulated radiotherapy (IMRT) and robust treatment planning. The plans with and without objectives for cortex sparing where compared based on dose-volume histograms (DVH) data of the main organs at risk. Additionally the cortex volume above a critical threshold of 28.6 Gy was elaborated. Furthermore, IMRT plans were compared with robust treatment plans regarding potential cortex sparing. Cortical dose constraints result in a statistically significant reduced cerebral cortex volume above 28.6 Gy without negative effects to the surrounding organs at risk independently of the optimization technique. For IMRT we found a mean volume reduction of doses beyond the threshold of 19%, and 16% for robust treatment planning, respectively. Robust plans delivered sharper dose gradients around the target volume in an order of 3 - 6%. Aside from that the integration of cortical sparing into the optimization process has the potential to reduce the dose around the target volume (4 - 8%). We were able to show that dose to the cerebral cortex can be significantly reduced both with robust treatment planning and IMRT while maintaining clinically adequate target coverage and without corrupting any organ at risk. Robust treatment plans delivered more conformal plans compared to IMRT and were superior in regards to cortical sparing.

  1. Robust detection of rare species using environmental DNA: the importance of primer specificity.

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    Wilcox, Taylor M; McKelvey, Kevin S; Young, Michael K; Jane, Stephen F; Lowe, Winsor H; Whiteley, Andrew R; Schwartz, Michael K

    2013-01-01

    Environmental DNA (eDNA) is being rapidly adopted as a tool to detect rare animals. Quantitative PCR (qPCR) using probe-based chemistries may represent a particularly powerful tool because of the method's sensitivity, specificity, and potential to quantify target DNA. However, there has been little work understanding the performance of these assays in the presence of closely related, sympatric taxa. If related species cause any cross-amplification or interference, false positives and negatives may be generated. These errors can be disastrous if false positives lead to overestimate the abundance of an endangered species or if false negatives prevent detection of an invasive species. In this study we test factors that influence the specificity and sensitivity of TaqMan MGB assays using co-occurring, closely related brook trout (Salvelinus fontinalis) and bull trout (S. confluentus) as a case study. We found qPCR to be substantially more sensitive than traditional PCR, with a high probability of detection at concentrations as low as 0.5 target copies/µl. We also found that number and placement of base pair mismatches between the Taqman MGB assay and non-target templates was important to target specificity, and that specificity was most influenced by base pair mismatches in the primers, rather than in the probe. We found that insufficient specificity can result in both false positive and false negative results, particularly in the presence of abundant related species. Our results highlight the utility of qPCR as a highly sensitive eDNA tool, and underscore the importance of careful assay design.

  2. Patient-specific workup of adrenal incidentalomas

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    Romy R. de Haan

    Full Text Available Purpose: : To develop a clinical prediction model to predict a clinically relevant adrenal disorder for patients with adrenal incidentaloma. Materials and methods: : This retrospective study is approved by the institutional review board, with waiver of informed consent. Natural language processing is used for filtering of adrenal incidentaloma cases in all thoracic and abdominal CT reports from 2010 till 2012. A total of 635 patients are identified. Stepwise logistic regression is used to construct the prediction model. The model predicts if a patient is at risk for malignancy or hormonal hyperfunction of the adrenal gland at the moment of initial presentation, thus generates a predicted probability for every individual patient. The prediction model is evaluated on its usefulness in clinical practice using decision curve analysis (DCA based on different threshold probabilities. For patients whose predicted probability is lower than the predetermined threshold probability, further workup could be omitted. Results: : A prediction model is successfully developed, with an area under the curve (AUC of 0.78. Results of the DCA indicate that up to 11% of patients with an adrenal incidentaloma can be avoided from unnecessary workup, with a sensitivity of 100% and specificity of 11%. Conclusion: : A prediction model can accurately predict if an adrenal incidentaloma patient is at risk for malignancy or hormonal hyperfunction of the adrenal gland based on initial imaging features and patient demographics. However, with most adrenal incidentalomas labeled as nonfunctional adrenocortical adenomas requiring no further treatment, it is likely that more patients could be omitting from unnecessary diagnostics. Keywords: Adrenal incidentaloma, Patient-specific workup, Prediction model

  3. Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses.

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    Stefan W Metz

    2016-10-01

    Full Text Available Dengue virus (DENV is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE, purified and adsorbed to poly (lactic-co-glycolic acid (PLGA nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.

  4. Disease gene prioritization by integrating tissue-specific molecular networks using a robust multi-network model.

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    Ni, Jingchao; Koyuturk, Mehmet; Tong, Hanghang; Haines, Jonathan; Xu, Rong; Zhang, Xiang

    2016-11-10

    Accurately prioritizing candidate disease genes is an important and challenging problem. Various network-based methods have been developed to predict potential disease genes by utilizing the disease similarity network and molecular networks such as protein interaction or gene co-expression networks. Although successful, a common limitation of the existing methods is that they assume all diseases share the same molecular network and a single generic molecular network is used to predict candidate genes for all diseases. However, different diseases tend to manifest in different tissues, and the molecular networks in different tissues are usually different. An ideal method should be able to incorporate tissue-specific molecular networks for different diseases. In this paper, we develop a robust and flexible method to integrate tissue-specific molecular networks for disease gene prioritization. Our method allows each disease to have its own tissue-specific network(s). We formulate the problem of candidate gene prioritization as an optimization problem based on network propagation. When there are multiple tissue-specific networks available for a disease, our method can automatically infer the relative importance of each tissue-specific network. Thus it is robust to the noisy and incomplete network data. To solve the optimization problem, we develop fast algorithms which have linear time complexities in the number of nodes in the molecular networks. We also provide rigorous theoretical foundations for our algorithms in terms of their optimality and convergence properties. Extensive experimental results show that our method can significantly improve the accuracy of candidate gene prioritization compared with the state-of-the-art methods. In our experiments, we compare our methods with 7 popular network-based disease gene prioritization algorithms on diseases from Online Mendelian Inheritance in Man (OMIM) database. The experimental results demonstrate that our methods

  5. Morphing patient-specific musculoskeletal models

    DEFF Research Database (Denmark)

    Rasmussen, John; Galibarov, Pavel E.; Al-Munajjed, Amir

    the generic model differs significantly from the patient in question. The scenario therefore entails two sets of data: (i) a generic musculoskeletal model representing a single (average) individual, and (ii) a set of 3-D medical imaging data, typically in the form of a DICOM file obtained from CT, MRI...... of dozens of man-years. Healthy humans differ significantly in size, shape and general morphology, and this variation is even larger for patients with pathological anatomies. Thus, patient-specific models are imperative for reliable biomechanical analyses on which decisions of surgical treatments...... the resulting models do indeed represent the patients’ biomechanics. As a particularly challenging case, foot deformities based only on point sets recovered from surface scans are considered as shown in the figure. The preliminary results are promising for the cases of severe flat foot and metatarsalgia while...

  6. Evaluation of Robustness to Setup and Range Uncertainties for Head and Neck Patients Treated With Pencil Beam Scanning Proton Therapy.

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    Malyapa, Robert; Lowe, Matthew; Bolsi, Alessandra; Lomax, Antony J; Weber, Damien C; Albertini, Francesca

    2016-05-01

    To evaluate the robustness of head and neck plans for treatment with intensity modulated proton therapy to range and setup errors, and to establish robustness parameters for the planning of future head and neck treatments. Ten patients previously treated were evaluated in terms of robustness to range and setup errors. Error bar dose distributions were generated for each plan, from which several metrics were extracted and used to define a robustness database of acceptable parameters over all analyzed plans. The patients were treated in sequentially delivered series, and plans were evaluated for both the first series and for the combined error over the whole treatment. To demonstrate the application of such a database in the head and neck, for 1 patient, an alternative treatment plan was generated using a simultaneous integrated boost (SIB) approach and plans of differing numbers of fields. The robustness database for the treatment of head and neck patients is presented. In an example case, comparison of single and multiple field plans against the database show clear improvements in robustness by using multiple fields. A comparison of sequentially delivered series and an SIB approach for this patient show both to be of comparable robustness, although the SIB approach shows a slightly greater sensitivity to uncertainties. A robustness database was created for the treatment of head and neck patients with intensity modulated proton therapy based on previous clinical experience. This will allow the identification of future plans that may benefit from alternative planning approaches to improve robustness. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Unsupervised analysis of classical biomedical markers: robustness and medical relevance of patient clustering using bioinformatics tools.

    Directory of Open Access Journals (Sweden)

    Michal Markovich Gordon

    Full Text Available MOTIVATION: It has been proposed that clustering clinical markers, such as blood test results, can be used to stratify patients. However, the robustness of clusters formed with this approach to data pre-processing and clustering algorithm choices has not been evaluated, nor has clustering reproducibility. Here, we made use of the NHANES survey to compare clusters generated with various combinations of pre-processing and clustering algorithms, and tested their reproducibility in two separate samples. METHOD: Values of 44 biomarkers and 19 health/life style traits were extracted from the National Health and Nutrition Examination Survey (NHANES. The 1999-2002 survey was used for training, while data from the 2003-2006 survey was tested as a validation set. Twelve combinations of pre-processing and clustering algorithms were applied to the training set. The quality of the resulting clusters was evaluated both by considering their properties and by comparative enrichment analysis. Cluster assignments were projected to the validation set (using an artificial neural network and enrichment in health/life style traits in the resulting clusters was compared to the clusters generated from the original training set. RESULTS: The clusters obtained with different pre-processing and clustering combinations differed both in terms of cluster quality measures and in terms of reproducibility of enrichment with health/life style properties. Z-score normalization, for example, dramatically improved cluster quality and enrichments, as compared to unprocessed data, regardless of the clustering algorithm used. Clustering diabetes patients revealed a group of patients enriched with retinopathies. This could indicate that routine laboratory tests can be used to detect patients suffering from complications of diabetes, although other explanations for this observation should also be considered. CONCLUSIONS: Clustering according to classical clinical biomarkers is a robust

  8. Maintenance-energy requirements and robustness of Saccharomyces cerevisiae at aerobic near-zero specific growth rates.

    Science.gov (United States)

    Vos, Tim; Hakkaart, Xavier D V; de Hulster, Erik A F; van Maris, Antonius J A; Pronk, Jack T; Daran-Lapujade, Pascale

    2016-06-17

    Saccharomyces cerevisiae is an established microbial platform for production of native and non-native compounds. When product pathways compete with growth for precursors and energy, uncoupling of growth and product formation could increase product yields and decrease formation of biomass as a by-product. Studying non-growing, metabolically active yeast cultures is a first step towards developing S. cerevisiae as a robust, non-growing cell factory. Microbial physiology at near-zero growth rates can be studied in retentostats, which are continuous-cultivation systems with full biomass retention. Hitherto, retentostat studies on S. cerevisiae have focused on anaerobic conditions, which bear limited relevance for aerobic industrial processes. The present study uses aerobic, glucose-limited retentostats to explore the physiology of non-dividing, respiring S. cerevisiae cultures, with a focus on industrially relevant features. Retentostat feeding regimes for smooth transition from exponential growth in glucose-limited chemostat cultures to near-zero growth rates were obtained by model-aided experimental design. During 20 days of retentostats cultivation, the specific growth rate gradually decreased from 0.025 h(-1) to below 0.001 h(-1), while culture viability remained above 80 %. The maintenance requirement for ATP (mATP) was estimated at 0.63 ± 0.04 mmol ATP (g biomass)(-1) h(-1), which is ca. 35 % lower than previously estimated for anaerobic retentostats. Concomitant with decreasing growth rate in aerobic retentostats, transcriptional down-regulation of genes involved in biosynthesis and up-regulation of stress-responsive genes resembled transcriptional regulation patterns observed for anaerobic retentostats. The heat-shock tolerance in aerobic retentostats far exceeded previously reported levels in stationary-phase batch cultures. While in situ metabolic fluxes in retentostats were intentionally low due to extreme caloric restriction, off-line measurements

  9. Robust spectral analysis of videocapsule images acquired from celiac disease patients

    Directory of Open Access Journals (Sweden)

    Bhagat Govind

    2011-09-01

    Full Text Available Abstract Background Dominant frequency (DF analysis of videocapsule endoscopy images is a new method to detect small intestinal periodicities that may result from mechanical rhythms such as peristalsis. Longer periodicity is related to greater image texture at areas of villous atrophy in celiac disease. However, extraneous features and spatiotemporal phase shift may mask DF rhythms. Method The robustness of Fourier and ensemble averaging spectral analysis to compute DF was tested. Videocapsule images from the distal duodenum of 11 celiac patients (frame rate 2/s and pixel resolution 576 × 576 were analyzed. For patients 1, 2, ... 11, respectively, a total of 10, 11, ..., 20 sequential images were extracted from a randomly selected time epoch. Each image sequence was artificially repeated to 200 frames, simulating periodicities of 0.2, 0.18, ..., 0.1Hz, respectively. Random white noise at four different levels, spatiotemporal phase shift, and frames with air bubbles were added. Power spectra were constructed pixel-wise over 200 frames, and an average spectrum was computed from the 576 × 576 individual spectra. The largest spectral peak in the average spectrum was the estimated DF. Error was defined as the absolute difference between actual DF and estimated DF. Results For Fourier analysis, the mean absolute error between estimated and actual DF was 0.032 ± 0.052Hz. Error increased with greater degree of random noise imposed. In contrast, all ensemble average estimates precisely predicted the simulated DF. Conclusions The ensemble average DF estimate of videocapsule images with simulated periodicity is robust to noise and spatiotemporal phase shift as compared with Fourier analysis. Accurate estimation of DF eliminates the need to impose complex masking, extraction, and/or corrective preprocessing measures.

  10. Update of patient-specific maxillofacial implant.

    Science.gov (United States)

    Owusu, James A; Boahene, Kofi

    2015-08-01

    Patient-specific implant (PSI) is a personalized approach to reconstructive and esthetic surgery. This is particularly useful in maxillofacial surgery in which restoring the complex three-dimensional (3D) contour can be quite challenging. In certain situations, the best results can only be achieved with implants custom-made to fit a particular need. Significant progress has been made over the past decade in the design and manufacture of maxillofacial PSIs. Computer-aided design (CAD)/computer-aided manufacturing (CAM) technology is rapidly advancing and has provided new options for fabrication of PSIs with better precision. Maxillofacial PSIs can now be designed using preoperative imaging data as input into CAD software. The designed implant is then fabricated using a CAM technique such as 3D printing. This approach increases precision and decreases or completely eliminates the need for intraoperative modification of implants. The use of CAD/CAM-produced PSIs for maxillofacial reconstruction and augmentation can significantly improve contour outcomes and decrease operating time. CAD/CAM technology allows timely and precise fabrication of maxillofacial PSIs. This approach is gaining increasing popularity in maxillofacial reconstructive surgery. Continued advances in CAD technology and 3D printing are bound to improve the cost-effectiveness and decrease the production time of maxillofacial PSIs.

  11. Robust cranial cavity segmentation in CT and CT perfusion images of trauma and suspected stroke patients.

    Science.gov (United States)

    Patel, Ajay; van Ginneken, Bram; Meijer, Frederick J A; van Dijk, Ewoud J; Prokop, Mathias; Manniesing, Rashindra

    2017-02-01

    A robust and accurate method is presented for the segmentation of the cranial cavity in computed tomography (CT) and CT perfusion (CTP) images. The method consists of multi-atlas registration with label fusion followed by a geodesic active contour levelset refinement of the segmentation. Pre-registration atlas selection based on differences in anterior skull anatomy reduces computation time whilst optimising performance. The method was evaluated on a large clinical dataset of 573 acute stroke and trauma patients that received a CT or CTP in our hospital in the period February 2015-December 2015. The database covers a large spectrum of the anatomical and pathological variations that is typically observed in everyday clinical practice. Three orthogonal slices were randomly selected per patient and manually annotated, resulting in 1659 reference annotations. Segmentations were initially visually inspected for the entire study cohort to assess failures. A total of 20 failures were reported. Quantitative evaluation in comparison to the reference dataset showed a mean Dice coefficient of 98.36 ±  2.59%. The results demonstrate that the method closely approaches the high performance of expert manual annotation. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A Robust Deep Model for Improved Classification of AD/MCI Patients.

    Science.gov (United States)

    Li, Feng; Tran, Loc; Thung, Kim-Han; Ji, Shuiwang; Shen, Dinggang; Li, Jiang

    2015-09-01

    Accurate classification of Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI), plays a critical role in possibly preventing progression of memory impairment and improving quality of life for AD patients. Among many research tasks, it is of a particular interest to identify noninvasive imaging biomarkers for AD diagnosis. In this paper, we present a robust deep learning system to identify different progression stages of AD patients based on MRI and PET scans. We utilized the dropout technique to improve classical deep learning by preventing its weight coadaptation, which is a typical cause of overfitting in deep learning. In addition, we incorporated stability selection, an adaptive learning factor, and a multitask learning strategy into the deep learning framework. We applied the proposed method to the ADNI dataset, and conducted experiments for AD and MCI conversion diagnosis. Experimental results showed that the dropout technique is very effective in AD diagnosis, improving the classification accuracies by 5.9% on average as compared to the classical deep learning methods.

  13. Death of a Simulated Pediatric Patient: Toward a More Robust Theoretical Framework.

    Science.gov (United States)

    McBride, Mary E; Schinasi, Dana Aronson; Moga, Michael Alice; Tripathy, Shreepada; Calhoun, Aaron

    2017-12-01

    A theoretical framework was recently proposed that encapsulates learner responses to simulated death due to action or inaction in the pediatric context. This framework, however, was developed at an institution that allows simulated death and thus does not address the experience of those centers at which this technique is not used. To address this, we performed a parallel qualitative study with the intent of augmenting the initial framework. We conducted focus groups, using a constructivist grounded theory approach, using physicians and nurses who have experienced a simulated cardiac arrest. The participants were recruited via e-mail. Transcripts were analyzed by coders blinded to the original framework to generate a list of provisional themes that were iteratively refined. These themes were then compared with the themes from the original article and used to derive a consensus model that incorporated the most relevant features of each. Focus group data yielded 7 themes. Six were similar to those developed in the original framework. One important exception was noted; however, those learners not exposed to patient death due to action or inaction often felt that the mannequin's survival was artificial. This additional theme was incorporated into a revised framework. The original framework addresses most aspects of learner reactions to simulated death. Our work suggests that adding the theme pertaining to the lack of realism that can be perceived when the mannequin is unexpectedly saved results in a more robust theoretical framework transferable to centers that do not allow mannequin death.

  14. Patient-specific modelling of whole heart anatomy, dynamics and haemodynamics from four-dimensional cardiac CT images

    OpenAIRE

    Mihalef, Viorel; Ionasec, Razvan Ioan; Sharma, Puneet; Georgescu, Bogdan; Voigt, Ingmar; Suehling, Michael; Comaniciu, Dorin

    2011-01-01

    There is a growing need for patient-specific and holistic modelling of the heart to support comprehensive disease assessment and intervention planning as well as prediction of therapeutic outcomes. We propose a patient-specific model of the whole human heart, which integrates morphology, dynamics and haemodynamic parameters at the organ level. The modelled cardiac structures are robustly estimated from four-dimensional cardiac computed tomography (CT), including all four chambers and valves a...

  15. Determination of all feasible robust PID controllers for open-loop unstable plus time delay processes with gain margin and phase margin specifications.

    Science.gov (United States)

    Wang, Yuan-Jay

    2014-03-01

    This paper proposes a novel alternative method to graphically compute all feasible gain and phase margin specifications-oriented robust PID controllers for open-loop unstable plus time delay (OLUPTD) processes. This method is applicable to general OLUPTD processes without constraint on system order. To retain robustness for OLUPTD processes subject to positive or negative gain variations, the downward gain margin (GM(down)), upward gain margin (GM(up)), and phase margin (PM) are considered. A virtual gain-phase margin tester compensator is incorporated to guarantee the concerned system satisfies certain robust safety margins. In addition, the stability equation method and the parameter plane method are exploited to portray the stability boundary and the constant gain margin (GM) boundary as well as the constant PM boundary. The overlapping region of these boundaries is graphically determined and denotes the GM and PM specifications-oriented region (GPMSOR). Alternatively, the GPMSOR characterizes all feasible robust PID controllers which achieve the pre-specified safety margins. In particular, to achieve optimal gain tuning, the controller gains are searched within the GPMSOR to minimize the integral of the absolute error (IAE) or the integral of the squared error (ISE) performance criterion. Thus, an optimal PID controller gain set is successfully found within the GPMSOR and guarantees the OLUPTD processes with a pre-specified GM and PM as well as a minimum IAE or ISE. Consequently, both robustness and performance can be simultaneously assured. Further, the design procedures are summarized as an algorithm to help rapidly locate the GPMSOR and search an optimal PID gain set. Finally, three highly cited examples are provided to illustrate the design process and to demonstrate the effectiveness of the proposed method. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  16. Robust cranial cavity segmentation in CT and CT perfusion images of trauma and suspected stroke patients

    NARCIS (Netherlands)

    Patel, A; Ginneken, B. van; Meijer, F.J.A.; Dijk, E.J. van; Prokop, M.; Manniesing, R.

    2017-01-01

    A robust and accurate method is presented for the segmentation of the cranial cavity in computed tomography (CT) and CT perfusion (CTP) images. The method consists of multi-atlas registration with label fusion followed by a geodesic active contour levelset refinement of the segmentation.

  17. Transphosphorylation of E. coli proteins during production of recombinant protein kinases provides a robust system to characterize kinase specificity

    Science.gov (United States)

    Protein kinase specificity is of fundamental importance to pathway regulation and signal transduction. Here, we report a convenient system to monitor the activity and specificity of recombinant protein kinases expressed in E.coli. We apply this to the study of the cytoplasmic domain of the plant rec...

  18. A general method to derive robust organ-specific gene expression-based differentiation indices: application to thyroid cancer diagnostic

    National Research Council Canada - National Science Library

    Tomás, G; Tarabichi, M; Gacquer, D; Hébrant, A; Dom, G; Dumont, J E; Keutgen, X; Fahey, 3rd, T J; Maenhaut, C; Detours, V

    2012-01-01

    .... Hence, a quantitative assessment of differentiation would be most useful. We propose an unbiased method to derive organ-specific differentiation indices from gene expression data and demonstrate its usefulness in thyroid cancer diagnosis...

  19. Multisite Machine Learning Analysis Provides a Robust Structural Imaging Signature of Schizophrenia Detectable Across Diverse Patient Populations and Within Individuals.

    Science.gov (United States)

    Rozycki, Martin; Satterthwaite, Theodore D; Koutsouleris, Nikolaos; Erus, Guray; Doshi, Jimit; Wolf, Daniel H; Fan, Yong; Gur, Raquel E; Gur, Ruben C; Meisenzahl, Eva M; Zhuo, Chuanjun; Ying, Hong; Yan, Hao; Yue, Weihua; Zhang, Dai; Davatzikos, Christos

    2017-11-24

    Past work on relatively small, single-site studies using regional volumetry, and more recently machine learning methods, has shown that widespread structural brain abnormalities are prominent in schizophrenia. However, to be clinically useful, structural imaging biomarkers must integrate high-dimensional data and provide reproducible results across clinical populations and on an individual person basis. Using advanced multi-variate analysis tools and pooled data from case-control imaging studies conducted at 5 sites (941 adult participants, including 440 patients with schizophrenia), a neuroanatomical signature of patients with schizophrenia was found, and its robustness and reproducibility across sites, populations, and scanners, was established for single-patient classification. Analyses were conducted at multiple scales, including regional volumes, voxelwise measures, and complex distributed patterns. Single-subject classification was tested for single-site, pooled-site, and leave-site-out generalizability. Regional and voxelwise analyses revealed a pattern of widespread reduced regional gray matter volume, particularly in the medial prefrontal, temporolimbic and peri-Sylvian cortex, along with ventricular and pallidum enlargement. Multivariate classification using pooled data achieved a cross-validated prediction accuracy of 76% (AUC = 0.84). Critically, the leave-site-out validation of the detected schizophrenia signature showed accuracy/AUC range of 72-77%/0.73-0.91, suggesting a robust generalizability across sites and patient cohorts. Finally, individualized patient classifications displayed significant correlations with clinical measures of negative, but not positive, symptoms. Taken together, these results emphasize the potential for structural neuroimaging data to provide a robust and reproducible imaging signature of schizophrenia. A web-accessible portal is offered to allow the community to obtain individualized classifications of magnetic resonance

  20. Multiplex PCR for specific and robust detection of Xanthomonas campestris pv. musacearum in pure culture and infected plant material

    DEFF Research Database (Denmark)

    Adriko, John; Aritua, V.; Mortensen, Carmen Nieves

    2012-01-01

    The present study developed a pathovar-specific PCR for the detection of Xanthomonas campestris pv. musacearum (Xcm), the cause of banana xanthomonas wilt, by amplification of a 265-bp region of the gene encoding the general secretion pathway protein D (GspD). A distinct DNA fragment of the expec......The present study developed a pathovar-specific PCR for the detection of Xanthomonas campestris pv. musacearum (Xcm), the cause of banana xanthomonas wilt, by amplification of a 265-bp region of the gene encoding the general secretion pathway protein D (GspD). A distinct DNA fragment...... was subsequently demonstrated in tests on artificially inoculated screenhouse cultivars of banana and field bananas with and without symptoms sampled from different parts of Uganda. This study therefore demonstrated a robust and specific Xcm diagnostic tool with the added advantage of applying internal PCR...

  1. T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Hannah K Bayes

    Full Text Available We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis.Peripheral blood human memory CD4(+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines.Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4(+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6(+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood.Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions.

  2. Specifics of nursing care for a patient with nutritional stoma.

    OpenAIRE

    MUSILOVÁ, Klára

    2017-01-01

    Main goal of the thesis was to map out the specifics of nursing care for a patient with a nutritious stoma. Three research questions have been identified in connection to this goal. First research question was focused on mapping out the nursing care for a patient prior applying the nutritious stoma. Second research question was focusing on nursing care for a patient while the nutritious stoma is being applied, and the last third question researches the nursing care for a patient after applyin...

  3. No specific time window distinguishes between community-, healthcare-, and hospital-acquired bacteremia, but they are prognostically robust

    DEFF Research Database (Denmark)

    Gradel, Kim Oren; Nielsen, Stig Lønberg; Pedersen, Court

    2014-01-01

    Objective. We examined whether specific time windows after hospital admission reflected a sharp transition between community and hospital acquisition of bacteremia. We further examined whether different time windows to distinguish between community acquisition, healthcare association (HCA......), and hospital acquisition influenced the results of prognostic models. Design. Population-based cohort study. Setting. Hospitals in 3 areas of Denmark (2.3 million inhabitants) during 2000-2011. Methods. We computed graphs depicting proportions of males, absence of comorbidity, microorganisms, and 30-day......) curve for 30-day mortality, adjusting for sex, age, comorbidity, and microorganisms. Results. For 56,606 bacteremic episodes, no sharp transitions were detected on a specific day after admission. Among the 8 combined time windows, ORs for 30-day mortality varied from 1.30 (95% confidence interval [CI...

  4. Robust Cardiomyocyte-Specific Gene Expression Following Systemic Injection of AAV: In Vivo Gene Delivery Follows a Poisson Distribution

    Science.gov (United States)

    Prasad, Konkal-Matt R.; Xu, Yaqin; Yang, Zequan; Acton, Scott T.; French, Brent A

    2010-01-01

    Newly-isolated serotypes of AAV readily cross the endothelial barrier to provide efficient transgene delivery throughout the body. However, tissue-specific expression is preferred in most experimental studies and gene therapy protocols. Previous efforts to restrict gene expression to the myocardium often relied on direct injection into heart muscle or intracoronary perfusion. Here, we report an AAV vector system employing the cardiac troponin T promoter (cTnT). Using luciferase and eGFP, the efficiency and specificity of cardiac reporter gene expression using AAV serotype capsids: AAV-1, 2, 6, 8 or 9 were tested after systemic administration to 1 week old mice. Luciferase assays showed that the cTnT promoter worked in combination with each of the AAV serotype capsids to provide cardiomyocyte-specific gene expression, but AAV-9 followed closely by AAV-8 was the most efficient. AAV9-mediated gene expression from the cTnT promoter was 640-fold greater in the heart compared to the next highest tissue (liver). eGFP fluorescence indicated a transduction efficiency of 96% using AAV-9 at a dose of only 3.15×1010 viral particles per mouse. Moreover, the intensity of cardiomyocyte eGFP fluorescence measured on a cell-by-cell basis revealed that AAV-mediated gene expression in the heart can be modeled as a Poisson distribution; requiring an average of nearly two vector genomes per cell to attain an 85% transduction efficiency. PMID:20703310

  5. Patient-specific finite element modeling of bones.

    Science.gov (United States)

    Poelert, Sander; Valstar, Edward; Weinans, Harrie; Zadpoor, Amir A

    2013-04-01

    Finite element modeling is an engineering tool for structural analysis that has been used for many years to assess the relationship between load transfer and bone morphology and to optimize the design and fixation of orthopedic implants. Due to recent developments in finite element model generation, for example, improved computed tomography imaging quality, improved segmentation algorithms, and faster computers, the accuracy of finite element modeling has increased vastly and finite element models simulating the anatomy and properties of an individual patient can be constructed. Such so-called patient-specific finite element models are potentially valuable tools for orthopedic surgeons in fracture risk assessment or pre- and intraoperative planning of implant placement. The aim of this article is to provide a critical overview of current themes in patient-specific finite element modeling of bones. In addition, the state-of-the-art in patient-specific modeling of bones is compared with the requirements for a clinically applicable patient-specific finite element method, and judgment is passed on the feasibility of application of patient-specific finite element modeling as a part of clinical orthopedic routine. It is concluded that further development in certain aspects of patient-specific finite element modeling are needed before finite element modeling can be used as a routine clinical tool.

  6. Knee Replacement for Women with Patient-Specific Instructions

    Medline Plus

    Full Text Available Knee Replacement for Women with Patient-Specific Instructions Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. All rights reserved.

  7. Increasing a Robust Antigen-Specific Cytotoxic T Lymphocyte Response by FMDV DNA Vaccination with IL-9 Expressing Construct

    Directory of Open Access Journals (Sweden)

    Qiang Zou

    2010-01-01

    Full Text Available Various chemokines and cytokines as adjuvants can be used to improve efficacy of DNA vaccination. In this study, we sought to investigate if a DNA construct expressing IL-9 (designed as proV-IL9 as a molecular adjuvant enhance antigen specific immune responses elicited by the pcD-VP1 DNA vaccination. Mice immunized with pcD-VP1 combined with proV-IL9 developed a strong humoral response. In addition, the coinoculation induced significant higher level of antigen-specific cell proliferation and cytotoxic response. This agreed well with higher expression level of IFN-γ and perforin in CD8+ T cells, but not with IL-17 in these T cells. The results indicate that IL-9 induces the development of IFN-γ-producing CD8+ T cells (Tc1, but not the IL-17-producing CD8+ T cells (Tc17. Up-regulated expressions of BCL-2 and BCL-XL were exhibited in these Tc1 cells, suggesting that IL-9 may trigger antiapoptosis mechanism in these cells. Together, these results demonstrated that IL-9 used as molecular adjuvant could enhance the immunogenicity of DNA vaccination, in augmenting humoral and cellular responses and particularly promoting Tc1 activations. Thus, the IL-9 may be utilized as a potent Tc1 adjuvant for DNA vaccines.

  8. Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries.

    Science.gov (United States)

    Lee, Yi-Ying; Hsu, Chih-Yuan; Lin, Ling-Jiun; Chang, Chih-Chun; Cheng, Hsiao-Chun; Yeh, Tsung-Hsien; Hu, Rei-Hsing; Lin, Che; Xie, Zhen; Chen, Bor-Sen

    2013-10-27

    Synthetic genetic transistors are vital for signal amplification and switching in genetic circuits. However, it is still problematic to efficiently select the adequate promoters, Ribosome Binding Sides (RBSs) and inducer concentrations to construct a genetic transistor with the desired linear amplification or switching in the Input/Output (I/O) characteristics for practical applications. Three kinds of promoter-RBS libraries, i.e., a constitutive promoter-RBS library, a repressor-regulated promoter-RBS library and an activator-regulated promoter-RBS library, are constructed for systematic genetic circuit design using the identified kinetic strengths of their promoter-RBS components.According to the dynamic model of genetic transistors, a design methodology for genetic transistors via a Genetic Algorithm (GA)-based searching algorithm is developed to search for a set of promoter-RBS components and adequate concentrations of inducers to achieve the prescribed I/O characteristics of a genetic transistor. Furthermore, according to design specifications for different types of genetic transistors, a look-up table is built for genetic transistor design, from which we could easily select an adequate set of promoter-RBS components and adequate concentrations of external inducers for a specific genetic transistor. This systematic design method will reduce the time spent using trial-and-error methods in the experimental procedure for a genetic transistor with a desired I/O characteristic. We demonstrate the applicability of our design methodology to genetic transistors that have desirable linear amplification or switching by employing promoter-RBS library searching.

  9. Patient Specific Simulation for Planning of Cochlear Implantation Surgery

    DEFF Research Database (Denmark)

    Vera, Sergio; Perez, Frederic; Balust, Clara

    2014-01-01

    Cochlear implantation is a surgical procedure that can restore the hearing capabilities to patients with severe or complete functional loss. However, the level of restoration varies highly between subjects and depends on patient-specific factors. This paper presents a software application for pla...

  10. The patient's perspective of the feasibility of a patient-specific instrument in physiotherapy goal setting

    NARCIS (Netherlands)

    Albère Köke; Trudy van der Weijden; Anna Beurskens; Anita Stevens; Albine Moser

    2016-01-01

    Background: Patient participation in goal setting is important to deliver client-centered care. In daily practice, however, patient involvement in goal setting is not optimal. Patient-specific instruments, such as the Patient Specific Complaints (PSC) instrument, can support the goal-setting process

  11. Surgeon Design Interface for Patient-Specific Concentric Tube Robots.

    Science.gov (United States)

    Morimoto, Tania K; Greer, Joseph D; Hsieh, Michael H; Okamura, Allison M

    2016-06-01

    Concentric tube robots have potential for use in a wide variety of surgical procedures due to their small size, dexterity, and ability to move in highly curved paths. Unlike most existing clinical robots, the design of these robots can be developed and manufactured on a patient- and procedure-specific basis. The design of concentric tube robots typically requires significant computation and optimization, and it remains unclear how the surgeon should be involved. We propose to use a virtual reality-based design environment for surgeons to easily and intuitively visualize and design a set of concentric tube robots for a specific patient and procedure. In this paper, we describe a novel patient-specific design process in the context of the virtual reality interface. We also show a resulting concentric tube robot design, created by a pediatric urologist to access a kidney stone in a pediatric patient.

  12. A new robust markerless method for automatic image-to-patient registration in image-guided neurosurgery system.

    Science.gov (United States)

    Liu, Yinlong; Song, Zhijian; Wang, Manning

    2017-12-01

    Compared with the traditional point-based registration in the image-guided neurosurgery system, surface-based registration is preferable because it does not use fiducial markers before image scanning and does not require image acquisition dedicated for navigation purposes. However, most existing surface-based registration methods must include a manual step for coarse registration, which increases the registration time and elicits some inconvenience and uncertainty. A new automatic surface-based registration method is proposed, which applies 3D surface feature description and matching algorithm to obtain point correspondences for coarse registration and uses the iterative closest point (ICP) algorithm in the last step to obtain an image-to-patient registration. Both phantom and clinical data were used to execute automatic registrations and target registration error (TRE) calculated to verify the practicality and robustness of the proposed method. In phantom experiments, the registration accuracy was stable across different downsampling resolutions (18-26 mm) and different support radii (2-6 mm). In clinical experiments, the mean TREs of two patients by registering full head surfaces were 1.30 mm and 1.85 mm. This study introduced a new robust automatic surface-based registration method based on 3D feature matching. The method achieved sufficient registration accuracy with different real-world surface regions in phantom and clinical experiments.

  13. Patient-specific modeling of human cardiovascular system elements

    Science.gov (United States)

    Kossovich, Leonid Yu.; Kirillova, Irina V.; Golyadkina, Anastasiya A.; Polienko, Asel V.; Chelnokova, Natalia O.; Ivanov, Dmitriy V.; Murylev, Vladimir V.

    2016-03-01

    Object of study: The research is aimed at development of personalized medical treatment. Algorithm was developed for patient-specific surgical interventions of the cardiovascular system pathologies. Methods: Geometrical models of the biological objects and initial and boundary conditions were realized by medical diagnostic data of the specific patient. Mechanical and histomorphological parameters were obtained with the help mechanical experiments on universal testing machine. Computer modeling of the studied processes was conducted with the help of the finite element method. Results: Results of the numerical simulation allowed evaluating the physiological processes in the studied object in normal state, in presence of different pathologies and after different types of surgical procedures.

  14. Examining the robustness of the obesity paradox in maintenance hemodialysis patients: a marginal structural model analysis.

    Science.gov (United States)

    Doshi, Megha; Streja, Elani; Rhee, Connie M; Park, Jongha; Ravel, Vanessa A; Soohoo, Melissa; Moradi, Hamid; Lau, Wei Ling; Mehrotra, Rajnish; Kuttykrishnan, Sooraj; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar; Chen, Joline L T

    2016-08-01

    The inverse association between body mass index (BMI) and mortality observed in patients treated with maintenance hemodialysis (MHD), also known as the obesity paradox, may be a result of residual confounding. Marginal structural model (MSM) analysis, a technique that accounts for time-varying confounders, may be more appropriate to investigate this association. We hypothesize that after applying MSM, the inverse association between BMI and mortality in MHD patients is attenuated. We examined the associations between BMI and all-cause mortality among 123 624 adult MHD patients treated during 2001-6. We examined baseline and time-varying BMI using Cox proportional hazards models and MSM while considering baseline and time-varying covariates, including demographics, comorbidities and markers of malnutrition and inflammation. The patients included 45% women and 32% African Americans with a mean age of 61(SD 15) years. In all models, BMI showed a linear incremental inverse association with mortality. Compared with the reference (BMI 25 to models including MSM analyses that more completely account for time-varying confounders and biases. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  15. Dynamic prediction of the need for renal replacement therapy in intensive care unit patients using a simple and robust model.

    Science.gov (United States)

    Erdfelder, Felix; Grigutsch, Daniel; Hoeft, Andreas; Reider, Evgeny; Matot, Idit; Zenker, Sven

    2017-02-01

    We aimed at identifying a model that dynamically predicts future need for renal replacement therapy (RRT) in intensive care unit (ICU) patients and can easily be implemented for online monitoring at the bedside. 7290 interdisciplinary ICU admissions were investigated. Patients with parameters that predicts the need for RRT 72 h ahead. Based on the calibration sample, stepwise discriminant analysis selected the serum values of (1) current urea, (2) current lactate, (3) the ratio of current and admission serum creatinine, and (4) the mean urine output of the previous 24 h. In the validation datasets, the model reached areas under the receiver operating characteristic curve of 0.866 and 0.833 in patients with normal and elevated serum creatinine at admission, respectively. Moreover, the model's predictive value extended to at least 5 days prior to initiation of RRT and exceeded that of the RIFLE classification at all investigated prediction intervals. We identified a robust model that dynamically predicts the future need for RRT successfully. This tool may help improve timing of therapy and prognosis in ICU patients.

  16. Robust pro-inflammatory immune response is associated with serological cure in patients with syphilis: an observational study.

    Science.gov (United States)

    Pastuszczak, Maciej; Gozdzialska, Anna; Jakiela, Bogdan; Obtulowicz, Aleksander; Jaskiewicz, Jerzy; Wojas-Pelc, Anna

    2017-02-01

    Approximately 15% of adequately treated patients with early syphilis remain serofast. Pathogenesis and clinical significance of this phenomenon is unclear. The objective of this study was to determine whether there is any association between host immune response and treatment outcome (serofast state or proper serological response). Forty-four patients with secondary syphilis were enrolled to this study. Levels of pro-inflammatory cytokines such as interferon-γ, tumour necrosis factor-α and interleukin-6 were measured before treatment and 8 hours after injection of antibiotic. After 1 year, based on the serological response patients were stratified into two groups: (1) proper serological response (n=31) and (2) serofast state (n=9). The serological cure rate was 77.5% at 12 months after treatment. Patients with proper serological response had significantly higher levels of analysed cytokines (at baseline and 8 hours after treatment) compared with the serofast state group (p<0.05). We showed that robust host pro-inflammatory immune response to infection may be the predictive factor of serological cure. The treatment outcome may be also associated with the magnitude of immune reaction occurring during the treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Patient Specific Modeling of Head-Up Tilt

    DEFF Research Database (Denmark)

    Williams, Nakeya; Wright, Andrew; Mehlsen, Jesper

    2014-01-01

    Short term cardiovascular responses to head-up tilt (HUT) experiments involve complex cardiovascular regulation in order to maintain blood pressure at homeostatic levels. This manuscript presents a patient specific compartmental model developed to predict dynamic changes in heart rate and arterial...

  18. Robust estimation of mammographic breast density: a patient-based approach

    Science.gov (United States)

    Heese, Harald S.; Erhard, Klaus; Gooßen, Andre; Bulow, Thomas

    2012-02-01

    Breast density has become an established risk indicator for developing breast cancer. Current clinical practice reflects this by grading mammograms patient-wise as entirely fat, scattered fibroglandular, heterogeneously dense, or extremely dense based on visual perception. Existing (semi-) automated methods work on a per-image basis and mimic clinical practice by calculating an area fraction of fibroglandular tissue (mammographic percent density). We suggest a method that follows clinical practice more strictly by segmenting the fibroglandular tissue portion directly from the joint data of all four available mammographic views (cranio-caudal and medio-lateral oblique, left and right), and by subsequently calculating a consistently patient-based mammographic percent density estimate. In particular, each mammographic view is first processed separately to determine a region of interest (ROI) for segmentation into fibroglandular and adipose tissue. ROI determination includes breast outline detection via edge-based methods, peripheral tissue suppression via geometric breast height modeling, and - for medio-lateral oblique views only - pectoral muscle outline detection based on optimizing a three-parameter analytic curve with respect to local appearance. Intensity harmonization based on separately acquired calibration data is performed with respect to compression height and tube voltage to facilitate joint segmentation of available mammographic views. A Gaussian mixture model (GMM) on the joint histogram data with a posteriori calibration guided plausibility correction is finally employed for tissue separation. The proposed method was tested on patient data from 82 subjects. Results show excellent correlation (r = 0.86) to radiologist's grading with deviations ranging between -28%, (q = 0.025) and +16%, (q = 0.975).

  19. Language-specific dysgraphia in Korean stroke patients.

    Science.gov (United States)

    Yoon, Ji Hye; Suh, Mee Kyung; Kim, HyangHee

    2010-12-01

    We investigated how changes in the writing of 14 Korean stroke patients reflect the unique features of the Korean writing system. The Korean writing system, Han-geul, has both linguistic and visuospatial/constructive characteristics. In the visuospatial construction of a syllable, the component consonant(s) and vowel(s) must be arranged from top-to-bottom and/or left-to-right within the form of a square. This syllabic organization, unique to Korean writing, may distinguish dysgraphia in Korean patients from the disorder in other languages, and reveal the effects of stroke on visuospatial/constructive abilities. We compared 2 groups of patients affected by stroke, 1 group with left hemisphere (LH) lesions and the other with right hemisphere (RH) lesions. We instructed them to write from a dictation of 90 monosyllabic stimuli, each presented with a real word cue. Patients had to repeat a target syllable and a word cue, and then to write the target syllable only. Patients with LH and RH lesions produced qualitatively different error patterns. While the LH lesion group produced primarily linguistic errors, visuospatial/constructive errors predominated in the group with RH lesions. With regard to language-specific features, these Korean patients with RH lesions produced diverse visuospatial/constructive errors not commonly observed in dysgraphia of the English language. Language-specific writing errors by Korean stroke patients reflect the unique characteristics of Korean writing, which include the arrangement of strokes and graphemes within a square syllabic form by dimensional and spatial rules. These findings support the notion that the Korean writing system possesses a language-specific nature with both linguistic and visuospatial/constructive processes. Distinctive patterns of dysgraphia in the Korean language also suggest interactivity between linguistic and visuospatial/constructive levels of processing. This study is noteworthy for its systematic description of

  20. 3D-printed patient-specific applications in orthopedics

    Directory of Open Access Journals (Sweden)

    Wong KC

    2016-10-01

    Full Text Available Kwok Chuen Wong Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong Abstract: With advances in both medical imaging and computer programming, two-dimensional axial images can be processed into other reformatted views (sagittal and coronal and three-dimensional (3D virtual models that represent a patients’ own anatomy. This processed digital information can be analyzed in detail by orthopedic surgeons to perform patient-specific orthopedic procedures. The use of 3D printing is rising and has become more prevalent in medical applications over the last decade as surgeons and researchers are increasingly utilizing the technology’s flexibility in manufacturing objects. 3D printing is a type of manufacturing process in which materials such as plastic or metal are deposited in layers to create a 3D object from a digital model. This additive manufacturing method has the advantage of fabricating objects with complex freeform geometry, which is impossible using traditional subtractive manufacturing methods. Specifically in surgical applications, the 3D printing techniques can not only generate models that give a better understanding of the complex anatomy and pathology of the patients and aid in education and surgical training, but can also produce patient-specific surgical guides or even custom implants that are tailor-made to the surgical requirements. As the clinical workflow of the 3D printing technology continues to evolve, orthopedic surgeons should embrace the latest knowledge of the technology and incorporate it into their clinical practice for patient-specific orthopedic applications. This paper is written to help orthopedic surgeons stay up-to-date on the emerging 3D technology, starting from the acquisition of clinical imaging to 3D printing for patient-specific applications in orthopedics. It 1 presents the necessary steps to prepare the medical images that are

  1. Patient specific ankle-foot orthoses using rapid prototyping

    Directory of Open Access Journals (Sweden)

    Sivak Seth

    2011-01-01

    Full Text Available Abstract Background Prefabricated orthotic devices are currently designed to fit a range of patients and therefore they do not provide individualized comfort and function. Custom-fit orthoses are superior to prefabricated orthotic devices from both of the above-mentioned standpoints. However, creating a custom-fit orthosis is a laborious and time-intensive manual process performed by skilled orthotists. Besides, adjustments made to both prefabricated and custom-fit orthoses are carried out in a qualitative manner. So both comfort and function can potentially suffer considerably. A computerized technique for fabricating patient-specific orthotic devices has the potential to provide excellent comfort and allow for changes in the standard design to meet the specific needs of each patient. Methods In this paper, 3D laser scanning is combined with rapid prototyping to create patient-specific orthoses. A novel process was engineered to utilize patient-specific surface data of the patient anatomy as a digital input, manipulate the surface data to an optimal form using Computer Aided Design (CAD software, and then download the digital output from the CAD software to a rapid prototyping machine for fabrication. Results Two AFOs were rapidly prototyped to demonstrate the proposed process. Gait analysis data of a subject wearing the AFOs indicated that the rapid prototyped AFOs performed comparably to the prefabricated polypropylene design. Conclusions The rapidly prototyped orthoses fabricated in this study provided good fit of the subject's anatomy compared to a prefabricated AFO while delivering comparable function (i.e. mechanical effect on the biomechanics of gait. The rapid fabrication capability is of interest because it has potential for decreasing fabrication time and cost especially when a replacement of the orthosis is required.

  2. Patient-specific dose estimation for pediatric chest CT

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P. [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 and Department of Radiology, Duke Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Department of Radiology, Duke Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Physics, Duke University, Durham, North Carolina 27710 (United States); and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 and Department of Radiology, Duke Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 and Global Applied Science Laboratory, GE Healthcare, Waukesha, Wisconsin 53188 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 and Department of Radiology, Division of Pediatric Radiology, Duke University Medical Center, Durham North Carolina 27710 (United States)

    2008-12-15

    Current methods for organ and effective dose estimations in pediatric CT are largely patient generic. Physical phantoms and computer models have only been developed for standard/limited patient sizes at discrete ages (e.g., 0, 1, 5, 10, 15 years old) and do not reflect the variability of patient anatomy and body habitus within the same size/age group. In this investigation, full-body computer models of seven pediatric patients in the same size/protocol group (weight: 11.9-18.2 kg) were created based on the patients' actual multi-detector array CT (MDCT) data. Organs and structures in the scan coverage were individually segmented. Other organs and structures were created by morphing existing adult models (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. Organ and effective dose of these patients from a chest MDCT scan protocol (64 slice LightSpeed VCT scanner, 120 kVp, 70 or 75 mA, 0.4 s gantry rotation period, pitch of 1.375, 20 mm beam collimation, and small body scan field-of-view) was calculated using a Monte Carlo program previously developed and validated to simulate radiation transport in the same CT system. The seven patients had normalized effective dose of 3.7-5.3 mSv/100 mAs (coefficient of variation: 10.8%). Normalized lung dose and heart dose were 10.4-12.6 mGy/100 mAs and 11.2-13.3 mGy/100 mAs, respectively. Organ dose variations across the patients were generally small for large organs in the scan coverage (<7%), but large for small organs in the scan coverage (9%-18%) and for partially or indirectly exposed organs (11%-77%). Normalized effective dose correlated weakly with body weight (correlation coefficient: r=-0.80). Normalized lung dose and heart dose correlated strongly with mid-chest equivalent diameter (lung: r=-0.99, heart: r=-0.93); these strong correlation relationships can be used to estimate patient-specific organ

  3. Sex-specific differences in patients with temporomandibular disorders.

    Science.gov (United States)

    Schmid-Schwap, Martina; Bristela, Margit; Kundi, Michael; Piehslinger, Eva

    2013-01-01

    To explore potential differences in characteristics of patients that might account for sex-specific differences in temporomandibular disorders (TMD). A total of 502 patients presenting with TMD during 2000 to 2002 at the Outpatient Unit for Functional Disorders of the Medical University of Vienna underwent detailed evaluation of their medical history and assessment of clinical findings. The data obtained were assessed for sex-specific differences by analysis of variance and multiple regression. Overall, 404 females (mean age ± SD: 40 ± 16 years; range 12 to 96 years) and 98 males (mean age 41 ± 16 years; range 16 to 78 years) were included. Their rating of their pain on a visual analog scale (VAS) showed a significantly higher pain intensity for females than for males (P = .004). Clinical assessment showed a significantly lower degree of mouth opening for females than for males (P TMJ) and for the bite class of the patients, bite anomalies were significantly more frequent in male patients (P = .03). Palpation of masticatory muscles and the TMJ revealed significantly higher tenderness on palpation in female as compared to male patients (P = .001). Grouping by clicking, crepitation, and bruxism also showed greater pain (VAS) and more tenderness on palpation in females versus males. Females also showed peaks of prevalence of TMD in the age group below 25 years and in the group 55 to 60 years, whereas males had a more even age distribution. No external factors, such as exposure to stress, were found that moderated the sex difference. Female TMD patients showed greater pain and muscle tenderness on palpation as compared to male TMD patients. They also showed a different age distribution of prevalence of TMD. These results were independent of subjective symptoms, clinical findings, and external factors.

  4. Feasibility of patient specific aortic blood flow CFD simulation.

    Science.gov (United States)

    Svensson, Johan; Gårdhagen, Roland; Heiberg, Einar; Ebbers, Tino; Loyd, Dan; Länne, Toste; Karlsson, Matts

    2006-01-01

    Patient specific modelling of the blood flow through the human aorta is performed using computational fluid dynamics (CFD) and magnetic resonance imaging (MRI). Velocity patterns are compared between computer simulations and measurements. The workflow includes several steps: MRI measurement to obtain both geometry and velocity, an automatic levelset segmentation followed by meshing of the geometrical model and CFD setup to perform the simulations follwed by the actual simulations. The computational results agree well with the measured data.

  5. Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1.

    Science.gov (United States)

    Dame, Keri; Cincotta, Steven; Lang, Alex H; Sanghrajka, Reeti M; Zhang, Liye; Choi, Jinyoung; Kwok, Letty; Wilson, Talitha; Kańduła, Maciej M; Monti, Stefano; Hollenberg, Anthony N; Mehta, Pankaj; Kotton, Darrell N; Ikonomou, Laertis

    2017-02-14

    The clinical importance of anterior foregut endoderm (AFE) derivatives, such as thyrocytes, has led to intense research efforts for their derivation through directed differentiation of pluripotent stem cells (PSCs). Here, we identify transient overexpression of the transcription factor (TF) NKX2-1 as a powerful inductive signal for the robust derivation of thyrocyte-like cells from mouse PSC-derived AFE. This effect is highly developmental stage specific and dependent on FOXA2 expression levels and precise modulation of BMP and FGF signaling. The majority of the resulting cells express thyroid TFs (Nkx2-1, Pax8, Foxe1, Hhex) and thyroid hormone synthesis-related genes (Tg, Tpo, Nis, Iyd) at levels similar to adult mouse thyroid and give rise to functional follicle-like epithelial structures in Matrigel culture. Our findings demonstrate that NKX2-1 overexpression converts AFE to thyroid epithelium in a developmental time-sensitive manner and suggest a general methodology for manipulation of cell-fate decisions of developmental intermediates. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Patient-specific modelling of whole heart anatomy, dynamics and haemodynamics from four-dimensional cardiac CT images.

    Science.gov (United States)

    Mihalef, Viorel; Ionasec, Razvan Ioan; Sharma, Puneet; Georgescu, Bogdan; Voigt, Ingmar; Suehling, Michael; Comaniciu, Dorin

    2011-06-06

    There is a growing need for patient-specific and holistic modelling of the heart to support comprehensive disease assessment and intervention planning as well as prediction of therapeutic outcomes. We propose a patient-specific model of the whole human heart, which integrates morphology, dynamics and haemodynamic parameters at the organ level. The modelled cardiac structures are robustly estimated from four-dimensional cardiac computed tomography (CT), including all four chambers and valves as well as the ascending aorta and pulmonary artery. The patient-specific geometry serves as an input to a three-dimensional Navier-Stokes solver that derives realistic haemodynamics, constrained by the local anatomy, along the entire heart cycle. We evaluated our framework with various heart pathologies and the results correlate with relevant literature reports.

  7. The FTD/ALS-associated RNA-binding protein TDP-43 regulates the robustness of neuronal specification through microRNA-9a in Drosophila.

    Science.gov (United States)

    Li, Zhaodong; Lu, Yubing; Xu, Xia-Lian; Gao, Fen-Biao

    2013-01-15

    TDP-43 is an evolutionarily conserved RNA-binding protein currently under intense investigation for its involvement in the molecular pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 is normally localized in the nucleus, but translocated to the cytoplasm in diseased neurons. The endogenous functions of TDP-43 in the nervous system remain poorly understood. Here, we show that the loss of Drosophila TDP-43 (dTDP-43) results in an increased production of sensory bristles and sensory organ precursor (SOP) cells on the notum of some but not all flies. The location of ectopic SOPs varies among mutant flies. The penetrance of this novel phenotype is dependent on the gender and sensitive to environmental influences. A similar SOP phenotype was also observed on the wing and in the embryos. Overexpression of dTDP-43 causes both loss and ectopic production of SOPs. Ectopic expression of ALS-associated mutant human TDP-43 (hTDP-43(M337V) and hTDP-43(Q331K)) produces a less severe SOP phenotype than hTDP-43(WT), indicating a partial loss of function of mutant hTDP-43. In dTDP-43 mutants, miR-9a expression is significantly reduced. Genetic interaction studies further support the notion that dTDP-43 acts through miR-9a to control the precision of SOP specification. These findings reveal a novel role for endogenous TDP-43 in neuronal specification and suggest that the FTD/ALS-associated RNA-binding protein TDP-43 functions to ensure the robustness of genetic control programs.

  8. Physically consistent data assimilation method based on feedback control for patient-specific blood flow analysis.

    Science.gov (United States)

    Ii, Satoshi; Adib, Mohd Azrul Hisham Mohd; Watanabe, Yoshiyuki; Wada, Shigeo

    2018-01-01

    This paper presents a novel data assimilation method for patient-specific blood flow analysis based on feedback control theory called the physically consistent feedback control-based data assimilation (PFC-DA) method. In the PFC-DA method, the signal, which is the residual error term of the velocity when comparing the numerical and reference measurement data, is cast as a source term in a Poisson equation for the scalar potential field that induces flow in a closed system. The pressure values at the inlet and outlet boundaries are recursively calculated by this scalar potential field. Hence, the flow field is physically consistent because it is driven by the calculated inlet and outlet pressures, without any artificial body forces. As compared with existing variational approaches, although this PFC-DA method does not guarantee the optimal solution, only one additional Poisson equation for the scalar potential field is required, providing a remarkable improvement for such a small additional computational cost at every iteration. Through numerical examples for 2D and 3D exact flow fields, with both noise-free and noisy reference data as well as a blood flow analysis on a cerebral aneurysm using actual patient data, the robustness and accuracy of this approach is shown. Moreover, the feasibility of a patient-specific practical blood flow analysis is demonstrated. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Patient-specific academic detailing for smoking cessation: feasibility study.

    Science.gov (United States)

    Jin, Margaret; Gagnon, Antony; Levine, Mitchell; Thabane, Lehana; Rodriguez, Christine; Dolovich, Lisa

    2014-01-01

    To describe and to determine the feasibility of a patient-specific academic detailing (PAD) smoking cessation (SC) program in a primary care setting. Descriptive cohort feasibility study. Hamilton, Ont. Pharmacists, physicians, nurse practitioners, and their patients. Integrated pharmacists received basic academic detailing training and education on SC and then delivered PAD to prescribers using structured verbal education and written materials. Data were collected using structured forms. Five main feasibility criteria were generated based on Canadian academic detailing programs: PAD coordinator time to train pharmacists less than 40 hours; median time of SC education per pharmacist less than 20 hours; median time per PAD session less than 60 minutes for initial visit; percentage of prescribers receiving PAD within 3 months greater than 50%; and number of new SC referrals to pharmacists at 6 months more than 10 patients per 1.0 full-time equivalent (FTE) pharmacist (total of approximately 30 patients). Eight pharmacists (5.8 FTE) received basic academic detailing training and education on SC PAD. Forty-eight physicians and 9 nurse practitioners consented to participate in the study. The mean PAD coordinator training time was 29.1 hours. The median time for SC education was 3.1 hours. The median times for PAD sessions were 15 and 25 minutes for an initial visit and follow-up visit, respectively. The numbers of prescribers who had received PAD at 3 and 6 months were 50 of 64 (78.1%) and 57 of 64 (89.1%), respectively. The numbers of new SC referrals at 3 and 6 months were 11 patients per FTE pharmacist (total of 66 patients) and 34 patients per FTE pharmacist (total of 200 patients), respectively. This study met the predetermined feasibility criteria with respect to the management, resources, process, and scientific components. Further study is warranted to determine whether PAD is more effective than conventional academic detailing.

  10. Patient-Specific Bacteroides Genome Variants in Pouchitis

    Directory of Open Access Journals (Sweden)

    Joseph H. Vineis

    2016-11-01

    Full Text Available A 2-year longitudinal microbiome study of 22 patients who underwent colectomy with an ileal pouch anal anastomosis detected significant increases in distinct populations of Bacteroides during 9 of 11 patient visits that coincided with inflammation (pouchitis. Oligotyping and metagenomic short-read annotation identified Bacteroides populations that occurred in early samples, bloomed during inflammation, and reappeared after antibiotic treatment. Targeted cultivation of Bacteroides isolates from the same individual at multiple time points and from several patients detected subtle genomic changes, including the identification of rapidly evolving genomic elements that differentiate isogenic strains of Bacteroides fragilis from the mucosa versus lumen. Each patient harbored Bacteroides spp. that are closely related to commonly occurring clinical isolates, including Bacteroides ovatus, B. thetaiotaomicron, B. vulgatus, and B. fragilis, which contained unique loci in different patients for synthesis of capsular polysaccharides. The presence of unique Bacteroides capsular polysaccharide loci within different hosts and between the lumen and mucosa may represent adaptations to stimulate, suppress, and evade host-specific immune responses at different microsites of the ileal pouch.

  11. Towards patient specific thermal modelling of the prostate

    Science.gov (United States)

    Van den Berg, Cornelis A. T.; Van de Kamer, Jeroen B.; DeLeeuw, Astrid A. C.; Jeukens, Cécile R. L. P. N.; Raaymakers, Bas W.; van Vulpen, Marco; Lagendijk, Jan J. W.

    2006-02-01

    The application of thermal modelling for hyperthermia and thermal ablation is severely hampered by lack of information about perfusion and vasculature. However, recently, with the advent of sophisticated angiography and dynamic contrast enhanced (DCE) imaging techniques, it has become possible to image small vessels and blood perfusion bringing the ultimate goal of patient specific thermal modelling closer within reach. In this study dynamic contrast enhanced multi-slice CT imaging techniques are employed to investigate the feasibility of this concept for regional hyperthermia treatment of the prostate. The results are retrospectively compared with clinical thermometry data of a patient group from an earlier trial. Furthermore, the role of the prostate vasculature in the establishment of the prostate temperature distribution is studied. Quantitative 3D perfusion maps of the prostate were constructed for five patients using a distributed-parameter tracer kinetics model to analyse dynamic CT data. CT angiography was applied to construct a discrete vessel model of the pelvis. Additionally, a discrete vessel model of the prostate vasculature was constructed of a prostate taken from a human corpse. Three thermal modelling schemes with increasing inclusion of the patient specific physiological information were used to simulate the temperature distribution of the prostate during regional hyperthermia. Prostate perfusion was found to be heterogeneous and T3 prostate carcinomas are often characterized by a strongly elevated tumour perfusion (up to 70-80 ml 100 g-1 min-1). This elevated tumour perfusion leads to 1-2 °C lower tumour temperatures than thermal simulations based on a homogeneous prostate perfusion. Furthermore, the comparison has shown that the simulations with the measured perfusion maps result in consistently lower prostate temperatures than clinically achieved. The simulations with the discrete vessel model indicate that significant pre-heating takes place

  12. Towards patient specific thermal modelling of the prostate.

    Science.gov (United States)

    Van den Berg, Cornelis A T; Van de Kamer, Jeroen B; De Leeuw, Astrid A C; Jeukens, Cécile R L P N; Raaymakers, Bas W; van Vulpen, Marco; Lagendijk, Jan J W

    2006-02-21

    The application of thermal modelling for hyperthermia and thermal ablation is severely hampered by lack of information about perfusion and vasculature. However, recently, with the advent of sophisticated angiography and dynamic contrast enhanced (DCE) imaging techniques, it has become possible to image small vessels and blood perfusion bringing the ultimate goal of patient specific thermal modelling closer within reach. In this study dynamic contrast enhanced multi-slice CT imaging techniques are employed to investigate the feasibility of this concept for regional hyperthermia treatment of the prostate. The results are retrospectively compared with clinical thermometry data of a patient group from an earlier trial. Furthermore, the role of the prostate vasculature in the establishment of the prostate temperature distribution is studied. Quantitative 3D perfusion maps of the prostate were constructed for five patients using a distributed-parameter tracer kinetics model to analyse dynamic CT data. CT angiography was applied to construct a discrete vessel model of the pelvis. Additionally, a discrete vessel model of the prostate vasculature was constructed of a prostate taken from a human corpse. Three thermal modelling schemes with increasing inclusion of the patient specific physiological information were used to simulate the temperature distribution of the prostate during regional hyperthermia. Prostate perfusion was found to be heterogeneous and T3 prostate carcinomas are often characterized by a strongly elevated tumour perfusion (up to 70-80 ml 100 g(-1) min(-1)). This elevated tumour perfusion leads to 1-2 degrees C lower tumour temperatures than thermal simulations based on a homogeneous prostate perfusion. Furthermore, the comparison has shown that the simulations with the measured perfusion maps result in consistently lower prostate temperatures than clinically achieved. The simulations with the discrete vessel model indicate that significant pre

  13. On the use of biomathematical models in patient-specific IMRT dose QA

    Energy Technology Data Exchange (ETDEWEB)

    Zhen Heming [UT Southwestern Medical Center, Dallas, Texas 75390 (United States); Nelms, Benjamin E. [Canis Lupus LLC, Merrimac, Wisconsin 53561 (United States); Tome, Wolfgang A. [Department of Radiation Oncology, Division of Medical Physics, Montefiore Medical Center and Institute of Onco-Physics, Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

    2013-07-15

    Purpose: To investigate the use of biomathematical models such as tumor control probability (TCP) and normal tissue complication probability (NTCP) as new quality assurance (QA) metrics.Methods: Five different types of error (MLC transmission, MLC penumbra, MLC tongue and groove, machine output, and MLC position) were intentionally induced to 40 clinical intensity modulated radiation therapy (IMRT) patient plans (20 H and N cases and 20 prostate cases) to simulate both treatment planning system errors and machine delivery errors in the IMRT QA process. The changes in TCP and NTCP for eight different anatomic structures (H and N: CTV, GTV, both parotids, spinal cord, larynx; prostate: CTV, rectal wall) were calculated as the new QA metrics to quantify the clinical impact on patients. The correlation between the change in TCP/NTCP and the change in selected DVH values was also evaluated. The relation between TCP/NTCP change and the characteristics of the TCP/NTCP curves is discussed.Results:{Delta}TCP and {Delta}NTCP were summarized for each type of induced error and each structure. The changes/degradations in TCP and NTCP caused by the errors vary widely depending on dose patterns unique to each plan, and are good indicators of each plan's 'robustness' to that type of error.Conclusions: In this in silico QA study the authors have demonstrated the possibility of using biomathematical models not only as patient-specific QA metrics but also as objective indicators that quantify, pretreatment, a plan's robustness with respect to possible error types.

  14. Tract specific analysis in patients with sickle cell disease

    Science.gov (United States)

    Chai, Yaqiong; Coloigner, Julie; Qu, Xiaoping; Choi, Soyoung; Bush, Adam; Borzage, Matt; Vu, Chau; Lepore, Natasha; Wood, John

    2015-12-01

    Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.

  15. Patient-specific modeling of the Assisted Bidirectional Glenn (ABG)

    Science.gov (United States)

    Shang, Jessica; Esmaily-Moghadam, Mahdi; Figliola, Richard; Hsia, Tain-Yen; Marsden, Alison

    2016-11-01

    The Assisted Bidirectional Glenn (ABG) is proposed as an early-stage palliative procedure for single ventricle neonates. The ABG augments the pulmonary flow of the Bidirectional Glenn (BDG) with a secondary high-velocity flow through a nozzle-like shunt between the innominate artery and the superior vena cava (SVC). The ABG would provide a superior cavopulmonary connection than the systemic-pulmonary shunt that is typically employed as a stage-I procedure (e.g., a modified Blalock-Taussig shunt) and would address the low pulmonary flow associated with the BDG. Following simulations in vitro and in silico that show the ABG successfully increased pulmonary flows in idealized models, we implemented the ABG in several patient-specific models coupled to a lumped parameter network tuned to clinical values for each patient. The ABG performed similarly across different patients; compared to the BDG, the pulmonary flow increased 20% with a similar increase in the SVC pressure. The performance of the ABG was the most sensitive to nozzle outlet area, compared to nozzle inlet area and location of the shunt anastomosis. The study verified that the ABG benefits a range of patients and identified key parameters for further optimization of the ABG. Stanford Cardiovascular Institute NIH T32.

  16. [TECHNICAL CHARACTERISTICS OF SPECIFIC FOOD PRODUCTS FOR PATIENTS WITH DYSPHAGIA].

    Science.gov (United States)

    Calleja Fernández, Alicia; Pintor de la Maza, Begoña; Vidal Casariego, Alfonso; Villar Taibo, Rocío; Urioste Fondo, Ana; Cano Rodríguez, Isidoro; Ballesteros Pomar, María D

    2015-10-01

    Dysphagia is a common problem among elderly and also in some pathological conditions such as neurodegenerative diseases or tumors. Making an adequate diet for this disease may present some difficulties. The aim of this document is to make a detailed technical report about the characteristics of the products that are available in Spain to hydrate and to feed patients with dysphagia. Food and pharmaceutical industries have developed a range of products designed to ensure homogeneous texture and a suitable viscosity to guaranty an adequate hydration. An adequate nutritional status is also achieved with these products for patients with dysphagia, without compromising their safety. The ingredients used to achieve a suitable viscosity are different types of starches, gums and other substances. It has been developed thickeners and gellified water for hydratation, and in case of food there are purees (dehydrated, lyophilized, pasteurized and sterilized), fruit purees, fruit pudding, and dehydrated cereal. Patients who do not meet their nutritional needs have also oral supplements with different viscosities. The industry offers extensive information about the technical characteristics of the products, except for viscosity. It would be recommended for the manufacturers to include in detail the technical specifications of the used methodology and the measurement and the results obtained in the analysis of viscosity that can be consulted by professionals of the Clinical Nutrition and Dietetics Units who treat these patients. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  17. Patient-Specific Dosimetry and Radiobiological Modeling of Targeted Radionuclide Therapy Grant - final report

    Energy Technology Data Exchange (ETDEWEB)

    George Sgouros, Ph.D.

    2007-03-20

    The broad, long-term objectives of this application are to 1. develop easily implementable tools for radionuclide dosimetry that can be used to predict normal organ toxicity and tumor response in targeted radionuclide therapy; and 2. to apply these tools to the analysis of clinical trial data in order to demonstrate dose-response relationships for radionuclide therapy treatment planning. The work is founded on the hypothesis that robust dose-response relationships have not been observed in targeted radionuclide therapy studies because currently available internal dosimetry methodologies are inadequate, failing to adequately account for individual variations in patient anatomy, radionuclide activity distribution/kinetics, absorbed dose-distribution, and absorbed dose-rate. To reduce development time the previously available software package, 3D-ID, one of the first dosimetry software packages to incorporate 3-D radionuclide distribution with individual patient anatomy; and the first to be applied for the comprehensive analysis of patient data, will be used as a platform to build the functionality listed above. The following specific aims are proposed to satisfy the long-term objectives stated above: 1. develop a comprehensive and validated methodology for converting one or more SPECT images of the radionuclide distribution to a 3-D representation of the cumulated activity distribution; 2. account for differences in tissue density and atomic number by incorporating an easily implementable Monte Carlo methodology for the 3-D dosimetry calculations; 3. incorporate the biologically equivalent dose (BED) and equivalent uniform dose (EUD) models to convert the spatial distribution of absorbed dose and dose-rate into equivalent single values that account for differences in dose uniformity and rate and that may be correlated with tumor response and normal organ toxicity; 4. test the hypothesis stated above by applying the resulting package to patient trials of targeted

  18. Designing patient-specific 3D printed craniofacial implants using a novel topology optimization method.

    Science.gov (United States)

    Sutradhar, Alok; Park, Jaejong; Carrau, Diana; Nguyen, Tam H; Miller, Michael J; Paulino, Glaucio H

    2016-07-01

    Large craniofacial defects require efficient bone replacements which should not only provide good aesthetics but also possess stable structural function. The proposed work uses a novel multiresolution topology optimization method to achieve the task. Using a compliance minimization objective, patient-specific bone replacement shapes can be designed for different clinical cases that ensure revival of efficient load transfer mechanisms in the mid-face. In this work, four clinical cases are introduced and their respective patient-specific designs are obtained using the proposed method. The optimized designs are then virtually inserted into the defect to visually inspect the viability of the design . Further, once the design is verified by the reconstructive surgeon, prototypes are fabricated using a 3D printer for validation. The robustness of the designs are mechanically tested by subjecting them to a physiological loading condition which mimics the masticatory activity. The full-field strain result through 3D image correlation and the finite element analysis implies that the solution can survive the maximum mastication of 120 lb. Also, the designs have the potential to restore the buttress system and provide the structural integrity. Using the topology optimization framework in designing the bone replacement shapes would deliver surgeons new alternatives for rather complicated mid-face reconstruction.

  19. Patient-Specific Bacteroides Genome Variants in Pouchitis.

    Science.gov (United States)

    Vineis, Joseph H; Ringus, Daina L; Morrison, Hilary G; Delmont, Tom O; Dalal, Sushila; Raffals, Laura H; Antonopoulos, Dionysios A; Rubin, David T; Eren, A Murat; Chang, Eugene B; Sogin, Mitchell L

    2016-11-15

    A 2-year longitudinal microbiome study of 22 patients who underwent colectomy with an ileal pouch anal anastomosis detected significant increases in distinct populations of Bacteroides during 9 of 11 patient visits that coincided with inflammation (pouchitis). Oligotyping and metagenomic short-read annotation identified Bacteroides populations that occurred in early samples, bloomed during inflammation, and reappeared after antibiotic treatment. Targeted cultivation of Bacteroides isolates from the same individual at multiple time points and from several patients detected subtle genomic changes, including the identification of rapidly evolving genomic elements that differentiate isogenic strains of Bacteroides fragilis from the mucosa versus lumen. Each patient harbored Bacteroides spp. that are closely related to commonly occurring clinical isolates, including Bacteroides ovatus, B. thetaiotaomicron, B. vulgatus, and B. fragilis, which contained unique loci in different patients for synthesis of capsular polysaccharides. The presence of unique Bacteroides capsular polysaccharide loci within different hosts and between the lumen and mucosa may represent adaptations to stimulate, suppress, and evade host-specific immune responses at different microsites of the ileal pouch. This longitudinal study provides an opportunity to describe shifts in the microbiomes of individual patients who suffer from ulcerative colitis (UC) prior to and following inflammation. Pouchitis serves as a model for UC with a predictable incidence of disease onset and enables prospective longitudinal investigations of UC etiology prior to inflammation. Because of insufficient criteria for predicting which patients will develop UC or pouchitis, the interpretation of cross-sectional study designs suffers from lack of information about the microbiome structure and host gene expression patterns that directly correlate with the onset of disease. Our unique longitudinal study design allows each

  20. Patient-Specific Variations in Biomarkers across Gingivitis and Periodontitis.

    Science.gov (United States)

    Nagarajan, Radhakrishnan; Miller, Craig S; Dawson, Dolph; Al-Sabbagh, Mohanad; Ebersole, Jeffrey L

    2015-01-01

    This study investigates the use of saliva, as an emerging diagnostic fluid in conjunction with classification techniques to discern biological heterogeneity in clinically labelled gingivitis and periodontitis subjects (80 subjects; 40/group) A battery of classification techniques were investigated as traditional single classifier systems as well as within a novel selective voting ensemble classification approach (SVA) framework. Unlike traditional single classifiers, SVA is shown to reveal patient-specific variations within disease groups, which may be important for identifying proclivity to disease progression or disease stability. Salivary expression profiles of IL-1ß, IL-6, MMP-8, and MIP-1α from 80 patients were analyzed using four classification algorithms (LDA: Linear Discriminant Analysis [LDA], Quadratic Discriminant Analysis [QDA], Naïve Bayes Classifier [NBC] and Support Vector Machines [SVM]) as traditional single classifiers and within the SVA framework (SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM). Our findings demonstrate that performance measures (sensitivity, specificity and accuracy) of traditional classification as single classifier were comparable to that of the SVA counterparts using clinical labels of the samples as ground truth. However, unlike traditional single classifier approaches, the normalized ensemble vote-counts from SVA revealed varying proclivity of the subjects for each of the disease groups. More importantly, the SVA identified a subset of gingivitis and periodontitis samples that demonstrated a biological proclivity commensurate with the other clinical group. This subset was confirmed across SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM. Heatmap visualization of their ensemble sets revealed lack of consensus between these subsets and the rest of the samples within the respective disease groups indicating the unique nature of the patients in these subsets. While the source of variation is not known, the results presented clearly elucidate the

  1. Patient-Specific Variations in Biomarkers across Gingivitis and Periodontitis.

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Nagarajan

    Full Text Available This study investigates the use of saliva, as an emerging diagnostic fluid in conjunction with classification techniques to discern biological heterogeneity in clinically labelled gingivitis and periodontitis subjects (80 subjects; 40/group A battery of classification techniques were investigated as traditional single classifier systems as well as within a novel selective voting ensemble classification approach (SVA framework. Unlike traditional single classifiers, SVA is shown to reveal patient-specific variations within disease groups, which may be important for identifying proclivity to disease progression or disease stability. Salivary expression profiles of IL-1ß, IL-6, MMP-8, and MIP-1α from 80 patients were analyzed using four classification algorithms (LDA: Linear Discriminant Analysis [LDA], Quadratic Discriminant Analysis [QDA], Naïve Bayes Classifier [NBC] and Support Vector Machines [SVM] as traditional single classifiers and within the SVA framework (SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM. Our findings demonstrate that performance measures (sensitivity, specificity and accuracy of traditional classification as single classifier were comparable to that of the SVA counterparts using clinical labels of the samples as ground truth. However, unlike traditional single classifier approaches, the normalized ensemble vote-counts from SVA revealed varying proclivity of the subjects for each of the disease groups. More importantly, the SVA identified a subset of gingivitis and periodontitis samples that demonstrated a biological proclivity commensurate with the other clinical group. This subset was confirmed across SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM. Heatmap visualization of their ensemble sets revealed lack of consensus between these subsets and the rest of the samples within the respective disease groups indicating the unique nature of the patients in these subsets. While the source of variation is not known, the results presented clearly

  2. Patient-Specific Variations in Biomarkers across Gingivitis and Periodontitis

    Science.gov (United States)

    Nagarajan, Radhakrishnan; Miller, Craig S.; Dawson, Dolph; Al-Sabbagh, Mohanad; Ebersole, Jeffrey L.

    2015-01-01

    This study investigates the use of saliva, as an emerging diagnostic fluid in conjunction with classification techniques to discern biological heterogeneity in clinically labelled gingivitis and periodontitis subjects (80 subjects; 40/group) A battery of classification techniques were investigated as traditional single classifier systems as well as within a novel selective voting ensemble classification approach (SVA) framework. Unlike traditional single classifiers, SVA is shown to reveal patient-specific variations within disease groups, which may be important for identifying proclivity to disease progression or disease stability. Salivary expression profiles of IL-1ß, IL-6, MMP-8, and MIP-1α from 80 patients were analyzed using four classification algorithms (LDA: Linear Discriminant Analysis [LDA], Quadratic Discriminant Analysis [QDA], Naïve Bayes Classifier [NBC] and Support Vector Machines [SVM]) as traditional single classifiers and within the SVA framework (SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM). Our findings demonstrate that performance measures (sensitivity, specificity and accuracy) of traditional classification as single classifier were comparable to that of the SVA counterparts using clinical labels of the samples as ground truth. However, unlike traditional single classifier approaches, the normalized ensemble vote-counts from SVA revealed varying proclivity of the subjects for each of the disease groups. More importantly, the SVA identified a subset of gingivitis and periodontitis samples that demonstrated a biological proclivity commensurate with the other clinical group. This subset was confirmed across SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM. Heatmap visualization of their ensemble sets revealed lack of consensus between these subsets and the rest of the samples within the respective disease groups indicating the unique nature of the patients in these subsets. While the source of variation is not known, the results presented clearly elucidate the

  3. Specific hyposensitization in patients allergic to Parietaria officinalis pollen allergen.

    Science.gov (United States)

    Cvitanović, S; Zekan, L; Capkun, V; Marusić, M

    1994-01-01

    The effects of specific hyposensitization in 40 patients with Parietaria officinalis-sensitive seasonal rhinoconjunctivitis were studied during three years of treatment. The patients were treated with subcutaneous injections of a new, partially purified, characterized and standardized pollen extract of P. officinalis allergen (alum-absorbed depot preparation). Treatment was applied from November to mid March and it was clinically assessed during the plant flowering season (mid March to end of June). Laboratory tests were performed yearly when beginning and ending treatment. Serum concentrations of P. officinalis pollen allergen-specific IgE antibodies decreased (first year: from 18.7 +/- 7.7 to 17.9 +/- 7.6 PRU/ml; second year: from 16.3 +/- 7.1 to 14.1 +/- 6.6 PRU/ml; third year: from 12.3 +/- 5.6 to 10.9 +/- 5.6 PRU/ml) and those of specific IgG increased (first year: from 15.3 +/- 13.2 to 21.7 +/- 14.0%; second year: from 28.5 +/- 13.0 to 36.3 +/- 15.9%; third year: from 29.9 +/- 14.1 to 38.9 +/- 16.8%) during the treatment. Histamine release from peripheral blood leukocytes challenged in vitro with the allergen decreased during the three years of the treatment (first year: from 42.3 +/- 13.0 to 33.1 +/- 10.8%; second year: from 31.9 +/- 11.9 to 19.1 +/- 8.5%; third year: from 19.4 +/- 4.6 to 14.3 +/- 4.6%), whereas the size of skin test reaction and the percentage of eosinophils among white blood cells remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Patient-Specific Contact Stress Does Not Predict Polyethylene Wear Rate in a Specific Pressfit Cup.

    Science.gov (United States)

    Matziolis, Georg; Krakow, Linda; Layher, Frank; Sander, Klaus; Bossert, Joerg; Brodt, Steffen

    2017-12-01

    The most common reason for revision total hip arthroplasty remains polyethylene wear. Development dysplasia of the hip and revision situations requires a conscious compromise of implant position. The surgeon should know about the consequence on wear via a possible change in hip contact force. The objective of this study is to investigate whether annual wear is dependent on hip contact force. Forty-five inserts (DuraLoc, DePuy) that were explanted in our department were included. Three-dimensional gravimetric determination of the wear was performed by fluid displacement. Then, the hip contact force was determined using radiographs according to the Blumentritt model. No correlation was found between patient-specific factors and the annual wear. The hip contact force estimated by the Blumentritt model also showed no correlation between hip contact force and annual wear. Two single model parameters correlated significantly with wear: VRECAB as a ratio of the lever length of the spinocrural and the pelvitrochanteric muscles and the angle Alpha as a measure of the position of the center of rotation in relation to the greater trochanter. The greater the ratio spinocrural/pelvitrochanteric lever arm (R = 0.408, P = .005) and the greater the Alpha angle (more valgus the femoral neck) (R = 0.377, P = .011) were, the greater was the wear. These results lead to the conclusion that neither patient-specific factors nor the estimated hip contact force have a major influence on annual wear in the case of DuraLoc cups. Only a coxa valga and a small femoral offset contribute in a limited amount to an increase in wear. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Respiratory gated radiotherapy-pretreatment patient specific quality assurance

    Directory of Open Access Journals (Sweden)

    Rajesh Thiyagarajan

    2016-01-01

    Full Text Available Organ motions during inter-fraction and intra-fraction radiotherapy introduce errors in dose delivery, irradiating excess of normal tissue, and missing target volume. Lung and heart involuntary motions cause above inaccuracies and gated dose delivery try to overcome above effects. Present work attempts a novel method to verify dynamic dose delivery using a four-dimensional (4D phantom. Three patients with mobile target are coached to maintain regular and reproducible breathing pattern. Appropriate intensity projection image set generated from 4D-computed tomography (4D-CT is used for target delineation. Intensity modulated radiotherapy plans were generated on selected phase using CT simulator (Siemens AG, Germany in conjunction with "Real-time position management" (Varian, USA to acquire 4D-CT images. Verification plans were generated for both ion chamber and Gafchromic (EBT film image sets. Gated verification plans were delivered on the phantom moving with patient respiratory pattern. We developed a MATLAB-based software to generate maximum intensity projection, minimum intensity projections, and average intensity projections, also a program to convert patient breathing pattern to phantom compatible format. Dynamic thorax quality assurance (QA phantom (Computerized Imaging Reference Systems type is used to perform the patient specific QA, which holds an ion chamber and film to measure delivered radiation intensity. Exposed EBT films are analyzed and compared with treatment planning system calculated dose. The ion chamber measured dose shows good agreement with planned dose within ± 0.5% (0.203 ± 0.57%. Gamma value evaluated from EBT film shows passing rates 92–99% (96.63 ± 3.84% for 3% dose and 3 mm distance criteria. Respiratory gated treatment delivery accuracy is found to be within clinically acceptable level.

  6. Patient-specific data fusion defines prognostic cancer subtypes.

    Directory of Open Access Journals (Sweden)

    Yinyin Yuan

    2011-10-01

    Full Text Available Different data types can offer complementary perspectives on the same biological phenomenon. In cancer studies, for example, data on copy number alterations indicate losses and amplifications of genomic regions in tumours, while transcriptomic data point to the impact of genomic and environmental events on the internal wiring of the cell. Fusing different data provides a more comprehensive model of the cancer cell than that offered by any single type. However, biological signals in different patients exhibit diverse degrees of concordance due to cancer heterogeneity and inherent noise in the measurements. This is a particularly important issue in cancer subtype discovery, where personalised strategies to guide therapy are of vital importance. We present a nonparametric Bayesian model for discovering prognostic cancer subtypes by integrating gene expression and copy number variation data. Our model is constructed from a hierarchy of Dirichlet Processes and addresses three key challenges in data fusion: (i To separate concordant from discordant signals, (ii to select informative features, (iii to estimate the number of disease subtypes. Concordance of signals is assessed individually for each patient, giving us an additional level of insight into the underlying disease structure. We exemplify the power of our model in prostate cancer and breast cancer and show that it outperforms competing methods. In the prostate cancer data, we identify an entirely new subtype with extremely poor survival outcome and show how other analyses fail to detect it. In the breast cancer data, we find subtypes with superior prognostic value by using the concordant results. These discoveries were crucially dependent on our model's ability to distinguish concordant and discordant signals within each patient sample, and would otherwise have been missed. We therefore demonstrate the importance of taking a patient-specific approach, using highly-flexible nonparametric

  7. Patient-specific radiation dose and cancer risk estimation in CT: Part II. Application to patients

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Toncheva, Greta; Yoshizumi, Terry T.; Frush, Donald P. [Medical Physics Graduate Program, Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Medical Physics Graduate Program, Department of Physics, and Department of Biomedical Engineering, Duke University Medical Center, Durham, North Carolina 27705 (United States); Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Medical Physics Graduate Program, Duke University Medical Center, Durham, North Carolina 27705 (United States); Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 and Department of Biomedical Engineering, University of North Carolina, Chapel Hill, North Carolina 27599 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Duke Radiation Dosimetry Laboratory, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Duke Radiation Dosimetry Laboratory, Department of Radiology, Medical Physics Graduate Program, Duke University Medical Center, Durham, North Carolina 27705 (United States); Division of Pediatric Radiology, Department of Radiology, Medical Physics Graduate Program, Duke University Medical Center, Durham, North Carolina 27710 (United States)

    2011-01-15

    Purpose: Current methods for estimating and reporting radiation dose from CT examinations are largely patient-generic; the body size and hence dose variation from patient to patient is not reflected. Furthermore, the current protocol designs rely on dose as a surrogate for the risk of cancer incidence, neglecting the strong dependence of risk on age and gender. The purpose of this study was to develop a method for estimating patient-specific radiation dose and cancer risk from CT examinations. Methods: The study included two patients (a 5-week-old female patient and a 12-year-old male patient), who underwent 64-slice CT examinations (LightSpeed VCT, GE Healthcare) of the chest, abdomen, and pelvis at our institution in 2006. For each patient, a nonuniform rational B-spine (NURBS) based full-body computer model was created based on the patient's clinical CT data. Large organs and structures inside the image volume were individually segmented and modeled. Other organs were created by transforming an existing adult male or female full-body computer model (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. A Monte Carlo program previously developed and validated for dose simulation on the LightSpeed VCT scanner was used to estimate patient-specific organ dose, from which effective dose and risks of cancer incidence were derived. Patient-specific organ dose and effective dose were compared with patient-generic CT dose quantities in current clinical use: the volume-weighted CT dose index (CTDI{sub vol}) and the effective dose derived from the dose-length product (DLP). Results: The effective dose for the CT examination of the newborn patient (5.7 mSv) was higher but comparable to that for the CT examination of the teenager patient (4.9 mSv) due to the size-based clinical CT protocols at our institution, which employ lower scan techniques for smaller

  8. Field-Specific Intensity-modulated Proton Therapy Optimization Technique for Breast Cancer Patients with Tissue Expanders Containing Metal Ports.

    Science.gov (United States)

    Kirk, Maura; Freedman, Gary; Ostrander, Thorsten; Dong, Lei

    2017-09-18

    This report aims to propose and present an evaluation of a robust pencil beam scanning proton multi-field optimized treatment planning technique for postmastectomy radiation of breast cancer patients with implanted tissue expanders containing an internal metal port. Field-specific split targets were created for optimization to prevent spots from traveling through the metal port, while providing uniform coverage of the target with the use of a multi-field intensity modulated optimization approach. Two beam angles were strategically selected to provide complementary target coverage and plan robustness. The plan was compared with an independently developed photon plan and evaluated for robustness with respect to isocenter shifts, range shifts, and variation of the water-equivalent thickness of the port. The proton plan resulted in clinically acceptable target coverage and dosage to neighboring normal tissues. The D95% coverage was 95.3% in the nominal proton plan, with a worst-case coverage of 90.1% (when considering 0.3 cm isocenter shifts combined with 3.5% range uncertainty), and the coverage varied less than 1% under a hypothetically extreme variation of the port density. The proton plan had improved dose homogeneity compared with the photon plan, and reduced ipsilateral lung and mean heart doses. We demonstrated that a practical, field-specific intensity-modulated proton therapy (IMPT) optimization technique can be used to deal with the challenge of metal port in breast cancer patients with tissue expanders. The resulting proton plan has superior dosimetric characteristics over the best-case scenario photon plan, and is also robust to setup and proton range uncertainties.

  9. SPECIFICITY OF COMMUNICATION DOCTOR – PATIENT, ONLINE, THROUGH SOCIAL NETWORKS

    Directory of Open Access Journals (Sweden)

    Florin-Alexandru LUCA

    2014-12-01

    Full Text Available A survey in 2013 of Division Market Research Group Rentrop Straton Romanian-German - "state services and private clinics. Comparative Analysis ", highlights the fact that into urban population in Romania, the internet is the most popular source of information on health services. According to the survey, 81.9% of respondents use the Internet to find out about the best doctors available to them. Preferences of respondents to the online environment as the main source of information translates into ease of access and the possibility of interaction, but also trust recommendations based on personal experiences, recommendations can be found through discussion forums, mostly or comments left on pages on social networking sites. In the present study we try to emphasize the specificity of communication physician - patient online through social networks.

  10. Robust surgery loading

    NARCIS (Netherlands)

    Hans, Elias W.; Wullink, Gerhard; van Houdenhoven, Mark; Kazemier, Geert

    2008-01-01

    We consider the robust surgery loading problem for a hospital’s operating theatre department, which concerns assigning surgeries and sufficient planned slack to operating room days. The objective is to maximize capacity utilization and minimize the risk of overtime, and thus cancelled patients. This

  11. Robust factorization

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Fisker, Rune; Åström, Kalle

    2002-01-01

    Factorization algorithms for recovering structure and motion from an image stream have many advantages, but they usually require a set of well-tracked features. Such a set is in generally not available in practical applications. There is thus a need for making factorization algorithms deal...... effectively with errors in the tracked features. We propose a new and computationally efficient algorithm for applying an arbitrary error function in the factorization scheme. This algorithm enables the use of robust statistical techniques and arbitrary noise models for the individual features....... These techniques and models enable the factorization scheme to deal effectively with mismatched features, missing features, and noise on the individual features. The proposed approach further includes a new method for Euclidean reconstruction that significantly improves convergence of the factorization algorithms...

  12. Patterns of patient specific dosimetry in total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Akino, Yuichi [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States); Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871 (Japan); McMullen, Kevin P.; Das, Indra J. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States)

    2013-04-15

    Purpose: Total body irradiation (TBI) has been used for bone marrow transplant for hematologic and immune deficiency conditions. The goal of TBI is to deliver a homogeneous dose to the entire body, with a generally accepted range of dose uniformity being within {+-}10% of the prescribed dose. The moving table technique for TBI could make dose uniform in whole body by adjusting couch speed. However, it is difficult to accurately estimate the actual dose by calculation and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors present patterns of patient-specific IVD in 161 TBI patients treated at our institution. Methods: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial Products, Inc., Fishers, IN) were used for TBI treatment. During treatment, OneDose{sup TM} (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect Transistor detectors were placed at patient body surface; both entrance and exit side of the beam at patient head, neck, mediastinum, umbilicus, and knee to estimate midplane dose. When large differences (>10%) between the prescribed and measured dose were observed, dose delivery was corrected for subsequent fractions by the adjustment of couch speed and/or bolus placement. Under IRB exempt status, the authors retrospectively analyzed the treatment records of 161 patients who received TBI treatment between 2006 and 2011. Results: Across the entire cohort, the median {+-} SD (range) percent variance between calculated and measured dose for head, neck, mediastinum, umbilicus, and knee was -2.3 {+-} 10.2% (-66.2 to +35.3), 1.1 {+-} 11.5% (-62.2 to +40.3), -1.9 {+-} 9.5% (-66.4 to +46.6), -1.1 {+-} 7.2% (-35.2 to +42.9), and 3.4 {+-} 12.2% (-47.9 to +108.5), respectively. More than half of treatments were within {+-}10% of the prescribed dose for all anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was within {+-}10

  13. Invasive fungal disease in specific at-risk patients

    Directory of Open Access Journals (Sweden)

    Rosario Urbino

    2013-01-01

    Full Text Available Hematological patients, such as patients with lymphoproliferative syndromes, pediatric patients and patients in ICU, are not conventionally classified as high risk patients for the development of IFI, however invasive fungal infections should not be underestimated. In this subset of patients, particularly patients with lymphoproliferative syndromes are classified at intermediate risk for IFI especially if treated with monoclonal antibodies, purine analogs or steroids. With regard to pediatric patients the incidence of IFD is lower than in adults and is greater in patients with acute myeloid leukemia and in allotransplant patients. Finally, in patients in ICU there is high incidence of mold and Candida. Factors associated with increased mortality is the delay in admission in intensive care units, high-dose corticosteroid therapy, and GvHD.  

  14. Impact of surgical shape on blood flow pattern for patient specific coronary artery bypass graft (CABG) surgery

    Science.gov (United States)

    Sankaran, Sethuraman; Marsden, Alison

    2010-11-01

    We present a numerical framework for studying blood flow patterns in patients who have undergone coronary artery bypass surgeries. We use a stabilized finite element framework for performing blood flow simulations. Specialized lumped parameter boundary conditions for the coronary arteries, aorta and its branches are utilized. Computational models of CABG patients are constructed from CT scan images. A comprehensive study of how surgical shape affects hemodynamics in patient-specific CABG surgery has not been performed till date. The objective of this work is to study the effect of surgical geometry on blood flow pattern, especially downstream and in the proximity of the suture locations of the bypass graft. Quantities such as energy efficiency, wall shear stresses and its gradients and oscillatory shear index are extracted and compared for different surgical shapes in a systematic fashion. A framework and results for robust optimization of bypass graft anastomoses in unsteady flow will be presented. Implications of surgical geometry on graft patency will be discussed.

  15. Violence and Personality in Forensic Patients: Is There a Forensic Patient-Specific Personality Profile?

    Science.gov (United States)

    Stupperich, Alexandra; Ihm, Helga; Strack, Micha

    2009-01-01

    Concerning the discussion about the connection of personality traits, personality disorders, and mental illness, this study focused on the personality profiles of male forensic patients, prison inmates, and young men without criminal reports. The main topic centered on group-specific personality profiles and identifying personality facets…

  16. Quantification of specific E. coli in gut mucosa from Crohn's disease patients

    DEFF Research Database (Denmark)

    Jensen, Stina Rikke; Fink, Lisbeth Nielsen; Struve, Carsten

    2011-01-01

    We here present a method based on qRT-PCR to quantify E. coli LF82 in intestinal human samples. Two different primer-probe sets were designed to detect LF82, and a third to target total E. coli. The assay showed high robustness and specificity for detection of LF82 in the presence of intestinal...

  17. The patient's perspective of the feasibility of a patient-specific instrument in physiotherapy goal setting: a qualitative study

    NARCIS (Netherlands)

    Stevens, A.; Moser, A.; Koke, A.; Weijden, T.T. van der; Beurskens, A.

    2016-01-01

    BACKGROUND: Patient participation in goal setting is important to deliver client-centered care. In daily practice, however, patient involvement in goal setting is not optimal. Patient-specific instruments, such as the Patient Specific Complaints (PSC) instrument, can support the goal-setting process

  18. A robust immune system conditions the response to abagovomab (anti-idiotypic monoclonal antibody mimicking the CA125 protein) vaccination in ovarian cancer patients.

    Science.gov (United States)

    Battaglia, Alessandra; Fossati, Marco; Buzzonetti, Alexia; Scambia, Giovanni; Fattorossi, Andrea

    2017-11-01

    Despite encouraging phase I and II study results, vaccination of ovarian cancer patients with abagovomab - an anti-idiotypic mAb that mimics the ovarian cancer CA125 protein - failed to demonstrate efficacy in the phase III trial named MIMOSA (NCT00418574). We postulated that in this trial patients with a more robust immune system did respond to abagovomab but went undetected among a larger number of non-responders. We also postulated that assessment of the immune system status ahead of abagovomab administration might predict patients' propensity to respond to abagovomab. The immune system status was assessed as percentage and absolute count of CD8+ T cells producing IFN-γ after stimulation with Staphylococcal Enterotoxin B (SEB) in 80 patients on abagovomab and 31 patients on placebo from the MIMOSA trial ahead of treatment. Optimal cutoffs of the two variables were calculated by the web application "Cutoff Finder" as the points with most significant (log-rank test) splits based on relapse-free survival (RFS). The Kaplan-Meier curves and log-rank test served to estimate and compare RFS in patients with percentage and absolute count of IFN-γ producing CD8+ T cells around the cutoffs. Patients on abagovomab with IFN-γ producing CD8+T cell percentage above the cutoff had a better RFS (p=0.042) than those with IFN-γ producing CD8+T cell percentage below the cutoff. Patients on abagovomab with IFN-γ producing CD8+T cell absolute count above the cutoff had a better RFS (p=0.019) than those with IFN-γ producing CD8+T cell absolute counts below the cutoff. Consistently, the RFS of patients on abagovomab with IFN-γ producing CD8+T cell percentage and absolute counts values below the respective cutoffs was identical to that of patients on placebo. Neither the percentage nor the absolute count of IFN-γ producing CD8+T cells correlated with RFS in patients on placebo. A robust immune system is essential to obtain a clinical response in OC patients undergoing

  19. Development of a patient-specific two-compartment anthropomorphic breast phantom

    Science.gov (United States)

    Prionas, Nicolas D.; Burkett, George W.; McKenney, Sarah E.; Chen, Lin; Stern, Robin L.; Boone, John M.

    2012-07-01

    distribution for a specific patient. The modular design of the phantom allows for studies of a single breast segment and the entire breast volume. Insertion of other devices, materials and tissues of interest into the phantom provide a robust platform for future breast imaging and dosimetry studies.

  20. Dynamics robustness of cascading systems.

    Directory of Open Access Journals (Sweden)

    Jonathan T Young

    2017-03-01

    Full Text Available A most important property of biochemical systems is robustness. Static robustness, e.g., homeostasis, is the insensitivity of a state against perturbations, whereas dynamics robustness, e.g., homeorhesis, is the insensitivity of a dynamic process. In contrast to the extensively studied static robustness, dynamics robustness, i.e., how a system creates an invariant temporal profile against perturbations, is little explored despite transient dynamics being crucial for cellular fates and are reported to be robust experimentally. For example, the duration of a stimulus elicits different phenotypic responses, and signaling networks process and encode temporal information. Hence, robustness in time courses will be necessary for functional biochemical networks. Based on dynamical systems theory, we uncovered a general mechanism to achieve dynamics robustness. Using a three-stage linear signaling cascade as an example, we found that the temporal profiles and response duration post-stimulus is robust to perturbations against certain parameters. Then analyzing the linearized model, we elucidated the criteria of when signaling cascades will display dynamics robustness. We found that changes in the upstream modules are masked in the cascade, and that the response duration is mainly controlled by the rate-limiting module and organization of the cascade's kinetics. Specifically, we found two necessary conditions for dynamics robustness in signaling cascades: 1 Constraint on the rate-limiting process: The phosphatase activity in the perturbed module is not the slowest. 2 Constraints on the initial conditions: The kinase activity needs to be fast enough such that each module is saturated even with fast phosphatase activity and upstream changes are attenuated. We discussed the relevance of such robustness to several biological examples and the validity of the above conditions therein. Given the applicability of dynamics robustness to a variety of systems, it

  1. An Exon-Specific U1snRNA Induces a Robust Factor IX Activity in Mice Expressing Multiple Human FIX Splicing Mutants

    Directory of Open Access Journals (Sweden)

    Dario Balestra

    2016-01-01

    Full Text Available In cellular models we have demonstrated that a unique U1snRNA targeting an intronic region downstream of a defective exon (Exon-specific U1snRNA, ExSpeU1 can rescue multiple exon-skipping mutations, a relevant cause of genetic disease. Here, we explored in mice the ExSpeU1 U1fix9 toward two model Hemophilia B-causing mutations at the 5′ (c.519A > G or 3′ (c.392-8T > G splice sites of F9 exon 5. Hydrodynamic injection of wt-BALB/C mice with plasmids expressing the wt and mutant (hFIX-2G5′ss and hFIX-8G3′ss splicing-competent human factor IX (hFIX cassettes resulted in the expression of hFIX transcripts lacking exon 5 in liver, and in low plasma levels of inactive hFIX. Coinjection of U1fix9, but not of U1wt, restored exon inclusion of variants and in the intrinsically weak FIXwt context. This resulted in appreciable circulating hFIX levels (mean ± SD; hFIX-2G5′ss, 1.0 ± 0.5 µg/ml; hFIX-8G3′ss, 1.2 ± 0.3 µg/ml; and hFIXwt, 1.9 ± 0.6 µg/ml, leading to a striking shortening (from ≃100 seconds of untreated mice to ≃80 seconds of FIX-dependent coagulation times, indicating a hFIX with normal specific activity. This is the first proof-of-concept in vivo that a unique ExSpeU1 can efficiently rescue gene expression impaired by distinct exon-skipping variants, which extends the applicability of ExSpeU1s to panels of mutations and thus cohort of patients.

  2. Incarcerated inguinal hernias surgical treatment specifics in elderly patients

    Directory of Open Access Journals (Sweden)

    Pešić Ivan

    2012-01-01

    Full Text Available Background/Aim. Incarcerated inguinal hernias surgical treatment represents one of the most frequent surgical treatments in elderly patients. The percentage of incarcerated inguinal hernias urgent surgical treatments is growing exponentially with the age in patients over 50. The aim of the study was to investigate some of the factors that may have impact on the incarcerated inguinal hernias surgical treatment outcome in elderly patients. Methods. The study included 180 patients classified in two groups: the study group (> 65 years of age and the control group (≤ 65, managed in the period from January 2005 till March 2009 at the General Surgery Clinic, Clinical Center Niš. Results. Most of the patients had right inguinal hernia (52.6%, the study group; 59.1%, the control group. All the study group patients suffered from some of accompanying chronic diseases (100%, opposite to 39 (59% patients of the control group. Synthetic material was implanted in 124 (68.9% patients, while the tension technique was performed in 65 (31.1% patients. The duration of incarceration more than 24 h (p = 0.015, previous abdominal surgery (p = 0.001, the American Society of Anesthesiologists physical status classification system (ASA classification (p = 0.033 and the presence of chronic diseases (p = 0.01 appeared to be statistically significant risk factors for performing intestinal resection in the study group, while in the control group they represented risk factors, but not at the level of statistical significance (p <0.05, except for the duration of incarceration (p = 0.007. A higher ASA stage (p = 0.001 and the presence of bowel resection (p <0.001 are the most important risk factors for lethal outcome in both groups of patients. Conclusion. Incarcerated inguinal hernia in elderly patients is a serious problem. A higher ASA score and the presence of bowel resection are the most important factors related to unfavorable outcome.

  3. Incarcerated inguinal hernias surgical treatment specifics in elderly patients.

    Science.gov (United States)

    Pesić, Ivan; Karanikolić, Aleksandar; Djordjević, Nebojsa; Stojanović, Miroslav; Stanojević, Goran; Radojković, Milan; Nestorović, Milica

    2012-09-01

    Incarcerated inguinal hernias surgical treatment represents one of the most frequent surgical treatments in elderly patients. The percentage of incarcerated inguinal hernias urgent surgical treatments is growing exponentially with the age in patients over 50. The aim of the study was to investigate some of the factors that may have impact on the incarcerated inguinal hernias surgical treatment outcome in elderly patients. The study included 180 patients classified in two groups: the study group (> 65 years of age) and the control group (Synthetic material was implanted in 124 (68.90%) patients, while the tension technique was performed in 65 (31.1%) patients. The duration of incarceration more than 24 h (p = 0.015), previous abdominal surgery (p = 0.001), the American Society of Anesthesiologists physical status classification system (ASA classification) (p = 0.033) and the presence of chronic diseases (p = 0.01) appeared to be statistically significant risk factors for performing intestinal resection in the study group, while in the control group they represented risk factors, but not at the level of statistical significance (p < 0.05), except for the duration of incarceration (p = 0.007). A higher ASA stage (p = 0.001) and the presence of bowel resection (p <0.001) are the most important risk factors for lethal outcome in both groups of patients. Incarcerated inguinal hernia in elderly patients is a serious problem. A higher ASA score and the presence of bowel resection are the most important factors related to unfavorable outcome.

  4. Improved patient specific seizure detection during pre-surgical evaluation.

    LENUS (Irish Health Repository)

    Chua, Eric C-P

    2011-04-01

    There is considerable interest in improved off-line automated seizure detection methods that will decrease the workload of EEG monitoring units. Subject-specific approaches have been demonstrated to perform better than subject-independent ones. However, for pre-surgical diagnostics, the traditional method of obtaining a priori data to train subject-specific classifiers is not practical. We present an alternative method that works by adapting the threshold of a subject-independent to a specific subject based on feedback from the user.

  5. Open-Source Radiation Exposure Extraction Engine (RE3) with Patient-Specific Outlier Detection.

    Science.gov (United States)

    Weisenthal, Samuel J; Folio, Les; Kovacs, William; Seff, Ari; Derderian, Vana; Summers, Ronald M; Yao, Jianhua

    2016-08-01

    We present an open-source, picture archiving and communication system (PACS)-integrated radiation exposure extraction engine (RE3) that provides study-, series-, and slice-specific data for automated monitoring of computed tomography (CT) radiation exposure. RE3 was built using open-source components and seamlessly integrates with the PACS. RE3 calculations of dose length product (DLP) from the Digital imaging and communications in medicine (DICOM) headers showed high agreement (R (2) = 0.99) with the vendor dose pages. For study-specific outlier detection, RE3 constructs robust, automatically updating multivariable regression models to predict DLP in the context of patient gender and age, scan length, water-equivalent diameter (D w), and scanned body volume (SBV). As proof of concept, the model was trained on 811 CT chest, abdomen + pelvis (CAP) exams and 29 outliers were detected. The continuous variables used in the outlier detection model were scan length (R (2)  = 0.45), D w (R (2) = 0.70), SBV (R (2) = 0.80), and age (R (2) = 0.01). The categorical variables were gender (male average 1182.7 ± 26.3 and female 1047.1 ± 26.9 mGy cm) and pediatric status (pediatric average 710.7 ± 73.6 mGy cm and adult 1134.5 ± 19.3 mGy cm).

  6. Feasibility of a 3D-printed anthropomorphic patient-specific head phantom for patient-specific quality assurance of intensity-modulated radiotherapy

    Science.gov (United States)

    Yea, Ji Woon; Park, Jae Won; Kim, Sung Kyu; Kim, Dong Youn; Kim, Jae Gu; Seo, Chan Young; Jeong, Won Hyo; Jeong, Man Youl

    2017-01-01

    This study evaluated the feasibility of utilizing a 3D-printed anthropomorphic patient-specific head phantom for patient-specific quality assurance (QA) in intensity-modulated radiotherapy (IMRT). Contoured left and right head phantoms were converted from DICOM to STL format. Fused deposition modeling (FDM) was used to construct an anthropomorphic patient-specific head phantom with a 3D printer. An established QA technique and the patient-specific head phantom were used to compare the calculated and measured doses. When the established technique was used to compare the calculated and measured doses, the gamma passing rate for γ ≤ 1 was 97.28%, while the gamma failure rate for γ > 1 was 2.72%. When the 3D-printed patient-specific head phantom was used, the gamma passing rate for γ ≤ 1 was 95.97%, and the gamma failure rate for γ > 1 was 4.03%. The 3D printed patient-specific head phantom was concluded to be highly feasible for patient-specific QA prior to complicated radiotherapy procedures such as IMRT. PMID:28727787

  7. Combining population and patient-specific characteristics for prostate segmentation on 3D CT images

    Science.gov (United States)

    Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Tade, Funmilayo; Schuster, David M.; Fei, Baowei

    2016-03-01

    Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance. Specifically, we train a population model based on the population data and train a patient-specific model based on the manual segmentation on three slice of the new patient. We compute the similarity between the two models to explore the influence of applicable population knowledge on the specific patient. By combining the patient-specific knowledge with the influence, we can capture the population and patient-specific characteristics to calculate the probability of a pixel belonging to the prostate. Finally, we smooth the prostate surface according to the prostate-density value of the pixels in the distance transform image. We conducted the leave-one-out validation experiments on a set of CT volumes from 15 patients. Manual segmentation results from a radiologist serve as the gold standard for the evaluation. Experimental results show that our method achieved an average DSC of 85.1% as compared to the manual segmentation gold standard. This method outperformed the population learning method and the patient-specific learning approach alone. The CT segmentation method can have various applications in prostate cancer diagnosis and therapy.

  8. Patient-specific rhytidectomy: finding the angle of maximal rejuvenation.

    Science.gov (United States)

    Jacono, Andrew A; Ransom, Evan R

    2012-09-01

    Rhytidectomy is fundamentally an operation of tissue release and resuspension, although the manner and direction of suspension are subject to perpetual debate. The authors describe a method for identifying the angle of maximal rejuvenation during rhytidectomy and quantify the resulting angle and its relationship to patient age. Patients were prospectively enrolled; demographic data, history, and operative details were recorded. Rhytidectomies were performed by the senior author (AAJ). After complete elevation, the face-lift flap was rotated in a medially-based arc (0-90°) while attention was given to the submental area, jawline, and midface. The angle of maximal rejuvenation for each hemiface was identified as described, and the flap was resuspended. During redraping, measurements of vertical and horizontal skin excess were recorded in situ. The resulting angle of lift was then calculated for each hemiface using trigonometry. Symmetry between sides was determined, and the effect of patient age on this angle was assessed. Three hundred hemifaces were operated (147 women; 3 men). Mean age was 60 years (range, 37-80 years). Mean resulting angle for the cohort was 60° from horizontal (range, 46-77°). This was inversely correlated with patient age (r = -.3). Younger patients (<50 years, 64°) had a significantly more vertical angle than older patients (≥70 years, 56°; P < .0002). No significant intersubject difference was found between hemifaces (P = .53). The authors present a method for identifying the angle of maximal rejuvenation during rhytidectomy. This angle was more superior than posterior in all cases and is intimately related to patient age. Lasting results demand a detailed anatomical understanding and strict attention to the direction and degree of laxity.

  9. Managing patients with acute and chronic non-specific neck pain: are Danish chiropractors compliant with guidelines?

    Science.gov (United States)

    Brockhusen, Simon Sidenius; Bussières, André; French, Simon David; Christensen, Henrik Wulff; Jensen, Tue Secher

    2017-01-01

    Non-specific neck pain represents a quarter of all chiropractic patient visits in Denmark. Evidence informed practice can help ensure providers use best available treatment, speed up patient recovery rate and reduce healthcare utilization. It is generally believed that Danish chiropractors treat according to best practice, but we do not know if this is true for management of neck-pain. The objective of this study was to investigate how Danish chiropractors treat patients with acute and chronic non-specific neck pain and determine if management is compliant with recent Canadian guideline recommendations. An online survey was sent to 554 members of the Danish chiropractic association. A three-part questionnaire was administered asking participants to: 1) rank the frequency of use of a list of treatment modalities; 2) rank treatment modalities they normally use for acute and chronic non-specific neck pain cases; and 3) provide demographic data. Treatment modalities ranked as "used often" were considered in further analysis and compared to the Canadian Guideline recommendations for neck pain. Chi-squared test was used to investigate differences between treatment and guideline compliance for chronic and acute patients. A 65% (362/544) response rate was achieved. The sample demographics were representative of a recent Danish study of the entire chiropractic profession. Danish chiropractors use a wide range of treatment modalities, including spinal manipulation, manual therapy, exercises and information/patient education on most of their acute neck pain patients. The use of other treatment modalities and especially exercises was more commonly used with chronic cases. Guideline compliance was 10% for recommendations for acute patients and 43% for chronic patients. Danish chiropractors use a wide range of treatment options for managing adult patients with acute and chronic non-specific neck-pain. However, there were important differences in treatments chiropractors offered

  10. Patient Specific Congestive Heart Failure Detection From Raw ECG signal

    Directory of Open Access Journals (Sweden)

    Yakup Kutlu

    2016-02-01

    Full Text Available In this study; in order to diagnose congestive heart failure (CHF patients, non-linear second-order difference plot (SODP obtained from raw 256 Hz sampled frequency and windowed record with different time of ECG records are used. All of the data rows are labelled with their belongings to classify much more realistically. SODPs are divided into different radius of quadrant regions and numbers of the points fall in the quadrants are computed in order to extract feature vectors. Fisher's linear discriminant, Naive Bayes, Radial basis function, and artificial neural network are used as classifier. The results are considered in two step validation methods as general k-fold cross-validation and patient based cross-validation. As a result, it is shown that using neural network classifier with features obtained from SODP, the constructed system could distinguish normal and CHF patients with 100% accuracy rate.

  11. [Specifics of Analgesia in Palliative Care Patients at Home].

    Science.gov (United States)

    Pautex, Sophie

    2015-02-25

    Pain management at home for a patient, suffering from one or more advanced progressive diseases, goes beyond the prescription of an opioid. Apart from the importance of finding the most suitable analgesic drug (controlled pain with least possible adverse effects), three important dimensions will be addressed: interprofessionnal care (shared care goals, evaluation, monitoring of pain and other symptoms; physiotherapy, etc.) information, education and support for patients and relatives in particular on the use of opioids, and finally the importance of anticipation. This includes for example the requirement of breakthrough pain treatment in case of pain exacerbation or the definition of the place of hospitalization in case of worsening general condition or of death.

  12. Cause-Specific Mortality Among Spouses of Parkinson Disease Patients

    DEFF Research Database (Denmark)

    Nielsen, Malene; Hansen, Jonni; Ritz, Beate

    2014-01-01

    BACKGROUND: Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. METHODS: All patients in Denmark with a first-time hospitalization for Parkinson...... disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. RESULTS: Among...... men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1...

  13. Patient Specific Congestive Heart Failure Detection From Raw ECG signal

    OpenAIRE

    Yakup Kutlu; Apdullah Yayık; Esen Yıldırım; Mustafa Yeniad; Serdar Yıldırım

    2016-01-01

    In this study; in order to diagnose congestive heart failure (CHF) patients, non-linear second-order difference plot (SODP) obtained from raw 256 Hz sampled frequency and windowed record with different time of ECG records are used. All of the data rows are labelled with their belongings to classify much more realistically. SODPs are divided into different radius of quadrant regions and numbers of the points fall in the quadrants are computed in order to extract feature vectors. Fisher's linea...

  14. Metabolic investigation of patients with urolithiasis in a specific region

    Directory of Open Access Journals (Sweden)

    Luis A. B. Peres

    2003-06-01

    Full Text Available OBJECTIVE: To assess the prevalence of the main metabolic alterations found in patients with recent diagnosis of urolithiasis in the West region of Paraná state, Brazil. MATERIALS AND METHODS: We made a retrospective study on 425 patients with evidence of recent formation of renal stones. Laboratory assessment consisted in 3 samples of 24-hour urine with dosing of calcium, uric acid, citrate, oxalate, sodium and creatinine. A urine culture was also made and qualitative cystinuria and urinary pH following 12-hour fasting and water restriction were evaluated. RESULTS: In 96.5% of patients a cause was detected for the urolithiasis. Metabolic alterations most frequently found were: hypercalciuria (38.3%, hypocitraturia (29.6% and hyperexcretion of uric acid (21.6%. Low urinary volume (17.9%, urinary tract infection (12.9%, hyperparathyroidism (3.3%, renal tubular acidosis (1.2%, cystinuria (0.9% and anatomical alterations (12.7% were also observed. CONCLUSIONS: Hypercalciuria, hypocitraturia and hyperuricuria are the most frequent metabolic disorders in the population under study and these data are in accordance to the literature.

  15. Specific changes of serum proteins in Parkinson's disease patients.

    Directory of Open Access Journals (Sweden)

    Wenwen Lu

    Full Text Available The aim of this study is to identify and validate protein change in the serum from PD patients. We used serum samples from 21 PD patients and 20 age-matched normal people as control to conduct a comparative proteomic study. We performed 2-DE and analyzed the differentially expressed protein spots by LC-MS/MS. In PD group 13 spots were shown to be differentially expressed compared to control group. They were identified as 6 proteins. Among these, 3 proteins were confirmed by Western blot analysis. It showed that the frequency of fibrinogen γ-chain (FGG appeared 70% in PD, which could not be detected in control group. The protein of inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4 was found to exist two forms in serum. The full size (120 kDa of the protein was increased and the fragmented ITI-H4 (35 kDa was decreased in PD group. The ratio of full size ITI-H4 to fragmented ITI-H4 in PD patients was 3.85 ± 0.29-fold higher than in control group. Furthermore, fragmented Apo A-IV (∼ 26 kDa was mainly detected in control group, while it was rare to be found in PD group. Above findings might be useful for diagnosis of PD. When the expressions of FGG and 120 kDa ITI-H4 are increase, as well as ∼ 26 kDa Apo A-IV disappear would provide strong evidence for PD.

  16. Specific Changes of Serum Proteins in Parkinson's Disease Patients

    Science.gov (United States)

    Lu, Wenwen; Wan, Xinhua; Liu, Bin; Rong, Xianfang; Zhu, Lei; Li, Pingping; Li, Jiang; Wang, Ling; Cui, Liying; Wang, Xiaoliang

    2014-01-01

    The aim of this study is to identify and validate protein change in the serum from PD patients. We used serum samples from 21 PD patients and 20 age-matched normal people as control to conduct a comparative proteomic study. We performed 2-DE and analyzed the differentially expressed protein spots by LC-MS/MS. In PD group 13 spots were shown to be differentially expressed compared to control group. They were identified as 6 proteins. Among these, 3 proteins were confirmed by Western blot analysis. It showed that the frequency of fibrinogen γ-chain (FGG) appeared 70% in PD, which could not be detected in control group. The protein of inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4) was found to exist two forms in serum. The full size (120 kDa) of the protein was increased and the fragmented ITI-H4 (35 kDa) was decreased in PD group. The ratio of full size ITI-H4 to fragmented ITI-H4 in PD patients was 3.85±0.29-fold higher than in control group. Furthermore, fragmented Apo A-IV (∼26 kDa) was mainly detected in control group, while it was rare to be found in PD group. Above findings might be useful for diagnosis of PD. When the expressions of FGG and 120 kDa ITI-H4 are increase, as well as ∼26 kDa Apo A-IV disappear would provide strong evidence for PD. PMID:24769800

  17. Induction of Robust B Cell Responses after Influenza mRNA Vaccination Is Accompanied by Circulating Hemagglutinin-Specific ICOS+ PD-1+ CXCR3+ T Follicular Helper Cells

    Directory of Open Access Journals (Sweden)

    Gustaf Lindgren

    2017-11-01

    Full Text Available Modified mRNA vaccines have developed into an effective and well-tolerated vaccine platform that offers scalable and precise antigen production. Nevertheless, the immunological events leading to strong antibody responses elicited by mRNA vaccines are largely unknown. In this study, we demonstrate that protective levels of antibodies to hemagglutinin were induced after two immunizations of modified non-replicating mRNA encoding influenza H10 encapsulated in lipid nanoparticles (LNP in non-human primates. While both intradermal (ID and intramuscular (IM administration induced protective titers, ID delivery generated this response more rapidly. Circulating H10-specific memory B cells expanded after each immunization, along with a transient appearance of plasmablasts. The memory B cell pool waned over time but remained detectable throughout the 25-week study. Following prime immunization, H10-specific plasma cells were found in the bone marrow and persisted over time. Germinal centers were formed in vaccine-draining lymph nodes along with an increase in circulating H10-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells, a population shown to correlate with high avidity antibody responses after seasonal influenza vaccination in humans. Collectively, this study demonstrates that mRNA/LNP vaccines potently induce an immunological repertoire associated with the generation of high magnitude and quality antibodies.

  18. Do cancer-specific websites meet patient's information needs?

    Science.gov (United States)

    Warren, Emily; Footman, Katharine; Tinelli, Michela; McKee, Martin; Knai, Cécile

    2014-04-01

    To evaluate commonly used cancer websites' information provision, we developed and applied an Information Comprehensiveness Tool to breast and prostate cancer websites. We first collated questions from a systematic literature review on patient information needs. We then classified the questions in terms of spectrum of care, theme, and nature of question. "Breast cancer" and "prostate cancer" were typed into Google, and websites listed on the first page of results were selected. Two researchers, blind to each others' scores, assessed the same websites using the coding system. Each question was scored on a 3-point scale as not (0%), partially (50%) and fully (100%) answered by two researchers. Average scores were calculated across all questions. Inter-rater reliability was assessed. We identified 79 general, 5 breast, and 5 prostate cancer questions. Inter-rater reliability was good, with an intraclass coefficient of 0.756 (95% CIs 0.729-0.781). 17 questions were not answered thoroughly by any website. Questions about "future planning", "monitoring", and "decision-making" were discussed least. Biomedical questions scored highest. More comprehensive information needs to be provided on breast and prostate cancer websites. This ICT can improve cancer information online and enable patients to engage more actively regarding their information needs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. A Case of Human Lassa Virus Infection With Robust Acute T-Cell Activation and Long-Term Virus-Specific T-Cell Responses.

    Science.gov (United States)

    McElroy, Anita K; Akondy, Rama S; Harmon, Jessica R; Ellebedy, Ali H; Cannon, Deborah; Klena, John D; Sidney, John; Sette, Alessandro; Mehta, Aneesh K; Kraft, Colleen S; Lyon, Marshall G; Varkey, Jay B; Ribner, Bruce S; Nichol, Stuart T; Spiropoulou, Christina F

    2017-06-15

    A nurse who acquired Lassa virus infection in Togo in the spring of 2016 was repatriated to the United States for care at Emory University Hospital. Serial sampling from this patient permitted the characterization of several aspects of the innate and cellular immune responses to Lassa virus. Although most of the immune responses correlated with the kinetics of viremia resolution, the CD8 T-cell response was of surprisingly high magnitude and prolonged duration, implying prolonged presentation of viral antigens. Indeed, long after viremia resolution, there was persistent viral RNA detected in the semen of the patient, accompanied by epididymitis, suggesting the male reproductive tract as 1 site of antigen persistence. Consistent with the magnitude of acute T-cell responses, the patient ultimately developed long-term, polyfunctional memory T-cell responses to Lassa virus. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  20. Preliminary experience with the patient-specific templating total knee arthroplasty

    OpenAIRE

    Boonen, Bert; Schotanus, Martijn G.M.; Kort, Nanne P.

    2012-01-01

    Background and purpose Patient-specific templating total knee arthroplasty (TKA) is a new method for alignment of a total knee arthroplasty that uses disposable guides. We present the results of the first 40 consecutive patients who were operated on using this technique. Methods In this case-control study, we compared blood loss, operation time, and alignment of 40 TKAs performed using a patient-specific templating alignment technique with values from a matched control group of patients who w...

  1. Specific Blood Pressure Targets for Patients With Diabetic Nephropathy?

    Science.gov (United States)

    Grassi, Guido; Mancia, Giuseppe; Nilsson, Peter M

    2016-08-01

    Diabetic nephropathy represents a condition frequently detected in current clinical practice characterized by a very high cardiovascular risk profile. Blood pressure reduction via antihypertension drug treatment represents a therapeutic approach capable of exerting favorable effects on renal and cardiovascular outcomes. The purpose of this article is to review the current literature and results of key clinical trials pertaining to blood pressure goals of antihypertension treatment in these patients. The pros and cons of a less or a more intensive blood pressure goal in diabetic nephropathy will be discussed, with particular emphasis on the cardiovascular and renal effects of each therapeutic strategy. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. A whole blood monokine-based reporter assay provides a sensitive and robust measurement of the antigen-specific T cell response

    Directory of Open Access Journals (Sweden)

    Bennett Sophia C

    2011-08-01

    Full Text Available Abstract Background The ability to measure T-cell responses to antigens is proving critical in the field of vaccine development and for understanding immunity to pathogens, allergens and self-antigens. Although a variety of technologies exist for this purpose IFNγ-ELISpot assays are widely used because of their sensitivity and simplicity. However, ELISpot assays cannot be performed on whole blood, and require relatively large volumes of blood to yield sufficient numbers of peripheral blood mononuclear cells. To address these deficiencies, we describe an assay that measures antigen-specific T cell responses through changes in monokine gene transcription. The biological amplification of the IFNγ signal generated by this assay provides sensitivity comparable to ELISpot, but with the advantage that responses can be quantified using small volumes of whole blood. Methods Whole blood or peripheral blood mononuclear cells (PBMCs from healthy controls and immunosuppressed recipients of solid organ transplants were incubated with peptide pools covering viral and control antigens or mitogen for 20 hours. Total RNA was extracted and reverse transcribed before amplification in a TaqMan qPCR reaction using primers and probes specific for MIG (CXCL9, IP-10 (CXCL10 and HPRT. The induction of MIG and IP-10 in response to stimuli was analysed and the results were compared with those obtained by ELISpot. Results Antigen-specific T cell responses can be measured through the induction of MIG or IP-10 gene expression in PBMCs or whole blood with results comparable to those achieved in ELISpot assays. The biological amplification generated by IFNγ-R signaling allows responses to be detected in as little as 25 μL of whole blood and enables the assay to retain sensitivity despite storage of samples for up to 48 hours prior to processing. Conclusions A monokine-based reporter assay provides a sensitive measure of antigen-specific T cell activation. Assays can be

  3. Methods for robustness programming

    NARCIS (Netherlands)

    Olieman, N.J.

    2008-01-01

    Robustness of an object is defined as the probability that an object will have properties as required. Robustness Programming (RP) is a mathematical approach for Robustness estimation and Robustness optimisation. An example in the context of designing a food product, is finding the best composition

  4. SU-C-210-05: Evaluation of Robustness: Dosimetric Effects of Anatomical Changes During Fractionated Radiation Treatment of Pancreatic Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Horst, A van der; Houweling, A C; Bijveld, M M C; Visser, J; Bel, A [Academic Medical Center, Amsterdam, Noord-Holland (Netherlands)

    2015-06-15

    Purpose: Pancreatic tumors show large interfractional position variations. In addition, changes in gastrointestinal air volume and body contour take place during treatment. We aim to investigate the robustness of the clinical treatment plans by quantifying the dosimetric effects of these anatomical changes. Methods: Calculations were performed for up to now 3 pancreatic cancer patients who had intratumoral fiducials for daily CBCT-based positioning during their 3-week treatment. For each patient, deformable image registration of the planning CT was used to assign Hounsfield Units to each of the 13—15 CBCTs; air volumes and body contour were copied from CBCT. The clinical treatment plan was used (CTV-PTV margin = 10 mm; 36Gy; 10MV; 1 arc VMAT). Fraction dose distributions were calculated and accumulated. The V95% of the clinical target volume (CTV) and planning target volume (PTV) were analyzed, as well as the dose to stomach, duodenum and liver. Dose accumulation was done for patient positioning based on the fiducials (as clinically used) as well as for positioning based on bony anatomy. Results: For all three patients, the V95% of the CTV remained 100%, for both fiducial- and bony anatomy-based positioning. For fiducial-based positioning, dose to duodenum en stomach showed no discernable differences with planned dose. For bony anatomy-based positioning, the PTV V95% of the patient with the largest systematic difference in tumor position (patient 1) decreased to 85%; the liver Dmax increased from 33.5Gy (planned) to 35.5Gy. Conclusion: When using intratumoral fiducials, CTV dose coverage was only mildly affected by the daily anatomical changes. When using bony anatomy for patient positioning, we found a decline in PTV dose coverage due to the interfractional tumor position variations. Photon irradiation treatment plans for pancreatic tumors are robust to variations in body contour and gastrointestinal gas, but the use of fiducial-based daily position verification

  5. Management of specific symptom complexes in patients receiving palliative care

    Science.gov (United States)

    Bruera, E; Neumann, C M

    1998-01-01

    During the past 10 years there have been major changes in the management of the most common symptoms of terminal cancer. Opioid agonists remain the mainstay in the management of cancer pain. Slow-release preparations are currently available for several of these agents. The increased use of opioids has led to the recognition of opioid-induced neurotoxic effects and to the development of effective adjuvant drugs and other strategies to counteract these side effects. A number of drugs are available for the management of symptoms of cachexia, including corticosteroids and progestational drugs. Prokinetic drugs, either alone or in combination with other agents such as corticosteroids, are highly effective in the treatment of chronic nausea. For patients with asthenia, it should first be determined whether there are any reversible causes; if not, corticosteroids and psychostimulants may diminish the symptoms. Haloperidol, other neuroleptics and benzodiazepines may be required to manage hyperactive delirium. Oxygen and opioids are effective in treating dyspnea, whereas there is limited evidence that benzodiazepines provide any relief of this symptom. More research on the assessment and management of these devastating clinical symptoms of cancer is badly needed. PMID:9676549

  6. Diabetes Mellitus Increased Mortality Rates More in Gender-Specific than in Nongender-Specific Cancer Patients: A Retrospective Study of 149,491 Patients

    Directory of Open Access Journals (Sweden)

    Wen-Ko Chiou

    2012-01-01

    Full Text Available Aims. Hyperinsulinemia in overweight status, obesity, and type 2 diabetes mellitus (DM is often accompanied by cancer. Gender is important in cancer epidemiology, clinical presentation, and response to therapy in different histological types of malignancy. Insufficient information is available concerning gender differences in DM with organ-specific and nonorgan-specific cancers. This study aimed to analyze gender differences in hospitalized cancer patients with or without type 2 DM. Methods. We retrospectively reviewed ten years of patients hospitalized in one institution, enrolling 36,457 female and 50,004 male cancer patients of which 5,992 females and 8,345 males were diagnosed as type 2 DM. Results. Statistically significant increases in incidence of type 2 DM were found in patients of both genders with pancreatic, liver, and urinary tract cancer. Increased incidence of type 2 DM was found in lung and hematologic malignancies in females and prostate cancer in males. Increases in mortality rates of females with type 2 DM (2.98% were higher than those in males. DM increased mortality rates in gender-specific cancers from 1.91% (uterus, HR: 1.33 to 5.04% (ovary, HR: 1.49. Conclusion. Type 2 DM increased mortality of cancer patients of both genders, with higher increases in gender-specific than in nongender-specific cancers.

  7. System Identification and Robust Control

    DEFF Research Database (Denmark)

    Tøffner-Clausen, S.

    The main purpose of this work is to develop a coherent system identification based robust control design methodology by combining recent results from system identification and robust control. In order to accomplish this task new theoretical results will be given in both fields. Firstly, however......, an introduction to modern robust control design analysis and synthesis will be given. It will be shown how the classical frequency domain techniques can be extended to multivariable systems using the singular value decomposition. An introduction to norms and spaces frequently used in modern control theory......, a non-trivial problem which to some extent has been neglected by the theoreticians of robust control. An uncertainty specification has simply been assumed given. One way of obtaining a perturbation model is by physical modelling. Application if the fundamental laws of thermodynamics, mechanics, physics...

  8. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model.

    Directory of Open Access Journals (Sweden)

    Iva Sovadinova

    Full Text Available Dysregulation of gap junctional intercellular communication (GJIC has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC.the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap

  9. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model

    Science.gov (United States)

    Sovadinova, Iva; Babica, Pavel; Böke, Hatice; Kumar, Esha; Wilke, Andrew; Park, Joon-Suk; Trosko, James E.; Upham, Brad L.

    2015-01-01

    Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. In conclusion: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap

  10. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model.

    Science.gov (United States)

    Sovadinova, Iva; Babica, Pavel; Böke, Hatice; Kumar, Esha; Wilke, Andrew; Park, Joon-Suk; Trosko, James E; Upham, Brad L

    2015-01-01

    Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap junction channels

  11. Gender disparities in disease-specific health status in postoperative patients with peripheral arterial disease

    DEFF Research Database (Denmark)

    Mastenbroek, M H; Hoeks, S E; Pedersen, Susanne S.

    2012-01-01

    To investigate gender disparities in disease-specific health status (HS), 3- and 5-year post-intervention in peripheral arterial disease (PAD) patients.......To investigate gender disparities in disease-specific health status (HS), 3- and 5-year post-intervention in peripheral arterial disease (PAD) patients....

  12. Serum HER-2: Sensitivity, specificity, and predictive values for detecting metastatic recurrence in breast cancer patients

    DEFF Research Database (Denmark)

    Sørensen, Patricia Diana; Jakobsen, Erik Hugger; Madsen, Jonna Skov

    2013-01-01

    The aim of this study was to determine the sensitivity, specificity, and predictive values of serum HER-2 for detecting metastatic recurrence in breast cancer patients.......The aim of this study was to determine the sensitivity, specificity, and predictive values of serum HER-2 for detecting metastatic recurrence in breast cancer patients....

  13. Implant positioning in TKA: comparison between conventional and patient-specific instrumentation.

    Science.gov (United States)

    Ferrara, Ferdinando; Cipriani, Antonio; Magarelli, Nicola; Rapisarda, Santi; De Santis, Vincenzo; Burrofato, Aaron; Leone, Antonio; Bonomo, Lorenzo

    2015-04-01

    The number of total knee arthroplasty (TKA) procedures continuously increases, with good to excellent results. In the last few years, new surgical techniques have been developed to improve prosthesis positioning. In this context, patient-specific instrumentation is included. The goal of this study was to compare the perioperative parameters and the spatial positioning of prosthetic components in TKA procedures performed with patient-specific instrumentation vs traditional TKA. In this prospective comparative randomized study, 15 patients underwent TKA with 3-dimensional magnetic resonance imaging (MRI) preoperative planning (patient-specific instrumentation group) and 15 patients underwent traditional TKA (non-patient-specific instrumentation group). All patients underwent postoperative computed tomography (CT) examination. In the patient-specific instrumentation group, preoperative data planning regarding femoral and tibial bone resection was correlated with intraoperative measurements. Surgical time, length of hospitalization, and intraoperative and postoperative bleeding were compared between the 2 groups. Positioning of implants on postoperative CT was assessed for both groups. Data planned with 3-dimensional MRI regarding the depth of bone cuts showed good to excellent correlation with intraoperative measurements. The patient-specific instrumentation group showed better perioperative outcomes and good correlation between the spatial positioning of prosthetic components planned preoperatively and that seen on postoperative CT. Less variability was found in the patient-specific instrumentation group than in the non-patient-specific instrumentation group in spatial orientation of prosthetic components. Preoperative planning with 3-dimensional MRI in TKA has a better perioperative outcome compared with the traditional method. Use of patient-specific instrumentation can also improve the spatial positioning of both prosthetic components. Copyright 2015, SLACK

  14. Oral Delivery of a Novel Recombinant Streptococcus mitis Vector Elicits Robust Vaccine Antigen-Specific Oral Mucosal and Systemic Antibody Responses and T Cell Tolerance.

    Directory of Open Access Journals (Sweden)

    Emily Xie

    Full Text Available The pioneer human oral commensal bacterium Streptococcus mitis has unique biologic features that make it an attractive mucosal vaccine or therapeutic delivery vector. S. mitis is safe as a natural persistent colonizer of the mouth, throat and nasopharynx and the oral commensal bacterium is capable of inducing mucosal antibody responses. A recombinant S. mitis (rS. mitis that stably expresses HIV envelope protein was generated and tested in the germ-free mouse model to evaluate the potential usefulness of this vector as a mucosal vaccine against HIV. Oral vaccination led to the efficient and persistent bacterial colonization of the mouth and the induction of both salivary and systemic antibody responses. Interestingly, persistently colonized animals developed antigen-specific systemic T cell tolerance. Based on these findings we propose the use of rS. mitis vaccine vector for the induction of mucosal antibodies that will prevent the penetration of the mucosa by pathogens such as HIV. Moreover, the first demonstration of rS. mitis having the ability to elicit T cell tolerance suggest the potential use of rS. mitis as an immunotherapeutic vector to treat inflammatory, allergic and autoimmune diseases.

  15. Oral Delivery of a Novel Recombinant Streptococcus mitis Vector Elicits Robust Vaccine Antigen-Specific Oral Mucosal and Systemic Antibody Responses and T Cell Tolerance

    Science.gov (United States)

    Xie, Emily; Kotha, Abhiroop; Biaco, Tracy; Sedani, Nikita; Zou, Jonathan; Stashenko, Phillip; Duncan, Margaret J.; Campos-Neto, Antonio; Cayabyab, Mark J.

    2015-01-01

    The pioneer human oral commensal bacterium Streptococcus mitis has unique biologic features that make it an attractive mucosal vaccine or therapeutic delivery vector. S. mitis is safe as a natural persistent colonizer of the mouth, throat and nasopharynx and the oral commensal bacterium is capable of inducing mucosal antibody responses. A recombinant S. mitis (rS. mitis) that stably expresses HIV envelope protein was generated and tested in the germ-free mouse model to evaluate the potential usefulness of this vector as a mucosal vaccine against HIV. Oral vaccination led to the efficient and persistent bacterial colonization of the mouth and the induction of both salivary and systemic antibody responses. Interestingly, persistently colonized animals developed antigen-specific systemic T cell tolerance. Based on these findings we propose the use of rS. mitis vaccine vector for the induction of mucosal antibodies that will prevent the penetration of the mucosa by pathogens such as HIV. Moreover, the first demonstration of rS. mitis having the ability to elicit T cell tolerance suggest the potential use of rS. mitis as an immunotherapeutic vector to treat inflammatory, allergic and autoimmune diseases. PMID:26618634

  16. MO-DE-207B-03: Improved Cancer Classification Using Patient-Specific Biological Pathway Information Via Gene Expression Data

    Energy Technology Data Exchange (ETDEWEB)

    Young, M; Craft, D [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

    2016-06-15

    Purpose: To develop an efficient, pathway-based classification system using network biology statistics to assist in patient-specific response predictions to radiation and drug therapies across multiple cancer types. Methods: We developed PICS (Pathway Informed Classification System), a novel two-step cancer classification algorithm. In PICS, a matrix m of mRNA expression values for a patient cohort is collapsed into a matrix p of biological pathways. The entries of p, which we term pathway scores, are obtained from either principal component analysis (PCA), normal tissue centroid (NTC), or gene expression deviation (GED). The pathway score matrix is clustered using both k-means and hierarchical clustering, and a clustering is judged by how well it groups patients into distinct survival classes. The most effective pathway scoring/clustering combination, per clustering p-value, thus generates various ‘signatures’ for conventional and functional cancer classification. Results: PICS successfully regularized large dimension gene data, separated normal and cancerous tissues, and clustered a large patient cohort spanning six cancer types. Furthermore, PICS clustered patient cohorts into distinct, statistically-significant survival groups. For a suboptimally-debulked ovarian cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00127) showed significant improvement over that of a prior gene expression-classified study (p = .0179). For a pancreatic cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00141) showed significant improvement over that of a prior gene expression-classified study (p = .04). Pathway-based classification confirmed biomarkers for the pyrimidine, WNT-signaling, glycerophosphoglycerol, beta-alanine, and panthothenic acid pathways for ovarian cancer. Despite its robust nature, PICS requires significantly less run time than current pathway scoring methods. Conclusion: This work validates the PICS method to improve

  17. How to grow a kidney: patient-specific kidney organoids come of age.

    Science.gov (United States)

    Schmidt-Ott, Kai M

    2017-01-01

    The notion of regrowing a patient's kidney in a dish has fascinated researchers for decades and has spurred visions of revolutionary clinical applications. Recently, this option has come closer to reality. Key technologies have been developed to generate patient-specific pluripotent stem cells and to edit their genome. Several laboratories have devised protocols to differentiate patient-specific pluripotent stem cells into kidney cells or into in vitro organoids that resemble the kidney with respect to cell types, tissue architecture and disease pathology. This was possible because of rapidly expanding knowledge regarding the cellular and molecular basis of embryonic kidney development. Generating kidney cells or organoids from patient-specific stem cells may prove to be clinically useful in several ways. First, patient-specific kidney cells or organoids could be used to predict an individual's response to stressors, toxins or medications and thereby develop personalized treatment decisions. Second, patient-specific stem cells harbour the individual's genetic defects. This may potentially enable genetic rescue attempts to establish the significance of a genetic defect in a stem cell-derived organoid or it may allow testing of patient-specific targeted therapies for kidney disease in vitro. From a tissue engineering perspective, patient-specific kidney organoids might provide a key advance towards engineering immunocompatible transplantable kidneys. This review article summarizes recent developments in the field and discusses its current limitations and future perspectives. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  18. Are There Gender-Specific Risk Factors for Suicidal Activity among Patients with Schizophrenia and Depression?

    Science.gov (United States)

    Kaplan, Kalman J.; Harrow, Martin; Faull, Robert N.

    2012-01-01

    Are there gender-specific risk factors for suicidal activity among patients with schizophrenia and depression? A total of 74 schizophrenia patients (51 men, 23 women) and 77 unipolar nonpsychotic depressed patients (26 men, 51 women) from the Chicago Follow-up Study were studied prospectively at 2 years posthospitalization and again at 7.5 years.…

  19. Prostate specific antigen levels and prostate cancer detection rates in patients with end stage renal disease.

    Science.gov (United States)

    Chen, Catherine J; Heldt, Jonathan P; Anderson, Kirk M; Ruckle, Herbert C; Agarwal, Gautum; Smith, Damien L; Schlaifer, Amy E; Richards, Gideon D; Arnold, Don C; Baldwin, D Duane

    2012-06-01

    Patients with end stage renal disease plus prostate cancer are ineligible to receive a renal transplant at most centers until an acceptable cancer-free period is demonstrated. To our knowledge previously established prostate specific antigen reference ranges have not been validated in patients with end stage renal disease. We determined age stratified 95th percentile prostate specific antigen reference ranges and the prostate cancer detection rate at specific prostate specific antigen intervals for patients with end stage renal disease. We retrospectively reviewed the records of 775 male patients with end stage renal disease on the waiting list for a renal transplant who had undergone a serum prostate specific antigen test. Prostate specific antigen was stratified by age at the time of the blood test and 95th percentile reference ranges were calculated for each decade. A total of 80 patients underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination. The cancer detection rate was calculated for specific prostate specific antigen reference ranges. The age specific 95th percentile prostate specific antigen references ranges were 0 to 4.0 ng/ml for ages 40 to 49 in 137 patients, 0 to 5.3 ng/ml for ages 50 to 59 in 257, 0 to 10.5 ng/ml for ages 60 to 69 in 265 and 0 to 16.6 ng/ml for ages 70 to 79 years in 69. The cancer detection rate was 44%, 38% and 67% for prostate specific antigen 2.5 to 4.0, 4 to 10 and greater than 10 ng/ml, respectively. In our study population of patients with end stage renal disease age stratified prostate specific antigen was higher than in the general population. The cancer detection rate was increased in our patients with end stage renal disease compared to that in patients with normal renal function at specific prostate specific antigen intervals. Lower prostate specific antigen cutoffs may be appropriate to recommend prostate biopsy in patients with end stage renal disease. Copyright

  20. Automated identification of brain tumors from single MR images based on segmentation with refined patient-specific priors.

    Science.gov (United States)

    Sanjuán, Ana; Price, Cathy J; Mancini, Laura; Josse, Goulven; Grogan, Alice; Yamamoto, Adam K; Geva, Sharon; Leff, Alex P; Yousry, Tarek A; Seghier, Mohamed L

    2013-01-01

    Brain tumors can have different shapes or locations, making their identification very challenging. In functional MRI, it is not unusual that patients have only one anatomical image due to time and financial constraints. Here, we provide a modified automatic lesion identification (ALI) procedure which enables brain tumor identification from single MR images. Our method rests on (A) a modified segmentation-normalization procedure with an explicit "extra prior" for the tumor and (B) an outlier detection procedure for abnormal voxel (i.e., tumor) classification. To minimize tissue misclassification, the segmentation-normalization procedure requires prior information of the tumor location and extent. We therefore propose that ALI is run iteratively so that the output of Step B is used as a patient-specific prior in Step A. We test this procedure on real T1-weighted images from 18 patients, and the results were validated in comparison to two independent observers' manual tracings. The automated procedure identified the tumors successfully with an excellent agreement with the manual segmentation (area under the ROC curve = 0.97 ± 0.03). The proposed procedure increases the flexibility and robustness of the ALI tool and will be particularly useful for lesion-behavior mapping studies, or when lesion identification and/or spatial normalization are problematic.

  1. Automated identification of brain tumours from single MR images based on segmentation with refined patient-specific priors

    Directory of Open Access Journals (Sweden)

    Ana eSanjuán

    2013-12-01

    Full Text Available Brain tumours can have different shapes or locations, making their identification very challenging. In functional MRI, it is not unusual that patients have only one anatomical image due to time and financial constraints. Here, we provide a modified automatic lesion identification (ALI procedure which enables brain tumour identification from single MR images. Our method rests on (A a modified segmentation-normalisation procedure with an explicit extra prior for the tumour and (B an outlier detection procedure for abnormal voxel (i.e. tumour classification. To minimise tissue misclassification, the segmentation-normalisation procedure requires prior information of the tumour location and extent. We therefore propose that ALI is run iteratively so that the output of Step B is used as a patient-specific prior in Step A. We test this procedure on real T1-weighted images from 18 patients, and the results were validated in comparison to two independent observers’ manual tracings. The automated procedure identified the tumours successfully with an excellent agreement with the manual segmentation (area under the ROC curve = 0.97 ± 0.03. The proposed procedure increases the flexibility and robustness of the ALI tool and will be particularly useful for lesion-behaviour mapping studies, or when lesion identification and/or spatial normalisation are problematic.

  2. Patient-specific modeling and quantification of the aortic and mitral valves from 4-D cardiac CT and TEE.

    Science.gov (United States)

    Ionasec, Razvan Ioan; Voigt, Ingmar; Georgescu, Bogdan; Wang, Yang; Houle, Helene; Vega-Higuera, Fernando; Navab, Nassir; Comaniciu, Dorin

    2010-09-01

    As decisions in cardiology increasingly rely on noninvasive methods, fast and precise image processing tools have become a crucial component of the analysis workflow. To the best of our knowledge, we propose the first automatic system for patient-specific modeling and quantification of the left heart valves, which operates on cardiac computed tomography (CT) and transesophageal echocardiogram (TEE) data. Robust algorithms, based on recent advances in discriminative learning, are used to estimate patient-specific parameters from sequences of volumes covering an entire cardiac cycle. A novel physiological model of the aortic and mitral valves is introduced, which captures complex morphologic, dynamic, and pathologic variations. This holistic representation is hierarchically defined on three abstraction levels: global location and rigid motion model, nonrigid landmark motion model, and comprehensive aortic-mitral model. First we compute the rough location and cardiac motion applying marginal space learning. The rapid and complex motion of the valves, represented by anatomical landmarks, is estimated using a novel trajectory spectrum learning algorithm. The obtained landmark model guides the fitting of the full physiological valve model, which is locally refined through learned boundary detectors. Measurements efficiently computed from the aortic-mitral representation support an effective morphological and functional clinical evaluation. Extensive experiments on a heterogeneous data set, cumulated to 1516 TEE volumes from 65 4-D TEE sequences and 690 cardiac CT volumes from 69 4-D CT sequences, demonstrated a speed of 4.8 seconds per volume and average accuracy of 1.45 mm with respect to expert defined ground-truth. Additional clinical validations prove the quantification precision to be in the range of inter-user variability. To the best of our knowledge this is the first time a patient-specific model of the aortic and mitral valves is automatically estimated from

  3. Kissing selectively decreases allergen-specific IgE production in atopic patients.

    Science.gov (United States)

    Kimata, H

    2006-05-01

    Stress enhanced allergic skin wheal responses and allergen-specific IgE production. In contrast, mothers' kissing caused relaxation in infants, and kissing by lovers or spouses to atopic patients reduced allergic skin wheal responses. I studied the effect of kissing on production of allergen-specific IgE and cytokines in atopic patients. Twenty-four patients with mild atopic eczema and 24 patients with mild allergic rhinitis kissed with lovers or spouses freely for 30 min while listening to soft music. Just before and immediately after kissing, blood mononuclear cells were separated cultured for allergen, and production of allergen-specific immunoglobulin and cytokine was measured. Kissing selectively decreased allergen-specific IgE production with skewing cytokine pattern toward Th1 type. Kissing may alleviate allergic symptoms by decrease in allergen-specific IgE production.

  4. Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir.

    Science.gov (United States)

    Hensel, Michael T; Marshall, Jason D; Dorwart, Michael R; Heeke, Darren S; Rao, Eileen; Tummala, Padmaja; Yu, Li; Cohen, Gary H; Eisenberg, Roselyn J; Sloan, Derek D

    2017-05-01

    Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Th1-inducing Toll-like receptor (TLR) agonists in vivo In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses. IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors

  5. Patient specific finite element model of the face soft tissues for computer-assisted maxillofacial surgery.

    Science.gov (United States)

    Chabanas, Matthieu; Luboz, Vincent; Payan, Yohan

    2003-06-01

    This paper addresses the prediction of face soft tissue deformations resulting from bone repositioning in maxillofacial surgery. A generic 3D Finite Element model of the face soft tissues was developed. Face muscles are defined in the mesh as embedded structures, with different mechanical properties (transverse isotropy, stiffness depending on muscle contraction). Simulations of face deformations under muscle actions can thus be performed. In the context of maxillofacial surgery, this generic soft-tissue model is automatically conformed to patient morphology by elastic registration, using skin and skull surfaces segmented from a CT scan. Some elements of the patient mesh could be geometrically distorted during the registration, which disables Finite Element analysis. Irregular elements are thus detected and automatically regularized. This semi-automatic patient model generation is robust, fast and easy to use. Therefore it seems compatible with clinical use. Six patient models were successfully built, and simulations of soft tissue deformations resulting from bone displacements performed on two patient models. Both the adequation of the models to the patient morphologies and the simulations of post-operative aspects were qualitatively validated by five surgeons. Their conclusions are that the models fit the morphologies of the patients, and that the predicted soft tissue modifications are coherent with what they would expect.

  6. Evidence for specific cognitive deficits in visual information processing in patients with OCD compared to patients with unipolar depression.

    Science.gov (United States)

    Rampacher, Friederike; Lennertz, Leonhard; Vogeley, Andrea; Schulze-Rauschenbach, Svenja; Kathmann, Norbert; Falkai, Peter; Wagner, Michael

    2010-08-16

    Neuropsychological studies comparing cognitive performance in patients suffering from Obsessive-Compulsive Disorder (OCD) or Major Depressive Disorder (MDD) revealed deficits in the domains of verbal fluency and viso-motor speed/set shifting in both groups. Spatial working memory deficits, however, have been identified as specific markers of OCD. As yet, it has not been substantiated whether deficits in visual organization and complex visual memory are also specific to OCD and are not shared by MDD. Test performance in seven cognitive domains was assessed in 40 OCD patients, 20 MDD patients, and 40 healthy controls. Patient groups were matched according to severity of depressive symptoms. Deficits shared by both patient groups, as compared to controls, were found in delayed spatial recall and verbal fluency while verbal memory was normal in both patient groups. Only patients with OCD, but not MDD patients were impaired in the domains visual memory, viso-motor speed/set shifting, visual organization, and problem solving. In addition, OCD patients differed significantly from MDD subjects in visual organization and problem solving. Visual organization scores correlated significantly with severity of current compulsions in the OCD group (r=-.324). OCD patients demonstrate difficulties in visual organization and mental manipulation of complex visual material, which are not accounted for by depressive symptoms and which constitute a specific cognitive deficit of the disorder. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  7. Accuracy and Reproducibility Using Patient-Specific Instrumentation in Total Ankle Arthroplasty.

    Science.gov (United States)

    Daigre, Justin; Berlet, Gregory; Van Dyke, Bryan; Peterson, Kyle S; Santrock, Robert

    2017-04-01

    Implant survivorship is dependent on accuracy of implantation and successful soft tissue balancing. System instrumentation for total ankle arthroplasty implantation has a key influence on surgeon accuracy and reproducibility. The purpose of this study was to determine the accuracy and reproducibility of implant position with patient-specific guides for total ankle arthroplasty across multiple surgeons at multiple facilities. This retrospective, multicenter study included 44 patients who received a total ankle implant (INBONE II Total Ankle System; Wright Medical Technology, Memphis, TN) using PROPHECY patient-specific guides from January 2012 to December 2014. Forty-four patients with an average age of 63.0 years underwent total ankle arthroplasty using this preoperative patient-specific system. Preoperative computed tomography (CT) scans were obtained to assess coronal plane deformity, assess mechanical and anatomic alignment, and build patient-specific guides that referenced bony anatomy. The mean preoperative coronal deformity was 4.6 ± 4.6 degrees (range, 14 degrees varus to 17 degrees valgus). The first postoperative weightbearing radiographs were used to measure coronal and sagittal alignment of the implant vs the anatomic axis of the tibia. In 79.5% of patients, the postoperative implant position of the tibia corresponded to the preoperative plan of the tibia within 3 degrees of the intended target, within 4 degrees in 88.6% of patients, and within 5 degrees in 100% of patients. The tibial component coronal size was correctly predicted in 98% of cases, whereas the talar component was correctly predicted in 80% of cases. The use of patient-specific instrumentation for total ankle arthroplasty provided reliable alignment and reproducibility in the clinical situation similar to that shown in cadaveric testing. This study has shown that the preoperative patient-specific instrumentation provided for accuracy and reproducibility of ankle arthroplasty implantation

  8. Applying machine learning to predict patient-specific current CD 4 ...

    African Journals Online (AJOL)

    Applying machine learning to predict patient-specific current CD4 cell count in order to determine the progression of human immunodeficiency virus (HIV) infection. Yashik Singh, Nitesh Narsai, Maurice Mars ...

  9. Patient-specific Modeling of the Heart: Estimation of Ventricular Fiber Orientations

    National Research Council Canada - National Science Library

    Vadakkumpadan, Fijoy; Arevalo, Hermenegild; Trayanova, Natalia A

    2013-01-01

    Patient-specific simulations of heart (dys)function aimed at personalizing cardiac therapy are hampered by the absence of in vivo imaging technology for clinically acquiring myocardial fiber orientations...

  10. Estimating patient-specific and anatomically correct reference model for craniomaxillofacial deformity via sparse representation.

    Science.gov (United States)

    Wang, Li; Ren, Yi; Gao, Yaozong; Tang, Zhen; Chen, Ken-Chung; Li, Jianfu; Shen, Steve G F; Yan, Jin; Lee, Philip K M; Chow, Ben; Xia, James J; Shen, Dinggang

    2015-10-01

    A significant number of patients suffer from craniomaxillofacial (CMF) deformity and require CMF surgery in the United States. The success of CMF surgery depends on not only the surgical techniques but also an accurate surgical planning. However, surgical planning for CMF surgery is challenging due to the absence of a patient-specific reference model. Currently, the outcome of the surgery is often subjective and highly dependent on surgeon's experience. In this paper, the authors present an automatic method to estimate an anatomically correct reference shape of jaws for orthognathic surgery, a common type of CMF surgery. To estimate a patient-specific jaw reference model, the authors use a data-driven method based on sparse shape composition. Given a dictionary of normal subjects, the authors first use the sparse representation to represent the midface of a patient by the midfaces of the normal subjects in the dictionary. Then, the derived sparse coefficients are used to reconstruct a patient-specific reference jaw shape. The authors have validated the proposed method on both synthetic and real patient data. Experimental results show that the authors' method can effectively reconstruct the normal shape of jaw for patients. The authors have presented a novel method to automatically estimate a patient-specific reference model for the patient suffering from CMF deformity.

  11. Development of disease-specific quality indicators for danish chiropractic patients with low back pain

    DEFF Research Database (Denmark)

    Sorensen, Line P; Krog, Birgitte R; Kongsted, Alice

    2011-01-01

    The purpose of this study is to develop disease-specific quality indicators for Danish chiropractic patients with low back pain (LBP) as an initial effort to include chiropractors in the Danish Health Care Quality Programme.......The purpose of this study is to develop disease-specific quality indicators for Danish chiropractic patients with low back pain (LBP) as an initial effort to include chiropractors in the Danish Health Care Quality Programme....

  12. From Patient-Specific Mathematical Neuro-Oncology to Precision Medicine

    Directory of Open Access Journals (Sweden)

    Anne eBaldock

    2013-04-01

    Full Text Available Gliomas are notoriously aggressive, malignant brain tumors that have variable response to treatment. These patients often have poor prognosis, informed primarily by histopathology. Mathematical neuro-oncology (MNO is a young and burgeoning field that leverages mathematical models to predict and quantify response to therapies. These mathematical models can form the basis of modern precision medicine approaches to tailor therapy in a patient-specific manner. Patient specific models (PSMs can be used to overcome imaging limitations, improve prognostic predictions, stratify patients and assess treatment response in silico. The information gleaned from such models can aid in the construction and efficacy of clinical trials and treatment protocols, accelerating the pace of clinical research in the war on cancer. This review focuses on the growing translation of PSM to clinical neuro-oncology. It will also provide a forward-looking view on a new era of patient-specific mathematical neuro-oncology.

  13. Robust multivariate analysis

    CERN Document Server

    J Olive, David

    2017-01-01

    This text presents methods that are robust to the assumption of a multivariate normal distribution or methods that are robust to certain types of outliers. Instead of using exact theory based on the multivariate normal distribution, the simpler and more applicable large sample theory is given.  The text develops among the first practical robust regression and robust multivariate location and dispersion estimators backed by theory.   The robust techniques  are illustrated for methods such as principal component analysis, canonical correlation analysis, and factor analysis.  A simple way to bootstrap confidence regions is also provided. Much of the research on robust multivariate analysis in this book is being published for the first time. The text is suitable for a first course in Multivariate Statistical Analysis or a first course in Robust Statistics. This graduate text is also useful for people who are familiar with the traditional multivariate topics, but want to know more about handling data sets with...

  14. Giving voice to cancer patients: assessing non-specific effects of an integrative oncology therapeutic program via short patient narratives.

    Science.gov (United States)

    Keshet, Yael; Schiff, Elad; Samuels, Noah; Ben-Arye, Eran

    2015-02-01

    The aim of this study was to assess patient perspectives regarding non-specific effects of a complementary medicine (CM) consultation and intervention within an integrative oncology setting. Patients undergoing chemotherapy in a community-based oncology service were referred by oncology healthcare providers to an integrative oncology physician trained in CM-oriented supportive care. Assessment of concerns and well-being was made using the Measure Yourself Concerns and Wellbeing questionnaire, at baseline and after 3 months of CM treatments, which were designed to improve quality of life (QoL) outcomes. Patients were asked to describe the most important aspects of the integrative treatment process. Free-text narratives were examined using content analysis with ATLAS.Ti software for systematic coding. Of 152 patients' narratives analyzed, 44% reported an experience of patient-centered care, including CM practitioners' approach of togetherness, uniqueness, and the invoking of an internal process. CM practitioner approach was experienced within a context of an enhanced sense of confidence; gaining a different perspective; and acquiring emotional resilience and empowerment. Short patient narratives should be considered for patient-reported outcomes, expressing perspectives of both effects and experience of care. CM may promote patient QoL-related outcomes through non-specific effects, enhancing patient-centered care. The benefits of CM dependent on general therapeutic incidental aspects (i.e., common factors) warrant attention regarding non-specific components of treatment. Copyright © 2014 John Wiley & Sons, Ltd.

  15. The specific IgE reactivity pattern of weed pollen-induced allergic rhinitis patients.

    Science.gov (United States)

    Han, Demin; Lai, Xuxin; Gjesing, Birgitte; Zhong, Nanshan; Zhang, Luo; Spangfort, Michael D

    2011-05-01

    Specific immunoglobulin E (IgE) reactivity towards the major mugwort allergen Art v 1 is a good indicator for Art v sensitization. Allergens from the ragweed species Amb t and Amb a possibly share common IgE-binding epitopes. The aim of this study was to investigate the reactivity pattern of IgE in Chinese patients with weed pollen-induced allergic rhinitis. Sera from 50 weed pollen-induced allergic rhinitis patients were tested for specific serum IgE reactivity against allergenic extracts of mugwort (Artemisia vulgaris, Art v), short ragweed (Ambrosia artemisiifolia, Amb a), giant ragweed (Ambrosia trifida, Amb t), and single allergens of Art v 1, Art v 3, Amb a 1, and profilin. Sera from 88% of the patients demonstrated positive specific IgE reactivity to Art v, and of these 82% were positive to Art v 1. Sera from 38% of the patients showed positive specific IgE reactivity to both ragweed species Amb t and Amb a. A strong correlation was found between the specific IgE levels of Amb t and Amb a. Of the Amb a IgE-positive patients, 38% were positive for Amb a 1. Of all patient sera tested, 12% were specific IgE-positive to profilin.

  16. Preserved antigen-specific immune response in patients with multiple sclerosis responding to IFNβ-therapy.

    Directory of Open Access Journals (Sweden)

    Matthias Mehling

    Full Text Available BACKGROUND: Interferon-beta (IFNβ regulates the expression of a complex set of pro- as well as anti-inflammatory genes. In cohorts of MS patients unstratified for therapeutic response to IFNβ, normal vaccine-specific immune responses have been observed. Data capturing antigen-specific immune responses in cohorts of subjects defined by response to IFNβ-therapy are not available. OBJECTIVE: To assess antigen-specific immune responses in a cohort of MS patients responding clinically and radiologically to IFNβ. METHODS: In 26 MS patients, clinical and MRI disease activity were assessed before and under treatment with IFNβ. Humoral and cellular immune response to influenza vaccine was prospectively characterized in these individuals, and 33 healthy controls by influenza-specific Enzyme-Linked Immunosorbent Assay (ELISA and Enzyme Linked Immuno Spot Technique (ELISPOT. RESULTS: Related to pre-treatment disease activity, IFNβ reduced clinical and radiological MS disease-activity. Following influenza vaccination, frequencies of influenza-specific T cells and concentrations of anti-influenza A and B IgM and IgG increased comparably in MS-patients and in healthy controls. CONCLUSIONS: By showing in a cohort of MS-patients responding to IFNβ vaccine-specific immune responses comparable to controls, this study indicates that antigen-specific immune responses can be preserved under successful IFNβ-therapy.

  17. [Specific variability of teicoplanin protein binding in patients receiving continuous hemodiafiltration-comparison with hypoalbuminemia patients].

    Science.gov (United States)

    Yanagimoto, Hiromi; Teramatsu, Tsuyoshi; Goto, Junko; Yanagisawa, Masahiko; Harii, Norikazu; Suzuki, Masahiko; Hanawa, Takehisa; Matsuda, Kenichi; Oguchi, Toshio

    2013-01-01

    Variation in protein binding ratio (PBR) of teicoplanin (TEIC) was investigated in continuous hemodiafiltration (CHDF) patients. TEIC is classified as a high PBR drug (≧90%), and it was reported that the PBR of TEIC decreased with an decrease in the serum albumin level in hypoalbuminemia patients. However, few reports can be found about the variation of PBR of TEIC for CHDF patient. An antibiotic activity is directly determined by the level of unbound antibiotics species (Cfree) in the target site, namely, an increase in the Cfree enhances the risks of TEIC as well as the therapeutic effect against Methicillin-resistant Staphylococcus aureus (MRSA). In this study, both the total concentration (Ctotal) and Cfree of TEIC were determined and the PBRs were compared between a patient with normal albumin level, hypoalbuminemia patients and CHDF patients. Similarly to the previous report, the lowering of PBR of TEIC was demonstrated in the hypoalbuminemia patients. On the other hand, the CHDF patients showed lower value of PBR suggesting some change in the protein binding ability, although showed higher values of serum albumin level in comparison with the hypoalbuminemia patients. It was not necessary to measure the Cfree value for the hypoalbuminemia patient routinely, but the monitoring of Cfree as well as Ctotal for the CHDF patients can be important for the proper TEIC use because of the potential specialty of PBR.

  18. DETECTION OF ALLERGEN SPECIFIC PLASMA CELLS IN ALLERGIC PATIENTS TREATED WITH SUBCUTANEOUS IMMUNOTHERAPY

    DEFF Research Database (Denmark)

    Schmid, Johannes Martin; Dahl, Ronald; Hoffmann, Hans Jürgen

    the immune response in allergic patients and results in an inhibition of the specific type 1 allergic response. This inhibition is mainly brought about by a change in the immunoglobulin response pattern from allergen specific IgE towards predominantly IgG. Seven days after vaccination with tetanus vaccine...

  19. Some like it specific: the difference between treatment goals of anxious and depressed patients.

    Science.gov (United States)

    Grosse Holtforth, Martin; Wyss, Tamara; Schulte, Dietmar; Trachsel, Manuel; Michalak, Johannes

    2009-09-01

    While clinical diagnoses are the primary criteria for differential indication in psychotherapy, treatment-goal themes may provide additional information on diagnosis-specific and extra-diagnostic aspects of treatment motivation. It is hypothesized that the goals of anxiety patients focus on symptom relief, while the goals of depression patients are thematically more heterogeneous. Additionally, it is hypothesized that patients with various specific anxiety disorders can be differentiated on their treatment-goal themes. To obtain a sufficiently large number of diagnostically non-comorbid patients, a sample of 328 patients with non-comorbid anxiety and depression patients was merged from two subsamples: 255 outpatients from a university-based clinic in Germany and 73 outpatients from a comparable clinic in German-speaking Switzerland. The treatment-goal themes of the 328 outpatients were coded using the Bern inventory of treatment goals. Patients with non-comorbid diagnoses of depression or anxiety differed as hypothesized. Anxiety patients' treatment goals predominantly focused on symptom relief, while depression patients' treatment goals were thematically more heterogeneous. In addition, patients with various specific anxiety disorders differed in their treatment-goal themes. Implications for clinical assessment and treatment planning are discussed.

  20. Cellular Reprogramming Allows Generation of Autologous Hematopoietic Progenitors From AML Patients That Are Devoid of Patient-Specific Genomic Aberrations

    Science.gov (United States)

    Salci, Kyle R; Lee, Jong-Hee; Laronde, Sarah; Dingwall, Steve; Kushwah, Rahul; Fiebig-Comyn, Aline; Leber, Brian; Foley, Ronan; Dal Cin, Arianna; Bhatia, Mickie

    2015-01-01

    Current treatments that use hematopoietic progenitor cell (HPC) transplantation in acute myeloid leukemia (AML) patients substantially reduce the risk of relapse, but are limited by the availability of immune compatible healthy HPCs. Although cellular reprogramming has the potential to provide a novel autologous source of HPCs for transplantation, the applicability of this technology toward the derivation of healthy autologous hematopoietic cells devoid of patient-specific leukemic aberrations from AML patients must first be evaluated. Here, we report the generation of human AML patient-specific hematopoietic progenitors that are capable of normal in vitro differentiation to myeloid lineages and are devoid of leukemia-associated aberration found in matched patient bone marrow. Skin fibroblasts were obtained from AML patients whose leukemic cells possessed a distinct, leukemia-associated aberration, and used to create AML patient-specific induced pluripotent stem cells (iPSCs). Through hematopoietic differentiation of AML patient iPSCs, coupled with cytogenetic interrogation, we reveal that AML patient-specific HPCs possess normal progenitor capacity and are devoid of leukemia-associated mutations. Importantly, in rare patient skin samples that give rise to mosaic fibroblast cultures that continue to carry leukemia-associated mutations; healthy hematopoietic progenitors can also be generated via reprogramming selection. Our findings provide the proof of principle that cellular reprogramming can be applied on a personalized basis to generate healthy HPCs from AML patients, and should further motivate advances toward creating transplantable hematopoietic stem cells for autologous AML therapy. Stem Cells 2013;33:1839–1849 PMID:25764124

  1. Patient-specific radiation dose and cancer risk estimation in pediatric chest CT: a study in 30 patients

    Science.gov (United States)

    Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

    2010-04-01

    Radiation-dose awareness and optimization in CT can greatly benefit from a dosereporting system that provides radiation dose and cancer risk estimates specific to each patient and each CT examination. Recently, we reported a method for estimating patientspecific dose from pediatric chest CT. The purpose of this study is to extend that effort to patient-specific risk estimation and to a population of pediatric CT patients. Our study included thirty pediatric CT patients (16 males and 14 females; 0-16 years old), for whom full-body computer models were recently created based on the patients' clinical CT data. Using a validated Monte Carlo program, organ dose received by the thirty patients from a chest scan protocol (LightSpeed VCT, 120 kVp, 1.375 pitch, 40-mm collimation, pediatric body scan field-of-view) was simulated and used to estimate patient-specific effective dose. Risks of cancer incidence were calculated for radiosensitive organs using gender-, age-, and tissue-specific risk coefficients and were used to derive patientspecific effective risk. The thirty patients had normalized effective dose of 3.7-10.4 mSv/100 mAs and normalized effective risk of 0.5-5.8 cases/1000 exposed persons/100 mAs. Normalized lung dose and risk of lung cancer correlated strongly with average chest diameter (correlation coefficient: r = -0.98 to -0.99). Normalized effective risk also correlated strongly with average chest diameter (r = -0.97 to -0.98). These strong correlations can be used to estimate patient-specific dose and risk prior to or after an imaging study to potentially guide healthcare providers in justifying CT examinations and to guide individualized protocol design and optimization.

  2. Prostate specific antigen in patients of benign prostate hypertrophy and carcinoma prostate

    OpenAIRE

    Malati, T.; Kumari, G. Rajani; Murthy, P. V. L. N.; Reddy, Ch.Ram; Prakash, B. Surya

    2006-01-01

    Prostate Specific Antigen (PSA) has emerged as the most applicable and important tumor marker for carcinoma prostate. In the present study PSA was determined in serum of healthy subjects, patients of benign prostate hypertrophy (BPH) and Carcinoma Prostate (Ca−P) to evaluate its diagnostic efficiency in day to day management of prostate cancer patients and in differentiating patients of early prostate cancer from those with BPH. Receiver operating characteristic curve (ROC) revealed 2 ng/ml a...

  3. Target Word-Specific Experiment by Detecting Event-Related Potential for ALS Patients

    Science.gov (United States)

    Kanou, Naoyuki; Sakuma, Kenji; Nakashima, Kenji

    For communication of ALS patients, the authors put emphasis on ERP. This paper described that ALS patient could get high rate of correct judgment on the target word-specific experiment by detecting ERP. For practical use, it is very important that ALS patients can communicate with surrounding person smoothly. The authors discussed how to shorten the time to specify the target word, and discussed the prevention of misjudgment.

  4. Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia.

    Directory of Open Access Journals (Sweden)

    Katrina Vanura

    Full Text Available Chronic lymphocytic leukemia (CLL is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200. CMV-DNA was detected in 3% (6/200 of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03 and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001. Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06 and mean decay values differed significantly from those of total IgG (p=0.034. Boosts of CMV-specific antibody levels were observed in 49% (22/45 of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively. VZV-specific IgG even became undetectable in 18% (9/50 of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered

  5. Patient specific root-analogue dental implants – additive manufacturing and finite element analysis

    Directory of Open Access Journals (Sweden)

    Gattinger Johannes

    2016-09-01

    Full Text Available Aim of this study was to prove the possibility of manufacturing patient specific root analogue two-part (implant and abutment implants by direct metal laser sintering. The two-part implant design enables covered healing of the implant. Therefore, CT-scans of three patients are used for reverse engineering of the implants, abutments and crowns. Patient specific implants are manufactured and measured concerning dimensional accuracy and surface roughness. Impacts of occlusal forces are simulated via FEA and compared to those of standard implants.

  6. Developing patient-specific anatomic models for validation of cardiac ablation guidance procedures

    Science.gov (United States)

    Holmes, David, III; Rettmann, Maryam; Cameron, Bruce; Camp, Jon; Robb, Richard

    2008-03-01

    Image-guided cardiac ablation has the potential to decrease procedure times and improve clinical outcome for patients with cardiac arrhythmias. There are several proposed methods for integrating patient-specific anatomy into the cardiac ablation procedure; however, these methods require thorough validation. One of the primary challenges in validation is determining ground truth as a standard for comparison. Some validation protocols have been developed for animals models and even in patients; however, these methods can be costly to implement and may increase the risk to patients. We have developed an approach to building realistic patient-specific anatomic models at a low-cost in order to validate the guidance procedure without introducing additional risk to the patients. Using a pre-procedural cardiac computed tomography scan, the blood pool of the left and right atria of a patient are segmented semi-manually. In addition, several anatomical landmarks are identified in the image data. The segmented atria and landmarks are converted into a polygonalized model which is used to build a thin-walled patient-specific blood pool model in a stereo-lithography system. Thumbscrews are inserted into the model at the landmarks. The entire model is embedded in a platinum silicone material which has been shown to have tissue-mimicking properties relative to ultrasound. Once the pliable mold has set, the blood pool model is extracted by dissolving the rigid material. The resulting physical model correctly mimics a specific patient anatomy with embedded fiducals which can be used for validation experiments. The patient-specific anatomic model approach may also be used for pre-surgical practice and training of new interventionalists.

  7. Development of an integrated CAD-FEA system for patient-specific design of spinal cages.

    Science.gov (United States)

    Zhang, Mingzheng; Pu, Fang; Xu, Liqiang; Zhang, Linlin; Liang, Hang; Li, Deyu; Wang, Yu; Fan, Yubo

    2017-03-01

    Spinal cages are used to create a suitable mechanical environment for interbody fusion in cases of degenerative spinal instability. Due to individual variations in bone structures and pathological conditions, patient-specific cages can provide optimal biomechanical conditions for fusion, strengthening patient recovery. Finite element analysis (FEA) is a valuable tool in the biomechanical evaluation of patient-specific cage designs, but the time- and labor-intensive process of modeling limits its clinical application. In an effort to facilitate the design and analysis of patient-specific spinal cages, an integrated CAD-FEA system (CASCaDeS, comprehensive analytical spinal cage design system) was developed. This system produces a biomechanical-based patient-specific design of spinal cages and is capable of rapid implementation of finite element modeling. By comparison with commercial software, this system was validated and proven to be both accurate and efficient. CASCaDeS can be used to design patient-specific cages with a superior biomechanical performance to commercial spinal cages.

  8. SU-E-T-529: Is MFO-IMPT Robust Enough for the Treatment of Head and Neck Tumors? A 2-Year Outcome Analysis Following Proton Therapy On the First 50 Oropharynx Patients at the MD Anderson Cancer Center

    Energy Technology Data Exchange (ETDEWEB)

    Frank, S; Garden, A; Anderson, M; Rosenthal, D; Morrison, W; Gunn, B; Fuller, C; Phan, J; Zhang, X; Poenisch, F; Wu, R; Li, H; Gautam, A; Sahoo, N; Gillin, M; Zhu, X [MD Anderson Cancer Ctr., Houston, TX (United States)

    2015-06-15

    Purpose: Multi-field optimization intensity modulated proton therapy (MFO-IMPT) for oropharyngeal tumors has been established using robust planning, robust analysis, and robust optimization techniques. While there are inherent uncertainties in proton therapy treatment planning and delivery, outcome reporting are important to validate the proton treatment process. The purpose of this study is to report the first 50 oropharyngeal tumor patients treated de-novo at a single institution with MFO-IMPT. Methods: The data from the first 50 patients with squamous cell carcinoma of the oropharynx treated at MD Anderson Cancer Center from January 2011 to December 2014 on a prospective IRB approved protocol were analyzed. Outcomes were analyzed to include local, regional, and distant treatment failures. Acute and late toxicities were analyzed by CTCAE v4.0. Results: All patients were treated with definitive intent. The median follow-up time of the 50 patients was 25 months. Patients by gender were male (84%) and female (16%). The average age was 61 years. 50% of patients were never smokers and 4% were current smokers. Presentation by stage; I–1, II–0, III– 9, IVA–37 (74%), IVB–3. 88% of patients were HPV/p16+. Patients were treated to 66–70 CGE. One local failure was reported at 13 months following treatment. One neck failure was reported at 12 months. 94% of patients were alive with no evidence of disease. One patient died without evidence of disease. There were no Grade 4 or Grade 5 toxicities. Conclusion: MFO-IMPT for oropharyngeal tumors is robust and provides excellent outcomes 2 years after treatment. A randomized trial is underway to determine if proton therapy will reduce chronic late toxicities of IMRT.

  9. Coupling of EIT with computational lung modeling for predicting patient-specific ventilatory responses.

    Science.gov (United States)

    Roth, Christian J; Becher, Tobias; Frerichs, Inéz; Weiler, Norbert; Wall, Wolfgang A

    2017-04-01

    Providing optimal personalized mechanical ventilation for patients with acute or chronic respiratory failure is still a challenge within a clinical setting for each case anew. In this article, we integrate electrical impedance tomography (EIT) monitoring into a powerful patient-specific computational lung model to create an approach for personalizing protective ventilatory treatment. The underlying computational lung model is based on a single computed tomography scan and able to predict global airflow quantities, as well as local tissue aeration and strains for any ventilation maneuver. For validation, a novel "virtual EIT" module is added to our computational lung model, allowing to simulate EIT images based on the patient's thorax geometry and the results of our numerically predicted tissue aeration. Clinically measured EIT images are not used to calibrate the computational model. Thus they provide an independent method to validate the computational predictions at high temporal resolution. The performance of this coupling approach has been tested in an example patient with acute respiratory distress syndrome. The method shows good agreement between computationally predicted and clinically measured airflow data and EIT images. These results imply that the proposed framework can be used for numerical prediction of patient-specific responses to certain therapeutic measures before applying them to an actual patient. In the long run, definition of patient-specific optimal ventilation protocols might be assisted by computational modeling.NEW & NOTEWORTHY In this work, we present a patient-specific computational lung model that is able to predict global and local ventilatory quantities for a given patient and any selected ventilation protocol. For the first time, such a predictive lung model is equipped with a virtual electrical impedance tomography module allowing real-time validation of the computed results with the patient measurements. First promising results

  10. Specific IgG for cat allergens in patients with allergic conjunctivitis.

    Science.gov (United States)

    Miyama, Anri; Mimura, Tatsuya; Noma, Hidetaka; Goto, Mari; Kamei, Yuko; Kondo, Aki; Saito, Yusuke; Okuma, Hiroko; Matsubara, Masao

    2015-08-01

    Immunoglobulin G (IgG) antibodies are involved in type II and type III hypersensitivity. We evaluated the relation between perennial allergic conjunctivitis and serum levels of specific IgG for cat allergens. A prospective study was conducted in patients with seasonal allergic conjunctivitis (seasonal group, n = 10), patients with perennial allergic conjunctivitis (perennial group, n = 10), and healthy control subjects (control group, n = 10). Serum levels of specific IgE and IgG for cat allergens and total tear IgE were measured, and a skin prick test was also performed. In addition, a severity score associated with allergic conjunctivitis was calculated (0-30). The positive rates and scores of for total tear IgE, serum cat-specific IgE, and serum cat-specific IgG were all higher in the seasonal and perennial groups than in the control group (all p cat-specific IgG levels were higher in the perennial group than in the seasonal group (p = 0.0156), but there was no significant difference in the grade of cat-specific IgE between the two groups (p = 0.3008). On multivariate analysis, the mean wheal diameter for cat allergen was associated with the serum level of cat-specific IgG (not IgE) in all patients [odds ratio (OR) = 31.979, p cat-specific IgG (OR = 23.015, p cat allergens.

  11. Presence of organ‑specific antibodies in patients with systemic sclerosis.

    Science.gov (United States)

    Wielosz, Ewa; Majdan, Maria; Koszarny, Arkadiusz; Dryglewska, Magdalena; Tabarkiewicz, Jacek

    2016-10-05

    INTRODUCTION According to the literature, organ‑specific antibodies may be present in the course of systemic sclerosis (SSc). OBJECTIVES The aim of this study was to assess the prevalence of antithyroid antibodies (antithyroid peroxidase antibodies [anti‑TPO] and antithyroglobulin antibodies) and of antimitochondrial antibodies (AMAs), as well as to evaluate their clinical significance in patients with SSc. PATIENTS AND METHODS The study involved 86 consecutive in‑hospital patients with SSc (32 patients with diffuse cutaneous SSc [dcSSc] and 54 with limited cutaneous SSc [lcSSc]). Patients were observed for autoimmune thyroid diseases (ATDs) and primary biliary cirrhosis (PBC). Serum samples were obtained from each patient. RESULTS Positive antithyroid antibody titers were observed in 27 patients (31%) and positive AMA titers-in 11 patients (13%). ATD was diagnosed in 26 patients (30%) and PBC-in 10 patients (12%) with SSc. No significant differences in the prevalence of antithyroid antibodies were found between patients with dcSSc and those with lcSSc, but the prevalence of AMAs was significantly higher in patients with lcSSc compared with those with dcSSc. The prevalence of anti‑Ro‑52 antibodies was significantly higher in the SSc group with positive anti‑TPO antibody titers compared with the SSc group with negative anti‑TPO antibody titers. The prevalence of anticentromere antibodies (ACAs) was significantly higher in the SSc group with positive AMA titers compared with the SSc group with negative AMA titers. CONCLUSIONS The prevalence of organ‑specific antibodies in SSc patients is relatively high. The prevalence of AMAs is higher in patients with lcSSc than in those with dcSSc and is strongly associated with the presence of ACAs. Patients with SSc should be evaluated for coexisting ATDs and PBC.

  12. RAST-specific IgE to egg and milk in Nigerian asthmatic patients.

    Science.gov (United States)

    Onyemelukwe, G C

    2011-03-01

    Food allergens have been described in studies in southern parts of Nigeria but rarely in northern parts of Nigeria. Furthermore, the role of specific antibody to such allergen moieties have not been determined. The aim of this study is to assess the role of two common food items in the aetiology of asthma in Zaria. RAST-specific IgE to milk and egg, which are two common foods in Nigeria, and skin prick tests were therefore studied in bronchial asthma patients and controls in Ahmadu Bello University Teaching Hospital, Zaria to determine their significance in the clinical manifestation of asthma patients. Total serum IgA, IgE and secretory IgA were also measured in patients and controls. RAST titres were poorly discriminating between controls and patients, although six patients had history of gastrointestinal symptoms after ingestion of egg while three patients had history of such symptoms, some with positive skin prick tests and high RAST-specific IgE titres. Asthmatic patients had significantly higher mean serum secretory IgA and total IgA levels than controls while total serum IgE levels were similarly distributed among patients and controls. It is suggested that provocation tests are mandatory to confirm bronchial allergic reactions to egg and milk and perhaps other food allergens in Nigerians in view of the non-discriminant RAST titres obtained in this study.

  13. Robustness in laying hens

    OpenAIRE

    Star, L.

    2008-01-01

    The aim of the project ‘The genetics of robustness in laying hens’ was to investigate nature and regulation of robustness in laying hens under sub-optimal conditions and the possibility to increase robustness by using animal breeding without loss of production. At the start of the project, a robust animal was defined as ‘an animal under a normal physical condition that has the potential to keep functioning and take short periods to recover under varying environmental conditions’. Next, parame...

  14. Humoral autoimmune response against specific collagen type II epitopes in Bulgarian patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Tsvetelina Batsalova

    2016-04-01

    Full Text Available Collagen type II (CII is a strong candidate autoantigen for rheumatoid arthritis (RA pathogenesis. CII is the main structural protein of synovial cartilage and it is attacked by both antibodies and T-cells during RA disease course. Experiments with mouse models have identified an immunodominant T-cell epitope from CII as well as several epitopes that are recognized by the majority of CII-specific autoantibodies. It has been shown that some epitope-specific anti-CII antibodies are arthritogenic and are associated with development of chronic arthritis. In addition, the immunodominant CII epitopes could be posttranslationally modified and these modified epitopes might be involved in induction and/or perpetuation of autoimmune humoral response and arthritic pathology. The aim of the present study was to evaluate the CII epitope- specific humoral response in a subgroup of Bulgarian patients with rheumatoid arthritis. Our results demonstrate that RA patients have significantly increased levels of anti-CII antibodies compared to healthy individuals and patients with other type of autoimmune disease. The majority of anti-CII antibodies in Bulgarian patients are directed against the U1 and J1 conserved epitopes. We show that D8 epitope-specific antibodies react to the triple-helical structure of the epitope and thus recognize both the native and the posttranslationally citrullinated D8. This is the first article presenting an evaluation of CII-specific humoral autoimmune response in Bulgarian patients with rheumatoid arthritis.

  15. Towards the patient-specific design of flow diverters made from helix-like wires: an optimization study.

    Science.gov (United States)

    Zhang, Mingzi; Anzai, Hitomi; Chopard, Bastien; Ohta, Makoto

    2016-12-28

    Flow diverter (FD) intervention is an emerging endovascular technique for treating intracranial aneurysms. High flow-diversion efficiency is desired to accelerate thrombotic occlusion inside the aneurysm; however, the risk of post-stenting stenosis in the parent artery is posed when flow-diversion efficiency is pursued by simply decreasing device porosity. For improving the prognosis of FD intervention, we develop an optimization method for the design of patient-specific FD devices that maintain high levels of porosity. An automated structure optimization method for FDs with helix-like wires was developed by applying a combination of lattice Boltzmann fluid simulation and simulated annealing procedure. Employing intra-aneurysmal average velocity as the objective function, the proposed method tailored the wire structure of an FD to a given vascular geometry by rearranging the starting phase of the helix wires. FD optimization was applied to two idealized (S and C) vascular models and one realistic (R) model. Without altering the original device porosity of 80%, the flow-reduction rates of optimized FDs were improved by 5, 2, and 28% for the S, C, and R models, respectively. Furthermore, the aneurysmal flow patterns after optimization exhibited marked alterations. We confirmed that the disruption of bundle of inflow is of great help in blocking aneurysmal inflow. Axial displacement tests suggested that the optimal FD implanted in the R model possesses good robustness to tolerate uncertain axial positioning errors. The optimization method developed in this study can be used to identify the FD wire structure with the optimal flow-diversion efficiency. For a given vascular geometry, custom-designed FD structure can maximally reduce the aneurysmal inflow with its porosity maintained at a high level, thereby lowering the risk of post-stenting stenosis. This method facilitates the study of patient-specific designs for FD devices.

  16. Patient-specific QA and delivery verification of scanned ion beam at NIRS-HIMAC

    Energy Technology Data Exchange (ETDEWEB)

    Furukawa, Takuji; Inaniwa, Taku; Hara, Yousuke; Mizushima, Kota; Shirai, Toshiyuki; Noda, Koji [Medical Physics Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2013-12-15

    Purpose: To evaluate a patient-specific QA program and system for constancy checking of a scanning delivery system developed at the National Institute of Radiological Sciences.Methods: For the patient-specific QA, all the planned beams are recalculated on a water phantom with treatment planning software (TPS). The recalculated dose distributions are compared with the measured distributions using a 2D ionization chamber array at several depths, and evaluated using gamma index analysis with criteria of 3% and 3 mm and a pass rate of 90%. For the constancy check, the authors developed the multiwire proportional chamber (MWPC), which can record the delivered 2D fluence images in a slice-by-slice manner. During irradiation for dosimetric QA with the 2D ionization chamber array and an accordion-type water phantom, the 2D fluence images are recorded using the MWPC in the delivery system. These recorded images are then compared to those taken in the treatment session to check the constancy check. This analysis also employs gamma index analysis using the same criteria as in the patient-specific QA. These patient-specific QA and constancy check evaluations were performed using the data of 122 patients.Results: In the patient-specific QA, the measured dose distributions agreed well with those calculated by the TPS, and the QA criteria were satisfied in all measurements. The additional check of the fluence comparison ensured the constancy of the delivered field during each treatment irradiation.Conclusions: The authors established a patient-specific QA program and additional check of delivery constancy in every treatment session. Fluence comparison is a strong tool for constancy checking of the delivery system.

  17. Patient-specific QA and delivery verification of scanned ion beam at NIRS-HIMAC.

    Science.gov (United States)

    Furukawa, Takuji; Inaniwa, Taku; Hara, Yousuke; Mizushima, Kota; Shirai, Toshiyuki; Noda, Koji

    2013-12-01

    To evaluate a patient-specific QA program and system for constancy checking of a scanning delivery system developed at the National Institute of Radiological Sciences. For the patient-specific QA, all the planned beams are recalculated on a water phantom with treatment planning software (TPS). The recalculated dose distributions are compared with the measured distributions using a 2D ionization chamber array at several depths, and evaluated using gamma index analysis with criteria of 3% and 3 mm and a pass rate of 90%. For the constancy check, the authors developed the multiwire proportional chamber (MWPC), which can record the delivered 2D fluence images in a slice-by-slice manner. During irradiation for dosimetric QA with the 2D ionization chamber array and an accordion-type water phantom, the 2D fluence images are recorded using the MWPC in the delivery system. These recorded images are then compared to those taken in the treatment session to check the constancy check. This analysis also employs gamma index analysis using the same criteria as in the patient-specific QA. These patient-specific QA and constancy check evaluations were performed using the data of 122 patients. In the patient-specific QA, the measured dose distributions agreed well with those calculated by the TPS, and the QA criteria were satisfied in all measurements. The additional check of the fluence comparison ensured the constancy of the delivered field during each treatment irradiation. The authors established a patient-specific QA program and additional check of delivery constancy in every treatment session. Fluence comparison is a strong tool for constancy checking of the delivery system.

  18. The patient's perspective of the feasibility of a patient-specific instrument in physiotherapy goal setting: a qualitative study.

    Science.gov (United States)

    Stevens, Anita; Moser, Albine; Köke, Albère; van der Weijden, Trudy; Beurskens, Anna

    2016-01-01

    Patient participation in goal setting is important to deliver client-centered care. In daily practice, however, patient involvement in goal setting is not optimal. Patient-specific instruments, such as the Patient Specific Complaints (PSC) instrument, can support the goal-setting process because patients can identify and rate their own problems. The aim of this study is to explore patients' experiences with the feasibility of the PSC, in the physiotherapy goal setting. We performed a qualitative study. Data were collected by observations of physiotherapy sessions (n=23) and through interviews with patients (n=23) with chronic conditions in physiotherapy practices. Data were analyzed using directed content analysis. The PSC was used at different moments and in different ways. Two feasibility themes were analyzed. First was the perceived ambiguity with the process of administration: patients perceived a broad range of experiences, such as emotional and supportive, as well as feeling a type of uncomfortableness. The second was the perceived usefulness: patients found the PSC useful for themselves - to increase awareness and motivation and to inform the physiotherapist - as well as being useful for the physiotherapist - to determine appropriate treatment for their personal needs. Some patients did not perceive any usefulness and were not aware of any relation with their treatment. Patients with a more positive attitude toward questionnaires, patients with an active role, and health-literate patients appreciated the PSC and felt facilitated by it. Patients who lacked these attributes did not fully understand the PSC's process or purpose and let the physiotherapist take the lead. The PSC is a feasible tool to support patient participation in the physiotherapy goal setting. However, in the daily use of the PSC, patients are not always fully involved and informed. Patients reported varied experiences related to their personal attributes and modes of administration. This

  19. Patient- and Disease-Specific Factors Associated With Operative Management of de Quervain Tendinopathy.

    Science.gov (United States)

    Kazmers, Nikolas H; Liu, Tiffany C; Gordon, Joshua A; Bozentka, David J; Steinberg, David R; Gray, Benjamin L

    2017-09-07

    It remains unclear which factors, patient- or disease-specific, are associated with electing to undergo operative management for de Quervain tendinopathy. Our null hypothesis was that no patient- or disease-specific factors would be associated with the choice of surgical treatment of de Quervain tendinopathy. We performed a retrospective review of consecutive patients diagnosed with de Quervain tendinopathy over 3 years by 1 of 3 fellowship-trained hand surgeons at an urban academic institution. Descriptive statistics were calculated for patient baseline and disease-specific characteristics. Cohorts were compared using bivariate analysis for all collected variables. Binary logistic regression with backward stepwise term selection was performed including independent predictors identified by bivariate analysis. A total of 200 patients were identified for inclusion. Bivariate analysis revealed that surgically treated patients were significantly more likely to have Medicaid insurance, psychiatric illness history, and disabled work status. Regression analysis revealed an association between surgical treatment and 2 of the factors evaluated: Medicaid insurance status and psychiatric illness history. Psychiatric illness and Medicaid insurance status are associated with undergoing surgical release of the first dorsal compartment. These findings support the use of a biopsychosocial framework when treating patients with de Quervain tendinopathy. Prognostic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  20. Modeling retinal degeneration using patient-specific induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Zi-Bing Jin

    Full Text Available Retinitis pigmentosa (RP is the most common inherited human eye disease resulting in night blindness and visual defects. It is well known that the disease is caused by rod photoreceptor degeneration; however, it remains incurable, due to the unavailability of disease-specific human photoreceptor cells for use in mechanistic studies and drug screening. We obtained fibroblast cells from five RP patients with distinct mutations in the RP1, RP9, PRPH2 or RHO gene, and generated patient-specific induced pluripotent stem (iPS cells by ectopic expression of four key reprogramming factors. We differentiated the iPS cells into rod photoreceptor cells, which had been lost in the patients, and found that they exhibited suitable immunocytochemical features and electrophysiological properties. Interestingly, the number of the patient-derived rod cells with distinct mutations decreased in vitro; cells derived from patients with a specific mutation expressed markers for oxidation or endoplasmic reticulum stress, and exhibited different responses to vitamin E than had been observed in clinical trials. Overall, patient-derived rod cells recapitulated the disease phenotype and expressed markers of cellular stresses. Our results demonstrate that the use of patient-derived iPS cells will help to elucidate the pathogenic mechanisms caused by genetic mutations in RP.

  1. Managing patients with acute and chronic non-specific neck pain

    DEFF Research Database (Denmark)

    Brockhusen, Simon Sidenius; Bussières, André; French, Simon David

    2017-01-01

    Background: Non-specific neck pain represents a quarter of all chiropractic patient visits in Denmark. Evidence informed practice can help ensure providers use best available treatment, speed up patient recovery rate and reduce healthcare utilization. It is generally believed that Danish...... chiropractors treat according to best practice, but we do not know if this is true for management of neck-pain. The objective of this study was to investigate how Danish chiropractors treat patients with acute and chronic non-specific neck pain and determine if management is compliant with recent Canadian...... and chronic non-specific neck pain cases; and 3) provide demographic data. Treatment modalities ranked as "used often" were considered in further analysis and compared to the Canadian Guideline recommendations for neck pain. Chi-squared test was used to investigate differences between treatment and guideline...

  2. Development and fabrication of patient-specific knee implant using additive manufacturing techniques

    Science.gov (United States)

    Zammit, Robert; Rochman, Arif

    2017-10-01

    Total knee replacement is the most effective treatment to relief pain and restore normal function in a diseased knee joint. The aim of this research was to develop a patient-specific knee implant which can be fabricated using additive manufacturing techniques and has reduced wear rates using a highly wear resistant materials. The proposed design was chosen based on implant requirements, such as reduction in wear rates as well as strong fixation. The patient-specific knee implant improves on conventional knee implants by modifying the articulating surfaces and bone-implant interfaces. Moreover, tribological tests of different polymeric wear couples were carried out to determine the optimal materials to use for the articulating surfaces. Finite element analysis was utilized to evaluate the stresses sustained by the proposed design. Finally, the patient-specific knee implant was successfully built using additive manufacturing techniques.

  3. Iterative robust multiprocessor scheduling

    NARCIS (Netherlands)

    Adyanthaya, S.; Geilen, M.; Basten, T.; Voeten, J.; Schiffelers, R.

    2015-01-01

    General purpose platforms are characterized by unpredictable timing behavior. Real-time schedules of tasks on general purpose platforms need to be robust against variations in task execution times. We define robustness in terms of the expected number of tasks that miss deadlines. We present an

  4. Robust plasmonic substrates

    DEFF Research Database (Denmark)

    Kostiučenko, Oksana; Fiutowski, Jacek; Tamulevicius, Tomas

    2014-01-01

    Robustness is a key issue for the applications of plasmonic substrates such as tip-enhanced Raman spectroscopy, surface-enhanced spectroscopies, enhanced optical biosensing, optical and optoelectronic plasmonic nanosensors and others. A novel approach for the fabrication of robust plasmonic...

  5. Microbial profile comparisons of saliva, pooled and site-specific subgingival samples in periodontitis patients

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Sembler-Møller, Maria Lynn; Grande, Maria Anastasia

    2017-01-01

    . DESIGN: Site specific subgingival plaque samples (n = 54), pooled subgingival plaque samples (n = 18) and stimulated saliva samples (n = 18) were collected from 18 patients with generalized chronic periodontitis. Subgingival and salivary microbiotas were characterized by means of HOMINGS (Human Oral......OBJECTIVES: The purpose of this study was to compare microbial profiles of saliva, pooled and site-specific subgingival samples in patients with periodontitis. We tested the hypotheses that saliva can be an alternative to pooled subgingival samples, when screening for presence of periopathogens...... by pooled subgingival samples. Presence of Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Filifactor alocis, Tannerella forsythia and Parvimona micra in site-specific subgingival samples were detected in saliva with an AUC of 0.79 (sensitivity: 0.61, specificity: 0.94), compared...

  6. Microbial profile comparisons of saliva, pooled and site-specific subgingival samples in periodontitis patients

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Sembler-Møller, Maria Lynn; Grande, Maria Anastasia

    2017-01-01

    OBJECTIVES: The purpose of this study was to compare microbial profiles of saliva, pooled and site-specific subgingival samples in patients with periodontitis. We tested the hypotheses that saliva can be an alternative to pooled subgingival samples, when screening for presence of periopathogens....... DESIGN: Site specific subgingival plaque samples (n = 54), pooled subgingival plaque samples (n = 18) and stimulated saliva samples (n = 18) were collected from 18 patients with generalized chronic periodontitis. Subgingival and salivary microbiotas were characterized by means of HOMINGS (Human Oral...... to an AUC of 0.76 (sensitivity: 0.56, specificity: 0.94) in pooled subgingival samples. CONCLUSIONS: Site-specific presence of periodontal pathogens was detected with comparable accuracy in stimulated saliva samples and pooled subgingival plaque samples. Consequently, saliva may be a reasonable surrogate...

  7. Patient-Specific Oscillometric Blood Pressure Measurement: Validation for Accuracy and Repeatability.

    Science.gov (United States)

    Liu, Jiankun; Cheng, Hao-Min; Chen, Chen-Huan; Sung, Shih-Hsien; Hahn, Jin-Oh; Mukkamala, Ramakrishna

    2017-01-01

    Oscillometric devices are widely used for automatic cuff blood pressure (BP) measurement. These devices estimate BP from the oscillometric cuff pressure waveform using population average methods. Hence, the devices may only be accurate over a limited BP range. The objective was to evaluate a new patient-specific method, which estimates BP by fitting a physiologic model to the same waveform. One-hundred and forty-five cardiac catheterization patients and normal adults were included for study. The oscillometric cuff pressure waveform was obtained with an office device, while reference BP was measured via brachial artery catheterization or auscultation, during baseline and/or nitroglycerin administration. Fifty-seven of the subject records were utilized for refining the patient-specific method, while the remaining 88 subject records were employed for evaluation. The precision errors for all BP levels of the patient-specific method ranged from 6.3 to 7.6 mmHg. These errors were significantly lower than those of the office device (by 29% on average) in subjects with high pulse pressure (>50 mmHg) while being comparable to those of the device in subjects with normal pulse pressure (<50 mmHg). The bias and precision of the differences in repeated estimates for all BP levels of the patient-specific method ranged from 0.1 to 1.1 and 2.1 to 5.9 mmHg, respectively. These precision differences were significantly lower than those of the office device (by 64% on average). The patient-specific method may afford more accurate automatic cuff BP measurement in patients with large artery stiffening while limiting the number of required cuff inflations/deflations per measurement.

  8. Prostate specific antigen in patients of benign prostate hypertrophy and carcinoma prostate.

    Science.gov (United States)

    Malati, T; Kumari, G Rajani; Murthy, P V L N; Reddy, Ch Ram; Prakash, B Surya

    2006-03-01

    Prostate Specific Antigen (PSA) has emerged as the most applicable and important tumor marker for carcinoma prostate. In the present study PSA was determined in serum of healthy subjects, patients of benign prostate hypertrophy (BPH) and Carcinoma Prostate (Ca-P) to evaluate its diagnostic efficiency in day to day management of prostate cancer patients and in differentiating patients of early prostate cancer from those with BPH. Receiver operating characteristic curve (ROC) revealed 2 ng/ml and 10 ng/ml cut off serum PSA level for BPH and untreated carcinoma prostate patients (Ca-P). An extremely significant increase (Pprostate patients when compared to healthy males. Clinical relevance of PSA was highlighted by a case study of cancer patient prior to any therapy till death.

  9. Robustness of structures

    DEFF Research Database (Denmark)

    Vrouwenvelder, T.; Sørensen, John Dalsgaard

    2009-01-01

    After the collapse of the World Trade Centre towers in 2001 and a number of collapses of structural systems in the beginning of the century, robustness of structural systems has gained renewed interest. Despite many significant theoretical, methodical and technological advances, structural...... robustness is still an issue of controversy and poses difficulties in regard to interpretation as well as regulation. Typically modern structural design codes require that ‘the consequence of damages to structures should not be disproportional to the causes of the damages'. However, despite the importance...... of robustness for structural design such requirements are not substantiated in more detail, nor have the engineering profession been able to agree on an interpretation of robustness which facilitates for its uantification. A European COST action TU 601 on ‘Robustness of structures' has started in 2007...

  10. Robustness of Structures

    DEFF Research Database (Denmark)

    Faber, Michael Havbro; Vrouwenvelder, A.C.W.M.; Sørensen, John Dalsgaard

    2011-01-01

    the development of a joint European project on structural robustness under the COST (European Cooperation in Science and Technology) programme and the decision to develop a more elaborate document on structural robustness in collaboration between experts from the JCSS and the IABSE. Accordingly, a project titled...... ‘COST TU0601: Robustness of Structures’ was initiated in February 2007, aiming to provide a platform for exchanging and promoting research in the area of structural robustness and to provide a basic framework, together with methods, strategies and guidelines enhancing robustness of structures....... The project will conclude in October 2011; a summary of the work carried out in this project and the major results achieved are described in this paper....

  11. Robust and validated models to predict high risk of non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node

    DEFF Research Database (Denmark)

    Tvedskov, Tove F; Jensen, Maj-Britt; Balslev, Eva

    2014-01-01

    micrometastases or isolated tumor cells are found in sentinel node. The aim of this study was to validate these models in an independent Danish dataset. MATERIAL AND METHODS: We included 720 breast cancer patients with micrometastases and 180 with isolated tumor cells in sentinel node operated in 2009-2010 from...... in the original cohort: 0.63 and 0.64, respectively. The sensitivity and specificity for predicting risk of non-sentinel node metastases over 30% was 0.36 and 0.81, respectively, in the validation cohort. AUC for the model for patients with isolated tumor cells decreased from 0.73 in the original cohort to 0.......60 in the validation cohort. When dividing patients with isolated tumor cells into high and low risk of non-sentinel node metastases according to number of risk factors present, 37% in the high-risk group had non-sentinel node metastases. Specificity and sensitivity was 0.48 and 0.88, respectively, in the validation...

  12. Computational biomechanics for medicine fundamental science and patient-specific applications

    CERN Document Server

    Miller, Karol; Wittek, Adam; Nielsen, Poul

    2014-01-01

    One of the greatest challenges facing the computational engineering community is to extend the success of computational mechanics to fields outside traditional engineering, in particular to biology, the biomedical sciences, and medicine. The Computational Biomechanics for Medicine titles provide an opportunity for specialists in computational biomechanics to present their latest methodologies and advancements. This latest installment comprises nine of the latest developments in both fundamental science and patient-specific applications, from researchers in Australia, New Zealand, USA, UK, France, Ireland, and China. Some of the interesting topics discussed are: cellular mechanics; tumor growth and modeling; medical image analysis; and both patient-specific fluid dynamics and solid mechanics simulations.

  13. Polymorphisms of STAT6 and specific serum IgE levels in patients with penicillin allergy.

    Science.gov (United States)

    Huang, Chen-Zheng; Zou, Dan; Yang, Jing; Qiao, Hai-Ling

    2012-07-01

    Signal transducer and activator of transcription (STAT) 6 signaling pathway is required for mediating the biologic functions of interleukin (IL)-4 which is proved to play an important role in the pathogenesis of allergic diseases and the induction of specific immunoglobulin (Ig) E synthesis. The current studies are conducted to evaluate the relationship between polymorphisms of STAT6, specific IgE and penicillin allergy. In 242 patients with penicillin allergy and 220 controls, polymorphisms of STAT6 in2SNP3 and 3'UTRSNP3 were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Eight kinds of specific IgE to penicillins were detected with radioallergosorbent test (RAST). For STAT6 in2SNP3, the frequency of the CC genotype was significantly higher in all patients than in controls (60 vs. 47%, p = 0.005). A similar result was observed between patients of the urticaria group and controls (70 vs. 47%, p = 0.005). With respect to allele frequency, the C-allele occurred more frequently in all patients and in the urticaria group than in controls (78 vs. 69%, p = 0.002; 83 vs. 69%, p = 0.007). Our finding suggests that STAT6 in2SNP3 is associated with penicillin allergy, but has no effect on the specific IgE levels of patients with penicillin allergy.

  14. [Establishment of hemophilia A patient-specific inducible pluripotent stem cells with urine cells].

    Science.gov (United States)

    Hu, Zhiqing; Hu, Xuyun; Pang, Jialun; Wang, Xiaolin; Lin Peng, Siyuan; Li, Zhuo; Wu, Yong; Wu, Lingqian; Liang, Desheng

    2015-10-01

    OBJECTIVE To generate hemophilia A (HA) patient-specific inducible pluripotent stem cells (iPSCs) and induce endothelial differentiation. METHODS Tubular epithelial cells were isolated and cultured from the urine of HA patients. The iPSCs were generated by forced expression of Yamanaka factors (Oct4, Sox2, c-Myc and Klf4) using retroviruses and characterized by cell morphology, pluripotent marker staining and in vivo differentiation through teratoma formation. Induced endothelial differentiation of the iPSCs was achieved with the OP9 cell co-culture method. RESULTS Patient-specific iPSCs were generated from urine cells of the HA patients, which could be identified by cell morphology, pluripotent stem cell surface marker staining and in vivo differentiation of three germ layers. The teratoma experiment has confirmed that such cells could differentiate into endothelial cells expressing the endothelial-specific markers CD144, CD31 and vWF. CONCLUSION HA patient-specific iPSCs could be generated from urine cells and can differentiate into endothelial cells. This has provided a new HA disease modeling approach and may serve as an applicable autologous cell source for gene correction and cell therapy studies for HA.

  15. Patients with Multiple Myeloma Develop SOX2-Specific Autoantibodies after Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sebastian Kobold

    2011-01-01

    Full Text Available The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS. However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM. Screening 1094 peripheral blood (PB sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2211–230 as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients’ BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT. Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n=74. Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.

  16. Patient-Specific Tailored Intervention Improves INR Time in Therapeutic Range and INR Variability in Heart Failure Patients.

    Science.gov (United States)

    Gotsman, Israel; Ezra, Orly; Hirsh Raccah, Bruria; Admon, Dan; Lotan, Chaim; Dekeyser Ganz, Freda

    2017-08-01

    Many patients with heart failure need anticoagulants, including warfarin. Good control is particularly challenging in heart failure patients, with failure. Patients with heart failure taking warfarin therapy (n = 145) were randomized to either standard care or a 1-time intervention assessing potential risk factors for lability of INR, in which they received patient-specific instructions. Time in therapeutic range (TTR) using Rosendaal's linear model was assessed 3 months before and after the intervention. The patient-tailored intervention significantly increased anticoagulation control. The median TTR levels before intervention were suboptimal in the interventional and control groups (53% vs 45%, P = .14). After intervention the median TTR increased significantly in the interventional group compared with the control group (80% [interquartile range, 62%-93%] vs 44% [29%-61%], P failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients

    Science.gov (United States)

    Zografos, Theodoros A; Gatselis, Nikolaos; Zachou, Kalliopi; Liaskos, Christos; Gabeta, Stella; Koukoulis, George K; Dalekos, George N

    2012-01-01

    AIM: To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in first-degree relatives (FDRs) of Greek PBC patients. METHODS: The presence of antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibodies (ANA) were determined using indirect immunofluorescence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymptomatic for liver-related symptoms FDRs of 44 PBC patients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepatitis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The prevalence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI): 12%-28.1% vs 2.5%, 95% CI: 0.1%-14.7%, P = 0.01; 18.8%, 95% CI: 12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI: 1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio: 3.92, 95% CI: 1.25-12.35, P = 0.02). CONCLUSION: In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs. PMID:23002341

  18. Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.

    Directory of Open Access Journals (Sweden)

    Daniel M Lombardo

    2016-08-01

    Full Text Available Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF. A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP morphology, action potential duration (APD restitution and conduction velocity (CV restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy.

  19. Patient-specific 3D simulation of cyclic CSF flow at the craniocervical region.

    Science.gov (United States)

    Rutkowska, G; Haughton, V; Linge, S; Mardal, K-A

    2012-10-01

    Flow simulations in patient-specific models of the subarachnoid space characterize CSF flow in more detail than MR flow imaging. We extended previous simulation studies by including cyclic CSF flow and patient-specific models in multiple patients with Chiari I. We compared simulation results with MR flow measurements. Volumetric high resolution image sets acquired in 7 patients with Chiari I, 3 patients who had previous craniovertebral decompression, and 3 controls were segmented and converted to mathematical models of the subarachnoid space. CSF flow velocities and pressures were calculated with high spatial and temporal resolution during simulated oscillatory flow in each model with the Navier-Stokes equations. Pressures, velocities, and bidirectional flow were compared in the groups (with Student t test). Peak velocities in the simulations were compared with peak velocities measured in vivo with PCMR. Flow visualization for patients and volunteers demonstrated nonuniform reversing patterns resembling those observed with PCMR. Velocities in the 13 subjects were greater between C2 and C5 than in the foramen magnum. Chiari patients had significantly greater peak systolic and diastolic velocities, synchronous bidirectional flow, and pressure gradients than controls. Peak velocities measured in PCMR correlated significantly (P = .003; regression analysis) despite differences between them. In simulations of CSF, patients with Chiari I had significantly greater peak systolic and diastolic velocities, synchronous bidirectional flow, and pressure gradients than controls.

  20. Site-specific endometrial injury improves implantation and pregnancy in patients with repeated implantation failures

    Directory of Open Access Journals (Sweden)

    Lin Chieh

    2011-10-01

    Full Text Available Abstract Background To test whether a site-specific hysteroscopic biopsy-induced injury in the endometrium during the controlled ovarian hyperstimulation cycle improves subsequent embryo implantation in patients with repeated implantation failure, a total of 30 patients who have had good responses to controlled ovulation stimulation but have failed to achieve pregnancy after two or more transfers of good-quality embryos were recruited in this prospective study. Methods A single, site-specific hysteroscopic biopsy-induced injury was generated on the posterior endometrium at midline 10-15 mm from the fundus during the D4-D7 period of the ongoing controlled ovarian hyperstimulation cycle in six patients. Results Patients received endometrial biopsy protocol achieved a pregnancy rate of 100%. By contrast, only 46% of patients with similar clinical characteristics (N = 24 achieved pregnancy without the hysteroscopic biopsy-induced endometrium injury (p Conclusions Our proof-of-concept study demonstrates that a site-specific hysteroscopic endometrium injury performed during the ongoing in vitro fertilization (IVF cycle, instead of injuries received during prior cycles, significantly improves clinical outcomes in patients with repeated implantation failure.

  1. Design of patient-specific concentric tube robots using path planning from 3-D ultrasound.

    Science.gov (United States)

    Morimoto, Tania K; Cerrolaza, Juan J; Hsieh, Michael H; Cleary, Kevin; Okamura, Allison M; Linguraru, Marius George

    2017-07-01

    Percutaneous techniques and robot-assisted surgical systems have enabled minimally invasive procedures that offer reduced scarring, recovery time, and complications compared to traditional open surgeries. Despite these improvements, access to diseased sites using the standard, straight needle-based percutaneous techniques is still limited for certain procedures due to intervening tissues. These limitations can be further exacerbated in specific patient groups, particularly pediatric patients, whose anatomy does not fit the traditional tools and systems. We therefore propose a patient-specific paradigm to design and fabricate dexterous, robotic tools based on the patient's preoperative images. In this paper, we present the main steps of our proposed paradigm - image-based path planning, robot design, and fabrication - along with an example case that focuses on a class of dexterous, snake-like tools called concentric tube robots. We demonstrate planning a safe path using a patient's preoperative ultrasound images. We then determine the concentric tube robot parameters needed to achieve this path, and finally, we use 3-D printing to fabricate the patient-specific robot.

  2. Correlations Between Allergen-Specific IgE Serum Levels in Patients With Ocular Allergy.

    Science.gov (United States)

    Polido, Júlia Gomes Fernandes; Cabral, Thiago; Perini, Paula de Resende Campos; Fernandes, Maria de Fátima Marcelos; de Freitas, Denise; dos Santos Araújo, Maria Emília Xavier; Serracarbassa, Pedro Durães

    2015-09-01

    To evaluate ocular allergies in patients at the Hospital do Servidor Publico Estadual de Sao Paulo (HSPE) and the correlations with serum allergen-specific immunoglobulin E levels. We performed a longitudinal study of patients with ocular allergies who were treated at the Cornea and Immunology and Allergy Department. Patients underwent an ophthalmologic examination to identify their primary presenting signs and symptoms. The allergy types were divided into 4 groups. We conducted the following laboratory tests and measurements: blood count, eosinophil count, total serum IgE, and specific IgE. Among 61 patients, 16 (26.2%) had a clinical diagnosis of seasonal allergic conjunctivitis, 23 (37.7%) had perennial allergic conjunctivitis, 19 (31.1%) had vernal keratoconjunctivitis, and 3 (4.9%) had atopic keratoconjunctivitis. Mixed dust mites were positive in 94.9% of patients. Dermatophagoides pteronyssinus (dp) and Dermatophagoides farinae (df) antigens were positive in 93.2% of patients followed by Blattella germanica, Blomia tropicalis, and mixed animal epithelia (81%, 75.9%, and 25.8%, respectively). Perennial allergic conjunctivitis was the most prevalent disorder and demonstrated higher positivity in class V/VI for specific antigens (mixed dust mites, dp, and df), indicating high antigenicity. Dust mites, D. pteronyssinus, D. farinae, B. germanica, and B. tropicalis were the primary triggers of the studied ocular allergies.

  3. Evaluation of Functional Correlation of Task-Specific Muscle Synergies with Motor Performance in Patients Poststroke

    Directory of Open Access Journals (Sweden)

    Si Li

    2017-07-01

    Full Text Available The central nervous system produces movements by activating specifically programmed muscle synergies that are also altered with injuries in the brain, such as stroke. In this study, we hypothesize that there exists a positive correlation between task-specific muscle synergy and motor functions at joint and task levels in patients following stroke. The purpose here is to define and evaluate neurophysiological metrics based on task-specific muscle synergy for assessing motor functions in patients. A patient group of 10 subjects suffering from stroke and a control group of nine age-matched healthy subjects were recruited to participate in this study. Electromyography (EMG signals and movement kinematics were recorded in patients and control subjects while performing arm reaching tasks. Muscle synergies of individual patients were extracted off-line from EMG records of each patient, and a baseline pattern of muscle synergy was obtained from the pooled EMG data of all nine control subjects. Peak velocities and movement durations of each reaching movement were computed from measured kinematics. Similarity indices of matching components to those of the baseline synergy were defined by synergy vectors and time profiles, respectively, as well as by a combined similarity of vector and time profile. Results showed that pathological synergies of patients were altered from the characteristics of baseline synergy with missing components, or varied vector patterns and time profiles. The kinematic performance measured by peak velocities and movement durations was significantly poorer for the patient group than the control group. In patients, all three similarity indices were found to correlate significantly to the kinematics of movements for the reaching tasks. The correlation to the Fugl-Meyer score of arm was the highest with the vector index, the lowest with the time profile index, and in between with the combined index. These findings illustrate that the

  4. Spontaneous presence of FOXO3-specific T cells in cancer patients

    DEFF Research Database (Denmark)

    Larsen, Stine Kiaer; Ahmad, Shamaila Munir; Idorn, Manja

    2014-01-01

    ) were able to specifically recognize and kill both FOXO3-expressing cancer cells as well as dendritic cells. Thus, FOXO3 was processed and presented by HLA-A2 on the cell surface of both immune cells and cancer cells. As FOXO3 programs TADCs to become tolerogenic, FOXO3 signaling thereby comprises...... a significant immunosuppressive mechanism, such that FOXO3 targeting by means of specific T cells is an attractive clinical therapy to boost anticancer immunity. In addition, the natural occurrence of FOXO3-specific CTLs in the periphery suggests that these T cells hold a function in the complex network...... of immune regulation in cancer patients....

  5. Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures

    Energy Technology Data Exchange (ETDEWEB)

    Rettmann, Maryam E., E-mail: rettmann.maryam@mayo.edu; Holmes, David R.; Camp, Jon J.; Cameron, Bruce M.; Robb, Richard A. [Biomedical Imaging Resource, Mayo Clinic College of Medicine, Rochester, Minnesota 55905 (United States); Kwartowitz, David M. [Department of Bioengineering, Clemson University, Clemson, South Carolina 29634 (United States); Gunawan, Mia [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington D.C. 20057 (United States); Johnson, Susan B.; Packer, Douglas L. [Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905 (United States); Dalegrave, Charles [Clinical Cardiac Electrophysiology, Cardiology Division Hospital Sao Paulo, Federal University of Sao Paulo, 04024-002 Brazil (Brazil); Kolasa, Mark W. [David Grant Medical Center, Fairfield, California 94535 (United States)

    2014-02-15

    Purpose: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. Methods: Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamicin vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. Results: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved

  6. Role of epidural and patient-controlled analgesia in site-specific laparoscopic colorectal surgery.

    Science.gov (United States)

    Kamiński, Jan P; Pai, Ajit; Ailabouni, Luay; Park, John J; Marecik, Slawomir J; Prasad, Leela M; Abcarian, Herand

    2014-01-01

    Limited data are available comparing epidural and patient-controlled analgesia in site-specific colorectal surgery. The aim of this study was to evaluate 2 modes of analgesia in patients undergoing laparoscopic right colectomy (RC) and low anterior resection (LAR). Prospectively collected data on 433 patients undergoing laparoscopic or laparoscopic-assisted colon surgery at a single institution were retrospectively reviewed from March 2004 to February 2009. Patients were divided into groups undergoing RC (n = 175) and LAR (n = 258). These groups were evaluated by use of analgesia: epidural analgesia, "patient-controlled analgesia" alone, and a combination of both. Demographic and perioperative outcomes were compared. Epidural analgesia was associated with a faster return of bowel function, by 1 day (P diabetes who underwent RC (P = .037), and patients after RC with combined analgesia (P = .011). Mean visual analogue scale pain scores were significantly lower with epidural analgesia compared with patient-controlled analgesia in both LAR and RC groups (P < .001). Epidural analgesia was associated with a faster return of bowel function in the laparoscopic LAR group but not the RC group. Epidural analgesia was superior to patient-controlled analgesia in controlling postoperative pain but was inadequate in 28% of patients and needed the addition of patient-controlled analgesia.

  7. SU-E-T-69: Cloud-Based Monte Carlo Patient-Specific Quality Assurance (QA) Method for Volumetric Modulated Arc Therapy (VMAT)

    Energy Technology Data Exchange (ETDEWEB)

    Chen, X; Xing, L; Luxton, G; Bush, K [Stanford University, Palo Alto, CA (United States); Azcona, J [Clinica Universidad de Navarra, Pamplona (Spain)

    2014-06-01

    Purpose: Patient-specific QA for VMAT is incapable of providing full 3D dosimetric information and is labor intensive in the case of severe heterogeneities or small-aperture beams. A cloud-based Monte Carlo dose reconstruction method described here can perform the evaluation in entire 3D space and rapidly reveal the source of discrepancies between measured and planned dose. Methods: This QA technique consists of two integral parts: measurement using a phantom containing array of dosimeters, and a cloud-based voxel Monte Carlo algorithm (cVMC). After a VMAT plan was approved by a physician, a dose verification plan was created and delivered to the phantom using our Varian Trilogy or TrueBeam system. Actual delivery parameters (i.e., dose fraction, gantry angle, and MLC at control points) were extracted from Dynalog or trajectory files. Based on the delivery parameters, the 3D dose distribution in the phantom containing detector were recomputed using Eclipse dose calculation algorithms (AAA and AXB) and cVMC. Comparison and Gamma analysis is then conducted to evaluate the agreement between measured, recomputed, and planned dose distributions. To test the robustness of this method, we examined several representative VMAT treatments. Results: (1) The accuracy of cVMC dose calculation was validated via comparative studies. For cases that succeeded the patient specific QAs using commercial dosimetry systems such as Delta- 4, MAPCheck, and PTW Seven29 array, agreement between cVMC-recomputed, Eclipse-planned and measured doses was obtained with >90% of the points satisfying the 3%-and-3mm gamma index criteria. (2) The cVMC method incorporating Dynalog files was effective to reveal the root causes of the dosimetric discrepancies between Eclipse-planned and measured doses and provide a basis for solutions. Conclusion: The proposed method offers a highly robust and streamlined patient specific QA tool and provides a feasible solution for the rapidly increasing use of VMAT

  8. Calculating patient-specific doses in X-ray diagnostics and from radiopharmaceuticals

    Science.gov (United States)

    Lampinen, Juha Sakari

    2000-06-01

    The risk associated with exposure to ionising radiation is dependent on the characteristics of the exposed individual. The size and structure of the individual influences the absorbed dose distribution in the organs. Traditional methods used to calculate the patient organ doses are based on standardised calculation phantoms, which neglect the variance of the patient size or even sex. Methods for patient specific dosimetry in the fields of X-ray diagnostics and diagnostic and therapeutic use of radiopharmaceuticals were proposed in this thesis. A computer program, ODS-60, for calculating organ doses from diagnostic X-ray exposures was presented. The calculation is done in a patient specific phantom with depth dose and profile algorithms fitted to Monte Carlo simulation data from a previous study. Improvements to the version reported earlier were introduced, e.g. bone attenuation was implemented. The applicability of the program to determine patient doses from complex X-ray examinations (barium enema examination) was studied. The conversion equations derived for female and male patients as a function of patient weight gave the smallest deviation from the actual patient doses when compared to previous studies. Another computer program, Intdose, was presented for calculation of the dose distribution from radiopharmaceuticals. The calculation is based on convolution of an isotope specific point dose kernel with activity distribution, obtained from single photon emission computed tomography (SPECT) images. Anatomical information is taken from magnetic resonance (MR) or computed tomography (CT) images. According to a phantom study, Intdose agreed within 3% with measurements. For volunteers administered diagnostic radiopharmaceuticals, the results given by Intdose were found to agree with traditional methods in cases of medium sized patients. For patients undergoing systemic radiation therapy, the results by Intdose differed from measurements due to dynamic biodistribution

  9. Challenge Test Results in Patients With Suspected Penicillin Allergy, but No Specific IgE

    OpenAIRE

    Holm, Anne; Mosbech, Holger

    2011-01-01

    Purpose Patients with a history of allergic reaction to penicillin, but with no detectable specific IgE, are common and pose a dilemma. Challenge tests are considered to be the diagnostic gold standard. The aim of this study was to identify subgroups of patients with very low risk for reactions who could be safely tested using a more rapid and simple procedure. Methods A total of 580 consecutively referred adult patients with a history of non-serious cutaneous allergic reactions to penicillin...

  10. Specificities of anti-neutrophil autoantibodies in patients with rheumatoid arthritis (RA)

    DEFF Research Database (Denmark)

    Brimnes, J; Halberg, P; Jacobsen, Søren

    1997-01-01

    The objective of this study was to characterize antigens recognized by neutrophil-specific autoantibodies from patients with RA. Sera from 62 RA patients were screened by indirect immunofluorescence (IIF). Positive sera were further tested by ELISAs for antibodies against various granule proteins......D from nuclei. In conclusion, anti-neutrophil autoantibodies from RA patients recognize different antigens in the cytoplasm and in the nucleus. Lactoferrin is one of the common antigens recognized, but also unknown nuclear antigens of 25-35 kD mol. wt are involved....

  11. Assessment of CT dose to the fetus and pregnant female patient using patient-specific computational models.

    Science.gov (United States)

    Xie, Tianwu; Poletti, Pierre-Alexandre; Platon, Alexandra; Becker, Christoph D; Zaidi, Habib

    2017-09-08

    This work provides detailed estimates of the foetal dose from diagnostic CT imaging of pregnant patients to enable the assessment of the diagnostic benefits considering the associated radiation risks. To produce realistic biological and physical representations of pregnant patients and the embedded foetus, we developed a methodology for construction of patient-specific voxel-based computational phantoms based on existing standardised hybrid computational pregnant female phantoms. We estimated the maternal absorbed dose and foetal organ dose for 30 pregnant patients referred to the emergency unit of Geneva University Hospital for abdominal CT scans. The effective dose to the mother varied from 1.1 mSv to 2.0 mSv with an average of 1.6 mSv, while commercial dose-tracking software reported an average effective dose of 1.9 mSv (range 1.7-2.3 mSv). The foetal dose normalised to CTDIvol varies between 0.85 and 1.63 with an average of 1.17. The methodology for construction of personalised computational models can be exploited to estimate the patient-specific radiation dose from CT imaging procedures. Likewise, the dosimetric data can be used for assessment of the radiation risks to pregnant patients and the foetus from various CT scanning protocols, thus guiding the decision-making process. • In CT examinations, the absorbed dose is non-uniformly distributed within foetal organs. • This work reports, for the first time, estimates of foetal organ-level dose. • The foetal brain and skeleton doses present significant correlation with gestational age. • The conceptus dose normalised to CTDI vol varies between 0.85 and 1.63. • The developed methodology is adequate for patient-specific CT radiation dosimetry.

  12. Sensitivity and specificity of the Distress Thermometer for depression in newly diagnosed breast cancer patients.

    Science.gov (United States)

    Hegel, Mark T; Collins, E Dale; Kearing, Stephen; Gillock, Karen L; Moore, Caroline P; Ahles, Tim A

    2008-06-01

    Receiving a new diagnosis of breast cancer is a distressing experience that may precipitate an episode of major depressive disorder. Efficient screening methods for detecting depression in the oncology setting are needed. This study evaluated the receiver operating characteristics (ROC) of the single-item Distress Thermometer (DT) for detecting depression in women newly diagnosed with Stage I-III breast cancer. We assessed 321 patients (of 345 consecutive patients) at the time of their pre-surgical consultation at a Comprehensive Breast Cancer Program. Patients were administered the DT along with the Patient Health Questionnaire 9-Item Depression Module (PHQ-9) as a gold standard diagnostic assessment of depression status. Mean DT scores (11-point scale, 0-10) were significantly higher for depressed versus non-depressed patients (8.1 versus 4.4). In ROC analyses the DT showed strong discriminatory power relative to the PHQ-9-derived diagnosis of depression, with an area under the curve of 0.87. Patient age, education, marital status and stage of disease resulted in similar operating characteristics. A score of 7 represented the optimal trade-off between sensitivity (0.81) and specificity (0.85) characteristics for detecting depression. The single-item DT performs satisfactorily relative to the PHQ-9 for detecting depression in newly diagnosed breast cancer patients. A cutoff score of 7 on the DT possesses the optimal sensitivity and specificity characteristics. The strength of these findings suggests that a careful psychosocial evaluation should follow a positive screen.

  13. Robustness Beamforming Algorithms

    Directory of Open Access Journals (Sweden)

    Sajad Dehghani

    2014-09-01

    Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

  14. Robustness Beamforming Algorithms

    Directory of Open Access Journals (Sweden)

    Sajad Dehghani

    2014-04-01

    Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

  15. Patient-specific bone modeling and analysis : The role of integration and automation in clinical adoption

    NARCIS (Netherlands)

    Zadpoor, Amir A.; Weinans, Harrie

    2015-01-01

    Patient-specific analysis of bones is considered an important tool for diagnosis and treatment of skeletal diseases and for clinical research aimed at understanding the etiology of skeletal diseases and the effects of different types of treatment on their progress. In this article, we discuss how

  16. High frequency of T cells specific for cryptic epitopes in melanoma patients

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Andersen, Sofie Ramskov; Hjortsø, Mads Duus

    2013-01-01

    epitopes by tumor infiltrating lymphocytes isolated from melanoma patients. Here, we show that such cryptic epitopes are more frequently recognized than antigens of the same class encoded by canonical reading frames. Furthermore, we report the presence of T cells specific for three cryptic epitopes encoded...

  17. Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients

    DEFF Research Database (Denmark)

    Jons, Christian; O-Uchi, Jin; Moss, Arthur J

    2011-01-01

    a subunit KCNQ1. We investigated whether mutation-specific changes in I(Ks) function can predict cardiac risk in LQT1. By correlating the clinical phenotype of 387 LQT1 patients with the cellular electrophysiological characteristics caused by an array of mutations in KCNQ1, we found that channels...

  18. Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke

    NARCIS (Netherlands)

    Elting, JW; De Keyser, J; Sulter, G.

    1998-01-01

    A detrimental effect of hyperglycemia in ischemic brain has been demonstrated in laboratory experiments and it has been found that hyperglycemia in ischemic stroke is a predictor of poor outcome. We determined serum neuron specific enolase (NSE) concentrations in 41 consecutive patients with a

  19. Cause-specific mortality in HPV+ and HPV- oropharyngeal cancer patients

    DEFF Research Database (Denmark)

    Nørregaard, Cecilie; Grønhøj, Christian; Jensen, David

    2017-01-01

    ; 1.00 year), secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16 status was the strongest predictor of improved survival across all causes of death. The only cause of death to decrease...... in incidence over the 2 years after treatment was death from OPSCC. HPV/p16 positivity was an independent factor for improved survival across all causes of death in patients with OPSCC. In addition, both HPV-positive and HPV-negative OPSCC patients faced high 5- and 10-year mortality rates. Implementing......Identifying the causes of death in head and neck cancer patients can optimize follow-up and therapeutic strategies, but studies in oropharyngeal squamous cell carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause-specific mortality in a population-based cohort of patients...

  20. Development of patient-specific phantoms for verification of stereotactic body radiation therapy planning in patients with metallic screw fixation

    Science.gov (United States)

    Oh, Dongryul; Hong, Chae-Seon; Ju, Sang Gyu; Kim, Minkyu; Koo, Bum Yong; Choi, Sungback; Park, Hee Chul; Choi, Doo Ho; Pyo, Hongryull

    2017-01-01

    A new technique for manufacturing a patient-specific dosimetric phantom using three-dimensional printing (PSDP_3DP) was developed, and its geometrical and dosimetric accuracy was analyzed. External body contours and structures of the spine and metallic fixation screws (MFS) were delineated from CT images of a patient with MFS who underwent stereotactic body radiation therapy for spine metastasis. Contours were converted into a STereoLithography file format using in-house program. A hollow, four-section PSDP was designed and manufactured using three types of 3DP to allow filling with a muscle-equivalent liquid and insertion of dosimeters. To evaluate the geometrical accuracy of PSDP_3DP, CT images were obtained and compared with patient CT data for volume, mean density, and Dice similarity coefficient for contours. The dose distribution in the PSDP_3DP was calculated by applying the same beam parameters as for the patient, and the dosimetric characteristics of the PSDP_3DP were compared with the patient plan. The registered CT of the PSDP_3DP was well matched with that of the real patient CT in the axial, coronal, and sagittal planes. The physical accuracy and dosimetric characteristics of PSDP_3DP were comparable to those of a real patient. The ability to manufacture a PSDP representing an extreme patient condition was demonstrated.

  1. Erythroid-specific transcriptional changes in PBMCs from pulmonary hypertension patients.

    Directory of Open Access Journals (Sweden)

    Chris Cheadle

    Full Text Available Gene expression profiling of peripheral blood mononuclear cells (PBMCs is a powerful tool for the identification of surrogate markers involved in disease processes. The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells.The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH, 19 patients with systemic sclerosis without pulmonary hypertension (SSc, 42 scleroderma-associated pulmonary arterial hypertensio patients (SSc-PAH, and 8 patients with SSc complicated by interstitial lung disease and pulmonary hypertension (SSc-PH-ILD were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Multiple gene expression signatures were identified which could distinguish various disease groups from controls. One of these signatures, specific for erythrocyte maturation, is enriched specifically in patients with PH. This association was validated in multiple published datasets. The erythropoiesis signature was strongly correlated with hemodynamic measures of increasing disease severity in IPAH patients. No significant correlation of the same type was noted for SSc-PAH patients, this despite a clear signature enrichment within this group overall. These findings suggest an association of the erythropoiesis signature in PBMCs from patients with PH with a variable presentation among different subtypes of disease.In PH, the expansion of immature red blood cell precursors may constitute a response to the increasingly hypoxic conditions prevalent in this syndrome. A correlation of this erythrocyte signature with more severe hypertension cases may provide an important biomarker of disease progression.

  2. Activity and High-Order Effective Connectivity Alterations in Sanfilippo C Patient-Specific Neuronal Networks

    Directory of Open Access Journals (Sweden)

    Isaac Canals

    2015-10-01

    Full Text Available Induced pluripotent stem cell (iPSC technology has been successfully used to recapitulate phenotypic traits of several human diseases in vitro. Patient-specific iPSC-based disease models are also expected to reveal early functional phenotypes, although this remains to be proved. Here, we generated iPSC lines from two patients with Sanfilippo type C syndrome, a lysosomal storage disorder with inheritable progressive neurodegeneration. Mature neurons obtained from patient-specific iPSC lines recapitulated the main known phenotypes of the disease, not present in genetically corrected patient-specific iPSC-derived cultures. Moreover, neuronal networks organized in vitro from mature patient-derived neurons showed early defects in neuronal activity, network-wide degradation, and altered effective connectivity. Our findings establish the importance of iPSC-based technology to identify early functional phenotypes, which can in turn shed light on the pathological mechanisms occurring in Sanfilippo syndrome. This technology also has the potential to provide valuable readouts to screen compounds, which can prevent the onset of neurodegeneration.

  3. Design and manufacturing of patient-specific orthodontic appliances by computer-aided engineering techniques.

    Science.gov (United States)

    Barone, Sandro; Neri, Paolo; Paoli, Alessandro; Razionale, Armando Viviano

    2018-01-01

    Orthodontic treatments are usually performed using fixed brackets or removable oral appliances, which are traditionally made from alginate impressions and wax registrations. Among removable devices, eruption guidance appliances are used for early orthodontic treatments in order to intercept and prevent malocclusion problems. Commercially available eruption guidance appliances, however, are symmetric devices produced using a few standard sizes. For this reason, they are not able to meet all the specific patient's needs since the actual dental anatomies present various geometries and asymmetric conditions. In this article, a computer-aided design-based methodology for the design and manufacturing of a patient-specific eruption guidance appliances is presented. The proposed approach is based on the digitalization of several steps of the overall process: from the digital reconstruction of patients' anatomies to the manufacturing of customized appliances. A finite element model has been developed to evaluate the temporomandibular joint disks stress level caused by using symmetric eruption guidance appliances with different teeth misalignment conditions. The developed model can then be used to guide the design of a patient-specific appliance with the aim at reducing the patient discomfort. At this purpose, two different customization levels are proposed in order to face both arches and single tooth misalignment issues. A low-cost manufacturing process, based on an additive manufacturing technique, is finally presented and discussed.

  4. Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins

    Science.gov (United States)

    Sahud, Mervyn A.; Caulfield, Michael; Clarke, Nigel; Koch, Robert; Bougie, Daniel; Aster, Richard

    2013-01-01

    Summary Amiodarone has been implicated as a cause of thrombocytopenia but the responsible mechanism is unknown. We performed studies in three patients to characterize the pathogenesis of this complication. No amiodarone-dependent, platelet-reactive antibodies were identified using conventional serological techniques. However, water-insoluble amiodarone solubilized in methanol and diluted to 1·0 mg/ml in aqueous buffer reproducibly promoted binding of IgG antibodies in patient serum to platelets. Solid phase assays identified drug-dependent antibodies specific for platelet gly coproteins (GP)Ia/IIa (integrin α2β1) in each patient and a second antibody specific for GPIIb/IIIa (αIIbβ3 integrin) in one patient. When studied by ion mobility analysis and transmission electron microscopy, the serologically active amiodarone preparation, a milky suspension, was found to consist of particles 2–30 nm in diameter, typical of a coacervate, a state characteristic of amiodarone in aqueous medium. The findings provide evidence that thrombocytopenia in the three patients studied was caused by drug-dependent antibodies specific for platelet glycoproteins GPIa/IIa and/or GPIIb/IIIa. We postulate that, in vivo, amiodarone may become incorporated into occult lipophilic domains in platelet glycoproteins, producing structural modifications that are immunogenic in some individuals, and that the resulting antibodies can cause platelet destruction in a person taking this drug. PMID:23952260

  5. Disease-specific Growth Charts of Marfan Syndrome Patients in Korea.

    Science.gov (United States)

    Kwun, Younghee; Kim, Su Jin; Lee, Jieun; Isojima, Tsuyoshi; Choi, Doo-Seok; Kim, Duk-Kyung; Huh, June; Kang, I-Seok; Chang, MiSun; Cho, Sung Yoon; Sohn, Young Bae; Park, Sung Won; Jin, Dong-Kyu

    2015-07-01

    Patients with Marfan syndrome (MFS) presents with primary skeletal manifestations such as tall stature, chest wall abnormality, and scoliosis. These primary skeletal manifestations affect the growth pattern in MFS. Therefore, it is not appropriate to use normal growth charts to evaluate the growth status of MFS. We aimed to develop disease-specific growth charts for Korean MFS patients and to use these growth charts for understanding the growth patterns in MFS and managing of patients with MFS. Anthropometric data were available from 187 males and 152 females with MFS through a retrospective review of medical records. Disease-specific growth charts were generated and 3, 25, 50, 75, and 97 percentiles were calculated using the LMS (refers to λ, μ, and σ, respectively) smoothing procedure for height and weight. Comparisons between MFS patients and the general population were performed using a one-sample t-test. With regard to the height, the 50th percentile of MFS is above the normative 97th percentile in both genders. With regard to the weight, the 50 percentile of MFS is above the normative 75th percentile in male and between the normative 50th percentile and the 75th percentile in female. The disease-specific growth charts for Korean patients with MFS can be useful for monitoring growth patterns, planning the timing of growth-reductive therapy, predicting adult height and recording responses to growth-reductive therapy.

  6. Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels.

    Science.gov (United States)

    Dai, Bo; Ye, Ding-Wei; Kong, Yun-Yi; Shen, Yi-Jin; Wang, Bo-Hua

    2008-03-01

    To evaluate the best individualized prostate biopsy strategies for Chinese patients with suspected prostate cancer. The present study included 221 Chinese patients who underwent transrectal ultrasound guided prostate biopsies for the first time. All patients underwent the same 10-core biopsy protocol. In addition to the Hodge sextant technique, four more biopsies were obtained from the base and middle regions of bilateral peripheral zones. The differences between 10-core and sextant strategies in cancer detection among patients with different prostate specific antigen (PSA) levels were evaluated. The relationship between PSA level, number of positive biopsy cores and organ-confined cancer rate in prostate cancer patients was also analyzed. The overall prostate cancer detection rate was 40.7% in the 221 patients. The 10-core strategy increased cancer detection by 6.67% (6/90) in our patients (P 50 ng/mL (P sextant strategy is recommended for those with PSA > 50 ng/mL. For patients with PSA ranging from 20.1 ng/mL to 50 ng/mL, the 10-core strategy should be applied in patients with life expectancy = or > 10 years and the sextant strategy should be applied in those with life expectancy < 10 years.

  7. Generic and disease-specific measures of quality of life in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Bhattacharya, Suvosree; Vogel, Asmus; Hansen, Marie-Louise H

    2010-01-01

    BACKGROUND/AIM: The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD). METHODS: The participants were 321 home-living patients with mild AD...... and their primary caregivers from the Danish Alzheimer Intervention Study. QoL was assessed using the generic EuroQol-5D with visual analogue scale (VAS) and the disease-specific Quality of Life in Alzheimer's Disease (QOL-AD) scales (both caregiver and patient rated). Depression, activities of daily living......, cognitive performance and neuropsychiatric symptom severity were also assessed. RESULTS: All 3 caregiver-rated QoL scales correlated significantly with each other (p Patient-rated QoL versions correlated inversely with depression (p

  8. A Framework for Patient-Specific Spinal Intervention Simulation: Application to Lumbar Spinal Durotomy Repair.

    Science.gov (United States)

    Lau, Jonathan C; Denning, Lynn; Lownie, Stephen P; Peters, Terry M; Chen, Elvis C S

    2016-01-01

    We present a functional and patient-specific lumbar phantom for the training of spinal durotomy and dura closure under microscopic view, consisting of a lumbar model, pressurized dural surrogate, together immersed in a tissue-mimicking layer simulating fat, muscle and skin. The lumbar model was derived from a patient computed tomography scan, preserving the natural shape and curvature of the lumbar column. The inclusion of the simulated soft-tissue layer was critical for preserving the surgical ergonomics and presented a realistic view under the surgical microscope. As the success of dura repair is indicated by the watertight closure of the thecal sac, the dura surrogate was connected to a pressurized and closed-loop water system to provide functional cerebrospinal fluid leakage during durotomy. This functional phantom is inexpensive to construct, provides a realistic tactile and visual environment for spinal durotomy repair, and can be easily extended to simulate other patient-specific spinal interventions.

  9. Expanding the guidelines for electronic communication with patients: application to a specific tool.

    Science.gov (United States)

    Prady, S L; Norris, D; Lester, J E; Hoch, D B

    2001-01-01

    In 1998, the American Medical Informatics Association (AMIA) published a white paper entitled "Guidelines for the Clinical Use of Electronic Mail with Patients," which outlined a practical framework for this interaction. Interest in the use of other Internet-based tools, such as the World Wide Web, to enhance clinical communication is increasing. In such systems, static information can be made centrally available to patients and interactive tools such as messaging systems, schedules, and individualized care regimens can be integrated within the site. Site-specific guidelines are needed to address potential problems inherent in the particular services being offered. This article presents advice on developing site-specific guidelines, with examples, based on experience gained in developing and refining guidelines for the use of PatientWeb at the Massachusetts General Hospital Department of Neurology.

  10. Rapid prototyping for patient-specific surgical orthopaedics guides: A systematic literature review.

    Science.gov (United States)

    Popescu, Diana; Laptoiu, Dan

    2016-06-01

    There has been a lot of hype surrounding the advantages to be gained from rapid prototyping processes in a number of fields, including medicine. Our literature review aims objectively to assess how effective patient-specific surgical guides manufactured using rapid prototyping are in a number of orthopaedic surgical applications. To this end, we carried out a systematic review to identify and analyse clinical and experimental literature studies in which rapid prototyping patient-specific surgical guides are used, focusing especially on those that entail quantifiable outcomes and, at the same time, providing details on the guides' design and type of manufacturing process. Here, it should be mentioned that in this field there are not yet medium- or long-term data, and no information on revisions. In the reviewed studies, the reported positive opinions on the use of rapid prototyping patient-specific surgical guides relate to the following main advantages: reduction in operating times, low costs and improvements in the accuracy of surgical interventions thanks to guides' personalisation. However, disadvantages and sources of errors which can cause patient-specific surgical guide failures are as well discussed by authors. Stereolithography is the main rapid prototyping process employed in these applications although fused deposition modelling or selective laser sintering processes can also satisfy the requirements of these applications in terms of material properties, manufacturing accuracy and construction time. Another of our findings was that individualised drill guides for spinal surgery are currently the favourite candidates for manufacture using rapid prototyping. Other emerging applications relate to complex orthopaedic surgery of the extremities: the forearm and foot. Several procedures such as osteotomies for radius malunions or tarsal coalition could become standard, thanks to the significant assistance provided by rapid prototyping patient-specific surgical

  11. Reduced autobiographical memory specificity is associated with impaired discrimination learning in anxiety disorder patients.

    Science.gov (United States)

    Lenaert, Bert; Boddez, Yannick; Vervliet, Bram; Schruers, Koen; Hermans, Dirk

    2015-01-01

    Associative learning plays an important role in the development of anxiety disorders, but a thorough understanding of the variables that impact such learning is still lacking. We investigated whether individual differences in autobiographical memory specificity are related to discrimination learning and generalization. In an associative learning task, participants learned the association between two pictures of female faces and a non-aversive outcome. Subsequently, six morphed pictures functioning as generalization stimuli (GSs) were introduced. In a sample of healthy participants (Study 1), we did not find evidence for differences in discrimination learning as a function of memory specificity. In a sample of anxiety disorder patients (Study 2), individuals who were characterized by low memory specificity showed deficient discrimination learning relative to high specific individuals. In contrast to previous findings, results revealed no effect of memory specificity on generalization. These results indicate that impaired discrimination learning, previously shown in patients suffering from an anxiety disorder, may be-in part-due to limited memory specificity. Together, these studies emphasize the importance of incorporating cognitive variables in associative learning theories and their implications for the development of anxiety disorders. In addition, re-analyses of the data (Study 3) showed that patients suffering from panic disorder showed higher outcome expectancies in the presence of the stimulus that was never followed by an outcome during discrimination training, relative to patients suffering from other anxiety disorders and healthy participants. Because we used a neutral, non-aversive outcome (i.e., drawing of a lightning bolt), these data suggest that learning abnormalities in panic disorder may not be restricted to fear learning, but rather reflect a more general associative learning deficit that also manifests in fear irrelevant contexts.

  12. Reduced autobiographical memory specificity is associated with impaired discrimination learning in anxiety disorder patients

    Directory of Open Access Journals (Sweden)

    Bert eLenaert

    2015-07-01

    Full Text Available Associative learning plays an important role in the development of anxiety disorders, but a thorough understanding of the variables that impact such learning is still lacking. We investigated whether individual differences in autobiographical memory specificity are related to discrimination learning and generalization. In an associative learning task, participants learned the association between two pictures of female faces and a non-aversive outcome. Subsequently, six morphed pictures functioning as generalization stimuli (GSs were introduced. In a sample of healthy participants (Study 1, we did not find evidence for differences in discrimination learning as a function of memory specificity. In a sample of anxiety disorder patients (Study 2, individuals who were characterized by low memory specificity showed deficient discrimination learning relative to high specific individuals. In contrast to previous findings, results revealed no effect of memory specificity on generalization. These results indicate that impaired discrimination learning, previously shown in patients suffering from an anxiety disorder, may be – in part – due to limited memory specificity. Together, these studies emphasize the importance of incorporating cognitive variables in associative learning theories and their implications for the development of anxiety disorders. In addition, re-analyses of the data (Study 3 showed that patients suffering from panic disorder showed higher outcome expectancies in the presence of the stimulus that was never followed by an outcome during discrimination training, relative to patients suffering from other anxiety disorders and healthy participants. Because we used a neutral, non-aversive outcome (i.e., drawing of a lightning bolt, these data suggest that learning abnormalities in panic disorder may not be restricted to fear learning, but rather reflect a more general associative learning deficit that also manifests in fear irrelevant

  13. Reduced autobiographical memory specificity is associated with impaired discrimination learning in anxiety disorder patients

    Science.gov (United States)

    Lenaert, Bert; Boddez, Yannick; Vervliet, Bram; Schruers, Koen; Hermans, Dirk

    2015-01-01

    Associative learning plays an important role in the development of anxiety disorders, but a thorough understanding of the variables that impact such learning is still lacking. We investigated whether individual differences in autobiographical memory specificity are related to discrimination learning and generalization. In an associative learning task, participants learned the association between two pictures of female faces and a non-aversive outcome. Subsequently, six morphed pictures functioning as generalization stimuli (GSs) were introduced. In a sample of healthy participants (Study 1), we did not find evidence for differences in discrimination learning as a function of memory specificity. In a sample of anxiety disorder patients (Study 2), individuals who were characterized by low memory specificity showed deficient discrimination learning relative to high specific individuals. In contrast to previous findings, results revealed no effect of memory specificity on generalization. These results indicate that impaired discrimination learning, previously shown in patients suffering from an anxiety disorder, may be—in part—due to limited memory specificity. Together, these studies emphasize the importance of incorporating cognitive variables in associative learning theories and their implications for the development of anxiety disorders. In addition, re-analyses of the data (Study 3) showed that patients suffering from panic disorder showed higher outcome expectancies in the presence of the stimulus that was never followed by an outcome during discrimination training, relative to patients suffering from other anxiety disorders and healthy participants. Because we used a neutral, non-aversive outcome (i.e., drawing of a lightning bolt), these data suggest that learning abnormalities in panic disorder may not be restricted to fear learning, but rather reflect a more general associative learning deficit that also manifests in fear irrelevant contexts. PMID

  14. Specificity of the stress electrocardiogram during adenosine myocardial perfusion imaging in patients taking digoxin.

    Science.gov (United States)

    Hart, C Y; Miller, T D; Hodge, D O; Gibbons, R J

    2000-12-01

    In patients taking digoxin, the exercise electrocardiogram has a lower specificity for detecting coronary artery disease. However, the effect of digoxin on adenosine-induced ST-segment depression is unknown. The purpose of this study was to evaluate the specificity of the electrocardiogram during adenosine myocardial perfusion imaging in patients taking digoxin. Between May 1991 and September 1997, patients (n = 99) taking digoxin who underwent adenosine stress imaging with thallium-201 or technetium-99m sestamibi and coronary angiography within 3 months were retrospectively identified. Exclusion criteria included prior myocardial infarction, coronary artery angioplasty or bypass surgery, left bundle branch block, paced ventricular rhythm, or significant valvular disease. Twelve-lead electrocardiograms were visually interpreted at baseline, during adenosine infusion, and during the recovery period. The stress electrocardiogram was considered positive if there was > or =1 mm additional horizontal or downsloping ST-segment depression or elevation 0.08 seconds after the J-point compared with the baseline tracing. ST-segment depression and/or elevation occurred in 24 of 99 patients. There were only 2 false-positive stress electrocardiograms, yielding a specificity of 87% and positive predictive value of 92%. All 8 patients with > or =2 mm ST segment depression had multivessel disease by coronary angiography. ST-segment depression or elevation during adenosine myocardial perfusion imaging in patients taking digoxin is highly specific for coronary artery disease. Marked (> or =2 mm) ST-segment depression and/or ST-segment elevation is associated with a high likelihood of multivessel disease.

  15. Preliminary experience with the patient-specific templating total knee arthroplasty.

    Science.gov (United States)

    Boonen, Bert; Schotanus, Martijn G M; Kort, Nanne P

    2012-08-01

    Patient-specific templating total knee arthroplasty (TKA) is a new method for alignment of a total knee arthroplasty that uses disposable guides. We present the results of the first 40 consecutive patients who were operated on using this technique. In this case-control study, we compared blood loss, operation time, and alignment of 40 TKAs performed using a patient-specific templating alignment technique with values from a matched control group of patients who were operated on by conventional intramedullary alignment technique. Alignment of the mechanical axis of the leg and flexion/extension and varus/valgus of the individual prosthesis components were measured on standing, long-leg, and standard lateral digital radiographs. The fraction of outliers (> 3˚) was determined. Mean mechanical axis of templating TKAs was 181° with a fraction of outliers of 0.3, and mean mechanical axis of conventional TKAs was 179˚ (outlier fraction 0.5). Fraction of outliers in the frontal plane for femoral components was 0.05 in the templating TKAs and 0.4 in the conventional TKAs, and for tibial components the corresponding values were 0.2 and 0.2. In the templating TKAs and conventional TKAs, fraction of outliers in the sagittal plane was 0.4 and 0.9, respectively, for femoral components and 0.4 and 0.6 for tibial components. Mean operation time was 10 min shorter and blood loss was 60 mL less for templating TKA than for intramedullary-aligned TKAs. Patient-specific templating TKA showed improved accuracy of alignment and a small reduction in blood loss and operating time compared to intramedullary-aligned TKA, but the fraction of outliers was relatively high. Larger RCTs are needed for further evaluation of the technique and to define the future role of patient-specific template alignment techniques for TKA.

  16. Robustness of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2008-01-01

    This paper describes the background of the robustness requirements implemented in the Danish Code of Practice for Safety of Structures and in the Danish National Annex to the Eurocode 0, see (DS-INF 146, 2003), (DS 409, 2006), (EN 1990 DK NA, 2007) and (Sørensen and Christensen, 2006). More...... frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new structures essential....... According to Danish design rules robustness shall be documented for all structures in high consequence class. The design procedure to document sufficient robustness consists of: 1) Review of loads and possible failure modes / scenarios and determination of acceptable collapse extent; 2) Review...

  17. 3D PRINTING TECHNIQUE FOR PATIENT-SPECIFIC INSTRUMENTATION IN TOTAL KNEE ARTHROPLASTY

    Directory of Open Access Journals (Sweden)

    N. N. Karyakin

    2017-01-01

    Full Text Available The aim of the study was to evaluate clinical and radiological outcomes of knee arthroplasty using patient specific guides produced using physical prototypes and 3D printing that are applied for positioning of resection blocks. Materials and methods. The authors analyzed the treatment outcomes of 4 patients during the period from 2015 to 2016 who underwent total knee arthroplasty for posttraumatic gonarthrosis of III-IV stage with the use of patient specific guides for resection blocks positioning. The mean age of patients was 59±12 years. Initially, all patients reported marked limitation of movement in the knee joint. The average flexion prior to surgery was 53.3±35.1°. According to FLFS roentgenography all patients had a varus deformity of the lower limb with an average value of 15.0±12.3°.Results. In all cases the axis of the lower limb was normalized postoperatively. The average KOOS score for “pain” was 85.2±14.0, for “daily physical activity” — 74.5±14.8, for “symptoms and stiffness” — 69.0±11.0, for “quality of life” — 62.5±12.5 points. Average knee ROM after arthroplasty: flexion 113.3±5.787° and full extension. Such outcomes can be considered as excellent considering preoperative marked knee movement limitations in all patients.Conclusion. Preoperative planning using the technology of producing patient specific guides and prototyping on physical tibia and femur models allowed to restore normal axis of the lower limb. The authors observed a significant improvement in joint function and a pain syndrome reduction in all patients. In authors’ opinion patient specific precision guides can be used in the following cases: inflammatory process or deformation of the femur in patient’s history; when the use of intramedullary guides is difficult and does not allow positioning of the prosthesis components with sufficient accuracy or is associated with an increased risk of a purulent-inflammatory process

  18. Robustness - theoretical framework

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Faber, Michael H.

    2010-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new struct...... of this fact sheet is to describe a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines....

  19. A robust dataset-agnostic heart disease classifier from Phonocardiogram.

    Science.gov (United States)

    Banerjee, Rohan; Dutta Choudhury, Anirban; Deshpande, Parijat; Bhattacharya, Sakyajit; Pal, Arpan; Mandana, K M

    2017-07-01

    Automatic classification of normal and abnormal heart sounds is a popular area of research. However, building a robust algorithm unaffected by signal quality and patient demography is a challenge. In this paper we have analysed a wide list of Phonocardiogram (PCG) features in time and frequency domain along with morphological and statistical features to construct a robust and discriminative feature set for dataset-agnostic classification of normal and cardiac patients. The large and open access database, made available in Physionet 2016 challenge was used for feature selection, internal validation and creation of training models. A second dataset of 41 PCG segments, collected using our in-house smart phone based digital stethoscope from an Indian hospital was used for performance evaluation. Our proposed methodology yielded sensitivity and specificity scores of 0.76 and 0.75 respectively on the test dataset in classifying cardiovascular diseases. The methodology also outperformed three popular prior art approaches, when applied on the same dataset.

  20. Prospective evaluation of patient satisfaction after the use of brachytherapy specific educational materials for cervical cancer.

    Science.gov (United States)

    Rash, Dominique; Hess, Clayton; Lentz, Susan; Tait, Lauren; Michaud, Anthony; Mayadev, Jyoti

    2016-01-01

    Cervical cancer patients are faced with an enormous amount of medical information in a complex oncology field with sophisticated treatments including brachytherapy. We investigated the use of enhanced vs. standard brachytherapy-specific educational materials on patient-reported satisfaction during the informed consent process for intracavitary high-dose-rate brachytherapy. A single-institution, prospective, randomized trial was performed to study patient-reported satisfaction with novel educational materials for high-dose-rate brachytherapy in women undergoing definitive radiation for cervical cancer. Fourteen women receiving informed consent with a customized educational booklet were randomized between no further intervention and take-home educational materials. The weighted average for 10 of 11 survey questions was higher in the intervention arm but ranged between 4 (agree) and 5 (strongly agree) for all questions in both arms. The mean weighted patient satisfaction scores ± standard deviations in the control arm and the intervention arms were 54.3 ± 6.4 and 57.5 ± 2.7, respectively (p = 0.26). Knowledge acquisition is presumed to be part of the coping process for women facing increased stress during a cancer diagnosis. A brachytherapy-specific, visual, patient-educational booklet and take-home materials used to supplement the informed consent process for high-dose-rate brachytherapy resulted in high levels of patient-reported satisfaction among women treated with cervical cancer. Published by Elsevier Inc.

  1. Language-specific dysgraphia in Korean patients with right brain stroke: influence of unilateral spatial neglect.

    Science.gov (United States)

    Jang, Dae-Hyun; Kim, Min-Wook; Park, Kyoung Ha; Lee, Jae Woo

    2015-03-01

    The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

  2. Towards patient-specific finite-element simulation of MitralClip procedure.

    Science.gov (United States)

    Mansi, T; Voigt, I; Assoumou Mengue, E; Ionasec, R; Georgescu, B; Noack, T; Seeburger, J; Comaniciu, D

    2011-01-01

    MitralClip is a novel minimally invasive procedure to treat mitral valve (MV) regurgitation. It consists in clipping the mitral leaflets together to close the regurgitant hole. A careful preoperative planning is necessary to select respondent patients and to determine the clipping sites. Although preliminary indications criteria are established, they lack prediction power with respect to complications and effectiveness of the therapy in specific patients. We propose an integrated framework for personalized simulation of MV function and apply it to simulate MitralClip procedure. A patient-specific dynamic model of the MV apparatus is computed automatically from 4D TEE images. A biomechanical model of the MV, constrained by the observed motion of the mitral annulus and papillary muscles, is employed to simulate valve closure and MitralClip intervention. The proposed integrated framework enables, for the first time, to quantitatively evaluate an MV finite-element model in-vivo, on eleven patients, and to predict the outcome of MitralClip intervention in one of these patients. The simulations are compared to ground truth and to postoperative images, resulting in promising accuracy (average point-to-mesh distance: 1.47 +/- 0.24 mm). Our framework may constitute a tool for MV therapy planning and patient management.

  3. Challenge Test Results in Patients With Suspected Penicillin Allergy, but No Specific IgE.

    Science.gov (United States)

    Holm, Anne; Mosbech, Holger

    2011-04-01

    Patients with a history of allergic reaction to penicillin, but with no detectable specific IgE, are common and pose a dilemma. Challenge tests are considered to be the diagnostic gold standard. The aim of this study was to identify subgroups of patients with very low risk for reactions who could be safely tested using a more rapid and simple procedure. A total of 580 consecutively referred adult patients with a history of non-serious cutaneous allergic reactions to penicillin, but with no IgE, were challenged with therapeutic doses of penicillin V (phenoxymethylpenicillin), penicillin G (benzylpenicillin), or both. Only 14 of 580 patients had a positive challenge test. In 11 of the 14, a reaction to challenge occurred within 2 hours, and none were anaphylactic. The year of the original reaction was known for 555 patients; a positive challenge was seen in only 0.4% of those with an original reaction >15 years before challenge, but in 4.6% of those with a more recent original reaction (P=0.001). Onset of a reaction within the first day of the original exposure was a predictive factor for a positive challenge (P=0.001) in patients challenged within 15 years of the original reaction. Among suspected penicillin-allergic patients with non-severe skin reactions and no detectable specific IgE, the subgroup of patients who originally reacted more than 15 years previously had very low risk for reacting to a challenge. The risk was higher in patients with a more recent original reaction, especially if the symptoms had occurred within the first day of exposure.

  4. Nutritional status influences generic and disease-specific quality of life measures in haemodialysis patients.

    Science.gov (United States)

    Moreira, Ana Catarina; Carolino, Elisabete; Domingos, Fernando; Gaspar, Augusta; Ponce, Pedro; Camilo, María Ermelinda

    2013-01-01

    Poor nutritional status and worse healthrelated quality of life (QoL) have been reported in haemodialysis (HD) patients. The utilization of generic and disease specific QoL questionnaires in the same population may provide a better understanding of the significance of nutrition in QoL dimensions. To assess nutritional status by easy to use parameters and to evaluate the potential relationship with QoL measured by generic and disease specific questionnaires. Nutritional status was assessed by subjective global assessment adapted to renal patients (SGA), body mass index (BMI), nutritional intake and appetite. QoL was assessed by the generic EuroQoL and disease specific Kidney Disease Quality of Life-Short Form (KDQoL-SF) questionnaires. The study comprised 130 patients of both genders, mean age 62.7 ± 14.7 years. The prevalence of undernutrition ranged from 3.1% by BMI ≤ 18.5 kg/m² to 75.4% for patients below energy and protein intake recommendations. With the exception of BMI classification, undernourished patients had worse scores in nearly all QoL dimensions (EuroQoL and KDQoL-SF), a pattern which was dominantly maintained when adjusted for demographics and disease-related variables. Overweight/ obese patients (BMI ≥ 25) also had worse scores in some QoL dimensions, but after adjustment the pattern was maintained only in the symptoms and problems dimension of KDQoL-SF (p = 0.011). Our study reveals that even in mildly undernourished HD patients, nutritional status has a significant impact in several QoL dimensions. The questionnaires used provided different, almost complementary perspectives, yet for daily practice EuroQoL is simpler. Assuring a good nutritional status, may positively influence QoL. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  5. A specific exercise strategy reduced the need for surgery in subacromial pain patients.

    Science.gov (United States)

    Hallgren, Hanna C Björnsson; Holmgren, Theresa; Oberg, Birgitta; Johansson, Kajsa; Adolfsson, Lars E

    2014-10-01

    A programme based on eccentric exercises for treating subacromial pain was in a previous study found effective at 3-month follow-up. The purposes of the present study were to investigate whether the results were maintained after 1 year and whether the baseline Constant-Murley score, rotator cuff status and radiological findings influenced the outcome. 97 patients on the waiting list for arthroscopic subacromial decompression had been randomised to a specific exercise programme or unspecific exercises (controls). After 3 months of exercises, the patients were asked whether they still wanted surgery and this option was available until a 1-year follow-up. 1 year after inclusion or 1 year after surgery, the number of patients who decided to have surgery in each group was compared. The choice of surgery was related to the baseline Constant-Murley score, ultrasound and radiographs taken at inclusion. All patients had improved significantly (p<0.0001) in the Constant-Murley score at the 1-year follow-up. Significantly more patients in the control group decided to have surgery (63%) than those in the specific exercise group (24%; p<0.0001). Patients who decided to have surgery had a significantly lower baseline Constant-Murley score and more often a full-thickness tear. Patients with partial tears did not differ from those with intact tendons. The positive short-term results of specific exercises were maintained after 1 year, and this exercise strategy reduces the need for surgery. Full-thickness tear and a low baseline Constant-Murley score appear to be a predictive marker for a less good outcome. Clinical trials NCT01037673. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Quality specifications: self pleasure for clinical laboratories or added value for patient management?

    Science.gov (United States)

    Plebani, Mario

    2007-01-01

    Analytical quality specifications play a key role in assuring and continuously improving high-quality laboratory services. However, I believe, that there are two "missing links" in the effective management of quality specifications in the delivery of laboratory services. The first is the evidence that pre-analytical variation and related problems are not taken into great consideration by laboratory professionals. The second missing link is the communication of quality specifications to clinicians and other possible stakeholders. If quality specifications represent "the level of performance required to facilitate clinical decision-making", they cannot be used only for internal quality management procedures but must be communicated to facilitate clinical reasoning, decision-making and patient management. A consensus should be achieved in the scientific community on these issues to assure better utilization of laboratory data and, ultimately, improved clinical outcomes.

  7. Cerebral Aneurysm Clipping Surgery Simulation Using Patient-Specific 3D Printing and Silicone Casting.

    Science.gov (United States)

    Ryan, Justin R; Almefty, Kaith K; Nakaji, Peter; Frakes, David H

    2016-04-01

    Neurosurgery simulator development is growing as practitioners recognize the need for improved instructional and rehearsal platforms to improve procedural skills and patient care. In addition, changes in practice patterns have decreased the volume of specific cases, such as aneurysm clippings, which reduces the opportunity for operating room experience. The authors developed a hands-on, dimensionally accurate model for aneurysm clipping using patient-derived anatomic data and three-dimensional (3D) printing. Design of the model focused on reproducibility as well as adaptability to new patient geometry. A modular, reproducible, and patient-derived medical simulacrum was developed for medical learners to practice aneurysmal clipping procedures. Various forms of 3D printing were used to develop a geometrically accurate cranium and vascular tree featuring 9 patient-derived aneurysms. 3D printing in conjunction with elastomeric casting was leveraged to achieve a patient-derived brain model with tactile properties not yet available from commercial 3D printing technology. An educational pilot study was performed to gauge simulation efficacy. Through the novel manufacturing process, a patient-derived simulacrum was developed for neurovascular surgical simulation. A follow-up qualitative study suggests potential to enhance current educational programs; assessments support the efficacy of the simulacrum. The proposed aneurysm clipping simulator has the potential to improve learning experiences in surgical environment. 3D printing and elastomeric casting can produce patient-derived models for a dynamic learning environment that add value to surgical training and preparation. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Do patients with different mental disorders show specific aspects of shame?

    Science.gov (United States)

    Scheel, Corinna N; Bender, Caroline; Tuschen-Caffier, Brunna; Brodführer, Anne; Matthies, Swantje; Hermann, Christiane; Geisse, Eva K; Svaldi, Jennifer; Brakemeier, Eva-Lotta; Philipsen, Alexandra; Jacob, Gitta A

    2014-12-15

    Shame is related to several mental disorders. We assume that facets of shame, namely bodily, cognitive and existential shame, may occur in typical patterns in mental and personality disorders. An excessive level of shame may lead to psychopathological symptoms. However, a lack of shame may also lead to distress, for instance as it may facilitate violation of social norms and thus may promote interpersonal problems. In this study we investigated facets of shame in females suffering from various mental disorders and personality disorders presumably associated with specific aspects of shame. Women suffering from borderline personality disorder (BPD, n=92), attention deficit hyperactivity disorder (ADHD, n=86), major depressive disorder (MDD, n=17), social anxiety disorder (SAD, n=33), and a community sample (COM, n=290) completed the SHAME questionnaire, which is a newly developed instrument to assess adaptive and maladaptive aspects of shame. BPD patients reported the highest level of existential shame compared to all other groups. Compared to the controls, SAD patients displayed stronger bodily and cognitive shame, and ADHD showed lower bodily shame. As assumed, specific aspects of shame were found in different patient groups. It may be important to specifically address these specific aspects of shame in psychotherapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

    Science.gov (United States)

    Haberman, Yael; Tickle, Timothy L.; Dexheimer, Phillip J.; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N.; Noe, Joshua D.; Rosh, Joel; Markowitz, James; Heyman, Melvin B.; Griffiths, Anne M.; Crandall, Wallace V.; Mack, David R.; Baker, Susan S.; Huttenhower, Curtis; Keljo, David J.; Hyams, Jeffrey S.; Kugathasan, Subra; Walters, Thomas D.; Aronow, Bruce; Xavier, Ramnik J.; Gevers, Dirk; Denson, Lee A.

    2014-01-01

    Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches. PMID:25003194

  10. Cytogenetic studies in 32 patients with myelodysplastic syndrome: insights to specific chromosomal abnormalities and prognosis.

    Science.gov (United States)

    Taniwaki, M; Horiike, S; Inazawa, J; Nishida, K; Misawa, S; Takino, T; Abe, T

    1987-06-01

    Cytogenetic studies were performed on a group of 32 patients with myelodysplastic syndrome (MDS). Five patients had refractory anemia (RA), four RA with ring sideroblasts (RARS), nine RA with excess blasts (RAEB), eight RAEB 'in transformation' (RAEB-T), three chronic myelomonocytic leukemia (CMML) and three secondary MDS (SMDS). Two patients in the SMDS group had been treated with alkylating agents for lung cancer and polycythemia vera, respectively. The other had been exposed to thorotrast. Chromosome analyses were performed with Q and G bandings on bone marrow cells incubated for 24 hr. A clonal chromosomal abnormality was observed in the marrow cells from 19 of the 32 patients (59%). Chromosomal abnormalities of nos. 5 and/or 7 were found in five patients, and were probably specific for RAEB-T and SMDS. Among the twelve patients with solely abnormal metaphases (AA), eight (67%) progressed to acute leukemia, a higher proportion than the three from the 13 patients (23%) with solely normal metaphases (NN) (P less than 0.05). One of the seven patients (14%) with both normal and abnormal metaphases (AN) developed acute leukemia (AA v. AN, P less than 0.03). In only two of the 12 patients who progressed to acute leukemia (17%), was complete remission achieved. The median survival time was only 4.0 months for patients with karyotype AA compared with 18.0 months for AN and 24.0 months for NN (AA v. AN, P less than 0.05, AA v. NN, P less than 0.05). The absence of cytogenetically normal cells indicated a poor prognosis with frequent progression to acute leukemia which is resistant to chemotherapy. Progression to acute leukemia depended not only on chromosomal abnormalities but also on morphological subtype classified according to French-American-British co-operative group criteria. Morphological findings and karyotype combined gave a good indication of the outcome for patients with MDS.

  11. Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Kanako; Masutani, Yoshitaka; Watadani, Takeyuki; Nakata, Yasuhiro; Yoshida, Mariko; Abe, Osamu; Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Bunkyo, Tokyo (Japan); Aoki, Shigeki [Juntendo University, Department of Radiology, Bunkyo, Tokyo (Japan); Iwata, Nobue K.; Terao, Yasuo; Tsuji, Shoji [University of Tokyo, Department of Neurology, Graduate School of Medicine, Bunkyo, Tokyo (Japan)

    2010-08-15

    The uncinate fasciculus (UF) consists of core fibers connecting the frontal and temporal lobes and is considered to be related to cognitive/behavioral function. Using diffusion tensor tractography, we quantitatively evaluated changes in fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the UF by tract-specific analysis to evaluate the damage of the UF in patients with amyotrophic lateral sclerosis (ALS). We obtained diffusion tensor images of 15 patients with ALS and 9 age-matched volunteers. Patients with ALS showed significantly lower mean FA (P = 0.029) compared with controls. No significant difference was seen in mean ADC. The results suggest that damage of the UF in patients with ALS can be quantitatively evaluated with FA. (orig.)

  12. Tumor-specific binding of radiolabeled G-22 monoclonal antibody in glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Jun; Wakabayashi, Toshihiko; Mizuno, Masaaki; Sugita, Kenichiro; Oshima, Motoo; Tadokoro, Masanori; Sakuma, Sadayuki (Nagoya Univ. (Japan). Faculty of Medicine); Seo, Hisao

    1992-03-01

    Iodine-131-labeled G-22 monoclonal antibody F(ab'){sub 2} fragment reacting specifically with a glioma-associated surface glycoprotein was administered to 12 glioma patients to investigate its use in radioimaging of intracranial gliomas. No immediate or delayed side effects were attributable to antibody injection. Nine patients received the radiolabeled complex intravenously. The images of low-grade gliomas were generally poor and disappeared within 4 days. High-contrast images were obtained beyond the 7th day in high-grade gliomas except one case in the pineal region. Three patients received intraventricular or intratumoral administration. Clear images of all tumors were demonstrated from the 2nd until later than the 7th day. One patient with cerebrospinal fluid (CSF) dissemination of brainstem glioma demonstrated negative CSF cytology after intraventricular administration. (author).

  13. Nationwide Assessment of Cause-Specific Mortality in Patients with Rosacea

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Fowler, Joseph F; Gislason, Gunnar H

    2016-01-01

    BACKGROUND: Emerging data suggest that rosacea is associated with several comorbidities; however, the causes of mortality in patients with rosacea have not yet been investigated. OBJECTIVE: We evaluated all-cause and cause-specific death rates in patients with rosacea in a population-based Danish...... cohort study. METHODS: All Danish individuals aged ≥18 years between 1 January 1997 and 31 December 2012 with rosacea diagnosed by hospital dermatologists were linked in nationwide registers and compared with age- and sex-matched general-population subjects (1:5 ratio). Death rates were calculated per...... 1000 person-years, and hazard ratios (HRs) were estimated using Cox regression models. RESULTS: The total cohort (n = 35,958) included 5993 patients with rosacea and 29,965 age- and sex-matched individuals from the general population. During the maximum 15 years of follow-up, 664 (11.1 %) patients...

  14. MTB-specific lymphocyte responses are impaired in tuberculosis patients with pulmonary cavities.

    Science.gov (United States)

    Wang, Jun; Dai, Yaping; Liu, Jun; Yin, Yongmei; Pei, Hao

    2017-01-26

    Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB), is a global health problem. Because the failing immune response in the lung can lead to formation of a pulmonary cavity, this study was designed to clarify MTB-specific lymphocyte responses in TB patients with pulmonary cavities. We utilized culture filtrate protein 10 (CFP-10) and early secretory antigenic target 6 (ESAT-6) as immunogenic MTB antigens following overnight stimulation of peripheral blood mononuclear cells (PBMCs). By flow cytometry, we then dissected CD4+ and CD8+ T lymphocytes secreting intracellular cytokines of IFN-γ and TNF-α to assess the local immune response of TB patients with pulmonary cavities compared with those having other radiological infiltrates. As expected, after 16 h of ex vivo activation using both ESAT-6 and CFP-10, the proportions of CD4+IFN-γ, CD4+TNF-α, CD8+TNF-α, and CD8+IFN-γ cells were all markedly increased in 46 patients with TB when compared with 23 household contacts. However, the IFN-γ and TNF-α responses of both CD4+ and CD8+ T lymphocytes were found to be relatively lower in 18 patients who had pulmonary cavities when compared with 28 patients who had radiological infiltrates. Moreover, patients with cavities had higher absolute numbers of neutrophils than patients with infiltrates. Further analysis indicated an inverse correlation between neutrophil counts and the proportions of IFN-γ-secreting T cells. MTB-specific lymphocyte responses are impaired in TB patients with pulmonary cavities that are likely to play an important role in the pathogenesis of cavitary TB.

  15. Prostate-specific antigen doubling time and response to cabazitaxel in a hormone-resistant metastatic prostate cancer patient

    OpenAIRE

    Ghosn, Marwan; Dagher, Alain; El-Karak, Fadi

    2014-01-01

    Abstract We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antigen doubling time and prostate-specific antigen absolute value. The prostate-specific antigen doubling time was found to be a good response predictor in the patient.

  16. Prostate-specific antigen doubling time and response to cabazitaxel in a hormone-resistant metastatic prostate cancer patient.

    Science.gov (United States)

    Ghosn, Marwan; Dagher, Alain; El-Karak, Fadi

    2015-09-01

    We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antigen doubling time and prostate-specific antigen absolute value. The prostate-specific antigen doubling time was found to be a good response predictor in the patient.

  17. Using vortex corelines to analyze the hemodynamics of patient specific cerebral aneurysm models

    Science.gov (United States)

    Byrne, Greg; Mut, Fernando; Cebral, Juan

    2012-02-01

    We construct one-dimensional sets known as vortex corelines for computational fluid dynamic (CFD) simulations of blood flow in patient specific cerebral aneurysm models. These sets identify centers of swirling blood flow that may play an important role in the biological mechanisms causing aneurysm growth, rupture, and thrombosis. We highlight three specific applications in which vortex corelines are used to assess flow complexity and stability in cerebral aneurysms, validate numerical models against PIV-based experimental data, and analyze the effects of flow diverting devices used to treat intracranial aneurysms.

  18. Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies

    Directory of Open Access Journals (Sweden)

    Receveur Marie-Catherine

    2009-12-01

    Full Text Available Abstract Background Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood. Case presentation We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection. Conclusions Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.

  19. Patient-specific indirectly 3D printed mitral valves for pre-operative surgical modelling

    Science.gov (United States)

    Ginty, Olivia; Moore, John; Xia, Wenyao; Bainbridge, Dan; Peters, Terry

    2017-03-01

    Significant mitral valve regurgitation affects over 2% of the population. Over the past few decades, mitral valve (MV) repair has become the preferred treatment option, producing better patient outcomes than MV replacement, but requiring more expertise. Recently, 3D printing has been used to assist surgeons in planning optimal treatments for complex surgery, thus increasing the experience of surgeons and the success of MV repairs. However, while commercially available 3D printers are capable of printing soft, tissue-like material, they cannot replicate the demanding combination of echogenicity, physical flexibility and strength of the mitral valve. In this work, we propose the use of trans-esophageal echocardiography (TEE) 3D image data and inexpensive 3D printing technology to create patient specific mitral valve models. Patient specific 3D TEE images were segmented and used to generate a profile of the mitral valve leaflets. This profile was 3D printed and integrated into a mold to generate a silicone valve model that was placed in a dynamic heart phantom. Our primary goal is to use silicone models to assess different repair options prior to surgery, in the hope of optimizing patient outcomes. As a corollary, a database of patient specific models can then be used as a trainer for new surgeons, using a beating heart simulator to assess success. The current work reports preliminary results, quantifying basic morphological properties. The models were assessed using 3D TEE images, as well as 2D and 3D Doppler images for comparison to the original patient TEE data.

  20. Patient-specific left atrial wall-thickness measurement and visualization for radiofrequency ablation

    Science.gov (United States)

    Inoue, Jiro; Skanes, Allan C.; White, James A.; Rajchl, Martin; Drangova, Maria

    2014-03-01

    INTRODUCTION: For radiofrequency (RF) catheter ablation of the left atrium, safe and effective dosing of RF energy requires transmural left atrium ablation without injury to extra-cardiac structures. The thickness of the left atrial wall may be a key parameter in determining the appropriate amount of energy to deliver. While left atrial wall-thickness is known to exhibit inter- and intra-patient variation, this is not taken into account in the current clinical workflow. Our goal is to develop a tool for presenting patient-specific left atrial thickness information to the clinician in order to assist in the determination of the proper RF energy dose. METHODS: We use an interactive segmentation method with manual correction to segment the left atrial blood pool and heart wall from contrast-enhanced cardiac CT images. We then create a mesh from the segmented blood pool and determine the wall thickness, on a per-vertex basis, orthogonal to the mesh surface. The thickness measurement is visualized by assigning colors to the vertices of the blood pool mesh. We applied our method to 5 contrast-enhanced cardiac CT images. RESULTS: Left atrial wall-thickness measurements were generally consistent with published thickness ranges. Variations were found to exist between patients, and between regions within each patient. CONCLUSION: It is possible to visually determine areas of thick vs. thin heart wall with high resolution in a patient-specific manner.

  1. Patient-specific rigorously methodological test of the mean phase coherence

    DEFF Research Database (Denmark)

    Henriksen, Jonas

    such a test using the mean phase coherence (MPC) feature. Methods: The MPC was implemented as described by Mormann et al., 2000. It was tested in a generic rigorously methodological way on the FSPEEG database, Winterhalder et al., 2003. 10 patients were used for training of the algorithm’s optimal settings.......55, 0.3/h}. For the 4 new patients the generic results were {0.91, 0.55/h}, {0.85, 0.71/h}, {0.29, 0.49/h}, and {0, 0.36/h} which is comparable to the FSPEEG database. The patient-specific approach yielded {0.81, 0.17/h}, {0.57, 0.13/h}, {0.81, 0.13/h}, and {0.60, 0.50/h} respectively, meaning......Purpose: Due to a confined amount of recordings in existing EEG databases, only few papers have described a patient-specific rigorously methodological test of features for seizure prediction. By extraction of intracranial EEG from epilepsy patients with at least 6 seizures, this study has conducted...

  2. Transition from pediatric to adult healthcare: assessment of specific needs of patients with chronic endocrine conditions.

    Science.gov (United States)

    Godbout, Ariane; Tejedor, Isabelle; Malivoir, Sabine; Polak, Michel; Touraine, Philippe

    2012-01-01

    Transition from pediatric to adult care is a challenging turning point. The aim was to evaluate the transition process and needs expressed by patients with chronic endocrine conditions at transition in order to ensure program optimization. Prospective assessment of the transition period was conducted through completion of standardized questionnaires given to targeted patients. Two types were created: (1) a general questionnaire (GQ) addressing universal aspects of transition, and (2) a specific questionnaire (SQ) exploring concerns related to each endocrine condition. Three endocrinopathies (congenital adrenal hyperplasia, hypogonadotropic hypogonadism and growth hormone deficiency) were selected for assessment since they present specific challenges requiring characterization. Over the last decade, 244 patients in transition were registered in our department and 153 were included since they presented one of the endocrinopathies selected. A total of 73 subjects completed both the GQ and the SQ. Over 80% of the patients were satisfied with the transition process in terms of organization, accessibility and medical care. The actual age of transition corresponded for most to the age considered by patients as ideal for transition. SQs identified psychosexual issues that must be addressed more systematically. This study identified key elements allowing the creation of an improved transition program tailored for our center and for each endocrine condition studied. Copyright © 2012 S. Karger AG, Basel.

  3. The multidimensional inventory of hypochondriacal traits: factor structure, specificity, reliability, and validity in patients with hypochondriasis.

    Science.gov (United States)

    Witthöft, Michael; Weck, Florian; Gropalis, Maria

    2015-06-01

    Severe health anxiety constitutes a disabling and costly clinical condition. The Multidimensional Inventory of Hypochondriacal Traits (MIHT) represents an innovative instrument that was developed according to cognitive-behavioral, cognitive-perceptual, interpersonal, and trait models of hypochondriasis. We aimed at evaluating the psychometric properties of the MIHT in a sample of patients with the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis of hypochondriasis. Using confirmatory factor analysis (CFA), the postulated four-factor structure of the MIHT was found in a first CFA in patients with hypochondriasis (n = 178) and in a second CFA based on a mixed sample, with other somatoform disorders (n = 27), panic disorder (n = 25), and healthy controls (n = 31) added to the original group of patients with hypochondriasis (n = 178). In terms of specificity, patients with hypochondriasis showed larger scores on all four MIHT subscales (i.e., affective, cognitive, behavioral, and perceptual) compared to all other groups. Analyses of convergent and discriminant validity revealed promising results concerning the MIHT affective and perceptual scales but also point to certain problematic issues concerning the MIHT cognitive and behavioral scales. The findings suggest that the proposed structure of the MIHT is valid also in patients with hypochondriasis and demonstrate the specificity of the four hypochondriacal traits assessed in the MIHT. © The Author(s) 2014.

  4. Are Hip-Specific Items Useful in a Quality of Life Questionnaire for Patients with Hip Fractures?

    Science.gov (United States)

    Yao, Kai-Ping Grace; Lee, Hsin-Yi; Tsauo, Jau-Yih

    2009-01-01

    Researchers measure the significance of hip fracture by the patient's impairment. The patient's quality of life (QOL) is usually also substantially affected. However, there is no specific quality of life (QOL) questionnaire for patients with hip fractures. This study was designed to determine whether adding a new set of specific questions about…

  5. Signaling pathway models as biomarkers: Patient-specific simulations of JNK activity predict the survival of neuroblastoma patients.

    Science.gov (United States)

    Fey, Dirk; Halasz, Melinda; Dreidax, Daniel; Kennedy, Sean P; Hastings, Jordan F; Rauch, Nora; Munoz, Amaya Garcia; Pilkington, Ruth; Fischer, Matthias; Westermann, Frank; Kolch, Walter; Kholodenko, Boris N; Croucher, David R

    2015-12-22

    Signaling pathways control cell fate decisions that ultimately determine the behavior of cancer cells. Therefore, the dynamics of pathway activity may contain prognostically relevant information different from that contained in the static nature of other types of biomarkers. To investigate this hypothesis, we characterized the network that regulated stress signaling by the c-Jun N-terminal kinase (JNK) pathway in neuroblastoma cells. We generated an experimentally calibrated and validated computational model of this network and used the model to extract prognostic information from neuroblastoma patient-specific simulations of JNK activation. Switch-like JNK activation mediates cell death by apoptosis. An inability to initiate switch-like JNK activation in the simulations was significantly associated with poor overall survival for patients with neuroblastoma with or without MYCN amplification, indicating that patient-specific simulations of JNK activation could stratify patients. Furthermore, our analysis demonstrated that extracting information about a signaling pathway to develop a prognostically useful model requires understanding of not only components and disease-associated changes in the abundance or activity of the components but also how those changes affect pathway dynamics. Copyright © 2015, American Association for the Advancement of Science.

  6. Generation of Transplantable Beta Cells for Patient-Specific Cell Therapy

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2012-01-01

    Full Text Available Islet cell transplantation offers a potential cure for type 1 diabetes, but it is challenged by insufficient donor tissue and side effects of current immunosuppressive drugs. Therefore, alternative sources of insulin-producing cells and isletfriendly immunosuppression are required to increase the efficiency and safety of this procedure. Beta cells can be transdifferentiated from precursors or another heterologous (non-beta-cell source. Recent advances in beta cell regeneration from somatic cells such as fibroblasts could circumvent the usage of immunosuppressive drugs. Therefore, generation of patient-specific beta cells provides the potential of an evolutionary treatment for patients with diabetes.

  7. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders

    Directory of Open Access Journals (Sweden)

    Kristen J. Brennand

    2015-12-01

    Full Text Available As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

  8. Distinct trajectories of disease-specific health status in heart failure patients undergoing cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H.; Pedersen, Susanne S.; Meine, Mathias

    2016-01-01

    PURPOSE: It is well known that a significant proportion of heart failure patients (10-44 %) do not show improvement in symptoms or functioning from cardiac resynchronization therapy (CRT), yet no study has examined patient-reported health status trajectories after implantation. METHODS: A cohort......-specific health status over time. RESULTS: All health status trajectories showed an initial small to large improvement from baseline to 2-month follow-up, whereafter most trajectories displayed a stable pattern between short- and long-term follow-up. Low educational level, NYHA class III/IV, smoking, no use...

  9. Patient-specific simulation of implant placement and function for cochlear implantation surgery planning.

    Science.gov (United States)

    Ceresa, Mario; Lopez, Nerea Mangado; Velardo, Hector Dejea; Herrezuelo, Noemi Carranza; Mistrik, Pavel; Kjer, Hans Martin; Vera, Sergio; Paulsen, Rasmus R; González Ballester, Miguel Angel

    2014-01-01

    We present a framework for patient specific electrical stimulation of the cochlea, that allows to perform in-silico analysis of implant placement and function before surgery. A Statistical Shape Model (SSM) is created from high-resolution human μCT data to capture important anatomical details. A Finite Element Model (FEM) is built and adapted to the patient using the results of the SSM. Electrical simulations based on Maxwell's equations for the electromagnetic field are performed on this personalized model. The model includes implanted electrodes and nerve fibers. We present the results for the bipolar stimulation protocol and predict the voltage spread and the locations of nerve excitation.

  10. Establishing construct validity for the thyroid-specific patient reported outcome measure (ThyPRO)

    DEFF Research Database (Denmark)

    Watt, Torquil; Bjorner, Jakob Bue; Groenvold, Mogens

    2009-01-01

    OBJECTIVE: To establish a reliable and valid scale structure of a patient-reported outcome measuring thyroid-specific quality of life. METHODS: The 98-item ThyPRO questionnaire was administered to patients with benign thyroid diseases at two university hospitals. Multi-trait scaling was performed...... complete convergent validity and only two instances of lack of discriminant validity. Pearson correlations yielded similar results. Across all subgroups, convergent validity was complete, and discriminant validity was found in 99.2% of tests. Lack of discriminant validity was mainly between physical...

  11. The utility of patient specific induced pluripotent stem cells for the modelling of Autistic Spectrum Disorders.

    Science.gov (United States)

    Cocks, Graham; Curran, Sarah; Gami, Priya; Uwanogho, Dafe; Jeffries, Aaron R; Kathuria, Annie; Lucchesi, Walter; Wood, Victoria; Dixon, Rosemary; Ogilvie, Caroline; Steckler, Thomas; Price, Jack

    2014-03-01

    Until now, models of psychiatric diseases have typically been animal models. Whether they were to be used to further understand the pathophysiology of the disorder, or as drug discovery tools, animal models have been the choice of preference in mimicking psychiatric disorders in an experimental setting. While there have been cellular models, they have generally been lacking in validity. This situation is changing with the advent of patient-specific induced pluripotent stem cells (iPSCs). In this article, we give a methodological evaluation of the current state of the iPS technology with reference to our own work in generating patient-specific iPSCs for the study of autistic spectrum disorder (ASD). In addition, we will give a broader perspective on the validity of this technology and to what extent it can be expected to complement animal models of ASD in the coming years.

  12. Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients

    Directory of Open Access Journals (Sweden)

    Meng-Lu Liu

    2016-01-01

    Full Text Available Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS. Here, we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs with skeletal muscles. Importantly, hiMNs converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification.

  13. Abnormal lactate levels in patients with polymyositis and dermatomyositis: the benefits of a specific rehabilitative program.

    Science.gov (United States)

    Bertolucci, F; Neri, R; Dalise, S; Venturi, M; Rossi, B; Chisari, C

    2014-04-01

    Polymyositis (PM) and Dermatomyositis (DM) are chronic, inflammatory and autoimmune skeletal muscle disorders characterized by reduced muscle strength, fatigue and myalgia. While inflammation causes muscle damage in the early phase, metabolic alterations such as an impairment of oxidative metabolism seem to be responsible for the disability in the chronic phase of the disease. To assess muscle oxidative efficiency and to test the effect of aerobic training in a group of PM/DM patients. A case-control study and a within-group comparison. SETTING. Outpatients of the Unit of Neurorehabilitation of the University Hospital of Pisa. 20 patients with myositis (15 PM and 5 DM) and 15 healthy subjects as a control group. The test consisted of an incremental, sub-maximal aerobic exercise on a treadmill; haematic lactate was assessed at rest and after 1', 5', 10' and 30' minutes from the end of the exercise. A within-group comparison was conducted on four of the PM patients (P group). They were subjected to six weeks aerobic training. Lactate curve and functional tests were assessed before and after the treatment. A precocious fatigability and significantly higher values of lactate at rest and after the exercise were observed in patients. In the P group mean lactate levels were significantly decreased after the treatment and an improvement of muscle performance was observed. Abnormal blood lactate levels suggested an impaired muscle oxidative efficiency in PM/DM patients. A specific aerobic training program reduced lactate levels and relieved fatigue symptoms in a within-group of four of the PM patients. Such a specific aerobic training program could be introduced in everyday practice for the rehabilitative treatment of PM/DM patients.

  14. SPECIFICITIES OF THE SUBSET PROFILE OF PERIPHERAL BLOOD IN PATIENTS WITH GLIOBLASTOMA: PATHOGENETIC AND CLINICAL ASSESSMENTS

    Directory of Open Access Journals (Sweden)

    V. A. Chumakov

    2006-01-01

    Full Text Available Abstract. In glioblastoma (GB, it is necessary to take into consideration GB-associated secondary immunodeficiency (SID, so-called syndrome of tumor-associated SID (STASID. Cell subsets having effector and regulatory functions, play an important role in developing STASID, and their proportions in patients with different forms of GB can be of pathogenetic importance and have clinical value for treatment and rehabilitation scheduling as well. The most pathogenically and clinically important features of cell subsets profile of peripheral blood were analyzed in patients with different clinical and morphological types of GB. The patients were divided into three groups, i.e., groups I and II were formed by patients with STASID (marked and slightly marked SID, accordingly; group III – patients with SIDTAS (tumor-associated autoimmune syndrome, associated with SID. Marked suppression of cell immunity is typical of group I - imbalance in T-lymphocytes, in a number of specific subsets, and in subsets clusters, as well as disproportions in the immunoregulatory indexes. In group II, the subset profiles of blood were slightly different from the norm. In patients with SIDTAS, activation of cell immunity was evident, forming SID with signs of autoimmune syndrome, affecting effector and regulatory chains of immunity, and influencing the severity and forecast of the disease. Specific features of the immune status in patients with GB identified can be resulted from different clinicalmorphological types of the tumor; the latter are to be considered in differential diagnostics of clinical course of GB and in scheduling of clinical-immunological efficient anti-tumor pharmacotherapy in pre- and postoperative periods.

  15. Influence of catheterization on the prostate specific antigen level in patient suffering from prostate disorder

    OpenAIRE

    Osman Sianipar, Osman Sianipar

    2015-01-01

    Background: The increase of life expectancy may increase the number of patients suffered from prostate disorder. In Indonesia prostate cancer is in the top ten malignancies in men and is the second most frequent malignancies in urology clinics. Early detection may decreasies its fatality rate and increase the quality of life. Prostate specific antigen (PSA) is clinically the most useful tumor marker; its serum level has positive correlation with the prostate cancer. Serum PSA level will also ...

  16. Viral respiratory infections in patients with chronic non-specific lung disease (CNSLD)

    OpenAIRE

    Roldaan, A.C.

    1981-01-01

    textabstractIt is a well known clinical phenomenon that patients suffering from bronchial obstructive disorders, usually covered by the term chronic non-specific lung disease (CNSLD) tend to react with exacerbations of their disease in the course of respiratory infections, especially if a viral or mycoplasmal agent is involved. However, there is no uniform opinion about the relative importance of viral respiratory infections in this respect, and much of the background of the features observed...

  17. Patient-specific estimation of detailed cochlear shape from clinical CT images

    DEFF Research Database (Denmark)

    Kjer, H Martin; Fagertun, Jens; Wimmer, Wilhelm

    2018-01-01

    of the detailed patient-specific cochlear shape from CT images. From a collection of temporal bone [Formula: see text]CT images, we build a cochlear statistical deformation model (SDM), which is a description of how a human cochlea deforms to represent the observed anatomical variability. The model is used...... to current best practice, we demonstrate competitive performance and some useful properties of our method....

  18. Pretreatment prostate specific antigen doubling time as prognostic factor in prostate cancer patients

    OpenAIRE

    Zharinov, Gennady M.; Bogomolov, Oleg A.; Neklasova, Natalia N.; Anisimov, Vladimir N.

    2017-01-01

    Despite the prostate-specific antigen (PSA) serum level commonly uses as tumor marker in diagnosis of prostate cancer, it seems that PSA doubling time (PSADT) could be more useful indicator of tumor behavior and of prognosis for patients. The results of hormone and radiation therapy were evaluated for 912 prostate cancer having at least 2 PSA tests before the treatment was started. Clustering procedure (selection of homogenous group) was performed by using PSADT as the classification marker. ...

  19. PCR Detection of DNA Specific for Trichosporon Species in Serum of Patients with Disseminated Trichosporonosis

    Science.gov (United States)

    Nagai, Hiroyuki; Yamakami, Yuriko; Hashimoto, Atsuro; Tokimatsu, Issei; Nasu, Masaru

    1999-01-01

    Deep-seated trichosporonosis is a lethal opportunistic infection that disseminates rapidly and widely in immunocompromised patients, and early diagnosis is crucial for the treatment of this infection. We developed a novel nested-PCR assay that detects DNA specific for clinically important strains of Trichosporon in serum samples from patients with disseminated trichosporonosis. In this assay, two sets of oligonucleotide primers were derived from the sequence of 26S rRNA genes of Trichosporon asahii. The specific fragment was amplified from T. asahii and T. mucoides, but not from other microorganisms, including some other basidiomycetous fungi (Cryptococcus, Malassezia, Rhodotorula, and Sporobolomyces). Target DNA was detected by the nested PCR with as little as 5 fg of the extracted DNA of T. asahii. In a study using 11 clinical samples, the specific fragment was detected by the nested PCR in 64% (7 of 11) of sera from patients with histologically diagnosed disseminated trichosporonosis, while glucuronoxylomannan antigen was detected in only 54% (6 of 11) of the samples. Our new nested-PCR assay using serum samples can be performed repeatedly throughout the course of the disease. In addition, not only can it be used for early diagnosis of trichosporonosis, but it may also be beneficial for monitoring its progress or response to therapy. PMID:9986834

  20. Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer.

    Science.gov (United States)

    Li, Chengwen; Wu, Shuqing; Albright, Blake; Hirsch, Matthew; Li, Wuping; Tseng, Yu-Shan; Agbandje-McKenna, Mavis; McPhee, Scott; Asokan, Aravind; Samulski, R Jude

    2016-02-01

    A major hindrance in gene therapy trials with adeno-associated virus (AAV) vectors is the presence of neutralizing antibodies (NAbs) that inhibit AAV transduction. In this study, we used directed evolution techniques in vitro and in mouse muscle to select novel NAb escape AAV chimeric capsid mutants in the presence of individual patient serum. AAV mutants isolated in vitro escaped broad patient-specific NAb activity but had poor transduction ability in vivo. AAV mutants isolated in vivo had enhanced NAb evasion from cognate serum and had high muscle transduction ability. More importantly, structural modeling identified a 100 amino acid motif from AAV6 in variable region (VR) III that confers this enhanced muscle tropism. In addition, a predominantly AAV8 capsid beta barrel template with a specific preference for AAV1/AAV9 in VR VII located at threefold symmetry axis facilitates NAb escape. Our data strongly support that chimeric AAV capsids composed of modular and nonoverlapping domains from various serotypes are capable of evading patient-specific NAbs and have enhanced muscle transduction.

  1. Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder.

    Science.gov (United States)

    Samalin, Ludovic; de Chazeron, Ingrid; Vieta, Eduard; Bellivier, Frank; Llorca, Pierre-Michel

    2016-03-01

    The aims of the present study were to confirm the impact of residual symptoms on overall functioning in a large sample of euthymic patients with bipolar disorder in real-life conditions and to explore the relationship between residual symptoms and specific areas of functional impairment. This was a multicenter, cross-sectional, non-interventional study of euthymic outpatients with bipolar disorder. The Functioning Assessment Short Test was used to assess overall and specific domains of functioning (autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time). Various residual symptoms were assessed (residual mood symptoms, emotional dysregulation, sleep and sexual disorders, stigma, and perceived cognitive impairment). Logistic regression was used to determine the best model of association between functional domains and residual symptoms. Almost half of the 468 patients included (42%) had poor overall functioning. Residual depressive symptoms appeared to have an impact on overall functioning and in nearly all areas of functioning. In addition, specific residual symptoms had significantly more negative effects on some domains of functioning in euthymic patients with bipolar disorder (residual manic symptoms and occupational stigma on autonomy, emotional inhibition on occupational functioning, residual manic symptoms on financial issues, family stigma on interpersonal relationships, and sexual function and occupational stigma on leisure time). Our findings highlight the importance of evaluating overall functioning in clinical practice as well as functional domains. They also indicate that some residuals symptoms in patients with bipolar disorder should be targeted in personalized treatment plans, in order to improve functioning in the domains in which the patient is most impaired. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Robustness in econometrics

    CERN Document Server

    Sriboonchitta, Songsak; Huynh, Van-Nam

    2017-01-01

    This book presents recent research on robustness in econometrics. Robust data processing techniques – i.e., techniques that yield results minimally affected by outliers – and their applications to real-life economic and financial situations are the main focus of this book. The book also discusses applications of more traditional statistical techniques to econometric problems. Econometrics is a branch of economics that uses mathematical (especially statistical) methods to analyze economic systems, to forecast economic and financial dynamics, and to develop strategies for achieving desirable economic performance. In day-by-day data, we often encounter outliers that do not reflect the long-term economic trends, e.g., unexpected and abrupt fluctuations. As such, it is important to develop robust data processing techniques that can accommodate these fluctuations.

  3. Robust Manufacturing Control

    CERN Document Server

    2013-01-01

    This contributed volume collects research papers, presented at the CIRP Sponsored Conference Robust Manufacturing Control: Innovative and Interdisciplinary Approaches for Global Networks (RoMaC 2012, Jacobs University, Bremen, Germany, June 18th-20th 2012). These research papers present the latest developments and new ideas focusing on robust manufacturing control for global networks. Today, Global Production Networks (i.e. the nexus of interconnected material and information flows through which products and services are manufactured, assembled and distributed) are confronted with and expected to adapt to: sudden and unpredictable large-scale changes of important parameters which are occurring more and more frequently, event propagation in networks with high degree of interconnectivity which leads to unforeseen fluctuations, and non-equilibrium states which increasingly characterize daily business. These multi-scale changes deeply influence logistic target achievement and call for robust planning and control ...

  4. Surface mesh to voxel data registration for patient-specific anatomical modeling

    Science.gov (United States)

    de Oliveira, Júlia E. E.; Giessler, Paul; Keszei, András.; Herrler, Andreas; Deserno, Thomas M.

    2016-03-01

    Virtual Physiological Human (VPH) models are frequently used for training, planning, and performing medical procedures. The Regional Anaesthesia Simulator and Assistant (RASimAs) project has the goal of increasing the application and effectiveness of regional anesthesia (RA) by combining a simulator of ultrasound-guided and electrical nerve-stimulated RA procedures and a subject-specific assistance system through an integration of image processing, physiological models, subject-specific data, and virtual reality. Individualized models enrich the virtual training tools for learning and improving regional anaesthesia (RA) skills. Therefore, we suggest patient-specific VPH models that are composed by registering the general mesh-based models with patient voxel data-based recordings. Specifically, the pelvis region has been focused for the support of the femoral nerve block. The processing pipeline is composed of different freely available toolboxes such as MatLab, the open Simulation framework (SOFA), and MeshLab. The approach of Gilles is applied for mesh-to-voxel registration. Personalized VPH models include anatomical as well as mechanical properties of the tissues. Two commercial VPH models (Zygote and Anatomium) were used together with 34 MRI data sets. Results are presented for the skin surface and pelvic bones. Future work will extend the registration procedure to cope with all model tissue (i.e., skin, muscle, bone, vessel, nerve, fascia) in a one-step procedure and extrapolating the personalized models to body regions actually being out of the captured field of view.

  5. Sensitivity and specificity of detecting reticular pseudodrusen in multimodal imaging in Japanese patients.

    Science.gov (United States)

    Ueda-Arakawa, Naoko; Ooto, Sotaro; Tsujikawa, Akitaka; Yamashiro, Kenji; Oishi, Akio; Yoshimura, Nagahisa

    2013-03-01

    To identify reticular pseudodrusen (RPD) in age-related macular degeneration using multiple imaging modalities, including the blue channel image of fundus photography, infrared reflectance (IR), fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT), and to compare the sensitivities and specificities of these modalities for detecting RPD. This study included 220 eyes from 114 patients with newly diagnosed age-related macular degeneration. Patients underwent fundus photography, IR, fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and SD-OCT in both eyes. Eyes were diagnosed with RPD if they showed reticular patterns on at least two of the seven imaging modalities. Thirty-seven eyes were diagnosed with RPD. However, SD-OCT and IR had the highest sensitivity (94.6%), and at the same time, SD-OCT had a high specificity (98.4%). The blue channel of color fundus photography, confocal blue reflectance, and indocyanine green angiography had a specificity of 100% but had lower sensitivity than that of SD-OCT and IR. For detecting RPD, IR and SD-OCT had the highest sensitivity. Although SD-OCT had the highest sensitivity and specificity, RPD detection should be confirmed using more than one modality for increased accuracy.

  6. Robust flight control of rotorcraft

    Science.gov (United States)

    Pechner, Adam Daniel

    With recent design improvement in fixed wing aircraft, there has been a considerable interest in the design of robust flight control systems to compensate for the inherent instability necessary to achieve desired performance. Such systems are designed for maximum available retention of stability and performance in the presence of significant vehicle damage or system failure. The rotorcraft industry has shown similar interest in adopting these reconfigurable flight control schemes specifically because of their ability to reject disturbance inputs and provide a significant amount of robustness for all but the most catastrophic of situations. The research summarized herein focuses on the extension of the pseudo-sliding mode control design procedure interpreted in the frequency domain. Application of the technique is employed and simulated on two well known helicopters, a simplified model of a hovering Sikorsky S-61 and the military's Black Hawk UH-60A also produced by Sikorsky. The Sikorsky helicopter model details are readily available and was chosen because it can be limited to pitch and roll motion reducing the number of degrees of freedom and yet contains two degrees of freedom, which is the minimum requirement in proving the validity of the pseudo-sliding control technique. The full order model of a hovering Black Hawk system was included both as a comparison to the S-61 helicopter design system and as a means to demonstrate the scaleability and effectiveness of the control technique on sophisticated systems where design robustness is of critical concern.

  7. Exhaustion of tumor-specific CD8⁺ T cells in metastases from melanoma patients

    National Research Council Canada - National Science Library

    Baitsch, Lukas; Baumgaertner, Petra; Devêvre, Estelle; Raghav, Sunil K; Legat, Amandine; Barba, Leticia; Wieckowski, Sébastien; Bouzourene, Hanifa; Deplancke, Bart; Romero, Pedro; Rufer, Nathalie; Speiser, Daniel E

    2011-01-01

    ... differences in T cells specific for persistent herpesviruses (EBV and CMV). In contrast, Melan-A/MART-1-specific T cells isolated from metastases from patients with melanoma expressed a large variety of genes associated with T cell exhaustion...

  8. The research of Proactive Coping Behavior of Patients with Chronic Non-Specific Lung Disease

    Directory of Open Access Journals (Sweden)

    Marija A. Yaroslavskaya

    2011-01-01

    Full Text Available The purpose of the research was to study the patterns of using proactive coping and adherences to it's different types in patients with chronic non-specifi c lung diseases. Participants of the study (N=180 were 30 to 60 years old. The Proactive Coping Inventory was used to assess the patients' psychological status. According to the results of the study patients with chronic non-specifi c lung diseases use dif-ferent types of proactive coping behavior while solving problematic and stressful situations. The research revealed that patients with bronchial asthma don't have the skills of independent decision making, definition of objectives, considering of options in solving conflicts or other inconvenient situations sufficiently developed. Patients with chronic obstructive pulmonary disease are less satisfied with the emotional support that they receive from their relatives and closest people, it's harder for them to reveal their feelings and emotions than for those who suffer from bronchial asthma and healthy ones. The results of the study may be useful in developing educational systems of proactive coping behavior skills for patients with chronic non-specific lung diseases for their health and well-being support.

  9. Resection accuracy of patient-specific cutting guides in total knee replacement.

    Science.gov (United States)

    Wernecke, Gregory C; Taylor, Scott; Wernecke, Penny; MacDessi, Samuel J; Chen, Darren B

    2017-11-01

    Patient-specific guides (PSGs) have been thoroughly investigated with regards to reconstitution of mechanical alignment in total knee arthroplasty (TKA). The ability to replicate the preoperative surgical plan is essential for optimal outcomes but intraoperative measurements to confirm accurate progression through the operation are limited. This leads to our clinical question: can PSGs replicate the planned bone resection depth during TKA? This is a prospective case series of 118 patients who underwent TKA using magnetic resonance imaging-based patient-specific cutting guides. Intraoperative bone resection thickness was measured and compared with the preoperative planned bone resections as a primary outcome. Secondary outcomes included the need for additional bone resections, the number of cases for which the PSG technique was abandoned, final component sizes and mechanical alignment. PSGs could not accurately recreate preoperative plan. PSGs resulted in over-resection in all bone cuts compared with the preoperative surgical resection plan. Secondary osteotomies were required in 37% of patients. PSGs had to be abandoned in 10.5% of cases, mostly due to suboptimal fit of the femoral block. The tibial component size was altered more frequently than the femoral. Intraoperatively, PSGs could not accurately recreate the preoperative plan. PSGs are marketed as user-friendly tools to simplify TKA but our research demonstrates the need for surgeons to monitor surgical progression and compensate for errors occurring during the use of PSGs. © 2017 Royal Australasian College of Surgeons.

  10. JC virus detection and JC virus-specific immunity in natalizumab-treated Multiple Sclerosis patients

    Directory of Open Access Journals (Sweden)

    Mancuso Roberta

    2012-12-01

    Full Text Available Abstract Background The use of natalizumab in multiple sclerosis (MS may favour JC virus reactivation; this phenomenon is usually asymptomatic but can, albeit rarely, evolve into frank progressive multifocal leucoencephalopathy (PML. Methods JCV-specific CD8+ T lymphocytes were evaluated by flow cytometry over a 24-month period in 24 natalizumab-treated MS patients in whom JCV DNA was or was not detected in blood using quantitative real-time polymerase chain reaction; all these cases were asymptomatic. Results Perforin- and grazymes-containing VP-1-specific CD8+ T lymphocytes were reduced whereas CD107a-expressing cells were increased in JCV positive patients, suggesting an active degranulation of these cells; naïve CD8+ T lymphocytes were also decreased whereas memory cells were increased in patients in whom JCV reactivation was observed. Conclusion The presence of a CD8+ T lymphocyte-mediated effector immune response offers a greater insight into reactivation of JCV and its clinical sequelae, and may help the monitoring of patients on natalizumab therapy.

  11. Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebæk; Brasso, Klaus; Berg, Kasper Drimer

    2016-01-01

    BACKGROUND: The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients...... were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3...... years: 16.3% (Gray's test: P associated with changes of 13-year risks of PCa...

  12. Specific features of clostridium difficile colitis in patients with inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mihai Catalina

    2015-01-01

    Full Text Available Through its specific biological, epidemiological, diagnostic and infection management features, Clostridium difficile infection (CDI can be considered a major health concern, especially in inflammatory bowel disease (IBD patients. In this particular infection, many IBD risk factors are triggered due to bowel inflammation, antibiotics use, microbiota changes, immunosuppressive therapy use and surgical intervention. Thus, each IBD and diarrhea patient must be tested for CDI. Clinical features show different initial infectious stages such as mild, fulminate and refractory. It has been shown that CDI presents recurrent episodes. CDI treatment consists of metronidazole, vancomycin or fidaxomicin, as well as prophylactic measures. It was recently shown that antibiotic doses must be gradually reduced in order to avoid CDI relapses. Fecal transplantation, effective in CDI management, remains controversial in CDI patients with concurrent IBD.

  13. Robustness - acceptance criteria

    DEFF Research Database (Denmark)

    Rizzuto, Enrico; Sørensen, John Dalsgaard; Kroon, Inger B.

    2010-01-01

    This factsheet describes the general framework on the bases of which acceptance criteria for requirements on the robustness of structures can be set. Such framework is based on the more general concept of risk-based assessment of engineering systems. The present factsheet is to be seen in conjunc......This factsheet describes the general framework on the bases of which acceptance criteria for requirements on the robustness of structures can be set. Such framework is based on the more general concept of risk-based assessment of engineering systems. The present factsheet is to be seen...

  14. Walking while talking in patients with multiple sclerosis: the impact of specific cognitive loads.

    Science.gov (United States)

    Allali, G; Laidet, M; Assal, F; Armand, S; Lalive, P H

    2014-01-01

    Gait and cognitive disorders are frequently reported in patients with multiple sclerosis, leading to decreased quality of live. The objective of this prospective study was to examine the impact of four specific cognitive tasks on gait in patients with relapsing-remitting multiple sclerosis (RRMS) with low disability. The mean±standard deviation (SD) of walking speed, stride time and stride length were measured in 25 patients with RRMS (age: 39.46±8.32years; Expanded Disability Status Scale [EDSS] score: 1.90±1.01; disease duration: 5.62±5.12years) and in 25 age-matched controls. Gait was assessed during single task and while doing four different cognitive tasks (forward counting, backward counting, semantic verbal fluency, phonemic verbal fluency). Spatiotemporal gait parameters were recorded by a 12-camera optoelectronic system. Patients walked slower and with a decrease stride length during the single task and the four dual tasks than controls, except for the condition of backward counting. RRMS patients and controls presented the same cognitive performances for the four conditions during walking. EDSS score was correlated with gait speed and stride length in single task, and in the dual tasks of the backward counting and phonemic fluency. Quantitative gait assessment reveals subtle gait disorders in patients with low disability of relapsing-remitting multiple sclerosis. The impact of different cognitive domains on gait induces specific gait disturbances that highlight the strong interaction between gait and cognition. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  15. Site-Specific Difference of Bone Geometry Indices in Hypoparathyroid Patients

    Directory of Open Access Journals (Sweden)

    Hye-Sun Park

    2017-02-01

    Full Text Available BackgroundHypoparathyroid patients often have a higher bone mineral density (BMD than the general population. However, an increase in BMD does not necessarily correlate with a solid bone microstructure. This study aimed to evaluate the bone microstructure of hypoparathyroid patients by using hip structure analysis (HSA.MethodsNinety-five hypoparathyroid patients >20 years old were enrolled and 31 of them had eligible data for analyzing bone geometry parameters using HSA. And among the control data, we extracted sex-, age-, and body mass index-matched three control subjects to each patient. The BMD data were reviewed retrospectively and the bone geometry parameters of the patients were analyzed by HSA.ResultsThe mean Z-scores of hypoparathyroid patients at the lumbar spine, femoral neck, and total hip were above zero (0.63±1.17, 0.48±1.13, and 0.62±1.10, respectively. The differences in bone geometric parameters were site specific. At the femoral neck and intertrochanter, the cross-sectional area (CSA and cortical thickness (C.th were higher, whereas the buckling ratio (BR was lower than in controls. However, those trends were opposite at the femoral shaft; that is, the CSA and C.th were low and the BR was high.ConclusionOur study shows the site-specific effects of hypoparathyroidism on the bone. Differences in bone components, marrow composition, or modeling based bone formation may explain these findings. However, further studies are warranted to investigate the mechanism, and its relation to fracture risk.

  16. Establishment of tumor-specific copy number alterations from plasma DNA of patients with cancer.

    Science.gov (United States)

    Heitzer, Ellen; Auer, Martina; Hoffmann, Eva Maria; Pichler, Martin; Gasch, Christin; Ulz, Peter; Lax, Sigurd; Waldispuehl-Geigl, Julie; Mauermann, Oliver; Mohan, Sumitra; Pristauz, Gunda; Lackner, Carolin; Höfler, Gerald; Eisner, Florian; Petru, Edgar; Sill, Heinz; Samonigg, Hellmut; Pantel, Klaus; Riethdorf, Sabine; Bauernhofer, Thomas; Geigl, Jochen B; Speicher, Michael R

    2013-07-15

    With the increasing number of available predictive biomarkers, clinical management of cancer is becoming increasingly reliant on the accurate serial monitoring of tumor genotypes. We tested whether tumor-specific copy number changes can be inferred from the peripheral blood of patients with cancer. To this end, we determined the plasma DNA size distribution and the fraction of mutated plasma DNA fragments with deep sequencing and an ultrasensitive mutation-detection method, i.e., the Beads, Emulsion, Amplification, and Magnetics (BEAMing) assay. When analyzing the plasma DNA of 32 patients with Stage IV colorectal carcinoma, we found that a subset of the patients (34.4%) had a biphasic size distribution of plasma DNA fragments that was associated with increased circulating tumor cell numbers and elevated concentration of mutated plasma DNA fragments. In these cases, we were able to establish genome-wide tumor-specific copy number alterations directly from plasma DNA. Thus, we could analyze the current copy number status of the tumor genome, which was in some cases many years after diagnosis of the primary tumor. An unexpected finding was that not all patients with progressive metastatic disease appear to release tumor DNA into the circulation in measurable quantities. When we analyzed plasma DNA from 35 patients with metastatic breast cancer, we made similar observations suggesting that our approach may be applicable to a variety of tumor entities. This is the first description of such a biphasic distribution in a surprisingly high proportion of cancer patients which may have important implications for tumor diagnosis and monitoring. Copyright © 2013 UICC.

  17. WE-D-BRA-05: Pseudo In Vivo Patient Dosimetry Using a 3D-Printed Patient-Specific Phantom

    Energy Technology Data Exchange (ETDEWEB)

    Ger, R; Craft, DF [The University of Texas Graduate School of Biomedical Sciences (United States); Burgett, EA [Idaho State University, Pocatello, idaho (United States); Price, RR [RANDJ Consulting, Frederick, MD (United States); Kry, SF; Howell, RM [The University of Texas Graduate School of Biomedical Sciences (United States); The University of Texas MD Anderson Cancer Ctr., Houston, TX (United States)

    2015-06-15

    Purpose: To test the feasibility of using 3D-printed patient-specific phantoms for intensity-modulated radiation therapy (IMRT) quality assurance (QA). Methods: We created a patient-specific whole-head phantom using a 3D printer. The printer data file was created from high-resolution DICOM computed tomography (CT) images of 3-year old child treated at our institution for medulloblastoma. A custom-modified extruder system was used to create tissue-equivalent materials. For the printing process, the Hounsfield Units from the CT images were converted to proportional volumetric densities. A 5-field IMRT plan was created from the patient CT and delivered to the 3D- phantom. Dose was measured by an ion chamber placed through the eye. The ion chamber was placed at the posterior edge of the planning target volume in a high dose gradient region. CT scans of the patient and 3D-phantom were fused by using commercial treatment planning software (TPS). The patient’s plan was calculated on the phantom CT images. The ion chamber’s active volume was delineated in the TPS; dose per field and total dose were obtained. Measured and calculated doses were compared. Results: The 3D-phantom dimensions and tissue densities were in good agreement with the patient. However, because of a printing error, there was a large discrepancy in the density in the frontal cortex. The calculated and measured treatment plan doses were 1.74 Gy and 1.72 Gy, respectively. For individual fields, the absolute dose difference between measured and calculated values was on average 3.50%. Conclusion: This study demonstrated the feasibility of using 3D-printed patient-specific phantoms for IMRT QA. Such phantoms would be particularly advantageous for complex IMRT treatment plans featuring high dose gradients and/or for anatomical sites with high variation in tissue densities. Our preliminary findings are promising. We anticipate that, once the printing process is further refined, the agreement between

  18. Lack of Utility of Specific Immunoglobulin G Antibody Avidity for Serodiagnosis of Reactivated Toxoplasmosis in Immunocompromised Patients

    OpenAIRE

    Mechain, Bénédicte; Garin, Yves Jean-François; Robert-Gangneux, Florence; Dupouy-Camet, Jean; Derouin, Francis

    2000-01-01

    The avidities of Toxoplasma-specific immunoglobulin G serum antibodies were measured in immunocompromised patients presenting with cerebral or extracerebral toxoplasmosis and/or serological reactivation. Since avidity remained high and stable in 39 of 40 patients with toxoplasmosis and 27 of 28 patients with serological reactivation, we conclude that this test cannot help diagnose toxoplasmosis in these patients.

  19. Cause-specific mortality in adult epilepsy patients from Tyrol, Austria: hospital-based study.

    Science.gov (United States)

    Granbichler, Claudia A; Oberaigner, Willi; Kuchukhidze, Giorgi; Bauer, Gerhard; Ndayisaba, Jean-Pierre; Seppi, Klaus; Trinka, Eugen

    2015-01-01

    Epilepsy is a devastating condition with a considerable increase in mortality compared to the general population. Few studies have focused on cause-specific mortality which we analyse in detail in over 4,000 well-characterized epilepsy patients. The cohort comprised of epilepsy patients ≥ 18, treated between 1970 and 2009 at the epilepsy clinic of Innsbruck Medical University, Austria, and living in the province of Tyrol, Austria. Epilepsy diagnosis was based on ILAE guidelines (1989); patients with brain tumor were excluded. Deceased patients and causes of death (ICD-codes) were obtained via record linkage to the national death registry. We computed age-, sex-, and period-adjusted standardized mortality rates (SMR) for 36 diagnoses subgroups in four major groups. Additional analyses were performed for an incidence cohort. Overall cohort: 4,295 patients, 60,649.1 person-years, 822 deaths, overall SMR 1.7 (95 % CI 1.6-1.9), highest elevated cause-specific SMR: congenital anomalies [7.1 (95 % CI 2.3-16.6)], suicide [4.2 (95 % CI 2.0-8.1)], alcohol dependence syndrome [3.9 (95 % CI 1.8-7.4)], malignant neoplasm of esophagus [3.1 (95 % CI 1.2-6.4)], pneumonia [2.7 (95 % CI 1.6-4.2)]. Incidence cohort: 1,299 patients, 14,215.4 person-years, 267 deaths, overall SMR 1.8 (95 % CI 1.6-2.1), highest elevated cause-specific SMR congenital anomalies [10.8 (95 % CI 1.3-39.3)], suicide [6.8 (95 % CI 1.4-19.8)], alcohol dependence syndrome (6.4 [95 % CI 1.8-16.5)], pneumonia [3.9 (95 % CI 1.8-7.4)], cerebrovascular disease at 3.5 (95 % CI 2.6-4.6). Mortality due to mental health problems, such as suicide or alcohol dependence syndrome, malignant neoplasms, and cerebrovascular diseases was highly increased in our study. In addition to aim for seizure freedom, we suggest improving general health promotion, including cessation of smoking, lowering of alcohol intake, and reduction of weight as well as early identification of psychiatric comorbidity in patients with epilepsy.

  20. HLA-DRB genotype and specific IgE responses in patients with allergies to penicillins.

    Science.gov (United States)

    Yang, Jing; Qiao, Hai-ling; Zhang, Yue-wen; Jia, Lin-jing; Tian, Xin; Gao, Na

    2006-03-20

    Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin. Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction. Compared with control subjects, a significantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (chi(2) = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, chi(2) = 4.057, P = 0.044). HLA-DRB gene may be involved in allergy to penicillins through modulating specific serum IgE to penicillins.

  1. No improvement in reducing outliers in coronal axis alignment with patient-specific instrumentation.

    Science.gov (United States)

    Maus, Uwe; Marques, Carlos J; Scheunemann, David; Lampe, Frank; Lazovic, Djordje; Hommel, Hagen; Vogel, Dennis; Haunschild, Martin; Pfitzner, Tilman

    2017-10-25

    Patient-specific instrumentation (PSI) uses 3D preoperative imaging to produce individualized cutting blocks specific to patients' anatomy and according to the preoperative plan with the aim to reduce the number of mechanical leg alignment (MLA) outliers, to improve implant positioning and to decrease surgery time. The primary purpose of this study was to investigate the efficacy of a specific PSI in comparison with standard instrumentation (SI) in reducing the number of MLA outliers. It was hypothesized that the number of MLA outliers would be significantly lower in the PSI group. A multicenter randomized controlled trial was implemented. There were 59 patients in the PSI group and 66 in the SI group. The absolute number of outliers outside the ± 3° target neutral MLA was compared between the groups with a Chi-square test. As secondary outcomes, the Knee Society Score (KSS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were compared between the groups preoperatively and at 90-day follow-up. There were 15 (26.3%) MLA outliers in the PSI group and 8 (12.3%) in the SI group. The number of outliers was not independent from the group ( X2 (1) = 3.8, p = 0.04; Relative risk = 1.5). Preoperatively, there were no significant differences between the groups when comparing their KSS and KOOS sub-scores. At 90 days postoperatively, the patients in the SI group showed better KOOS-Quality of Life (KOSS-QOL) in comparison with the PSI group (p MLA outliers in comparison with SI. There were no differences when comparing the achieved mean MLA of both groups. Level I, prospective randomized controlled trial.

  2. Modeling of hemophilia A using patient-specific induced pluripotent stem cells derived from urine cells.

    Science.gov (United States)

    Jia, Bei; Chen, Shen; Zhao, Zhiju; Liu, Pengfei; Cai, Jinglei; Qin, Dajiang; Du, Juan; Wu, Changwei; Chen, Qianyu; Cai, Xiujuan; Zhang, Hui; Yu, Yanhong; Pei, Duanqing; Zhong, Mei; Pan, Guangjin

    2014-07-11

    Hemophilia A (HA) is a severe, congenital bleeding disorder caused by the deficiency of clotting factor VIII (FVIII). For years, traditional laboratory animals have been used to study HA and its therapies, although animal models may not entirely mirror the human pathophysiology. Human induced pluripotent stem cells (iPSCs) can undergo unlimited self-renewal and differentiate into all cell types. This study aims to generate hemophilia A (HA) patient-specific iPSCs that differentiate into disease-affected hepatocyte cells. These hepatocytes are potentially useful for in vitro disease modeling and provide an applicable cell source for autologous cell therapy after genetic correction. In this study, we mainly generated iPSCs from urine collected from HA patients with integration-free episomal vectors PEP4-EO2S-ET2K containing human genes OCT4, SOX2, SV40LT and KLF4, and differentiated these iPSCs into hepatocyte-like cells. We further identified the genetic phenotype of the FVIII genes and the FVIII activity in the patient-specific iPSC derived hepatic cells. HA patient-specific iPSCs (HA-iPSCs) exhibited typical pluripotent properties evident by immunostaining, in vitro assays and in vivo assays. Importantly, we showed that HA-iPSCs could differentiate into functional hepatocyte-like cells and the HA-iPSC-derived hepatocytes failed to produce FVIII, but otherwise functioned normally, recapitulating the phenotype of HA disease in vitro. HA-iPSCs, particular those generated from the urine using a non-viral approach, provide an efficient way for modeling HA in vitro. Furthermore, HA-iPSCs and their derivatives serve as an invaluable cell source that can be used for gene and cell therapy in regenerative medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. The technique for 3D printing patient-specific models for auricular reconstruction.

    Science.gov (United States)

    Flores, Roberto L; Liss, Hannah; Raffaelli, Samuel; Humayun, Aiza; Khouri, Kimberly S; Coelho, Paulo G; Witek, Lukasz

    2017-06-01

    Currently, surgeons approach autogenous microtia repair by creating a two-dimensional (2D) tracing of the unaffected ear to approximate a three-dimensional (3D) construct, a difficult process. To address these shortcomings, this study introduces the fabrication of patient-specific, sterilizable 3D printed auricular model for autogenous auricular reconstruction. A high-resolution 3D digital photograph was captured of the patient's unaffected ear and surrounding anatomic structures. The photographs were exported and uploaded into Amira, for transformation into a digital (.stl) model, which was imported into Blender, an open source software platform for digital modification of data. The unaffected auricle as digitally isolated and inverted to render a model for the contralateral side. The depths of the scapha, triangular fossa, and cymba were deepened to accentuate their contours. Extra relief was added to the helical root to further distinguish this structure. The ear was then digitally deconstructed and separated into its individual auricular components for reconstruction. The completed ear and its individual components were 3D printed using polylactic acid filament and sterilized following manufacturer specifications. The sterilized models were brought to the operating room to be utilized by the surgeon. The models allowed for more accurate anatomic measurements compared to 2D tracings, which reduced the degree of estimation required by surgeons. Approximately 20 g of the PLA filament were utilized for the construction of these models, yielding a total material cost of approximately $1. Using the methodology detailed in this report, as well as departmentally available resources (3D digital photography and 3D printing), a sterilizable, patient-specific, and inexpensive 3D auricular model was fabricated to be used intraoperatively. This technique of printing customized-to-patient models for surgeons to use as 'guides' shows great promise. Copyright © 2017 European

  4. Fluid structure interaction of patient specific abdominal aortic aneurysms: a comparison with solid stress models.

    Science.gov (United States)

    Leung, James H; Wright, Andrew R; Cheshire, Nick; Crane, Jeremy; Thom, Simon A; Hughes, Alun D; Xu, Yun

    2006-05-19

    Abdominal aortic aneurysm (AAA) is a dilatation of the aortic wall, which can rupture, if left untreated. Previous work has shown that, maximum diameter is not a reliable determinant of AAA rupture. However, it is currently the most widely accepted indicator. Wall stress may be a better indicator and promising patient specific results from structural models using static pressure, have been published. Since flow and pressure inside AAA are non-uniform, the dynamic interaction between the pulsatile flow and wall may influence the predicted wall stress. The purpose of the present study was to compare static and dynamic wall stress analysis of patient specific AAAs. Patient-specific AAA models were created from CT scans of three patients. Two simulations were performed on each lumen model, fluid structure interaction (FSI) model and static structural (SS) model. The AAA wall was created by dilating the lumen with a uniform 1.5 mm thickness, and was modeled as a non-linear hyperelastic material. Commercial finite element code Adina 8.2 was used for all simulations. The results were compared between the FSI and SS simulations. Results are presented for the wall stress patterns, wall shear stress patterns, pressure, and velocity fields within the lumen. It is demonstrated that including fluid flow can change local wall stresses slightly. However, as far as the peak wall stress is concerned, this effect is negligible as the difference between SS and FSI models is less than 1%. The results suggest that fully coupled FSI simulation, which requires considerable computational power to run, adds little to rupture risk prediction. This justifies the use of SS models in previous studies.

  5. Fluid structure interaction of patient specific abdominal aortic aneurysms: a comparison with solid stress models

    Directory of Open Access Journals (Sweden)

    Thom Simon A

    2006-05-01

    Full Text Available Abstract Background Abdominal aortic aneurysm (AAA is a dilatation of the aortic wall, which can rupture, if left untreated. Previous work has shown that, maximum diameter is not a reliable determinant of AAA rupture. However, it is currently the most widely accepted indicator. Wall stress may be a better indicator and promising patient specific results from structural models using static pressure, have been published. Since flow and pressure inside AAA are non-uniform, the dynamic interaction between the pulsatile flow and wall may influence the predicted wall stress. The purpose of the present study was to compare static and dynamic wall stress analysis of patient specific AAAs. Method Patient-specific AAA models were created from CT scans of three patients. Two simulations were performed on each lumen model, fluid structure interaction (FSI model and static structural (SS model. The AAA wall was created by dilating the lumen with a uniform 1.5 mm thickness, and was modeled as a non-linear hyperelastic material. Commercial finite element code Adina 8.2 was used for all simulations. The results were compared between the FSI and SS simulations. Results Results are presented for the wall stress patterns, wall shear stress patterns, pressure, and velocity fields within the lumen. It is demonstrated that including fluid flow can change local wall stresses slightly. However, as far as the peak wall stress is concerned, this effect is negligible as the difference between SS and FSI models is less than 1%. Conclusion The results suggest that fully coupled FSI simulation, which requires considerable computational power to run, adds little to rupture risk prediction. This justifies the use of SS models in previous studies.

  6. Automatically gated image-guided breath-hold IMRT is a fast, precise, and dosimetrically robust treatment for lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Simeonova-Chergou, Anna; Jahnke, Anika; Siebenlist, Kerstin; Stieler, Florian; Mai, Sabine; Boda-Heggemann, Judit; Wenz, Frederik; Lohr, Frank; Jahnke, Lennart [University Medical Center Mannheim, University of Heidelberg, Department of Radiotherapy and Oncology, Mannheim (Germany)

    2016-03-15

    High-dose radiotherapy of lung cancer is challenging. Tumors may move by up to 2 cm in craniocaudal and anteroposterior directions as a function of breathing cycle. Tumor displacement increases with treatment time, which consequentially increases the treatment uncertainty. This study analyzed whether automatically gated cone-beam-CT (CBCT)-controlled intensity modulated fast deep inspiration breath hold (DIBH) stereotactic body radiation therapy (SBRT) in flattening filter free (FFF) technique and normofractionated lung DIBH intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT) treatments delivered with a flattening filter can be applied with sufficient accuracy within a clinically acceptable timeslot. Plans of 34 patients with lung tumors were analyzed. Of these patients, 17 received computer-controlled fast DIBH SBRT with a dose of 60 Gy (5 fractions of 12 Gy or 12 fractions of 5 Gy) in an FFF VMAT technique (FFF-SBRT) every other day and 17 received conventional VMAT with a flattening filter (conv-VMAT) and 2-Gy daily fractional doses (cumulative dose 50-70 Gy). FFF-SBRT plans required more monitor units (MU) than conv-VMAT plans (2956.6 ± 885.3 MU for 12 Gy/fraction and 1148.7 ± 289.2 MU for 5 Gy/fraction vs. 608.4 ± 157.5 MU for 2 Gy/fraction). Total treatment and net beam-on times were shorter for FFF-SBRT plans than conv-VMAT plans (268.0 ± 74.4 s vs. 330.2 ± 93.6 s and 85.8 ± 25.3 s vs. 117.2 ± 29.6 s, respectively). Total slot time was 13.0 min for FFF-SBRT and 14.0 min for conv-VMAT. All modalities could be delivered accurately despite multiple beam-on/-off cycles and were robust against multiple interruptions. Automatically gated CBCT-controlled fast DIBH SBRT in VMAT FFF technique and normofractionated lung DIBH VMAT can be applied with a low number of breath-holds in a short timeslot, with excellent dosimetric accuracy. In clinical routine, these approaches combine optimally reduced lung tissue irradiation with maximal

  7. Characteristics and Ramadan-specific diabetes education trends of patients with diabetes (CARE): a multinational survey (2014).

    Science.gov (United States)

    Ahmedani, M Y; Alvi, S F D

    2016-08-01

    To observe characteristics of fasting patients, trends of Ramadan-specific diabetes education and implementation of diabetes management recommendations in patients with diabetes during Ramadan. This observational study was conducted in seven countries. Patients were recruited in the study immediately after the end of Ramadan (August 2014) until December 2014. Standardized questionnaire-based, face-to-face interview conducted on one-to-one basis. An identical questionnaire used in each country. A total of 6610 patients with diabetes participated in the survey. Ramadan-specific diabetes education was received by 3142 (47.5%) patients, drug dosage and timings altered in 4371 (66.1%) patients and dietary advice received by 4636 (70.1%) patients with diabetes before Ramadan. Severe hypoglycaemia observed in 29 (1.0%) patients and severe hyperglycaemia noticed in 44 (1.7%) patients with diabetes during Ramadan. Patients who received Ramadan-specific diabetes education before Ramadan were significantly better (p Ramadan-specific diabetes management recommendations during Ramadan. On further analysis, patients who received Ramadan-specific diabetes education through any mode i.e. one to one session, group session or written education material were found to be significantly better (p Ramadan-specific diabetes management recommendations during Ramadan compared with patients who did not receive education. It was observed that patients who received Ramadan-specific diabetes education followed Ramadan-specific diabetes management recommendations better compared with patients who did not receive education. Ramadan-specific diabetes management recommendations are still not completely implemented. © 2016 John Wiley & Sons Ltd.

  8. Robustness of spatial micronetworks

    Science.gov (United States)

    McAndrew, Thomas C.; Danforth, Christopher M.; Bagrow, James P.

    2015-04-01

    Power lines, roadways, pipelines, and other physical infrastructure are critical to modern society. These structures may be viewed as spatial networks where geographic distances play a role in the functionality and construction cost of links. Traditionally, studies of network robustness have primarily considered the connectedness of large, random networks. Yet for spatial infrastructure, physical distances must also play a role in network robustness. Understanding the robustness of small spatial networks is particularly important with the increasing interest in microgrids, i.e., small-area distributed power grids that are well suited to using renewable energy resources. We study the random failures of links in small networks where functionality depends on both spatial distance and topological connectedness. By introducing a percolation model where the failure of each link is proportional to its spatial length, we find that when failures depend on spatial distances, networks are more fragile than expected. Accounting for spatial effects in both construction and robustness is important for designing efficient microgrids and other network infrastructure.

  9. Robustness Envelopes of Networks

    NARCIS (Netherlands)

    Trajanovski, S.; Martín-Hernández, J.; Winterbach, W.; Van Mieghem, P.

    2013-01-01

    We study the robustness of networks under node removal, considering random node failure, as well as targeted node attacks based on network centrality measures. Whilst both of these have been studied in the literature, existing approaches tend to study random failure in terms of average-case

  10. Patient-Specific Modeling of Interventricular Hemodynamics in Single Ventricle Physiology

    Science.gov (United States)

    Vedula, Vijay; Feinstein, Jeffrey; Marsden, Alison

    2016-11-01

    Single ventricle (SV) congenital heart defects, in which babies are born with only functional ventricle, lead to significant morbidity and mortality with over 30% of patients developing heart failure prior to adulthood. Newborns with SV physiology typically undergo three palliative surgeries, in which the SV becomes the systemic pumping chamber. Depending on which ventricle performs the systemic function, patients are classified as having either a single left ventricle (SLV) or a single right ventricle (SRV), with SRV patients at higher risk of failure. As the native right ventricles are not designed to meet systemic demands, they undergo remodeling leading to abnormal hemodynamics. The hemodynamic characteristics of SLVs compared with SRVs is not well established. We present a validated computational framework for performing patient-specific modeling of ventricular flows, and apply it across 6 SV patients (3SLV + 3SRV), comparing hemodynamic conditions between the two subgroups. Simulations are performed with a stabilized finite element method coupled with an immersed boundary method for modeling heart valves. We discuss identification of hemodynamic biomarkers of ventricular remodeling for early risk assessment of failure. This research is supported in part by the Stanford Child Health Research Institute and the Stanford NIH-NCATS-CTSA through Grant UL1 TR001085 and due to U.S. National Institute of Health through NIH NHLBI R01 Grants 5R01HL129727-02 and 5R01HL121754-03.

  11. NY-ESO-1-specific immunological pressure and escape in a patient with metastatic melanoma.

    Science.gov (United States)

    von Boehmer, Lotta; Mattle, Muriel; Bode, Peter; Landshammer, Alexandro; Schäfer, Carolin; Nuber, Natko; Ritter, Gerd; Old, Lloyd; Moch, Holger; Schäfer, Niklaus; Jäger, Elke; Knuth, Alexander; van den Broek, Maries

    2013-01-01

    During cancer progression, malignant cells may evade immunosurveillance. However, evidence for immunological escape in humans is scarce. We report here the clinical course of a melanoma patient whose initial tumor was positive for the antigens NY-ESO-1, MAGE-C1, and Melan-A. Upon immunization with a recombinant vaccinia/fowlpox NY-ESO-1 construct, the patient experienced a mixed clinical response and spreading of the NY-ESO-1 epitopes in the CD4+ T cell compartment. After NY-ESO-1 protein + CpG immunization, the patient's anti-NY-ESO-1 IgG response increased. Over the following years, progressing lesions were resected and found to be NY-ESO-1-negative while being positive for MAGE-C1, Melan-A, and MHC-I. The fatal, inoperable brain metastasis was analyzed after his death and also proved to be NY-ESO-1-negative, while being positive for MAGE-C1 and Melan-A, as well as MHC-I. We propose that cancer control and cancer escape in this patient were governed by NY-ESO-1-specific immunological pressure. Our findings provide evidence for the existence of immunoediting and immunoescape in this cancer patient.

  12. Seizure outcomes of temporal lobe epilepsy surgery in patients with normal MRI and without specific histopathology.

    Science.gov (United States)

    Ivanovic, Jugoslav; Larsson, Pål G; Østby, Ylva; Hald, John; Krossnes, Bård K; Fjeld, Jan G; Pripp, Are H; Alfstad, Kristin Å; Egge, Arild; Stanisic, Milo

    2017-05-01

    Seizure outcome following surgery in pharmacoresistant temporal lobe epilepsy patients with normal magnetic resonance imaging and normal or non-specific histopathology is not sufficiently presented in the literature. In a retrospective design, we reviewed data of 263 patients who had undergone temporal lobe epilepsy surgery and identified 26 (9.9%) who met the inclusion criteria. Seizure outcomes were determined at 2-year follow-up. Potential predictors of Engel class I (satisfactory outcome) were identified by logistic regression analyses. Engel class I outcome was achieved in 61.5% of patients, 50% being completely seizure free (Engel class IA outcome). The strongest predictors of satisfactory outcome were typical ictal seizure semiology (p = 0.048) and localised ictal discharges on scalp EEG (p = 0.036). Surgery might be an effective treatment choice for the majority of these patients, although outcomes are less favourable than in patients with magnetic resonance imaging-defined lesional temporal lobe epilepsy. Typical ictal seizure semiology and localised ictal discharges on scalp EEG were predictors of Engel class I outcome.

  13. Wildtype p53-specific Antibody and T-Cell Responses in Cancer Patients

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Stryhn, Anette; Justesen, Sune

    2011-01-01

    Mutation in the p53 gene based on single amino acid substitutions is a frequent event in human cancer. Accumulated mutant p53 protein is released to antigen presenting cells of the immune system and anti-p53 immune responses even against wt p53 is induced and observed in a number of human cancer...... patients. Detection of antibodies against wt p53 protein has been used as a diagnostic and prognostic marker and discovery of new T-cell epitopes has enabled design of cancer vaccination protocols with promising results. Here, we identified wt p53-specific antibodies in various cancer patients......(264-272) in breast cancer patients and against HLA-A*01:01 binding peptide wt p53(226-234) and HLA-B*07:02 binding peptide wt p53(74-82) in renal cell cancer and breast cancer patients, respectively. Finally, we analyzed antibody and T-cell responses against wt p53 15-mer peptides in patients with metastatic renal...

  14. Patient-specific model-based investigation of speech intelligibility and movement during deep brain stimulation.

    Science.gov (United States)

    Aström, Mattias; Tripoliti, Elina; Hariz, Marwan I; Zrinzo, Ludvic U; Martinez-Torres, Irene; Limousin, Patricia; Wårdell, Karin

    2010-01-01

    Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson's disease. The aim of this study was to investigate the anatomical aspects of the electric field in relation to effects on speech and movement during DBS in the subthalamic nucleus. Patient-specific finite element models of DBS were developed for simulation of the electric field in 10 patients. In each patient, speech intelligibility and movement were assessed during 2 electrical settings, i.e. 4 V (high) and 2 V (low). The electric field was simulated for each electrical setting. Movement was improved in all patients for both high and low electrical settings. In general, high-amplitude stimulation was more consistent in improving the motor scores than low-amplitude stimulation. In 6 cases, speech intelligibility was impaired during high-amplitude electrical settings. Stimulation of part of the fasciculus cerebellothalamicus from electrodes positioned medial and/or posterior to the center of the subthalamic nucleus was recognized as a possible cause of the stimulation-induced dysarthria. Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus. 2010 S. Karger AG, Basel.

  15. Improved alignment and operating room efficiency with patient-specific instrumentation for TKA.

    Science.gov (United States)

    Renson, Luc; Poilvache, Pascal; Van den Wyngaert, Hans

    2014-12-01

    Achieving accurate alignment in total knee arthroplasty (TKA) remains a concern. Patient-specific instrumentation (PSI) produced using preoperative 3D models was developed to offer surgeons a simplified, reliable, efficient and customised TKA procedure. In this prospective study, 60 patients underwent TKA with conventional instrumentation and 71 patients were operated on using PSI. The primary endpoint was surgical time. Secondary endpoints included operating room (OR) time, the number of instrument trays used and postoperative radiographic limb alignment. Compared to conventional instrumentation, PSI significantly reduced total surgical time by 8.9 ± 3.3 min (p=0.038), OR time by 8.6 ± 4.2 min (p=0.043), and the number of instrument trays by six trays (p3° was observed in 13% of PSI patients versus 29% with conventional instrumentation (p=0.043). PSI predicted the size of the femoral and tibial components actually used in 85.9% and 78.9% of cases, respectively. PSI improves alignment, surgical and OR time, reduces the number of instruments trays used compared to conventional instrumentation in patients undergoing TKA and results in fewer outliers in overall mechanical alignment in the coronal plane. Prospective comparative therapeutic study. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Patient-Specific Classification of ICU Sedation Levels From Heart Rate Variability.

    Science.gov (United States)

    Nagaraj, Sunil B; Biswal, Siddharth; Boyle, Emily J; Zhou, David W; McClain, Lauren M; Bajwa, Ednan K; Quraishi, Sadeq A; Akeju, Oluwaseun; Barbieri, Riccardo; Purdon, Patrick L; Westover, M Brandon

    2017-07-01

    To develop a personalizable algorithm to discriminate between sedation levels in ICU patients based on heart rate variability. Multicenter, pilot study. Several ICUs at Massachusetts General Hospital, Boston, MA. We gathered 21,912 hours of routine electrocardiogram recordings from a heterogenous group of 70 adult ICU patients. All patients included in the study were mechanically ventilated and were receiving sedatives. As "ground truth" for developing our method, we used Richmond Agitation Sedation Scale scores grouped into four levels denoted "comatose" (-5), "deeply sedated" (-4 to -3), "lightly sedated" (-2 to 0), and "agitated" (+1 to +4). We trained a support vector machine learning algorithm to calculate the probability of each sedation level from heart rate variability measures derived from the electrocardiogram. To estimate algorithm performance, we calculated leave-one-subject out cross-validated accuracy. The patient-independent version of the proposed system discriminated between the four sedation levels with an overall accuracy of 59%. Upon personalizing the system supplementing the training data with patient-specific calibration data, consisting of an individual's labeled heart rate variability epochs from the preceding 24 hours, accuracy improved to 67%. The personalized system discriminated between light- and deep-sedation states with an average accuracy of 75%. With further refinement, the methodology reported herein could lead to a fully automated system for depth of sedation monitoring. By enabling monitoring to be continuous, such technology may help clinical staff to monitor sedation levels more effectively and to reduce complications related to over- and under sedation.

  17. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases.

    Science.gov (United States)

    Licarete, Emilia; Ganz, Susanne; Recknagel, Martin J; Di Zenzo, Giovanni; Hashimoto, Takashi; Hertl, Michael; Zambruno, Giovanna; Hundorfean, Gheorghe; Mudter, Jonas; Neurath, Markus F; Bruckner-Tuderman, Leena; Sitaru, Cassian

    2012-04-04

    Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA), but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50), Crohn's disease (CD, n = 50), ulcerative colitis (UC, n = 50), bullous pemphigoid (BP, n = 76), and pemphigus vulgaris (PV, n = 42) and healthy donors (n = 245). By ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005), allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%), 2 CD (4%; 95% CI: 0%-9.43%), 8 UC (16%; 95% CI: 5.8%-26%), 2 BP (2.63%; 95% CI: 0%-6.23%), and 4 PV (9.52%; 95% CI: 0%-18.4%) patients as well as from 4 (1.63%; 95% CI: 0%-3.21%) healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen. Using a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should prove a useful tool for clinical and translational

  18. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Licarete Emilia

    2012-04-01

    Full Text Available Abstract Background Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA, but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Methods Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50, Crohn's disease (CD, n = 50, ulcerative colitis (UC, n = 50, bullous pemphigoid (BP, n = 76, and pemphigus vulgaris (PV, n = 42 and healthy donors (n = 245. Results By ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005, allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%, 2 CD (4%; 95% CI: 0%-9.43%, 8 UC (16%; 95% CI: 5.8%-26%, 2 BP (2.63%; 95% CI: 0%-6.23%, and 4 PV (9.52%; 95% CI: 0%-18.4% patients as well as from 4 (1.63%; 95% CI: 0%-3.21% healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen. Conclusions Using a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should

  19. Patient-specific atrium models for training and pre-procedure surgical planning

    Science.gov (United States)

    Laing, Justin; Moore, John; Bainbridge, Daniel; Drangova, Maria; Peters, Terry

    2017-03-01

    Minimally invasive cardiac procedures requiring a trans-septal puncture such as atrial ablation and MitraClip® mitral valve repair are becoming increasingly common. These procedures are performed on the beating heart, and require clinicians to rely on image-guided techniques. For cases of complex or diseased anatomy, in which fluoroscopic and echocardiography images can be difficult to interpret, clinicians may benefit from patient-specific atrial models that can be used for training, surgical planning, and the validation of new devices and guidance techniques. Computed tomography (CT) images of a patient's heart were segmented and used to generate geometric models to create a patient-specific atrial phantom. Using rapid prototyping, the geometric models were converted into physical representations and used to build a mold. The atria were then molded using tissue-mimicking materials and imaged using CT. The resulting images were segmented and used to generate a point cloud data set that could be registered to the original patient data. The absolute distance of the two point clouds was compared and evaluated to determine the model's accuracy. The result when comparing the molded model point cloud to the original data set, resulted in a maximum Euclidean distance error of 4.5 mm, an average error of 0.5 mm and a standard deviation of 0.6 mm. Using our workflow for creating atrial models, potential complications, particularly for complex repairs, may be accounted for in pre-operative planning. The information gained by clinicians involved in planning and performing the procedure should lead to shorter procedural times and better outcomes for patients.

  20. Assessment of the Sensitivity, Specificity, and Accuracy of Thermography in Identifying Patients with TMD.

    Science.gov (United States)

    Woźniak, Krzysztof; Szyszka-Sommerfeld, Liliana; Trybek, Grzegorz; Piątkowska, Dagmara

    2015-05-23

    The purpose of the present study was to evaluate the sensitivity, specificity, and accuracy of thermography in identifying patients with temporomandibular dysfunction (TMD). The study sample consisted of 50 patients (27 women and 23 men) ages 19.2 to 24.5 years (mean age 22.43±1.04) with subjective symptoms of TMD (Ai II-III) and 50 patients (25 women and 25 men) ages 19.3 to 25.1 years (mean age 22.21±1.18) with no subjective symptoms of TMD (Ai I). The anamnestic interviews were conducted according to the three-point anamnestic index of temporomandibular dysfunction (Ai). The thermography was performed using a ThermaCAM TMSC500 (FLIR Systems AB, Sweden) independent thermal vision system. Thermography was closely combined with a 10-min chewing test. The results of our study indicated that the absolute difference in temperature between the right and left side (ΔT) has the highest diagnostic value. The diagnostic effectiveness of this parameter increased after the chewing test. The cut-off points for values of temperature differences between the right and left side and identifying 95.5% of subjects with no functional disorders according to the temporomandibular dysfunction index Di (specificity 95.5%) were 0.26°C (AUC=0.7422, sensitivity 44.3%, accuracy 52.4%) before the chewing test and 0.52°C (AUC=0.7920, sensitivity 46.4%, accuracy 56.3%) after it. The evaluation of thermography demonstrated its diagnostic usefulness in identifying patients with TMD with limited effectiveness. The chewing test helped in increasing the diagnostic efficiency of thermography in identifying patients with TMD.

  1. AML-specific cytotoxic antibodies in patients with durable graft versus leukemia responses.

    Science.gov (United States)

    Gillissen, Marijn A; Kedde, Martijn; de Jong, Greta; Moiset, Gemma; Yasuda, Etsuko; Levie, Sophie E; Bakker, Arjen Q; Claassen, Yvonne B; Wagner, Koen; Böhne, Martino; Hensbergen, Paul J; Speijer, Dave; van Helden, Pauline M; Beaumont, Tim; Spits, Hergen; Hazenberg, Mette D

    2017-10-23

    Most acute myeloid leukemia (AML) patients can only be cured when an allogeneic hematopoietic stem cell transplantation (HSCT) induces a graft versus leukemia immune response (GvL). While the role of T cells and NK cells in tumor immunology has been established, less is known about the contribution of B cells. From B cells of high-risk AML patients with potent and lasting GvL responses we isolated monoclonal antibodies directed against antigens expressed on the cell surface of AML cells but not on normal hematopoietic and non-hematopoietic cells. A number of these donor-derived antibodies recognized the U5 snRNP200 complex, a component of the spliceosome that in normal cells is found in the cell. In AML however, the U5 snRNP200 complex is exposed on the cell membrane of leukemic blasts. U5 snRNP200 complex-specific antibodies induced death of AML cells in a FcR dependent way in the absence of cytotoxic leukocytes or complement. In an AML mouse model, treatment with U5 snRNP200 complex-specific antibodies led to significant tumor growth inhibition. Thus, donor derived U5 snRNP200 complex-recognizing AML-specific antibodies may contribute to anti-tumor responses. Copyright © 2017 American Society of Hematology.

  2. Affective tasks elicit material-specific memory effects in temporal lobectomy patients.

    Science.gov (United States)

    Burton, Leslie A; Vardy, Susan Bernstein; Frohlich, Jonathan; Dimitri, Diana; Wyatt, Gwinne; Rabin, Laura; Labar, Douglas

    2004-11-01

    Eighteen patients who had undergone a right (9) or left (9) temporal lobectomy (RTL, LTL) including removal of the amygdala and hippocampus were evaluated. Sixteen male and sixteen female undergraduate subjects were evaluated for normative comparison. All subjects were administered Verbal (words) and Visual (faces) paired associates tasks. The present study sought to evaluate material-specific memory after temporal lobectomy, and to compare affective versus neutral memory as well. Thus, there were 4 tasks: Verbal Affective, Verbal Neutral, Visual Affective, and Visual Neutral. The material-specific effects of better Verbal memory performance by the RTL subjects compared to the LTL subjects and better Visual memory performance by the LTL subjects than the RTL subjects were only significant for the Affective tasks, and not the Neutral tasks. Perhaps adding an affective dimension to the material-specific memory tasks engaged the amygdala in addition to the other structures known to be important in memory. A strong interpretaion of the present data is made difficult by task differences and the low average IQ and possible reorganization of function that may have occurred in the patient sample.

  3. Fascial release effects on patients with non-specific cervical or lumbar pain.

    Science.gov (United States)

    Tozzi, Paolo; Bongiorno, Davide; Vitturini, Claudio

    2011-10-01

    Myofascial Release (MFR) and Fascial Unwinding (FU) are widely used manual fascial techniques (MFTs), generally incorporated in treatment protocols to release fascial restrictions and restore tissue mobility. However, the effects of MFT on pain perception, and the mobility of fascial layers, have not previously been investigated using dynamic ultrasound (US) in patients with neck pain (NP) and low back pain (LBP). a) To show that US screening can be a useful tool to assess dysfunctional alteration of organ mobility in relation to their fascial layers, in people with non-specific NP or LBP, in the absence of any organ disease; b) To assess, by dynamic US screening, the change of sliding movements between superficial and deep fascia layers in the neck, in people with non-specific NP, before and after application of MFTs c) To assess, by dynamic US screening, the variation of right reno-diaphragmatic (RD) distance and of neck bladder (NB) mobility, in patients with non-specific LBP, before and after application of MFTs d) To evaluate 'if' and 'at what degree' pain perception may vary in patients with NP or LBP, after MFTs are applied, over the short term. An Experimental group of 60 subjects, 30 with non-specific NP and 30 with non-specific LBP, were assessed in the area of complaint, by Dynamic Ultrasound Topographic Anatomy Evaluation (D.US.T.A.-E.), before and after MFTs were applied in situ, in the corresponding painful region, for not more than 12 min. The results were compared with those from the respective Sham-Control group of 30 subjects. For the NP sub-groups, the pre- to post- US recorded videos of each subject were compared and assessed randomly and independently by two blinded experts in echographic screening. They were asked to rate the change observed in the cervical fascia sliding motions as 'none', 'discrete' or 'radical'. For the LBP sub-groups, a pre- to post- variation of the right RD distances and NB mobility were calculated on US imaging and

  4. Evaluation of effectiveness of specific subcutaneous immunotherapy for patients with allergic rhinitis and asthma

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zandkarimi

    2013-06-01

    Full Text Available Background: Allergen immunotherapy involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. This study evaluated the clinical efficacy of immunotherapy with extracts of common aeroallergens North-East of Iran in asthma and allergic rhinitis. Material and Methods: In this prospective study 156 cases were chosen randomley. The mean age of patients was 37 years (range 5-65 years. The patients with mild to moderate asthma and allergic rhinitis and history of atopy were selected for immunotherapy when they showed no effective response to medical treatment.Immunotherapy materials were made from common aeroallergens in north-eastern region of Iran by Dome Hollister US company. Immunotherapy schedule for injection of the extract with vial dilution of 1:10000pg was one injection every week for ten weeks and one injection with dilution of 1:1000pg every other week for the other ten weeks and one injection monthly from dilution of 1:100pg for two years. Results: One hundred twenty (77% of cases had allergic rhinitis 29(18.5% cases had allergic asthma and 7(4.5% cases were mixed. Mean age of patients were 37 years old. 48(30.8% cases were male. Analysis of efficacy of treatment showed that immunotherapy significantlyimproved the signs and symptoms of all the groups. In allergic rhinitis group 84(70% cases completely improved, 22(18.4% patients moderately responded and no response to immunotherapy was observed in 14(11.6% patients. In allergic asthma group, 22(75% cases completely improved 4(13.6% cases moderately responded and no response to immunotherapy was detected in 3(11.4% cases. In mixed group, 3(42.8% cases completely improved, 3(42.8% cases moderately responded and no response was observed in 1(14.4% case. Conclusion: Specific allergen immunotherapy for patients with allergic persistent

  5. Prevalence of specific anti-skin autoantibodies in a cohort of patients with inherited epidermolysis bullosa.

    Science.gov (United States)

    Tampoia, Marilina; Bonamonte, Domenico; Filoni, Angela; Garofalo, Lucrezia; Morgese, Maria Grazia; Brunetti, Luigia; Di Giorgio, Chiara; Annicchiarico, Giuseppina

    2013-09-04

    Inherited epidermolysis bullosa (EB) is a group of skin diseases characterized by blistering of the skin and mucous membranes.There are four major types of EB (EB simplex, junctional EB, dystrophic EB and Kindler syndrome) caused by different gene mutations. Dystrophic EB is derived from mutations in the type VII collagen gene (COL7A1), encoding a protein which is the predominant component of the anchoring fibrils at the dermal-epidermal junction.For the first time in literature, we have evaluated the presence of anti-skin autoantibodies in a wider cohort of patients suffering from inherited EB and ascertained whether they may be a marker of disease activity. Sera from patients with inherited EB, 17 with recessive dystrophic EB (RDEB), 10 with EB simplex (EBS) were analysed. As much as 20 patients with pemphigus vulgaris, 21 patients with bullous pemphigoid and 20 healthy subjects were used as controls.Anti-skin autoantibodies were tested in all samples with the Indirect Immunofluorescence (IIF) method and the currently available ELISA method in order to detect anti-type VII collagen, anti-BP180 and anti-BP230 autoantibodies. The mean concentrations of anti-type VII collagen autoantibodies titres, anti-BP180 and anti-BP230 autoantibodies were statistically higher in RDEB patients than in EBS patients.The sensitivity and specificity of the anti-type VII collagen ELISA test were 88.2% and 96.7%. The Birmingham Epidermolysis Bullosa Severity score, which is used to evaluate the severity of the disease, correlated with anti-skin autoantibodies titres. The precise pathogenic role of circulating anti-skin autoantibodies in RDEB is unclear. There is a higher prevalence of both anti-type VII collagen and other autoantibodies in patients with RDEB, but their presence can be interpreted as an epiphenomenon.

  6. Patient-specific modeling of corneal refractive surgery outcomes and inverse estimation of elastic property changes.

    Science.gov (United States)

    Roy, Abhijit Sinha; Dupps, William J

    2011-01-01

    The purpose of this study is to develop a 3D patient-specific finite element model (FEM) of the cornea and sclera to compare predicted and in vivo refractive outcomes and to estimate the corneal elastic property changes associated with each procedure. Both eyes of a patient who underwent laser-assisted in situ keratomileusis (LASIK) for myopic astigmatism were modeled. Pre- and postoperative Scheimpflug anterior and posterior corneal elevation maps were imported into a 3D corneo-scleral FEM with an unrestrained limbus. Preoperative corneal hyperelastic properties were chosen to account for meridional anisotropy. Inverse FEM was used to determine the undeformed corneal state that produced aberration were compared at clinical intraocular pressure. The magnitude of elastic weakening of the residual corneal bed required to maximize the agreement with clinical axial power was calculated and compared with the changes in ocular response analyzer (ORA) measurements. The models produced curvature maps and spherical aberrations equivalent to in vivo measurements. For the preoperative property values used in this study, predicted elastic weakening with LASIK was as high as 55% for a radially uniform model of residual corneal weakening and 65% at the point of maximum ablation in a spatially varying model of weakening. Reductions in ORA variables were also observed. A patient-specific FEM of corneal refractive surgery is presented, which allows the estimation of surgically induced changes in corneal elastic properties. Significant elastic weakening after LASIK was required to replicate clinical topographic outcomes in this two-eye pilot study.

  7. [Copy number alterations in adult patients with mature B acute lymphoblastic leukemia treated with specific immunochemotherapy].

    Science.gov (United States)

    Ribera, Jordi; Zamora, Lurdes; García, Olga; Hernández-Rivas, Jesús-María; Genescà, Eulàlia; Ribera, Josep-Maria

    2016-12-02

    Unlike Burkitt lymphoma, molecular abnormalities other than C-MYC rearrangements have scarcely been studied in patients with mature B acute lymphoblastic leukemia (B-ALL). The aim of this study was to analyze the frequency and prognostic significance of copy number alterations (CNA) in genes involved in lymphoid differentiation, cell cycle and tumor suppression in adult patients with B-ALL. We have analyzed by multiplex ligation-dependent probe amplification the genetic material from bone marrow at diagnosis from 25 adult B-ALL patients treated with rituximab and specific chemotherapy. The most frequent CNA were alterations in the 14q32.33 region (11 cases, 44%) followed by alterations in the cell cycle regulator genes CDKN2A/B and RB1 (16%). No correlation between the presence of specific CNA and the clinical-biologic features or the response to therapy was found. The high frequency of CNA in the 14q32.33 region, CDKN2A/B and RB1 found in our study could contribute to the aggressiveness and invasiveness of mature B-ALL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  8. Compliant Buckled Foam Actuators and Application in Patient-Specific Direct Cardiac Compression.

    Science.gov (United States)

    Mac Murray, Benjamin C; Futran, Chaim C; Lee, Jeanne; O'Brien, Kevin W; Amiri Moghadam, Amir A; Mosadegh, Bobak; Silberstein, Meredith N; Min, James K; Shepherd, Robert F

    2018-02-01

    We introduce the use of buckled foam for soft pneumatic actuators. A moderate amount of residual compressive strain within elastomer foam increases the applied force ∼1.4 × or stroke ∼2 × compared with actuators without residual strain. The origin of these improved characteristics is explained analytically. These actuators are applied in a direct cardiac compression (DCC) device design, a type of implanted mechanical circulatory support that avoids direct blood contact, mitigating risks of clot formation and stroke. This article describes a first step toward a pneumatically powered, patient-specific DCC design by employing elastomer foam as the mechanism for cardiac compression. To form the device, a mold of a patient's heart was obtained by 3D printing a digitized X-ray computed tomography or magnetic resonance imaging scan into a solid model. From this model, a soft, robotic foam DCC device was molded. The DCC device is compliant and uses compressed air to inflate foam chambers that in turn apply compression to the exterior of a heart. The device is demonstrated on a porcine heart and is capable of assisting heart pumping at physiologically relevant durations (∼200 ms for systole and ∼400 ms for diastole) and stroke volumes (∼70 mL). Although further development is necessary to produce a fully implantable device, the material and processing insights presented here are essential to the implementation of a foam-based, patient-specific DCC design.

  9. A Computational Chemo-Fluidic Modeling for the Investigation of Patient-Specific Left Ventricle Thrombogenesis

    Science.gov (United States)

    Mittal, Rajat; Seo, Jung Hee; Abd, Thura; George, Richard T.

    2015-11-01

    Patients recovering from myocardial infarction (MI) are considered at high-risk for cardioembolic stroke due to the formation of left ventricle thrombus (LVT). The formation of LVT is the result of a complex interplay between the fluid dynamics inside the ventricle and the chemistry of coagulation, and the role of LV flow pattern on the thrombogenesis was not well understood. The previous computational study performed with the model ventricles suggested that the local flow residence time is the key variable governing the accumulation of coagulation factors. In the present study, a coupled, chemo-fluidic computational modeling is applied to the patient-specific cases of infracted ventricles to investigate the interaction between the LV hemodynamics and thrombogensis. In collaboration with the Johns Hopkins hospital, patient-specific LV models are constructed using the multi-modality medical imaging data. Blood flow in the left ventricle is simulated by solving the incompressible Navier-Stokes equations and the biochemical reactions for the thrombus formation are modeled with convection-diffusion-reaction equations. The formation and deposition of key coagulation chemical factors are then correlated with the hemodynamic flow metrics to explore the biophysics underlying LVT risk. Supported by the Johns Hopkins Medicine Discovery Fund and NSF Grant: CBET-1511200, Computational resource by XSEDE NSF grant TG-CTS100002.

  10. Patient-specific computer modelling of coronary bifurcation stenting: the John Doe programme.

    Science.gov (United States)

    Mortier, Peter; Wentzel, Jolanda J; De Santis, Gianluca; Chiastra, Claudio; Migliavacca, Francesco; De Beule, Matthieu; Louvard, Yves; Dubini, Gabriele

    2015-01-01

    John Doe, an 81-year-old patient with a significant distal left main (LM) stenosis, was treated using a provisional stenting approach. As part of an European Bifurcation Club (EBC) project, the complete stenting procedure was repeated using computational modelling. First, a tailored three-dimensional (3D) reconstruction of the bifurcation anatomy was created by fusion of multislice computed tomography (CT) imaging and intravascular ultrasound. Second, finite element analysis was employed to deploy and post-dilate the stent virtually within the generated patient-specific anatomical bifurcation model. Finally, blood flow was modelled using computational fluid dynamics. This proof-of-concept study demonstrated the feasibility of such patient-specific simulations for bifurcation stenting and has provided unique insights into the bifurcation anatomy, the technical aspects of LM bifurcation stenting, and the positive impact of adequate post-dilatation on blood flow patterns. Potential clinical applications such as virtual trials and preoperative planning seem feasible but require a thorough clinical validation of the predictive power of these computer simulations.

  11. Determinants of generic and specific health-related quality of life in patients with Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Xiao-Jing Tu

    Full Text Available Generic and disease-specific health-related quality of life (HRQoL instruments may reflect different aspects of lives in patients with Parkinson's disease (PD and thus be associated with different determinants. We used the same cluster of predictors for the generic and disease-specific HRQoL instruments to examine and compare the determinants of HRQoL.HRQoL was measured in 92 patients with PD by the 36-item Short-Form Health Survey (SF-36 and the 39-item Parkinson's Disease Questionnaire (PDQ-39. The predictors included demographic and disease characteristics, and motor and non-motor symptoms. Multiple regression analyses were used to identify HRQoL determinants.Depressive symptoms and motor difficulties of daily living were the first two significant determinants for both instruments. The other significant determinant for the SF-36 was fatigue and non-motor difficulties of daily living, and for the PDQ-39 was motor signs of PD.The results suggest the importance of the evaluation and intervention focused on depressive symptoms and motor difficulties of daily living in patients with PD. In addition, the SF-36 seems more related to non-motor symptoms, while the PDQ-39 appears more associated with motor symptoms. This information is important for understanding results from these two instruments and for choosing which to use.

  12. Patient pools and the use of "patient means" are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay

    DEFF Research Database (Denmark)

    Hinge, Maja; Lund, Erik D.; Brandslund, Ivan

    2016-01-01

    AND RESULTS: The present study reports an example where a shift in a BAP assay was detected by use of a patient pool and supported by a retrospective calculation of "patient mean", while the external QC and specific assay control material were unaffected by the shift. CONCLUSIONS: Patient pools and the use...... of patient means remain a useful and inexpensive procedure for internal QC....

  13. Search for specific biomarkers of IFNβ bioactivity in patients with multiple sclerosis.

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    Sunny Malhotra

    Full Text Available Myxovirus A (MxA, a protein encoded by the MX1 gene with antiviral activity, has proven to be a sensitive measure of IFNβ bioactivity in multiple sclerosis (MS. However, the use of MxA as a biomarker of IFNβ bioactivity has been criticized for the lack of evidence of its role on disease pathogenesis and the clinical response to IFNβ. Here, we aimed to identify specific biomarkers of IFNβ bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB to IFNβ at 12 and/or 24 months of treatment and patients who remained NAB negative. Nine genes followed patterns in gene expression over time similar to the MX1, which was considered the gold standard gene, and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments in PBMC from healthy controls revealed specific induction of selected biomarkers by IFNβ but not IFNγ, and several markers, in particular USP18 and HERC5, were shown to be significantly induced at lower IFNβ concentrations and more selective than the MX1 as biomarkers of IFNβ bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p = 0.0004. We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFNβ bioactivity, and to further explore their implication in MS pathogenesis.

  14. An automatic CFD-based flow diverter optimization principle for patient-specific intracranial aneurysms.

    Science.gov (United States)

    Janiga, Gábor; Daróczy, László; Berg, Philipp; Thévenin, Dominique; Skalej, Martin; Beuing, Oliver

    2015-11-05

    The optimal treatment of intracranial aneurysms using flow diverting devices is a fundamental issue for neuroradiologists as well as neurosurgeons. Due to highly irregular manifold aneurysm shapes and locations, the choice of the stent and the patient-specific deployment strategy can be a very difficult decision. To support the therapy planning, a new method is introduced that combines a three-dimensional CFD-based optimization with a realistic deployment of a virtual flow diverting stent for a given aneurysm. To demonstrate the feasibility of this method, it was applied to a patient-specific intracranial giant aneurysm that was successfully treated using a commercial flow diverter. Eight treatment scenarios with different local compressions were considered in a fully automated simulation loop. The impact on the corresponding blood flow behavior was evaluated qualitatively as well as quantitatively, and the optimal configuration for this specific case was identified. The virtual deployment of an uncompressed flow diverter reduced the inflow into the aneurysm by 24.4% compared to the untreated case. Depending on the positioning of the local stent compression below the ostium, blood flow reduction could vary between 27.3% and 33.4%. Therefore, a broad range of potential treatment outcomes was identified, illustrating the variability of a given flow diverter deployment in general. This method represents a proof of concept to automatically identify the optimal treatment for a patient in a virtual study under certain assumptions. Hence, it contributes to the improvement of virtual stenting for intracranial aneurysms and can support physicians during therapy planning in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Patient-specific in vitro models for hemodynamic analysis of congenital heart disease - Additive manufacturing approach.

    Science.gov (United States)

    Medero, Rafael; García-Rodríguez, Sylvana; François, Christopher J; Roldán-Alzate, Alejandro

    2017-03-21

    Non-invasive hemodynamic assessment of total cavopulmonary connection (TCPC) is challenging due to the complex anatomy. Additive manufacturing (AM) is a suitable alternative for creating patient-specific in vitro models for flow measurements using four-dimensional (4D) Flow MRI. These in vitro systems have the potential to serve as validation for computational fluid dynamics (CFD), simulating different physiological conditions. This study investigated three different AM technologies, stereolithography (SLA), selective laser sintering (SLS) and fused deposition modeling (FDM), to determine differences in hemodynamics when measuring flow using 4D Flow MRI. The models were created using patient-specific MRI data from an extracardiac TCPC. These models were connected to a perfusion pump circulating water at three different flow rates. Data was processed for visualization and quantification of velocity, flow distribution, vorticity and kinetic energy. These results were compared between each model. In addition, the flow distribution obtained in vitro was compared to in vivo. The results showed significant difference in velocities measured at the outlets of the models that required internal support material when printing. Furthermore, an ultrasound flow sensor was used to validate flow measurements at the inlets and outlets of the in vitro models. These results were highly correlated to those measured with 4D Flow MRI. This study showed that commercially available AM technologies can be used to create patient-specific vascular models for in vitro hemodynamic studies at reasonable costs. However, technologies that do not require internal supports during manufacturing allow smoother internal surfaces, which makes them better suited for flow analyses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Validation of a Cochlear Implant Patient Specific Model of the Voltage Distribution in a Clinical Setting

    Directory of Open Access Journals (Sweden)

    Waldo Nogueira

    2016-11-01

    Full Text Available Cochlear Implants (CIs are medical implantable devices that can restore the sense of hearing in people with profound hearing loss. Clinical trials assessing speech intelligibility in CI users have found large inter-subject variability. One possibility to explain the variability is the individual differences in the interface created between electrodes of the CI and the auditory nerve. In order to understand the variability, models of the voltage distribution of the electrically stimulated cochlea may be useful. With this purpose in mind, we developed a parametric model that can be adapted to each CI user based on landmarks from individual cone beam computed tomography (CBCT scans of the cochlea before and after implantation. The conductivity values of each cochlea compartment as well as the weighting factors of different grounding modes have been also parameterized. Simulations were performed modeling the cochlea and electrode positions of 12 CI users. Three models were compared with different levels of detail: A homogeneous model (HM, a non-patient specific model (NPSM and a patient specific model (PSM. The model simulations were compared with voltage distribution measurements obtained from the backward telemetry of the 12 CI users. Results show that the PSM produces the lowest error when predicting individual voltage distributions. Given a patient specific geometry and electrode positions we show an example on how to optimize the parameters of the model and how to couple it to an auditory nerve model. The model here presented may help to understand speech performance variability and support the development of new sound coding strategies for CIs.

  17. Patient-specific coronary blood supply territories for quantitative perfusion analysis

    Science.gov (United States)

    Zakkaroff, Constantine; Biglands, John D.; Greenwood, John P.; Plein, Sven; Boyle, Roger D.; Radjenovic, Aleksandra; Magee, Derek R.

    2018-01-01

    Abstract Myocardial perfusion imaging, coupled with quantitative perfusion analysis, provides an important diagnostic tool for the identification of ischaemic heart disease caused by coronary stenoses. The accurate mapping between coronary anatomy and under-perfused areas of the myocardium is important for diagnosis and treatment. However, in the absence of the actual coronary anatomy during the reporting of perfusion images, areas of ischaemia are allocated to a coronary territory based on a population-derived 17-segment (American Heart Association) AHA model of coronary blood supply. This work presents a solution for the fusion of 2D Magnetic Resonance (MR) myocardial perfusion images and 3D MR angiography data with the aim to improve the detection of ischaemic heart disease. The key contribution of this work is a novel method for the mediated spatiotemporal registration of perfusion and angiography data and a novel method for the calculation of patient-specific coronary supply territories. The registration method uses 4D cardiac MR cine series spanning the complete cardiac cycle in order to overcome the under-constrained nature of non-rigid slice-to-volume perfusion-to-angiography registration. This is achieved by separating out the deformable registration problem and solving it through phase-to-phase registration of the cine series. The use of patient-specific blood supply territories in quantitative perfusion analysis (instead of the population-based model of coronary blood supply) has the potential of increasing the accuracy of perfusion analysis. Quantitative perfusion analysis diagnostic accuracy evaluation with patient-specific territories against the AHA model demonstrates the value of the mediated spatiotemporal registration in the context of ischaemic heart disease diagnosis. PMID:29392098

  18. Institutional Patient-specific IMRT QA Does Not Predict Unacceptable Plan Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Kry, Stephen F., E-mail: sfkry@mdanderson.org [Imaging and Radiation Oncology Core at Houston, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Molineu, Andrea [Imaging and Radiation Oncology Core at Houston, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kerns, James R.; Faught, Austin M.; Huang, Jessie Y.; Pulliam, Kiley B.; Tonigan, Jackie [Imaging and Radiation Oncology Core at Houston, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); The University of Texas Health Science Center Houston, Graduate School of Biomedical Sciences, Houston, Texas (United States); Alvarez, Paola [Imaging and Radiation Oncology Core at Houston, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Stingo, Francesco [The University of Texas Health Science Center Houston, Graduate School of Biomedical Sciences, Houston, Texas (United States); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Followill, David S. [Imaging and Radiation Oncology Core at Houston, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); The University of Texas Health Science Center Houston, Graduate School of Biomedical Sciences, Houston, Texas (United States)

    2014-12-01

    Purpose: To determine whether in-house patient-specific intensity modulated radiation therapy quality assurance (IMRT QA) results predict Imaging and Radiation Oncology Core (IROC)-Houston phantom results. Methods and Materials: IROC Houston's IMRT head and neck phantoms have been irradiated by numerous institutions as part of clinical trial credentialing. We retrospectively compared these phantom results with those of in-house IMRT QA (following the institution's clinical process) for 855 irradiations performed between 2003 and 2013. The sensitivity and specificity of IMRT QA to detect unacceptable or acceptable plans were determined relative to the IROC Houston phantom results. Additional analyses evaluated specific IMRT QA dosimeters and analysis methods. Results: IMRT QA universally showed poor sensitivity relative to the head and neck phantom, that is, poor ability to predict a failing IROC Houston phantom result. Depending on how the IMRT QA results were interpreted, overall sensitivity ranged from 2% to 18%. For different IMRT QA methods, sensitivity ranged from 3% to 54%. Although the observed sensitivity was particularly poor at clinical thresholds (eg 3% dose difference or 90% of pixels passing gamma), receiver operator characteristic analysis indicated that no threshold showed good sensitivity and specificity for the devices evaluated. Conclusions: IMRT QA is not a reasonable replacement for a credentialing phantom. Moreover, the particularly poor agreement between IMRT QA and the IROC Houston phantoms highlights surprising inconsistency in the QA process.

  19. The effect of comorbidity on stage-specific survival in resected non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Lüchtenborg, Margreet; Jakobsen, Erik; Krasnik, Mark

    2012-01-01

    To quantify the effect of comorbidity on stage-specific survival in resected non-small cell lung cancer (NSCLC) patients.......To quantify the effect of comorbidity on stage-specific survival in resected non-small cell lung cancer (NSCLC) patients....

  20. On the relationship between pain intensity and postural sway in patients with non-specific neck pain

    DEFF Research Database (Denmark)

    Ruhe, Alexander; Fejer, René; Walker, Bruce

    2013-01-01

    Increased center of pressure excursions are well documented in patients with non-specific neck pain. While a linear relationship between pain intensity and postural sway has been described in low back pain patients, no such investigation has been conducted in adults with non-specific neck pain....

  1. Circulating Muscle-specific miRNAs in Duchenne Muscular Dystrophy Patients

    Directory of Open Access Journals (Sweden)

    Xihua Li

    2014-01-01

    Full Text Available Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for Duchenne muscular dystrophy (DMD patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the serum levels of six muscle-specific miRNAs (miR-1/206/133/499/208a/208b, also known as myomiRs were all elevated in DMD patients (P 6 years. Fibroblast growth factor, transforming growth factor-β, and tumor necrosis factor-α could affect the secretion of myomiRs, suggesting that circulating myomiRs might reflect the effects of cytokines and growth factors on degenerating and regenerating muscles. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for DMD diagnosis and disease progression.

  2. Ansys Fluent versus Sim Vascular for 4-D patient-specific computational hemodynamics in renal arteries

    Science.gov (United States)

    Mumbaraddi, Avinash; Yu, Huidan (Whitney); Sawchuk, Alan; Dalsing, Michael

    2015-11-01

    The objective of this clinical-need driven research is to investigate the effect of renal artery stenosis (RAS) on the blood flow and wall shear stress in renal arteries through 4-D patient-specific computational hemodynamics (PSCH) and search for possible critical RASs that significantly alter the pressure gradient across the stenosis by manually varying the size of RAS from 50% to 95%. The identification of the critical RAS is important to understand the contribution of RAS to the overall renal resistance thus appropriate clinical therapy can be determined in order to reduce the hypertension. Clinical CT angiographic data together with Doppler Ultra sound images of an anonymous patient are used serving as the required inputs of the PSCH. To validate the PSCH, we use both Ansys Fluent and Sim Vascular and compare velocity, pressure, and wall-shear stress under identical conditions. Renal Imaging Technology Development Program (RITDP) Grant.

  3. Intra-aneurysmal blood flow based on patient-specific CT angiogram

    Science.gov (United States)

    Morino, Taku; Tanoue, Tetsuya; Tateshima, Satoshi; Vinuela, Fernando; Tanishita, Kazuo

    2010-08-01

    To discuss the validity of the hemodynamic hypothesis of aneurysm rupture, we used a patient-specific, realistic aneurysm model to reveal the flow structure and wall shear stress distribution in two cases: one with an unruptured aneurysm and the other with a ruptured aneurysm. We used particle imaging velocimetry and laser Doppler velocimetry to measure velocity profiles of intra-aneurysmal flow. Both cases had a circulating flow along the aneurysm wall, although the second case had a recirculating zone only in the minimum phase. Differences in the wall shear stress profile may identify aneurysm rupture.

  4. Investigation of patient-specific characteristics associated with treatment outcomes for chronic urticaria.

    Science.gov (United States)

    Amin, Priyal; Levin, Linda; Holmes, Sarah J; Picard, Jillian; Bernstein, Jonathan A

    2015-01-01

    Identifying clinical characteristics of patients with chronic urticaria (CU) responsive to medication may help guide clinicians select treatment. The objective of this study was to investigate patient characteristics and medication use associated with urticaria control. A retrospective longitudinal chart review of adult patients with CU was conducted at a multisite allergy practice. Inclusion criteria required at least 4 CU office visits to allow for pre- and posttreatment assessment. Control corresponding to medication(s) used was assessed each visit. Univariate analysis followed by multiple logistic regression was performed. A total of 221 patients with CU were included; 140 (63%) achieved complete control. The average time to control was 1.4 ± 2.7 years, which required 1-3 classes of medications. Dermatographia odds ratio (OR) = 1.85 (95% CI 1.3-2.7) or other physical urticarias, OR = 1.51 (1-2.4) and neutrophilic infiltrates on skin biopsy were markers of poor control. Thyroid autoantibodies were associated with better control using an H1-antihistamine. Whereas 22% were controlled on a second-generation H1-receptor antagonist plus a leukotriene receptor antagonist (LTRA), an additional 33% were controlled when cyclosporine was added. Use of a first or second H1-antagonist or LTRA was associated with a 3.5-16.9 times higher odds of complete CU control in those with dermatographia. The odds of achieving control for other forms of physical urticaria was greatest when colchicine was added (aOR = 32.6 [12.7-83.2]). Patient-specific CU characteristics associated with medication-disease control may be useful for selecting treatment regimens. A subset of CU patients remains poorly controlled that indicates an unmet need for novel therapeutic agents. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Reliability, validity and responsiveness of a new leisure index: the Patient-Specific Leisure Scale (PSLS).

    Science.gov (United States)

    Wikström, Ingegerd; Arvidsson, Barbro; Nilsson, Käth; Roos, Ewa; Jacobsson, Lennart T H

    2009-09-01

    To investigate the reliability, validity and responsiveness of a new Patient-Specific Leisure Scale (PSLS), constructed to identify goals and outcomes for individual patients with rheumatoid arthritis (RA). Forty-nine patients with RA were used to evaluate test-retest reliability, and 100 consecutive RA patients were used for construct validity. Twenty-five RA patients, commencing with treatment on tumour necrosis factor (TNF) inhibitors, were evaluated before the start and after three months of therapy, to test responsiveness. The most important leisure activity (as judged by the patients) was used when evaluating reliability and validity. The perceived difficulty with each activity was scored from 0 to 10 (0 = able to perform activity without difficulty, 10 = unable to perform activity). Test-retest reliability indicated a good agreement (0.62-0.87) using weighted kappa. Construct validity was demonstrated by modest positive correlation between leisure activity and Health Assessment Questionnaire (HAQ) (r(s) = 0.27, p = 0.005) visual analogue scale (VAS) pain (r(s) = 0.28, p = 0.004) VAS global (r(s) = 0.22, p = 0.027), VAS fatigue (r(s) = 0.24, p = 0.013), joint index of 28 swollen joints (r(s) = 0.22, p = 0.027) and negative correlations with short-form-36 (SF-36) physical functioning (r(s) = -0.18, p = 0.008), bodily pain (r(s) = -0.31, p valid and responsive for measuring leisure activities in RA. It provides both an individual result which is useful in clinical work, and results at a group level.

  6. Disease-specific quality of life in young patients with tourette syndrome.

    Science.gov (United States)

    Cavanna, Andrea E; Luoni, Chiara; Selvini, Claudia; Blangiardo, Rosanna; Eddy, Clare M; Silvestri, Paola R; Calì, Paola V; Gagliardi, Emanuela; Balottin, Umberto; Cardona, Francesco; Rizzo, Renata; Termine, Cristiano

    2013-02-01

    Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating "pure" Tourette syndrome from Tourette syndrome "plus" behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Craniofacial reconstruction using patient-specific implants polyether ether ketone with computer-assisted planning.

    Science.gov (United States)

    Manrique, Oscar J; Lalezarzadeh, Frank; Dayan, Erez; Shin, Joseph; Buchbinder, Daniel; Smith, Mark

    2015-05-01

    Reconstruction of bony craniofacial defects requires precise understanding of the anatomic relationships. The ideal reconstructive technique should be fast as well as economical, with minimal donor-site morbidity, and provide a lasting and aesthetically pleasing result. There are some circumstances in which a patient's own tissue is not sufficient to reconstruct defects. The development of sophisticated software has facilitated the manufacturing of patient-specific implants (PSIs). The aim of this study was to analyze the utility of polyether ether ketone (PEEK) PSIs for craniofacial reconstruction. We performed a retrospective chart review from July 2009 to July 2013 in patients who underwent craniofacial reconstruction using PEEK-PSIs using a virtual process based on computer-aided design and computer-aided manufacturing. A total of 6 patients were identified. The mean age was 46 years (16-68 y). Operative indications included cancer (n = 4), congenital deformities (n = 1), and infection (n = 1). The mean surgical time was 3.7 hours and the mean hospital stay was 1.5 days. The mean surface area of the defect was 93.4 ± 43.26 cm(2), the mean implant cost was $8493 ± $837.95, and the mean time required to manufacture the implants was 2 weeks. No major or minor complications were seen during the 4-year follow-up. We found PEEK implants to be useful in the reconstruction of complex calvarial defects, demonstrating a low complication rate, good outcomes, and high patient satisfaction in this small series of patients. Polyether ether ketone implants show promising potential and warrant further study to better establish the role of this technology in cranial reconstruction.

  8. SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Balkanov

    2016-01-01

    Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

  9. Pre-treatment patient-specific stopping power by combining list-mode proton radiography and x-ray CT

    Science.gov (United States)

    Collins-Fekete, Charles-Antoine; Brousmiche, Sébastien; Hansen, David C.; Beaulieu, Luc; Seco, Joao

    2017-09-01

    The relative stopping power (RSP) uncertainty is the largest contributor to the range uncertainty in proton therapy. The purpose of this work was to develop a systematic method that yields accurate and patient-specific RSPs by combining (1) pre-treatment x-ray CT and (2) daily proton radiography of the patient. The method was formulated as a penalized least squares optimization problem (argmin(\\Vert {A}{x}-{b}\\Vert _22 )). The parameter A represents the cumulative path-length crossed by the proton in each material, separated by thresholding on the HU. The material RSPs (water equivalent thickness/physical thickness) are denoted by x. The parameter b is the list-mode proton radiography produced using Geant4 simulations. The problem was solved using a non-negative linear-solver with {x}≥slant0 . A was computed by superposing proton trajectories calculated with a cubic or linear spline approach to the CT. The material’s RSP assigned in Geant4 were used for reference while the clinical HU-RSP calibration curve was used for comparison. The Gammex RMI-467 phantom was first investigated. The standard deviation between the estimated material RSP and the calculated RSP is 0.45%. The robustness of the techniques was then assessed as a function of the number of projections and initial proton energy. Optimization with two initial projections yields precise RSP (⩽1.0%) for 330 MeV protons. 250 MeV protons have shown higher uncertainty (⩽2.0%) due to the loss of precision in the path estimate. Anthropomorphic phantoms of the head, pelvis, and lung were subsequently evaluated. Accurate RSP has been obtained for the head (μ =0.21+/-1.63% ), the lung (μ=0.06+/-0.99% ) and the pelvis (μ=0.90+/-3.87% ). The range precision has been optimized using the calibration curves obtained with the algorithm, yielding a mean R80 difference to the reference of 0.11  ±0.09%, 0.28  ±  0.34% and 0.05 +/- 0.06% in the same order. The solution’s accuracy is limited by the

  10. A comprehensive validation of patient-specific CFD simulations of cerebral aneurysm flow with virtual angiography

    Science.gov (United States)

    Sun, Qi; Groth, Alexandra; Bertram, Matthias; Brina, Olivier; Pereira, Vitor Mendes; Aach, Til

    2011-03-01

    Recently, image-based computational fluid dynamic simulations (CFD) have been proposed to investigate the local hemodynamics inside human cerebral aneurysms. It is suggested that the knowledge of the computed three-dimensional flow fields can be used to assist clinical risk assessment and treatment decision making. However, the reliability of CFD for accurately representing the human cerebral blood flow is difficult to assess due to the impossibility of ground truth measurements. A recently proposed virtual angiography method has been used to indirectly validate CFD results by comparing virtually constructed and clinically acquired angiograms. However, the validations are not yet comprehensive as they lack either from patient-specific boundary conditions (BCs) required for CFD simulations or from quantitative comparison methods. In this work, a simulation pipeline is built up including image-based geometry reconstruction, CFD simulations solving the dynamics of blood flow and contrast agent (CA), and virtual angiogram generation. In contrast to previous studies, the patient-specific blood flow rates obtained by transcranial color coded Doppler (TCCD) ultrasound are used to impose CFD BCs. Quantitative measures are defined to thoroughly evaluate the correspondence between the clinically acquired and virtually constructed angiograms, and thus, the reliability of CFD simulations. Exemplarily, two patient cases are presented. Close similarities are found in terms of spatial and temporal variations of CA distribution between acquired and virtual angiograms. Besides, for both patient cases, discrepancies of less than 15% are found for the relative root mean square errors (rRMSE) in time intensity curve (TIC) comparisons from selected characteristic positions.

  11. Haemodynamic impact of stent implantation for lateral tunnel Fontan stenosis: a patient-specific computational assessment.

    Science.gov (United States)

    Tang, Elaine; McElhinney, Doff B; Restrepo, Maria; Valente, Anne M; Yoganathan, Ajit P

    2016-01-01

    The physiological importance of the lateral tunnel stenosis in the Fontan pathway for children with single ventricle physiology can be difficult to determine. The impact of the stenosis and stent implantation on total cavopulmonary connection resistance has not been characterized, and there are no clear guidelines for intervention. Methods and results A computational framework for haemodynamic assessment of stent implantation in patients with lateral tunnel stenosis was developed. Cardiac magnetic resonances images were reconstructed to obtain total cavopulmonary connection anatomies before stent implantation. Stents with 2-mm diameter increments were virtually implanted in each patient to understand the impact of stent diameter. Numerical simulations were performed in all geometries with patient-specific flow rates. Exercise conditions were simulated by doubling and tripling the lateral tunnel flow rate. The resulting total cavopulmonary connection vascular resistances were computed. A total of six patients (age: 14.4 ± 3.1 years) with lateral tunnel stenosis were included for preliminary analysis. The mean baseline resistance was 1.54 ± 1.08 WU · m(2) and dependent on the stenosis diameter. It was further exacerbated during exercise. It was observed that utilising a stent with a larger diameter lowered the resistance, but the resistance reduction diminished at larger diameters. Using a computational framework to assess the severity of lateral tunnel stenosis and the haemodynamic impact of stent implantation, it was observed that stenosis in the lateral tunnel pathway was associated with higher total cavopulmonary connection resistance than unobstructed pathways, which was exacerbated during exercise. Stent implantation could reduce the resistance, but the improvement was specific to the minimum diameter.

  12. Patient-specific pediatric silicone heart valve models based on 3D ultrasound

    Science.gov (United States)

    Ilina, Anna; Lasso, Andras; Jolley, Matthew A.; Wohler, Brittany; Nguyen, Alex; Scanlan, Adam; Baum, Zachary; McGowan, Frank; Fichtinger, Gabor

    2017-03-01

    PURPOSE: Patient-specific heart and valve models have shown promise as training and planning tools for heart surgery, but physically realistic valve models remain elusive. Available proprietary, simulation-focused heart valve models are generic adult mitral valves and do not allow for patient-specific modeling as may be needed for rare diseases such as congenitally abnormal valves. We propose creating silicone valve models from a 3D-printed plastic mold as a solution that can be adapted to any individual patient and heart valve at a fraction of the cost of direct 3D-printing using soft materials. METHODS: Leaflets of a pediatric mitral valve, a tricuspid valve in a patient with hypoplastic left heart syndrome, and a complete atrioventricular canal valve were segmented from ultrasound images. A custom software was developed to automatically generate molds for each valve based on the segmentation. These molds were 3D-printed and used to make silicone valve models. The models were designed with cylindrical rims of different sizes surrounding the leaflets, to show the outline of the valve and add rigidity. Pediatric cardiac surgeons practiced suturing on the models and evaluated them for use as surgical planning and training tools. RESULTS: Five out of six surgeons reported that the valve models would be very useful as training tools for cardiac surgery. In this first iteration of valve models, leaflets were felt to be unrealistically thick or stiff compared to real pediatric leaflets. A thin tube rim was preferred for valve flexibility. CONCLUSION: The valve models were well received and considered to be valuable and accessible tools for heart valve surgery training. Further improvements will be made based on surgeons' feedback.

  13. Patient-specific electronic decision support reduces prescription of excessive doses.

    Science.gov (United States)

    Seidling, H M; Schmitt, S P W; Bruckner, T; Kaltschmidt, J; Pruszydlo, M G; Senger, C; Bertsche, T; Walter-Sack, I; Haefeli, W E

    2010-10-01

    Prescription of excessive doses is the most common prescription error, provoking dose-dependent adverse drug reactions. Clinical decision support systems (CDSS) can prevent prescription errors especially when mainly clinically relevant warnings are issued. We have built and evaluated a CDSS providing upper dose limits personalised to individual patient characteristics thus guaranteeing for specific warnings. For 170 compounds, detailed information on upper dose limits (according to the drug label) was compiled. A comprehensive software-algorithm extracted relevant patient information from the electronic chart (eg, age, renal function, comedication). The CDSS was integrated into the local prescribing platform for outpatients and patients at discharge, providing immediate dosage feedback. Its impact was evaluated in a 90-day intervention study (phase 1: baseline; phase 2: intervention). Outcome measures were frequency of excessive doses before and after intervention considering potential induction of new medication errors. Moreover, predictors for alert adherence were analysed. In phase 1, 552 of 12,197 (4.5%) prescriptions exceeded upper dose limits. In phase 2, initially 559 warnings were triggered (4.8%, p=0.37). Physicians were responsive to one in four warnings mostly adjusting dosages. Thus, the final prescription rate of excessive doses was reduced to 3.6%, with 20% less excessive doses compared with baseline (pprescription errors were induced. Physicians' alert adherence correlated with patients' age, prescribed drug class, and reason for the alert. During the 90-day study, implementation of a highly specific algorithm-based CDSS substantially improved prescribing quality with a high acceptance rate compared with previous studies.

  14. Patient-specific Immune States before Surgery are Strong Correlates of Surgical Recovery

    Science.gov (United States)

    Fragiadakis, Gabriela K.; Gaudillière, Brice; Ganio, Edward A.; Aghaeepour, Nima; Tingle, Martha; Nolan, Garry P.; Angst, Martin S.

    2015-01-01

    Background Recovery after surgery is highly variable. Risk-stratifying patients based on their predicted recovery profile will afford individualized perioperative management strategies. Recently, application of mass cytometry in patients undergoing hip arthroplasty revealed strong immune correlates of surgical recovery in blood samples collected shortly after surgery. However, the ability to interrogate a patient’s immune state before surgery and predict recovery is highly desirable in perioperative medicine. Methods To evaluate a patient’s pre-surgical immune state, cell-type specific intracellular signaling responses to ex-vivo ligands (LPS, IL-6, IL-10, IL-2/GM-CSF) were quantified by mass cytometry in pre-surgical blood samples. Selected ligands modulate signaling processes perturbed by surgery. Twenty-three cell surface and 11 intracellular markers were used for the phenotypic and functional characterization of major immune cell subsets. Evoked immune responses were regressed against patient-centered outcomes contributing to protracted recovery including functional impairment, postoperative pain, and fatigue. Results Evoked signaling responses varied significantly and defined patient-specific pre-surgical immune states. Eighteen signaling responses correlated significantly with surgical recovery parameters (|R|=0.37–0.70; FDRpost-surgical samples. Conclusion Convergent findings in pre- and post-surgical analyses provide validation of reported immune correlates and suggest a critical role of the TLR4 signaling pathway in monocytes for the clinical recovery process. The comprehensive assessment of patients’ preoperative immune state is promising for predicting important recovery parameters and may lead to clinical tests using standard flow cytometry. PMID:26655308

  15. Patient experience in cystic fibrosis care: Development of a disease-specific questionnaire.

    Science.gov (United States)

    Stahl, Katja; Steinkamp, Gratiana; Ullrich, Gerald; Schulz, Wolfgang; van Koningsbruggen-Rietschel, Silke; Heuer, Hans-Eberhard; Ellemunter, Helmut; Schwarz, Carsten

    2015-06-01

    The aim of this study was to develop valid and reliable disease-specific questionnaires for adult patients with cystic fibrosis and for parents of minors with cystic fibrosis for assessing patient experience with cystic fibrosis care. The pilot versions of the questionnaires were developed based on a literature review, interviews with health professionals and focus groups. A postal survey with two reminders was conducted in 56 German cystic fibrosis centres recruiting 2874 participants. Psychometric evaluation was done via exploratory factor analysis and reliability and regression analysis. The questionnaires' ability to differentiate between subgroups and between cystic fibrosis centres was evaluated. Response rates were 74% for both adult patients and parents. Ten factors were extracted for both the adult and the parents' models (Cronbach's alpha between 0.6 and 0.9), explaining 50% and 48% of the variance, respectively. The factors organisation & access and the doctor-patient/parent-interaction had the highest relevance for a good overall care experience. The questionnaires were able to distinguish between different cystic fibrosis centres. The questionnaires are well suited for use in internal and external quality management of cystic fibrosis care due to their good psychometric properties, the ability to differentiate between centres and its practicability. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  16. Circulating interleukin-18: A specific biomarker for atherosclerosis-prone patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Nemoto Shinji

    2011-01-01

    Full Text Available Abstract Background Metabolic syndrome (MetS is associated with an increased risk of the development of atherosclerotic cardiovascular disease (CVD. Interleukin-18 (IL-18, which is a pleiotropic proinflammatory cytokine with important regulatory functions in the innate immune response system, plays a crucial role in vascular pathologies. IL-18 is also a predictor of cardiovascular death in patients with CVD and is involved in atherosclerotic plaque destabilization. Results In order to determine if circulating levels of IL-18 can serve as a specific biomarker for distinguishing MetS patients from pre-MetS subjects, we studied 78 patients with visceral fat deposition and 14 age-matched control subjects. Increased levels of IL-18 were observed more frequently in patients with MetS than in pre-MetS subjects and were positively associated with waist circumference. Serum levels of IL-18 were significantly reduced by a change in weight caused by lifestyle modifications. There was a significant interaction between waist circumference and serum IL-18 concentration. Weight loss of at least 5% of the body weight caused by lifestyle modification decreased IL-18 circulating levels relative to the reduction in waist circumference and blood pressure, suggesting that this degree of weight loss benefits the cardiovascular system. Conclusion IL-18 may be a useful biomarker of the clinical manifestations of MetS and for the management of the risk factors of CVD.

  17. The Effect of Femoral Cutting Guide Design Improvements for Patient-Specific Instruments

    Directory of Open Access Journals (Sweden)

    Oh-Ryong Kwon

    2015-01-01

    Full Text Available Although the application of patient-specific instruments (PSI for total knee arthroplasty (TKA increases the cost of the surgical procedure, PSI may reduce operative time and improve implant alignment, which could reduce the number of revision surgeries. We report our experience with TKA using PSI techniques in 120 patients from March to December 2014. PSI for TKA were created from data provided by computed tomography (CT scans or magnetic resonance imaging (MRI; which imaging technology is more reliable for the PSI technique remains unclear. In the first 20 patients, the accuracy of bone resection and PSI stability were compared between CT and MRI scans with presurgical results as a reference; MRI produced better results. In the second and third groups, each with 50 patients, the results of bone resection and stability were compared in MRI scans with respect to the quality of scanning due to motion artifacts and experienced know-how in PSI design, respectively. The optimized femoral cutting guide design for PSI showed the closest outcomes in bone resection and PSI stability with presurgical data. It is expected that this design could be a reasonable guideline in PSI.

  18. Pretreatment prostate specific antigen doubling time as prognostic factor in prostate cancer patients.

    Science.gov (United States)

    Zharinov, Gennady M; Bogomolov, Oleg A; Neklasova, Natalia N; Anisimov, Vladimir N

    2017-01-01

    Despite the prostate-specific antigen (PSA) serum level commonly uses as tumor marker in diagnosis of prostate cancer, it seems that PSA doubling time (PSADT) could be more useful indicator of tumor behavior and of prognosis for patients. The results of hormone and radiation therapy were evaluated for 912 prostate cancer having at least 2 PSA tests before the treatment was started. Clustering procedure (selection of homogenous group) was performed by using PSADT as the classification marker. The rate of PSADT was estimated for different dissemination rate, age, Gleasons's score and education level. PSADT index inversely correlated with the rate of prostate cancer dissemination, Gleason's score and the level of education were directly correlated with the age of patients. Survival time was longer and PSADT index was higher in "slow" tumor growing subgroups in local, local-advanced and metastatic prostate cancer patients than these in "fast" subgroups. The study confirmed the prognostic value of pretreatment PSADT in prostate cancer patients independently of cancer progression. No significant relationship exists between the authors and the companies/organizations whose products or services may be referenced in this article.

  19. Circulating interleukin-18: A specific biomarker for atherosclerosis-prone patients with metabolic syndrome.

    Science.gov (United States)

    Yamaoka-Tojo, Minako; Tojo, Taiki; Wakaume, Kazuki; Kameda, Ryo; Nemoto, Shinji; Takahira, Naonobu; Masuda, Takashi; Izumi, Tohru

    2011-01-20

    Metabolic syndrome (MetS) is associated with an increased risk of the development of atherosclerotic cardiovascular disease (CVD). Interleukin-18 (IL-18), which is a pleiotropic proinflammatory cytokine with important regulatory functions in the innate immune response system, plays a crucial role in vascular pathologies. IL-18 is also a predictor of cardiovascular death in patients with CVD and is involved in atherosclerotic plaque destabilization. In order to determine if circulating levels of IL-18 can serve as a specific biomarker for distinguishing MetS patients from pre-MetS subjects, we studied 78 patients with visceral fat deposition and 14 age-matched control subjects. Increased levels of IL-18 were observed more frequently in patients with MetS than in pre-MetS subjects and were positively associated with waist circumference. Serum levels of IL-18 were significantly reduced by a change in weight caused by lifestyle modifications. There was a significant interaction between waist circumference and serum IL-18 concentration. Weight loss of at least 5% of the body weight caused by lifestyle modification decreased IL-18 circulating levels relative to the reduction in waist circumference and blood pressure, suggesting that this degree of weight loss benefits the cardiovascular system. IL-18 may be a useful biomarker of the clinical manifestations of MetS and for the management of the risk factors of CVD.

  20. Bone-specific antibodies in sera from patients with celiac disease: characterization and implications in osteoporosis.

    Science.gov (United States)

    Sugai, Emilia; Cherñavsky, Alejandra; Pedreira, Silvia; Smecuol, Edgardo; Vazquez, Horacio; Niveloni, Sonia; Mazure, Roberto; Mauriro, Eduardo; Rabinovich, Gabriel A; Bai, Julio C

    2002-11-01

    Osteopenia and osteoporosis are well-known complications detected in celiac disease patients with still obscure pathogenesis. In the present study we investigated the presence of circulating anti-bone autoantibodies in patients with celiac disease and explored their role in the associated bone disease. We evaluated serum samples from 33 patients at the time of diagnosis and from 20 of them after treatment. Sera from patients with inflammatory bowel disease (n = 9), nonceliac osteoporotic (n = 18), and healthy individuals (n = 10) were used as controls. The presence of IgA specific anti-bone antibodies was first investigated using indirect immunofluorescence on cryosections of fetal rat tibia (20-day pregnancy). Furthermore, samples were homogenized and total tissue extracts were subjected to Western blot analysis to confirm immunoreactivity. At diagnosis, sera from 51.5% (17/33) of celiac patients had antibodies that recognized antigenic structures in chondrocytes and the extracellular matrix along mature cartilage, bone interface, and perichondrium of fetal rat bone. Among controls, only two osteoporotic patients showed very low titles of anti-bone autoantibodies. The immunostaining was localized in areas where an active mineralization process occurred and was similar to the distribution of the native bone tissue transglutaminase. The frequency of patients with positive baseline titers of anti-bone antibodies diminished significantly after treatment (P = 0.048). Western blot assays confirmed the presence of autoantibodies in sera from patients with a positive immunofluorescence staining. Autoantibodies recognized a major protein band on tissue extracts with a molecular weight of 77-80 kDa, which could be displaced when sera were preadsorbed with human recombinant tissue transglutaminase. We provide original evidence that patients with celiac disease have IgA-type circulating autoantibodies against intra- and extracellular structures of fetal rat tibia. Our

  1. Robust Affine Invariant Descriptors

    Directory of Open Access Journals (Sweden)

    Jianwei Yang

    2011-01-01

    Full Text Available An approach is developed for the extraction of affine invariant descriptors by cutting object into slices. Gray values associated with every pixel in each slice are summed up to construct affine invariant descriptors. As a result, these descriptors are very robust to additive noise. In order to establish slices of correspondence between an object and its affine transformed version, general contour (GC of the object is constructed by performing projection along lines with different polar angles. Consequently, affine in-variant division curves are derived. A slice is formed by points fall in the region enclosed by two adjacent division curves. To test and evaluate the proposed method, several experiments have been conducted. Experimental results show that the proposed method is very robust to noise.

  2. Robust AVS Audio Watermarking

    Science.gov (United States)

    Wang, Yong; Huang, Jiwu

    Part III of AVS(China Audio and Video Coding Standard) is the first standard for Hi-Fi audio proposed in China and is becoming more popular in some IT industries. For MP3 audio, some efforts have been made to solve the problems such as copyright pirating and malicious modifications by the way of watermarking. But till now little efforts have been made to solve the same problems for AVS audio. In this paper, we present a novel robust watermarking algorithm which can protect the AVS audio from the above problems. The watermark is embedded into the AVS compressed bit stream. At the extracting end, the watermark bits can be extracted from the compressed bit stream directly without any computation. This algorithm achieves robustness to decoding/recoding attacks, and low complexity of both embedding and extracting while preserves the quality of the audio signals.

  3. Robust Self Tuning Controllers

    DEFF Research Database (Denmark)

    Poulsen, Niels Kjølstad

    1985-01-01

    The present thesis concerns robustness properties of adaptive controllers. It is addressed to methods for robustifying self tuning controllers with respect to abrupt changes in the plant parameters. In the thesis an algorithm for estimating abruptly changing parameters is presented. The estimator...... has several operation modes and a detector for controlling the mode. A special self tuning controller has been developed to regulate plant with changing time delay....

  4. The Crane Robust Control

    Directory of Open Access Journals (Sweden)

    Marek Hicar

    2004-01-01

    Full Text Available The article is about a control design for complete structure of the crane: crab, bridge and crane uplift.The most important unknown parameters for simulations are burden weight and length of hanging rope. We will use robustcontrol for crab and bridge control to ensure adaptivity for burden weight and rope length. Robust control will be designed for current control of the crab and bridge, necessary is to know the range of unknown parameters. Whole robust will be splitto subintervals and after correct identification of unknown parameters the most suitable robust controllers will be chosen.The most important condition at the crab and bridge motion is avoiding from burden swinging in the final position. Crab and bridge drive is designed by asynchronous motor fed from frequency converter. We will use crane uplift with burden weightobserver in combination for uplift, crab and bridge drive with cooperation of their parameters: burden weight, rope length and crab and bridge position. Controllers are designed by state control method. We will use preferably a disturbance observerwhich will identify burden weight as a disturbance. The system will be working in both modes at empty hook as well asat maximum load: burden uplifting and dropping down.

  5. Aberrant allele-specific replication, independent of parental origin, in blood cells of cancer patients

    Directory of Open Access Journals (Sweden)

    Ramon Jacob

    2008-12-01

    Full Text Available Abstract Background Allelic counterparts of biallelically expressed genes display an epigenetic symmetry normally manifested by synchronous replication, different from genes subjected to monoallelic expression, which normally are characterized by an asynchronous mode of replication (well exemplified by the SNRPN imprinted locus. Malignancy was documented to be associated with gross modifications in the inherent replication-timing coordination between allelic counterparts of imprinted genes as well as of biallelically expressed loci. The cancer-related allelic replication timing aberrations are non-disease specific and appear in peripheral blood cells of cancer patients, including those with solid tumors. As such they offer potential blood markers for non-invasive cancer test. The present study was aimed to gain some insight into the mechanism leading to the replication timing alterations of genes in blood lymphocytes of cancer patients. Methods Peripheral blood samples derived from patients with prostate cancer were chosen to represent the cancerous status, and samples taken from patients with no cancer but with benign prostate hyperplasia were used to portray the normal status. Fluorescence In Situ Hybridization (FISH replication assay, applied to phytohemagglutinin (PHA-stimulated blood lymphocytes, was used to evaluate the temporal order (either synchronous or asynchronous of genes in the patients' cells. Results We demonstrated that: (i the aberrant epigenetic profile, as delineated by the cancer status, is a reversible modification, evidenced by our ability to restore the normal patterns of replication in three unrelated loci (CEN15, SNRPN and RB1 by introducing an archetypical demethylating agent, 5-azacytidine; (ii following the rehabilitating effect of demethylation, an imprinted gene (SNRPN retains its original parental imprint; and (iii the choice of an allele between early or late replication in the aberrant asynchronous replication

  6. Predictors of psychological distress in patients starting IVF treatment: infertility-specific versus general psychological characteristics.

    Science.gov (United States)

    Van den Broeck, Uschi; D'Hooghe, Thomas; Enzlin, Paul; Demyttenaere, Koen

    2010-06-01

    The distress that couples experience in IVF treatment is well-documented though research exploring factors that might contribute to the distress is scarce and the role of infertility-specific versus more general psychological characteristics in predicting psychological distress remains unexplored. This exploratory study aimed to describe, explore and test a self-constructed conceptual framework designed to understand the relative impact of infertility-specific and general psychological characteristics, in predicting psychological distress. Validated self-report questionnaires that measured the concepts of the encompassing framework (personality characteristics self-criticism and dependency, attachment in the partner relationship, child wish, coping, intrusiveness, infertility-related stress and general psychological distress) were completed by 106 women and 102 men before starting the first IVF/ICSI treatment at a university hospital-based fertility centre. Data were analysed by hierarchical multivariate linear regression analysis and path analysis. The overall conceptual psychological framework explained 55% of the variance in psychological distress. The strongest predictors of psychological distress were general psychological characteristics: passive and active coping, self-criticism and dependency and intrusiveness. A path analysis confirmed the framework and highlighted the mediating role of coping and intrusiveness. In the final analysis, none of the infertility-specific variables significantly predicted psychological distress. The current study of patients starting IVF-treatment demonstrated that general psychological characteristics, specifically active and passive coping, personality characteristics, dependency and self-criticism and intrusiveness, are more important in predicting the variability in psychological distress than infertility-specific concerns. The results raise important questions for infertility counselling. However, the cross

  7. Robust synthesis for real-time systems

    DEFF Research Database (Denmark)

    Larsen, Kim Guldstrand; Legay, Axel; Traonouez, Louis-Marie

    2014-01-01

    specification to an implementation, we need to reason about the possibility to effectively implement the theoretical specifications on physical systems, despite their limited precision. In the literature, this implementation problem has been linked to the robustness problem that analyzes the consequences......Specification theories for real-time systems allow reasoning about interfaces and their implementation models, using a set of operators that includes satisfaction, refinement, logical and parallel composition. To make such theories applicable throughout the entire design process from an abstract...

  8. Parametric model of human body shape and ligaments for patient-specific epidural simulation.

    Science.gov (United States)

    Vaughan, Neil; Dubey, Venketesh N; Wee, Michael Y K; Isaacs, Richard

    2014-10-01

    This work is to build upon the concept of matching a person's weight, height and age to their overall body shape to create an adjustable three-dimensional model. A versatile and accurate predictor of body size and shape and ligament thickness is required to improve simulation for medical procedures. A model which is adjustable for any size, shape, body mass, age or height would provide ability to simulate procedures on patients of various body compositions. Three methods are provided for estimating body circumferences and ligament thicknesses for each patient. The first method is using empirical relations from body shape and size. The second method is to load a dataset from a magnetic resonance imaging (MRI) scan or ultrasound scan containing accurate ligament measurements. The third method is a developed artificial neural network (ANN) which uses MRI dataset as a training set and improves accuracy using error back-propagation, which learns to increase accuracy as more patient data is added. The ANN is trained and tested with clinical data from 23,088 patients. The ANN can predict subscapular skinfold thickness within 3.54 mm, waist circumference 3.92 cm, thigh circumference 2.00 cm, arm circumference 1.21 cm, calf circumference 1.40 cm, triceps skinfold thickness 3.43 mm. Alternative regression analysis method gave overall slightly less accurate predictions for subscapular skinfold thickness within 3.75 mm, waist circumference 3.84 cm, thigh circumference 2.16 cm, arm circumference 1.34 cm, calf circumference 1.46 cm, triceps skinfold thickness 3.89 mm. These calculations are used to display a 3D graphics model of the patient's body shape using OpenGL and adjusted by 3D mesh deformations. A patient-specific epidural simulator is presented using the developed body shape model, able to simulate needle insertion procedures on a 3D model of any patient size and shape. The developed ANN gave the most accurate results for body shape, size and ligament thickness. The

  9. HIT'nDRIVE: patient-specific multidriver gene prioritization for precision oncology.

    Science.gov (United States)

    Shrestha, Raunak; Hodzic, Ermin; Sauerwald, Thomas; Dao, Phuong; Wang, Kendric; Yeung, Jake; Anderson, Shawn; Vandin, Fabio; Haffari, Gholamreza; Collins, Colin C; Sahinalp, S Cenk

    2017-09-01

    Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the "random walk facility location" (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: "multihitting time," the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene. When applied to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver genes. We also demonstrated that it is possible to perform accurate phenotype prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interaction networks. In addition, we identified a number of breast cancer subtype-specific driver modules that are associated with patients' survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer cell lines, accurately predicted drug efficacy using the driver genes and their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize massive multiomics data in therapeutic decision making, enabling widespread implementation of precision oncology. © 2017 Shrestha et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Just-in-time Design and Additive Manufacture of Patient-specific Medical Implants

    Science.gov (United States)

    Shidid, Darpan; Leary, Martin; Choong, Peter; Brandt, Milan

    Recent advances in medical imaging and manufacturing science have enabled the design and production of complex, patient-specific orthopaedic implants. Additive Manufacture (AM) generates three-dimensional structures layer by layer, and is not subject to the constraints associated with traditional manufacturing methods. AM provides significant opportunities for the design of novel geometries and complex lattice structures with enhanced functional performance. However, the design and manufacture of patient-specific AM implant structures requires unique expertise in handling various optimization platforms. Furthermore, the design process for complex structures is computationally intensive. The primary aim of this research is to enable the just-in-time customisation of AM prosthesis; whereby AM implant design and manufacture be completed within the time constraints of a single surgical procedure, while minimising prosthesis mass and optimising the lattice structure to match the stiffness of the surrounding bone tissue. In this research, a design approach using raw CT scan data is applied to the AM manufacture of femoral prosthesis. Using the proposed just-in-time concept, the mass of the prosthesis was rapidly designed and manufactured while satisfying the associated structural requirements. Compressive testing of lattice structures manufactured using proposed method shows that the load carrying capacity of the resected composite bone can be recovered by up to 85% and the compressive stiffness of the AM prosthesis is statistically indistinguishable from the stiffness of the initial bone.

  11. Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

    Science.gov (United States)

    Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

    2016-12-01

    Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

  12. Manufacture of patient-specific vascular replicas for endovascular simulation using fast, low-cost method

    Science.gov (United States)

    Kaneko, Naoki; Mashiko, Toshihiro; Ohnishi, Taihei; Ohta, Makoto; Namba, Katsunari; Watanabe, Eiju; Kawai, Kensuke

    2016-12-01

    Patient-specific vascular replicas are essential to the simulation of endovascular treatment or for vascular research. The inside of silicone replica is required to be smooth for manipulating interventional devices without resistance. In this report, we demonstrate the fabrication of patient-specific silicone vessels with a low-cost desktop 3D printer. We show that the surface of an acrylonitrile butadiene styrene (ABS) model printed by the 3D printer can be smoothed by a single dipping in ABS solvent in a time-dependent manner, where a short dip has less effect on the shape of the model. The vascular mold is coated with transparent silicone and then the ABS mold is dissolved after the silicone is cured. Interventional devices can pass through the inside of the smoothed silicone vessel with lower pushing force compared to the vessel without smoothing. The material cost and time required to fabricate the silicone vessel is about USD $2 and 24 h, which is much lower than the current fabrication methods. This fast and low-cost method offers the possibility of testing strategies before attempting particularly difficult cases, while improving the training of endovascular therapy, enabling the trialing of new devices, and broadening the scope of vascular research.

  13. Generation and performance of patient-specific forward models for breast imaging with EIT

    Science.gov (United States)

    Tizzard, A.; Borsic, A.; Halter, R.; Bayford, R.

    2010-04-01

    It has now been well established that accurate geometric conformity of the forward model for EIT reconstruction has significant benefits for artefact reduction and localisation of conductivity changes within the domain. The problems of generation of patient specific forward models need to be addressed as segmentation of volumetric data from CT or MRI is inadequate for time-critical clinical use. This group has pioneered methods of generating patient-specific surface models from known landmarks and electrode positions and have used this data to warp finite element models for EIT reconstruction. This paper presents a further application of these methods to use known electrode positions for breast imaging to generate an accurate B-Spline surface model of a subject and to warp an existing finite element model to the surface using elastic deformation. Results will show that a forward model can be generated, conforming more realistically to actual subject geometry, that will further enhance the performance of the reconstruction algorithm offering significant benefits to clinical EIT breast imaging.

  14. Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis.

    Science.gov (United States)

    Mimura, Tatsuya; Yamagami, Satoru; Noma, Hidetaka; Kamei, Yuko; Goto, Mari; Kondo, Aki; Matsubara, Masao

    2015-03-01

    Allergy to hydrolyzed wheat protein in facial soap has become a major social issue in Japan. It has been reported that the most frequent early symptoms of allergy to hydrolyzed wheat protein in soap are allergic conjunctivitis and rhinitis, while wheat-dependent exercise-induced anaphylaxis can be induced by long-term use. We evaluated the relation between tear fluid levels of specific IgE for wheat and the features of allergic conjunctivitis. A prospective, non-randomized, cross-sectional study was conducted in 103 patients with moderate to severe allergic conjunctivitis (allergic group) and 20 age- and sex-matched healthy control subjects (control group). Specific IgE for wheat was measured in tear fluid with an immunochromatography assay, and a skin prick test (SPT) was also performed. Symptoms (sneezing, rhinorrhea, nasal obstruction, ocular itching, and lacrimation) were assessed in each subject along with the activities of daily living (ADL) score and the total ocular symptom score for allergic conjunctivitis. A severity score (0, 1, 2, or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions associated with allergic conjunctivitis. The IgE positive rate and specific IgE score were both higher in the allergic group than in the control group (71.8% versus 40.0% and 1.9 ± 0.7 versus 1.4 ± 0.5). A positive SPT for wheat was also more frequent in the allergic group than in the control group (6.8% versus 0.0%). Within the allergic group, patients with a positive SPT had higher specific IgE scores than patients with a negative SPT (3.3 ± 0.5 versus 1.8 ± 0.6, p conjunctivitis symptoms, including ocular itching (r = 0.665), tearing (r = 0.672), and the total ocular symptom score (r = 0.204). Wheat IgE in tear fluid was also correlated with the severity of rhinitis symptoms, including sneezing (r = 0.610), nose blowing (r = 0.640), and nasal obstruction (r = 0.677). Furthermore, the tear fluid wheat

  15. Generation of disease-specific induced pluripotent stem cells from patients with rheumatoid arthritis and osteoarthritis.

    Science.gov (United States)

    Lee, Jaecheol; Kim, Youngkyun; Yi, Hyoju; Diecke, Sebastian; Kim, Juryun; Jung, Hyerin; Rim, Yeri Alice; Jung, Seung Min; Kim, Myungshin; Kim, Yong Goo; Park, Sung-Hwan; Kim, Ho-Youn; Ju, Ji Hyeon

    2014-02-04

    Since the concept of reprogramming mature somatic cells to generate induced pluripotent stem cells (iPSCs) was demonstrated in 2006, iPSCs have become a potential substitute for embryonic stem cells (ESCs) given their pluripotency and "stemness" characteristics, which resemble those of ESCs. We investigated to reprogram fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) to generate iPSCs using a 4-in-1 lentiviral vector system. A 4-in-1 lentiviral vector containing Oct4, Sox2, Klf4, and c-Myc was transduced into RA and OA FLSs isolated from the synovia of two RA patients and two OA patients. Immunohistochemical staining and real-time PCR studies were performed to demonstrate the pluripotency of iPSCs. Chromosomal abnormalities were determined based on the karyotype. SCID-beige mice were injected with iPSCs and sacrificed to test for teratoma formation. After 14 days of transduction using the 4-in-1 lentiviral vector, RA FLSs and OA FLSs were transformed into spherical shapes that resembled embryonic stem cell colonies. Colonies were picked and cultivated on matrigel plates to produce iPSC lines. Real-time PCR of RA and OA iPSCs detected positive markers of pluripotency. Immunohistochemical staining tests with Nanog, Oct4, Sox2, Tra-1-80, Tra-1-60, and SSEA-4 were also positive. Teratomas that comprised three compartments of ectoderm, mesoderm, and endoderm were formed at the injection sites of iPSCs. Established iPSCs were shown to be compatible by karyotyping. Finally, we confirmed that the patient-derived iPSCs were able to differentiate into osteoblast, which was shown by an osteoimage mineralization assay. FLSs derived from RA and OA could be cell resources for iPSC reprogramming. Disease- and patient-specific iPSCs have the potential to be applied in clinical settings as source materials for molecular diagnosis and regenerative therapy.

  16. Relationship of specific MRI findings to treatment outcomes in patients receiving transforaminal epidural steroid injections

    Energy Technology Data Exchange (ETDEWEB)

    Lechmann, Marco; Rosskopf, Andrea; Ehrmann, Christine; Sutter, Reto; Pfirrmann, Christian W.A.; Peterson, Cynthia K. [University of Zuerich, Department of Radiology, Orthopaedic University Hospital Balgrist, Zuerich (Switzerland)

    2016-12-15

    To determine whether specific MRI findings are related to outcomes after lumbar transforaminal epidural steroid injections (TFESI) and to assess the inter-rater reliability of imaging diagnosis. A prospective outcomes study on 156 consecutive patients with 1-month follow-up outcomes data and MRI within 3 months of TFESI was conducted. Pain levels (numerical rating scale) (NRS) were recorded prior to injection. Overall 'improvement' was determined using the Patients Global Impression of Change (PGIC) scale and NRS data were collected at three time points post injection. Two radiologists independently evaluated all images blinded to treatment outcome for reliability of diagnosis. The Chi-square test compared MRI findings for the senior radiologist to 'improvement'. NRS change scores were compared to MRI findings with the unpaired t-test or ANOVA. Kappa and percent agreement assessed inter-rater agreement of diagnosis. The only abnormality linked to 'improvement' (p = 0.03) and higher NRS change scores (p = 0.0001) at 1 month was the disc herniation morphology 'protrusion + sequestration'. Patients with degeneration by osteophytes (p = 0.034), grade 3 foraminal nerve root compression (p = 0.01) and foraminal/extraforaminal location of herniation (p = 0.014) also had higher 1 month NRS change scores. Reliability of diagnosis was 'fair' to 'substantial' depending on MRI findings. Patients with disc protrusion plus sequestration were significantly more likely to report overall improvement and more pain reduction at 1 month. Higher pain reduction was noted in patients with degeneration by osteophytes, grade 3 foraminal nerve root compression, or foraminal/extraforaminal disc herniation location. (orig.)

  17. Template of patient-specific summaries facilitates education and outcomes in paediatric cardiac surgery units.

    Science.gov (United States)

    Agarwal, Hemant S; Wolfram, Karen B; Slayton, Jennifer M; Saville, Benjamin R; Cutrer, William B; Bichell, David P; Harris, Zena L; Barr, Frederick E; Deshpande, Jayant K

    2013-10-01

    Few educational opportunities exist in paediatric cardiac critical care units (PCCUs). We introduced a new educational activity in the PCCU in the form of of patient-specific summaries (TPSS). Our objective was to study the role of TPSS in the provision of a positive learning experience to the multidisciplinary clinical team of PCCUs and in improving patient-related clinical outcomes in the PCCU. Prospective educational intervention with simultaneous clinical assessment was undertaken in PCCU in an academic children's hospital. TPSS was developed utilizing the case presentation format for upcoming week's surgical cases and delivered once every week to each PCCU clinical team member. Role of TPSS to provide clinical education was assessed using five-point Likert-style scale responses in an anonymous survey 1 year after TPSS provision. Paediatric cardiac surgery patients admitted to the PCCU were evaluated for postoperative outcomes for TPSS provision period of 1 year and compared with a preintervention period of 1 year. TPSS was delivered to 259 clinical team members including faculty, fellows, residents, nurse practitioners, nurses, respiratory therapists and others from the Divisions of Anesthesia, Cardiology, Cardio-Thoracic Surgery, Critical Care, and Pediatrics working in the PCCU. Two hundred and twenty-four (86%) members responded to the survey and assessed the role of TPSS in providing clinical education to be excellent based on mean Likert-style scores of 4.32 ± 0.71 in survey responses. Seven hundred patients were studied for the two time periods and there were no differences in patient demographics, complexity of cardiac defect and surgical details. The length of mechanical ventilation for the TPSS period (57.08 ± 141.44 h) was significantly less when compared with preintervention period (117.39 ± 433.81 h) (P education to multidisciplinary clinical teams and may be associated with improved clinical outcome.

  18. Postmyocarditis ventricular tachycardia in patients with epicardial-only scar: a specific entity requiring a specific approach.

    Science.gov (United States)

    Berte, Benjamin; Sacher, Frederic; Cochet, Hubert; Mahida, Saagar; Yamashita, Seigo; Lim, Han; Denis, Arnaud; Derval, Nicolas; Hocini, Mélèze; Haïssaguerre, Michel; Jaïs, Pierre

    2015-01-01

    Nonischemic cardiomyopathy is a heterogeneous condition providing a favorable substrate for ventricular tachycardia (VT). The purpose of this study is to further characterize the substrate in a subset of postmyocarditis patients with epicardial-only scar. Twelve postmyocarditis patients (11 male, 49 ± 14 years, left ventricular ejection fraction 49 ± 12%) with VT and epicardial-only scar were included for analysis comparing automatic high-amplitude normal activity (HANA) maps to manually adjusted maps of based on local abnormal ventricular activity (LAVA) electrograms when present. A combined endocardial (endo) and epicardial (epi) approach was used in 11/12 with usual bipolar/unipolar voltage thresholds and analyzed using image integration. A delayed enhancement MRI scar area of 52 cm(2) (38, 59) and multidetector CT wall thinning area of 18 cm(2) (14, 35) was found. Bipolar voltage substrate mapping (160 points [101, 239] endo, 553 points [232, 713] epi and LAVA were found only epicardially [443 LAVA points] in all) illustrated a low-voltage area of HANA: 1 cm(2) (0, 10) endo, 25 cm(2) (22, 39) epi and LAVA: 1 cm(2) (0, 10) endo, 39 cm(2) (28, 51) epi. Manual maps performed better than automatic maps for delineating low-voltage area with a higher overlap with scar area on delayed enhancement magnetic resonance imaging (DE-MRI; 76% [66, 94] vs. 45% [35, 62]; P = 0.04). In addition, manual voltage maps also showed a higher overlap with location of LAVA (LAVA in normal voltage area: 3% [0, 9] vs. 35% [32, 41]; P scar, automatic voltage mapping may miss or minimize the electrical VT substrate. DE-MRI and manual LAVA-based voltage mapping are necessary to optimize scar delineation. Epicardial access is critical for mapping and ablation in this condition. © 2014 Wiley Periodicals, Inc.

  19. Machine learning-based patient specific prompt-gamma dose monitoring in proton therapy.

    Science.gov (United States)

    Gueth, P; Dauvergne, D; Freud, N; Létang, J M; Ray, C; Testa, E; Sarrut, D

    2013-07-07

    Online dose monitoring in proton therapy is currently being investigated with prompt-gamma (PG) devices. PG emission was shown to be correlated with dose deposition. This relationship is mostly unknown under real conditions. We propose a machine learning approach based on simulations to create optimized treatment-specific classifiers that detect discrepancies between planned and delivered dose. Simulations were performed with the Monte-Carlo platform Gate/Geant4 for a spot-scanning proton therapy treatment and a PG camera prototype currently under investigation. The method first builds a learning set of perturbed situations corresponding to a range of patient translation. This set is then used to train a combined classifier using distal falloff and registered correlation measures. Classifier performances were evaluated using receiver operating characteristic curves and maximum associated specificity and sensitivity. A leave-one-out study showed that it is possible to detect discrepancies of 5 mm with specificity and sensitivity of 85% whereas using only distal falloff decreases the sensitivity down to 77% on the same data set. The proposed method could help to evaluate performance and to optimize the design of PG monitoring devices. It is generic: other learning sets of deviations, other measures and other types of classifiers could be studied to potentially reach better performance. At the moment, the main limitation lies in the computation time needed to perform the simulations.

  20. Evolution of design considerations in complex craniofacial reconstruction using patient-specific implants.

    Science.gov (United States)

    Peel, Sean; Bhatia, Satyajeet; Eggbeer, Dominic; Morris, Daniel S; Hayhurst, Caroline

    2017-06-01

    Previously published evidence has established major clinical benefits from using computer-aided design, computer-aided manufacturing, and additive manufacturing to produce patient-specific devices. These include cutting guides, drilling guides, positioning guides, and implants. However, custom devices produced using these methods are still not in routine use, particularly by the UK National Health Service. Oft-cited reasons for this slow uptake include the following: a higher up-front cost than conventionally fabricated devices, material-choice uncertainty, and a lack of long-term follow-up due to their relatively recent introduction. This article identifies a further gap in current knowledge - that of design rules, or key specification considerations for complex computer-aided design/computer-aided manufacturing/additive manufacturing devices. This research begins to address the gap by combining a detailed review of the literature with first-hand experience of interdisciplinary collaboration on five craniofacial patient case studies. In each patient case, bony lesions in the orbito-temporal region were segmented, excised, and reconstructed in the virtual environment. Three cases translated these digital plans into theatre via polymer surgical guides. Four cases utilised additive manufacturing to fabricate titanium implants. One implant was machined from polyether ether ketone. From the literature, articles with relevant abstracts were analysed to extract design considerations. In all, 19 frequently recurring design considerations were extracted from previous publications. Nine new design considerations were extracted from the case studies - on the basis of subjective clinical evaluation. These were synthesised to produce a design considerations framework to assist clinicians with prescribing and design engineers with modelling. Promising avenues for further research are proposed.

  1. Towards Effective and Efficient Patient-Specific Quality Assurance for Spot Scanning Proton Therapy

    Directory of Open Access Journals (Sweden)

    X. Ronald. Zhu

    2015-04-01

    Full Text Available An intensity-modulated proton therapy (IMPT patient-specific quality assurance (PSQA program based on measurement alone can be very time consuming due to the highly modulated dose distributions of IMPT fields. Incorporating independent dose calculation and treatment log file analysis could reduce the time required for measurements. In this article, we summarize our effort to develop an efficient and effective PSQA program that consists of three components: measurements, independent dose calculation, and analysis of patient-specific treatment delivery log files. Measurements included two-dimensional (2D measurements using an ionization chamber array detector for each field delivered at the planned gantry angles with the electronic medical record (EMR system in the QA mode and the accelerator control system (ACS in the treatment mode, and additional measurements at depths for each field with the ACS in physics mode and without the EMR system. Dose distributions for each field in a water phantom were calculated independently using a recently developed in-house pencil beam algorithm and compared with those obtained using the treatment planning system (TPS. The treatment log file for each field was analyzed in terms of deviations in delivered spot positions from their planned positions using various statistical methods. Using this improved PSQA program, we were able to verify the integrity of the data transfer from the TPS to the EMR to the ACS, the dose calculation of the TPS, and the treatment delivery, including the dose delivered and spot positions. On the basis of this experience, we estimate that the in-room measurement time required for each complex IMPT case (e.g., a patient receiving bilateral IMPT for head and neck cancer is less than 1 h using the improved PSQA program. Our experience demonstrates that it is possible to develop an efficient and effective PSQA program for IMPT with the equipment and resources available in the clinic.

  2. Nationwide population-based study of cause-specific death rates in patients with psoriasis

    DEFF Research Database (Denmark)

    Salahadeen, E.; Torp-Pedersen, Christian; Gislason, G.

    2015-01-01

    BACKGROUND: Psoriasis is a common chronic disease, mediated by type 1 and 17 helper T cell-driven inflammation. Epidemiological studies have demonstrated a wide range of comorbidities and increased mortality rates. However, the current evidence on psoriasis-related mortality is limited...... and nationwide data have not been presented previously. METHODS: In a nationwide population-based cohort we evaluated all-cause and cause-specific death rates in patients with psoriasis as compared to the general population. RESULTS: The entire Danish population aged 18 and above, corresponding to a total of 5......,458,627 individuals (50.7% female, 40.9 years ± 19.7), including 94,069 with mild psoriasis (53% female, 42.0 ± 17.0 years) and 28,253 with severe psoriasis (53.4% female, 43.0 ± 16.5 years), was included. A total of 884,661 deaths were recorded, including 10 916 in patients with mild psoriasis and 3699 in patients...

  3. Exome sequencing reveals a potential mutational trajectory and treatments for a specific pancreatic cancer patient

    Directory of Open Access Journals (Sweden)

    Cotterell J

    2014-05-01

    Full Text Available James Cotterell1,21Center for Genomic Regulation, Barcelona, Spain; 2Garvan Institute for Medical Research, Sydney, NSW, AustraliaAbstract: Pancreatic cancer is the fourth biggest killer, and has one of the worst prognoses, of any cancer type. Approximately 95% of patients diagnosed with pancreatic cancer will not survive beyond 5 years post diagnosis, and these statistics have barely improved in over 40 years. Here, genomic changes in one particular patient with stage IV metastatic pancreatic cancer were explored to suggest a potential personalized treatment. In particular, exome sequencing of genomic DNA extracted from blood and the cancer biopsy was utilized with the aim of identifying mutational drivers of the cancer. This analysis revealed a splice site mutation in RBCK1 as the most promising driver of the cancer and a therapy based on a pan-cyclin-dependent kinase (pan-CDK inhibitor, flavopiridol. This study suggests that drugs whose effectiveness is unclear for general populations of cancer sufferers should possibly be reconsidered for specific patients where the drug could be rationally argued to improve outcome.Keyword: personalized medicine, driver mutation identification, next generation sequencing

  4. Development of patient-specific molecular imaging phantoms using a 3D printer.

    Science.gov (United States)

    Gear, J I; Long, C; Rushforth, D; Chittenden, S J; Cummings, C; Flux, G D

    2014-08-01

    The aim of the study was to investigate rapid prototyping technology for the production of patient-specific, cost-effective liquid fillable phantoms directly from patient CT data. Liver, spleen, and kidney volumes were segmented from patient CT data. Each organ was converted to a shell and filling holes and leg supports were added using computer aided design software and prepared for printing. Additional fixtures were added to the liver to allow lesion inserts to be fixed within the structure. Phantoms were printed from an ultraviolet curable photopolymer using polyjet technology on an Objet EDEN 500V 3D printer. The final print material is a clear solid acrylic plastic which is watertight, rigid, and sufficiently durable to withstand multiple assembly and scanning protocols. Initial scans of the phantoms have been performed with Tc-99m SPECT and F-18 PET/CT. The organ geometry showed good correspondence with anatomical references. The methodology developed can be generally applied to other anatomical or geometrical phantoms for molecular imaging.

  5. Cardiopulmonary Exercise Testing in Patients with Heart Failure with Specific Comorbidities.

    Science.gov (United States)

    Piepoli, Massimo F; Corrà, Ugo; Agostoni, Piergiuseppe

    2017-07-01

    Exercise capacity is one of the most powerful predicting factors of life expectancy, both in patients with and those without cardiac disease. Cardiopulmonary exercise testing provides a global assessment of the integrative exercise responses involving the pulmonary, cardiovascular, hematopoietic, neuropsychological, and skeletal muscle systems, which are not adequately reflected through the measurement of individual organ system function. This relatively noninvasive, dynamic, physiologic overview allows the evaluation of both submaximal and peak exercise responses, providing the physician with relevant information for clinical decision-making. Chronic heart failure is a significant cause of worldwide mortality and morbidity, whose clinical picture is characterized by exercise intolerance and impaired quality of life. The purpose of this review is to provide an update of the role of cardiopulmonary exercise testing in patients with heart failure with specific comorbidities. Patients with heart failure frequently present concomitant clinical conditions, such as obesity, anemia, lung or kidney disease, diabetes mellitus, cancer, depression, and psychogenic disorders, which could affect length and quality of life, including everyday activities and exercise performance. Poor effort and malingering may be suspected when early discontinuation of the exercise test with irregular breathing occurs.

  6. Recent advancements in medical simulation: patient-specific virtual reality simulation.

    Science.gov (United States)

    Willaert, Willem I M; Aggarwal, Rajesh; Van Herzeele, Isabelle; Cheshire, Nicholas J; Vermassen, Frank E

    2012-07-01

    Patient-specific virtual reality simulation (PSVR) is a new technological advancement that allows practice of upcoming real operations and complements the established role of VR simulation as a generic training tool. This review describes current developments in PSVR and draws parallels with other high-stake industries, such as aviation, military, and sports. A review of the literature was performed using PubMed and Internet search engines to retrieve data relevant to PSVR in medicine. All reports pertaining to PSVR were included. Reports on simulators that did not incorporate a haptic interface device were excluded from the review. Fifteen reports described 12 simulators that enabled PSVR. Medical procedures in the field of laparoscopy, vascular surgery, orthopedics, neurosurgery, and plastic surgery were included. In all cases, source data was two-dimensional CT or MRI data. Face validity was most commonly reported. Only one (vascular) simulator had undergone face, content, and construct validity. Of the 12 simulators, 1 is commercialized and 11 are prototypes. Five simulators have been used in conjunction with real patient procedures. PSVR is a promising technological advance within medicine. The majority of simulators are still in the prototype phase. As further developments unfold, the validity of PSVR will have to be examined much like generic VR simulation for training purposes. Nonetheless, similar to the aviation, military, and sport industries, operative performance and patient safety may be enhanced by the application of this novel technology.

  7. Specific IgG antibodies in sera in patients with penicillin allergy.

    Science.gov (United States)

    Qiao, Hai-Ling; Gao, Na; Jia, Lin-Jing; Yang, Jing; Tian, Xin

    2009-06-01

    The role of IgG antibodies in inducing or modifying allergic reaction has not been sufficiently clarified. The objective of this investigation is to elucidate the relationship between IgG antibodies and penicillin allergy, between IgG and IgE antibodies in allergic patients. Enzyme-linked immunosorbent assay and Radioallergosorbent test were used to examine eight kinds of specific IgG and IgE antibodies, including major antigenic determinants: benzylpenicilloyl (BPO), ampicilloyl (APO), amoxicilloyl (AXO) and phenoxomethylpenicilloyl (PVO), and minor antigenic determinants: benzylpenicillanyl (BPA), ampicillanyl (APA), amoxicillanyl (AXA) and phenoxomethylpenicillany (PVA), in the sera of 249 patients with penicillin allergy. Except BPA-IgG, seven kinds of antigenic determinants IgG antibodies levels were significantly higher than that of control group (P penicillin administration when skin tests were negative was significantly higher than that of patients with positive skin test (P penicillin allergy with negative skin test and IgG antibodies to major antigenic determinants probably play a more important role in the process of allergic reaction.

  8. Influence of foot ulceration on cause-specific mortality in patients with diabetes mellitus.

    Science.gov (United States)

    Brownrigg, Jack R W; Griffin, Michelle; Hughes, Cian O; Jones, Keith G; Patel, Natasha; Thompson, Matthew M; Hinchliffe, Robert J

    2014-10-01

    The purpose of this study was to assess the odds of all-cause mortality in individuals with diabetic foot ulceration (DFU) compared with those with diabetes and no history of DFU. In addition, we sought to determine the strength of association of DFU with cardiovascular and nonvascular mortality. We obtained data for a cohort of patients who attended a secondary care diabetic foot clinic or a general diabetes clinic between 2009 and 2010. A clinic cohort of patients with diabetes and no history of DFU provided a control group. Cause-specific mortality was recorded during a median follow-up duration of 3.6 years (interquartile range, 3.3-4.2 years). The association between DFU and all-cause mortality was evaluated by Cox regression. The association between DFU and cardiovascular mortality was determined by competing risk modeling. We recorded 145 events of all-cause mortality and 27 events of cardiovascular mortality among 869 patients with diabetes. After adjustment for potential confounders, DFU was associated with both cardiovascular disease (hazard ratio, 2.53; 95% confidence interval, 0.98-6.49; P = .05) and all-cause mortality (hazard ratio, 3.98; 95% confidence interval, 2.55-6.21; P diabetes only and 19% with DFU; P = .91). DFU is associated with premature death from vascular and nonvascular causes. Copyright © 2014 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  9. Evaluation of Dosimetry Check software for IMRT patient-specific quality assurance.

    Science.gov (United States)

    Narayanasamy, Ganesh; Zalman, Travis; Ha, Chul S; Papanikolaou, Niko; Stathakis, Sotirios

    2015-05-08

    The purpose of this study is to evaluate the use of the Dosimetry Check system for patient-specific IMRT QA. Typical QA methods measure the dose in an array dosimeter surrounded by homogenous medium for which the treatment plan has been recomputed. With the Dosimetry Check system, fluence measurements acquired on a portal dosimeter is applied to the patient's CT scans. Instead of making dose comparisons in a plane, Dosimetry Check system produces isodose lines and dose-volume histograms based on the planning CT images. By exporting the dose distribution from the treatment planning system into the Dosimetry Check system, one is able to make a direct comparison between the calculated dose and the planned dose. The versatility of the software is evaluated with respect to the two IMRT techniques - step and shoot and volumetric arc therapy. The system analyzed measurements made using EPID, PTW seven29, and IBA MatriXX, and an intercomparison study was performed. Plans from patients previously treated at our institution with treated anatomical site on brain, head & neck, liver, lung, and prostate were analyzed using Dosimetry Check system for any anatomical site dependence. We have recommendations and possible precautions that may be necessary to ensure proper QA with the Dosimetry Check system.

  10. A priori patient-specific collision avoidance in radiotherapy using consumer grade depth cameras.

    Science.gov (United States)

    Cardan, Rex A; Popple, Richard A; Fiveash, John

    2017-07-01

    In this study, we demonstrate and evaluate a low cost, fast, and accurate avoidance framework for radiotherapy treatments. Furthermore, we provide an implementation which is patient specific and can be implemented during the normal simulation process. Four patients and a treatment unit were scanned with a set of consumer depth cameras to create a polygon mesh of each object. Using a fast polygon interference algorithm, the models were virtually collided to map out feasible treatment positions of the couch and gantry. The actual physical collision space was then mapped in the treatment room by moving the gantry and couch until a collision occurred with either the patient or hardware. The physical and virtual collision spaces were then compared to determine the accuracy of the system. To improve the collision predictions, a buffer geometry was added to the scanned gantry mesh and performance was assessed as a function of buffer thickness. Each patient was optically scanned during simulation in less than 1 min. The average time to virtually map the collision space for 64, 800 gantry/couch states was 5.40 ± 2.88 s. The system had an average raw accuracy and negative prediction rate (NPR) across all patients of 97.3% ± 2.4% and 96.9% ± 2.2% respectively. Using a polygon buffer of 6 cm over the gantry geometry, the NPR was raised to unity for all patients, signifying the detection of all collision events. However, the average accuracy fell from 95.3% ± 3.1% to 91.5% ± 3.6% between the 3 and 6 cm buffer as more false positives were detected. We successfully demonstrated a fast and low cost framework which can map an entire collision space a priori for a given patient during the time of simulation. All collisions can be avoided using polygon interference, but a polygon buffer may be required to account for geometric uncertainties of scanned objects. © 2017 American Association of Physicists in Medicine.

  11. Improvement in Neuropathy Specific Quality of Life in Patients with Diabetes after Vitamin D Supplementation

    Directory of Open Access Journals (Sweden)

    Uazman Alam

    2017-01-01

    Full Text Available Objective. To assess the effect of vitamin D supplementation on neuropathy specific quality of life (NeuroQoL in patients with painful diabetic neuropathy. Methods. This prospective, open label study was conducted between June 2012 and April 2013. Patients with symptomatic diabetic neuropathy were given a single dose of 600,000 IU intramuscular vitamin D, and NeuroQol was assessed at baseline and at five follow-up visits every 4 weeks. Results. Of 143 participants, 41.3% were vitamin D deficient (vitamin D < 20 ng/ml. Treatment with vitamin D resulted in a significant increase in 25(OHD (P<0.0001 and a significant improvement in the NeuroQoL subscale score for emotional distress (P=0.04, with no significant change in the other NeuroQoL domains of painful symptoms and paresthesia, loss of temperature and touch sensation, unsteadiness, limitation in daily activities, and interpersonal problems. There was a significant reduction in patient perception about foot problems on QoL of “quite a lot” (P<0.05 and “very much” (P<0.0001 with a significant reduction in the baseline response of having a “poor” QoL from 5.2% to 0.7% (P<0.0001 and an increase in the response of an “excellent QoL” from 1.5% to 7.4% (P<0.0001. Conclusion. Vitamin D is effective in improving quality of life in patients with painful diabetic neuropathy.

  12. Quality of Life of Head and Neck Cancer Patients Receiving Cancer Specific Treatments

    Directory of Open Access Journals (Sweden)

    James Gonsalves

    2013-01-01

    Full Text Available Background: Head and neck cancer (HNC remains a considerable challenge to both patient and health care provider as the disease can have profound effect on Quality of life (QOL. Aims and Objectives: To assess the QOL and performance status of HNC patients, to find relation between domains of QOL and to find association between QOL and demographic and disease variables. Settings and Design: The study was conducted at Manipal group of hospitals, Manipal and Mangalore, using descriptive survey design. Material and Methods: The study comprised of 89 samples with all stages of HNC. Patients primarily diagnosed with HNC and undergoing disease specific treatment were included in the study. Tool on demographic, disease variables and quality of life were developed and content validity was established. Reliability of the tool was established. Karnofsky Performance Status (KPS scale was used to assess performance status. Corelational analysis was done to find relation between the domains of QOL. Association was found between the quality of life and demographic and disease variables. Results: Majority (83% of the participants were males, 39% had cancer arising from oral cavity, and 35% each were in cancer stage III and IV. Quality of life was poor among 30% of the subjects and 65% had KPS scores<80 %. There was moderate positive relation between the domains of QOL and a positive correlation between the QOL and performance status. No statistically significant association was found between QOL and disease and demographic variables. Conclusion: Physical, psychological, social and spiritual domains of QOL and functional status are affected in patients with HNC. The impact on one domain area of well being, significantly affects the other domain of QOL and there is relationship between the performance status and QOL

  13. A patient-specific version of the Disabilities of the Arm, Shoulder, and Hand Questionnaire.

    Science.gov (United States)

    Vranceanu, Ana-Maria; Kadzielski, John; Hwang, Ray; Ring, David

    2010-05-01

    We modified the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire to be weighted according to a patient's priorities (patient-specific [PS-DASH]) and compared it with the DASH in terms of its mean and variance and its relationship with coping styles (pain avoidance, pain catastrophizing, anxiety sensitivity, and hypochondriasis), depression, and overall stress. Ninety-eight patients with carpal tunnel syndrome completed questionnaires measuring depression, pain catastrophizing, avoidance, hypochondriasis, anxiety sensitivity, and ordinal measures of self-reported stress and disability. They also completed the DASH and a modification of the DASH that weighted each item according to personal priorities. The DASH scores had a significantly higher mean and greater standard deviation than the PS-DASH (mean +/- standard deviation, 54.1 +/- 16.8 vs 32.7 +/- 11.0). Health anxiety (r = 0.355), anxiety sensitivity (r = 0.258), and pain catastrophizing (r = 0.421) were significantly related to PS-DASH; health anxiety (r = 0.298), depression (r = 0.225), and pain catastrophizing (r = .350) were significantly related to DASH. Multivariable regression analyses were statistically significant, but accounted for only 35% of the variance in PS-DASH and 17% of the variance in DASH. Pain catastrophizing and gender were the sole significant predictors for PS-DASH (B = 0.290, B = 0.384), whereas only pain catastrophizing predicted DASH (B = 0.251). A version of the DASH weighted according to patient priorities narrowed the variability in DASH scores but did not appear to have sufficient advantage over DASH to warrant this much more cumbersome questionnaire. Copyright 2010. Published by Elsevier Inc.

  14. Automatized Patient-Specific Methodology for Numerical Determination of Biomechanical Corneal Response.

    Science.gov (United States)

    Ariza-Gracia, M Á; Zurita, J; Piñero, D P; Calvo, B; Rodríguez-Matas, J F

    2016-05-01

    This work presents a novel methodology for building a three-dimensional patient-specific eyeball model suitable for performing a fully automatic finite element (FE) analysis of the corneal biomechanics. The reconstruction algorithm fits and smooths the patient's corneal surfaces obtained in clinic with corneal topographers and creates an FE mesh for the simulation. The patient's corneal elevation and pachymetry data is kept where available, to account for all corneal geometric features (central corneal thickness-CCT and curvature). Subsequently, an iterative free-stress algorithm including a fiber's pull-back is applied to incorporate the pre-stress field to the model. A convergence analysis of the mesh and a sensitivity analysis of the parameters involved in the numerical response is also addressed to determine the most influential features of the FE model. As a final step, the methodology is applied on the simulation of a general non-commercial non-contact tonometry diagnostic test over a large set of 130 patients-53 healthy, 63 keratoconic (KTC) and 14 post-LASIK surgery eyes. Results show the influence of the CCT, intraocular pressure (IOP) and fibers (87%) on the numerical corneal displacement (U(Num)) the good agreement of the U(Num) with clinical results, and the importance of considering the corneal pre-stress in the FE analysis. The potential and flexibility of the methodology can help improve understanding of the eye biomechanics, to help to plan surgeries, or to interpret the results of new diagnosis tools (i.e., non-contact tonometers).

  15. Robust Vertex Fitters

    CERN Document Server

    Speer, Thomas; Vanlaer, Pascal; Waltenberger, Wolfgang

    2005-01-01

    While linear least-square estimators are optimal when the model is linear and all random noise is Gaussian, they are very sensitive to outlying tracks. Non-linear vertex reconstruction algorithms offer a higher degree of robustness against such outliers Two of the algorithms presented, the Adaptive filter and the Trimmed Kalman filter are able to down-weight or discard these outlying tracks, while a third, the Gaussian-sum filter, offers a better treatment of non-Gaussian distributions of track parameter errors when these are modelled by Gaussian mixtures.

  16. Robust Instrumentation[Water treatment for power plant]; Robust Instrumentering

    Energy Technology Data Exchange (ETDEWEB)

    Wik, Anders [Vattenfall Utveckling AB, Stockholm (Sweden)

    2003-08-01

    Cementa Slite Power Station is a heat recovery steam generator (HRSG) with moderate steam data; 3.0 MPa and 420 deg C. The heat is recovered from Cementa, a cement industry, without any usage of auxiliary fuel. The Power station commenced operation in 2001. The layout of the plant is unusual, there are no similar in Sweden and very few world-wide, so the operational experiences are limited. In connection with the commissioning of the power plant a R and D project was identified with the objective to minimise the manpower needed for chemistry management of the plant. The lean chemistry management is based on robust instrumentation and chemical-free water treatment plant. The concept with robust instrumentation consists of the following components; choice of on-line instrumentation with a minimum of O and M and a chemical-free water treatment. The parameters are specific conductivity, cation conductivity, oxygen and pH. In addition to that, two fairly new on-line instruments were included; corrosion monitors and differential pH calculated from specific and cation conductivity. The chemical-free water treatment plant consists of softening, reverse osmosis and electro-deionisation. The operational experience shows that the cycle chemistry is not within the guidelines due to major problems with the operation of the power plant. These problems have made it impossible to reach steady state and thereby not viable to fully verify and validate the concept with robust instrumentation. From readings on the panel of the online analysers some conclusions may be drawn, e.g. the differential pH measurements have fulfilled the expectations. The other on-line analysers have been working satisfactorily apart from contamination with turbine oil, which has been noticed at least twice. The corrosion monitors seem to be working but the lack of trend curves from the mainframe computer system makes it hard to draw any clear conclusions. The chemical-free water treatment has met all

  17. Clinical and Phenomenological Characteristics of Patients with Task-Specific Lingual Dystonia: Possible Association with Occupation

    Directory of Open Access Journals (Sweden)

    Kazuya Yoshida

    2017-12-01

    Full Text Available BackgroundLingual dystonia is a subtype of oromandibular dystonia, which is a movement disorder characterized by involuntary sustained or intermittent contraction of the masticatory and/or tongue muscles. Lingual dystonia interferes with important daily activities, such as speaking, chewing, and swallowing, resulting in vocational and social disability.ObjectiveThe aim of this study was to investigate a possible relationship between occupation and the development of lingual dystonia.MethodsPhenomenological and clinical characteristics of 95 patients [53 females (55.8% and 42 males (44.2%, mean age 48.0 years] with task-specific, speech-induced lingual dystonia were analyzed. Structured interviews were carried out to obtain information regarding primary occupation, including overtime work and stress during work. The factors that might have influenced the development of lingual dystonia were estimated using multivariate logistic regression analysis of the 95 patients with lingual dystonia and 95 controls [68 females (71.6% and 27 males (28.4%, mean age 47.2 years] with temporomandibular disorders.ResultsOverall, 84.2% of the patients had regular occupations; 73.8% of the patients with regular occupations reported working overtime more than twice a week, and 63.8% of them experienced stress at the workplace. Furthermore, 82.1% of the patients had engaged in occupations that required them to talk to customers or other people under stressful situations over prolonged periods of time for many years (mean: 15.6 years. The most common occupation was sales representative (17.9%, followed by telephone operator (13.7%, customer service representative (10.5%, health care worker (9.5%, waiter or waitress (5.3%, receptionist (5.3%, and cashier (5.3%. Twenty-nine patients (30.5% had tardive lingual dystonia. Logistic regression analyses revealed that frequent requirements for professional speaking (p = 0.011, odds ratio: 5.66, high stress during work

  18. Serum Adiponectin Predicts Cancer-specific Survival of Patients with Renal Cell Carcinoma.

    Science.gov (United States)

    de Martino, Michela; Leitner, Carmen V; Hofbauer, Sebastian L; Lucca, Ilaria; Haitel, Andrea; Shariat, Shahrokh F; Klatte, Tobias

    2016-06-01

    Prediction of outcomes in patients with renal cell carcinoma (RCC) is crucial for clinical decision-making. The limited accuracy of conventional prognostic factors such as stage and grade may be increased by the use of biomarkers. To evaluate the association of serum adiponectin and leptin and polymorphisms in the leptin and leptin receptor genes with RCC histopathology and prognosis. Adiponectin and leptin levels were measured in preoperative serum samples from 131 consecutive patients with sporadic unilateral RCC. The polymorphisms G-2548A (rs7799039) in the leptin gene (LEP) and Gln223Arg (Q223R, A668G, rs1137101) in the leptin receptor gene (LEPR) were genotyped in 233 patients. Multivariable associations with RCC-specific survival were analyzed using Cox models. Median preoperative serum adiponectin was 15.8μg/ml (interquartile range 10.0-23.1). Adiponectin was lower in patients with distant metastases (p=0.017) or histologic tumor necrosis (p=0.015). On multivariable analysis adjusted for the effects of variables in the Karakiewicz nomogram, each 1-μg/ml increase in adiponectin was associated with a 8% decrease in the hazard of death from RCC (hazard ratio 0.92, 95% confidence interval 0.86-0.98; p=0.007). The discrimination of the Karakiewicz nomogram increased by 0.6% on inclusion of adiponectin. Leptin levels, LEP G-2548A and LEPR Q223R were not associated with either RCC pathology or outcomes. Limitations include the retrospective study design, the low numbers of patients, and a lack of standardized follow-up. This study suggests that lower preoperative serum adiponectin is associated with features of biologically aggressive RCC, metastasis, and survival. We assessed the relationship between outcomes and blood levels of adiponectin and leptin and genetic changes in leptin and leptin receptor genes. We found that patients with lower adiponectin levels have more aggressive tumors and poorer survival. Copyright © 2015 European Association of Urology

  19. Minimizing patient-specific tracer dose in myocardial perfusion imaging using CZT SPECT.

    Science.gov (United States)

    van Dijk, Joris D; Jager, Pieter L; Ottervanger, Jan Paul; Slump, Cornelis H; de Boer, Jaep; Oostdijk, Adrianus H J; van Dalen, Jorn A

    2015-03-01

    Myocardial perfusion imaging (MPI) with SPECT is widely adopted in clinical practice but is associated with a relatively high radiation dose. The aim of this study was to determine the minimum product of tracer dose and scan time that will maintain diagnostic value for cadmium zinc telluride (CZT) SPECT MPI. Twenty-four patients underwent clinically indicated stress MPI using CZT SPECT and a body weight-dependent (3 MBq/kg) (99m)Tc-tetrofosmin tracer dose. Data were acquired for 8 min in list mode. Next, images were reconstructed using 2-, 4-, 6-, and 8-min time frames. Differences between the 8-min reference scan and the shorter scans were determined in segmental uptake values (using the 17-segment cardiac model), ejection fraction, and end-diastolic volume. A 5% difference in segmental uptake was considered to significantly influence the diagnostic value. Next, the quality of the 4-, 6-, and 8-min scans was scored on a 4-point scale by consensus by 3 experienced nuclear medicine physicians. The physicians did not know the scan time or patient information. Differences in segmental uptake values, ejection fraction, and end-diastolic volume were greater for shorter scans than for the 8-min reference scan. On average, the diagnostic value was influenced in 7.7 segments per patient using the 2-min scans, in comparison to 2.0 and 0.8 segments per patient using the 4- and 6-min scans, respectively. In addition, the 4-min scans led to a significantly reduced image quality compared with the 8-min scans (P < 0.05). This was not the case for the 6-min scan. Six minutes was the shortest acquisition time in stress MPI using CZT SPECT that did not affect the diagnostic value for a tracer dose of 3 MBq/kg. Hence, the patient-specific product of tracer dose and scan time can be reduced to a minimum of 18 MBq·min/kg, which may lower the effective radiation dose for patients to values below 1 mSv. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  20. Patient-specific dose calculation methods for high-dose-rate iridium-192 brachytherapy

    Science.gov (United States)

    Poon, Emily S.

    In high-dose-rate 192Ir brachytherapy, the radiation dose received by the patient is calculated according to the AAPM Task Group 43 (TG-43) formalism. This table-based dose superposition method uses dosimetry parameters derived with the radioactive 192Ir source centered in a water phantom. It neglects the dose perturbations caused by inhomogeneities, such as the patient anatomy, applicators, shielding, and radiographic contrast solution. In this work, we evaluated the dosimetric characteristics of a shielded rectal applicator with an endocavitary balloon injected with contrast solution. The dose distributions around this applicator were calculated by the GEANT4 Monte Carlo (MC) code and measured by ionization chamber and GAFCHROMIC EBT film. A patient-specific dose calculation study was then carried out for 40 rectal treatment plans. The PTRAN_CT MC code was used to calculate the dose based on computed tomography (CT) images. This study involved the development of BrachyGUI, an integrated treatment planning tool that can process DICOM-RT data and create PTRAN_CT input initialization files. BrachyGUI also comes with dose calculation and evaluation capabilities. We proposed a novel scatter correction method to account for the reduction in backscatter radiation near tissue-air interfaces. The first step requires calculating the doses contributed by primary and scattered photons separately, assuming a full scatter environment. The scatter dose in the patient is subsequently adjusted using a factor derived by MC calculations, which depends on the distances between the point of interest, the 192Ir source, and the body contour. The method was validated for multicatheter breast brachytherapy, in which the target and skin doses for 18 patient plans agreed with PTRAN_CT calculations better than 1%. Finally, we developed a CT-based analytical dose calculation method. It corrects for the photon attenuation and scatter based upon the radiological paths determined by ray tracing

  1. Toward optimizing patient-specific IMRT QA techniques in the accurate detection of dosimetrically acceptable and unacceptable patient plans

    Energy Technology Data Exchange (ETDEWEB)

    McKenzie, Elizabeth M. [Graduate School of Biomedical Sciences, The University of Texas Health Science Center Houston, Houston, Texas, 77030 (United States); Balter, Peter A. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Stingo, Francesco C. [Department of Biostatistics, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Jones, Jimmy [Porter Adventist Hospital, Denver, Colorado 80210 (United States); Followill, David S.; Kry, Stephen F., E-mail: sfkry@mdanderson.org [Imaging and Radiation Oncology Core at Houston and Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States)

    2014-12-15

    Purpose: The authors investigated the performance of several patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA) dosimeters in terms of their ability to correctly identify dosimetrically acceptable and unacceptable IMRT patient plans, as determined by an in-house-designed multiple ion chamber phantom used as the gold standard. A further goal was to examine optimal threshold criteria that were consistent and based on the same criteria among the various dosimeters. Methods: The authors used receiver operating characteristic (ROC) curves to determine the sensitivity and specificity of (1) a 2D diode array undergoing anterior irradiation with field-by-field evaluation, (2) a 2D diode array undergoing anterior irradiation with composite evaluation, (3) a 2D diode array using planned irradiation angles with composite evaluation, (4) a helical diode array, (5) radiographic film, and (6) an ion chamber. This was done with a variety of evaluation criteria for a set of 15 dosimetrically unacceptable and 9 acceptable clinical IMRT patient plans, where acceptability was defined on the basis of multiple ion chamber measurements using independent ion chambers and a phantom. The area under the curve (AUC) on the ROC curves was used to compare dosimeter performance across all thresholds. Optimal threshold values were obtained from the ROC curves while incorporating considerations for cost and prevalence of unacceptable plans. Results: Using common clinical acceptance thresholds, most devices performed very poorly in terms of identifying unacceptable plans. Grouping the detector performance based on AUC showed two significantly different groups. The ion chamber, radiographic film, helical diode array, and anterior-delivered composite 2D diode array were in the better-performing group, whereas the anterior-delivered field-by-field and planned gantry angle delivery using the 2D diode array performed less well. Additionally, based on the AUCs, there

  2. Toward optimizing patient-specific IMRT QA techniques in the accurate detection of dosimetrically acceptable and unacceptable patient plans.

    Science.gov (United States)

    McKenzie, Elizabeth M; Balter, Peter A; Stingo, Francesco C; Jones, Jimmy; Followill, David S; Kry, Stephen F

    2014-12-01

    The authors investigated the performance of several patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA) dosimeters in terms of their ability to correctly identify dosimetrically acceptable and unacceptable IMRT patient plans, as determined by an in-house-designed multiple ion chamber phantom used as the gold standard. A further goal was to examine optimal threshold criteria that were consistent and based on the same criteria among the various dosimeters. The authors used receiver operating characteristic (ROC) curves to determine the sensitivity and specificity of (1) a 2D diode array undergoing anterior irradiation with field-by-field evaluation, (2) a 2D diode array undergoing anterior irradiation with composite evaluation, (3) a 2D diode array using planned irradiation angles with composite evaluation, (4) a helical diode array, (5) radiographic film, and (6) an ion chamber. This was done with a variety of evaluation criteria for a set of 15 dosimetrically unacceptable and 9 acceptable clinical IMRT patient plans, where acceptability was defined on the basis of multiple ion chamber measurements using independent ion chambers and a phantom. The area under the curve (AUC) on the ROC curves was used to compare dosimeter performance across all thresholds. Optimal threshold values were obtained from the ROC curves while incorporating considerations for cost and prevalence of unacceptable plans. Using common clinical acceptance thresholds, most devices performed very poorly in terms of identifying unacceptable plans. Grouping the detector performance based on AUC showed two significantly different groups. The ion chamber, radiographic film, helical diode array, and anterior-delivered composite 2D diode array were in the better-performing group, whereas the anterior-delivered field-by-field and planned gantry angle delivery using the 2D diode array performed less well. Additionally, based on the AUCs, there was no significant difference

  3. Patient-specific Monte Carlo dose calculations for 103Pd breast brachytherapy

    Science.gov (United States)

    Miksys, N.; Cygler, J. E.; Caudrelier, J. M.; Thomson, R. M.

    2016-04-01

    This work retrospectively investigates patient-specific Monte Carlo (MC) dose calculations for 103Pd permanent implant breast brachytherapy, exploring various necessary assumptions for deriving virtual patient models: post-implant CT image metallic artifact reduction (MAR), tissue assignment schemes (TAS), and elemental tissue compositions. Three MAR methods (thresholding, 3D median filter, virtual sinogram) are applied to CT images; resulting images are compared to each other and to uncorrected images. Virtual patient models are then derived by application of different TAS ranging from TG-186 basic recommendations (mixed adipose and gland tissue at uniform literature-derived density) to detailed schemes (segmented adipose and gland with CT-derived densities). For detailed schemes, alternate mass density segmentation thresholds between adipose and gland are considered. Several literature-derived elemental compositions for adipose, gland and skin are compared. MC models derived from uncorrected CT images can yield large errors in dose calculations especially when used with detailed TAS. Differences in MAR method result in large differences in local doses when variations in CT number cause differences in tissue assignment. Between different MAR models (same TAS), PTV {{D}90} and skin {{D}1~\\text{c{{\\text{m}}3}}} each vary by up to 6%. Basic TAS (mixed adipose/gland tissue) generally yield higher dose metrics than detailed segmented schemes: PTV {{D}90} and skin {{D}1~\\text{c{{\\text{m}}3}}} are higher by up to 13% and 9% respectively. Employing alternate adipose, gland and skin elemental compositions can cause variations in PTV {{D}90} of up to 11% and skin {{D}1~\\text{c{{\\text{m}}3}}} of up to 30%. Overall, AAPM TG-43 overestimates dose to the PTV ({{D}90} on average 10% and up to 27%) and underestimates dose to the skin ({{D}1~\\text{c{{\\text{m}}3}}} on average 29% and up to 48%) compared to the various MC models derived using the post-MAR CT images studied

  4. Patient-specific Monte Carlo dose calculations for (103)Pd breast brachytherapy.

    Science.gov (United States)

    Miksys, N; Cygler, J E; Caudrelier, J M; Thomson, R M

    2016-04-07

    This work retrospectively investigates patient-specific Monte Carlo (MC) dose calculations for (103)Pd permanent implant breast brachytherapy, exploring various necessary assumptions for deriving virtual patient models: post-implant CT image metallic artifact reduction (MAR), tissue assignment schemes (TAS), and elemental tissue compositions. Three MAR methods (thresholding, 3D median filter, virtual sinogram) are applied to CT images; resulting images are compared to each other and to uncorrected images. Virtual patient models are then derived by application of different TAS ranging from TG-186 basic recommendations (mixed adipose and gland tissue at uniform literature-derived density) to detailed schemes (segmented adipose and gland with CT-derived densities). For detailed schemes, alternate mass density segmentation thresholds between adipose and gland are considered. Several literature-derived elemental compositions for adipose, gland and skin are compared. MC models derived from uncorrected CT images can yield large errors in dose calculations especially when used with detailed TAS. Differences in MAR method result in large differences in local doses when variations in CT number cause differences in tissue assignment. Between different MAR models (same TAS), PTV [Formula: see text] and skin [Formula: see text] each vary by up to 6%. Basic TAS (mixed adipose/gland tissue) generally yield higher dose metrics than detailed segmented schemes: PTV [Formula: see text] and skin [Formula: see text] are higher by up to 13% and 9% respectively. Employing alternate adipose, gland and skin elemental compositions can cause variations in PTV [Formula: see text] of up to 11% and skin [Formula: see text] of up to 30%. Overall, AAPM TG-43 overestimates dose to the PTV ([Formula: see text] on average 10% and up to 27%) and underestimates dose to the skin ([Formula: see text] on average 29% and up to 48%) compared to the various MC models derived using the post-MAR CT images

  5. Assessing usability, label comprehension, pen robustness and pharmacokinetics of a self-administered prefilled autoinjector pen of methotrexate in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Jaime A Pachon

    2014-12-01

    Full Text Available Objective: To assess usability, bioavailability, and safety of subcutaneous self-administration of 0.3 mL of methotrexate 50 mg/mL solution via a prefilled autoinjector pen (methotrexate pen in patients with rheumatoid arthritis. Methods: The study enrolled methotrexate-naïve and methotrexate-experienced patients aged ≥16 years. Visit 1 (Day 1 included methotrexate pen usage training with documentation, patient self-injection, and a patient-training questionnaire completed by the healthcare professional. Visit 2 (Days 8–10 included evaluation of patient self-injection through four scenarios: holding needle in place for 5 s, confirming methotrexate delivery, skin pinch, and pen disposal. At Visit 2, patient opinion and training retention (since Visit 1 were also assessed. Pharmacokinetic parameters were assessed in 25 patients, who were stratified by body weight and randomized to receive injections in the abdomen or the upper thigh. Results: At Visit 1, 12 of 106 patients had questions about the pen, and 4 required self-injection assistance. At Visit 2, the mean performance rating for all scenarios was ≥9.8 (scale: 1 (very difficult−10 (very easy. Successful completion rates were 96.2%–100%; 91.3%–100% of patients required no assistance. Impressions of the pen were favorable; 98.1% of patients passed the written examination. All methotrexate pens effectively delivered 0.3 mL methotrexate and were intact after use. Body weight >100 kg significantly decreased total and peak methotrexate exposure when administered abdominally. No adverse effects resulted in drug discontinuation. Conclusion: The methotrexate pen was used with a high degree of effectiveness, satisfaction, and safety, indicating that this delivery system may be a viable option for patients requiring subcutaneous methotrexate.

  6. Assessing usability, label comprehension, pen robustness and pharmacokinetics of a self-administered prefilled autoinjector pen of methotrexate in patients with rheumatoid arthritis.

    Science.gov (United States)

    Pachon, Jaime A; Kivitz, Alan J; Heuer, Kay-Uwe; Pichlmeier, Uwe

    2014-01-01

    To assess usability, bioavailability, and safety of subcutaneous self-administration of 0.3 mL of methotrexate 50 mg/mL solution via a prefilled autoinjector pen (methotrexate pen) in patients with rheumatoid arthritis. The study enrolled methotrexate-naïve and methotrexate-experienced patients aged ≥16 years. Visit 1 (Day 1) included methotrexate pen usage training with documentation, patient self-injection, and a patient-training questionnaire completed by the healthcare professional. Visit 2 (Days 8-10) included evaluation of patient self-injection through four scenarios: holding needle in place for 5 s, confirming methotrexate delivery, skin pinch, and pen disposal. At Visit 2, patient opinion and training retention (since Visit 1) were also assessed. Pharmacokinetic parameters were assessed in 25 patients, who were stratified by body weight and randomized to receive injections in the abdomen or the upper thigh. At Visit 1, 12 of 106 patients had questions about the pen, and 4 required self-injection assistance. At Visit 2, the mean performance rating for all scenarios was ≥9.8 (scale: 1 (very difficult)-10 (very easy)). Successful completion rates were 96.2%-100%; 91.3%-100% of patients required no assistance. Impressions of the pen were favorable; 98.1% of patients passed the written examination. All methotrexate pens effectively delivered 0.3 mL methotrexate and were intact after use. Body weight >100 kg significantly decreased total and peak methotrexate exposure when administered abdominally. No adverse effects resulted in drug discontinuation. The methotrexate pen was used with a high degree of effectiveness, satisfaction, and safety, indicating that this delivery system may be a viable option for patients requiring subcutaneous methotrexate.

  7. Fluid-structure interaction modeling of a patient-specific cerebral aneurysm: influence of structural modeling

    Science.gov (United States)

    Torii, Ryo; Oshima, Marie; Kobayashi, Toshio; Takagi, Kiyoshi; Tezduyar, Tayfun E.

    2008-12-01

    Fluid-structure interaction (FSI) simulations of a cerebral aneurysm with the linearly elastic and hyper-elastic wall constitutive models are carried out to investigate the influence of the wall-structure model on patient-specific FSI simulations. The maximum displacement computed with the hyper-elastic model is 36% smaller compared to the linearly elastic material model, but the displacement patterns such as the site of local maxima are not sensitive to the wall models. The blood near the apex of an aneurysm is likely to be stagnant, which causes very low wall shear stress and is a factor in rupture by degrading the aneurysmal wall. In this study, however, relatively high flow velocities due to the interaction between the blood flow and aneurysmal wall are seen to be independent of the wall model. The present results indicate that both linearly elastic and hyper-elastic models can be useful to investigate aneurysm FSI.

  8. Patient-specific computer modeling of blood flow in cerebral arteries with aneurysm and stent

    Science.gov (United States)

    Takizawa, Kenji; Schjodt, Kathleen; Puntel, Anthony; Kostov, Nikolay; Tezduyar, Tayfun E.

    2012-12-01

    We present the special arterial fluid mechanics techniques we have developed for patient-specific computer modeling of blood flow in cerebral arteries with aneurysm and stent. These techniques are used in conjunction with the core computational technique, which is the space-time version of the variational multiscale (VMS) method and is called "DST/SST-VMST." The special techniques include using NURBS for the spatial representation of the surface over which the stent mesh is built, mesh generation techniques for both the finite- and zero-thickness representations of the stent, techniques for generating refined layers of mesh near the arterial and stent surfaces, and models for representing double stent. We compute the unsteady flow patterns in the aneurysm and investigate how those patterns are influenced by the presence of single and double stents. We also compare the flow patterns obtained with the finite- and zero-thickness representations of the stent.

  9. Characterization of the transport topology in patient-specific abdominal aortic aneurysm models

    Science.gov (United States)

    Arzani, Amirhossein; Shadden, Shawn C.

    2012-08-01

    Abdominal aortic aneurysm (AAA) is characterized by disturbed blood flow patterns that are hypothesized to contribute to disease progression. The transport topology in six patient-specific abdominal aortic aneurysms was studied. Velocity data were obtained by image-based computational fluid dynamics modeling, with magnetic resonance imaging providing the necessary simulation parameters. Finite-time Lyapunov exponent (FTLE) fields were computed from the velocity data, and used to identify Lagrangian coherent structures (LCS). The combination of FTLE fields and LCS was used to characterize topological flow features such as separation zones, vortex transport, mixing regions, and flow impingement. These measures offer a novel perspective into AAA flow. It was observed that all aneurysms exhibited coherent vortex formation at the proximal segment of the aneurysm. The evolution of the systolic vortex strongly influences the flow topology in the aneurysm. It was difficult to predict the vortex dynamics from the aneurysm morphology, motivating the application of image-based flow modeling.

  10. Improving assessment of congenital heart disease through rapid patient specific modeling.

    Science.gov (United States)

    Gilbert, Kathleen; Farrar, Genevieve; Cowan, Brett; Suinesiaputra, Avan; Occleshaw, Christopher; Pontre, Beau; Perry, James; Hegde, Sanjeet; Omens, Jeffrey; McCulloch, Andrew; Young, Alistair

    2016-08-01

    Congenital heart disease is the most common birth defect, with an incidence of 75 in every 1000 births. As a result of improved interventions, 90% of people with congenital heart disease now survive to adulthood. They must undergo regular imaging to assess their biventricular (left and right ventricular) function. Analysis of the images is problematic due to the large variety of shapes and complex geometry. In this paper we extend a biventricular modeling method to improve the analysis of MR images from congenital heart disease patients. We used a subdivision surface method to create three customizable exemplars, representing common manifestations of anatomy, and incorporated these as priors into an interactive biventricular customization procedure. The CHD-specific priors were tested on 60 cases representing a variety of congenital heart diseases for which the gold standard manual contours were available. The introduction of multiple priors showed a significant decrease in analysis time while maintaining good correlation between the two methods (R2 >.82).

  11. Topological optimization for designing patient-specific large craniofacial segmental bone replacements

    Science.gov (United States)

    Sutradhar, Alok; Paulino, Glaucio H.; Miller, Michael J.; Nguyen, Tam H.

    2010-01-01

    Restoring normal function and appearance after massive facial injuries with bone loss is an important unsolved problem in surgery. An important limitation of the current methods is heuristic ad hoc design of bone replacements by the operating surgeon at the time of surgery. This problem might be addressed by incorporating a computational method known as topological optimization into routine surgical planning. We tested the feasibility of using a multiresolution three-dimensional topological optimization to design replacements for massive midface injuries with bone loss. The final solution to meet functional requirements may be shaped differently than the natural human bone but be optimized for functional needs sufficient to support full restoration using a combination of soft tissue repair and synthetic prosthetics. Topological optimization for designing facial bone tissue replacements might improve current clinical methods and provide essential enabling technology to translate generic bone tissue engineering methods into specific solutions for individual patients. PMID:20628014

  12. Wall Shear Stress Distribution in a Patient-Specific Cerebral Aneurysm Model using Reduced Order Modeling

    Science.gov (United States)

    Han, Suyue; Chang, Gary Han; Schirmer, Clemens; Modarres-Sadeghi, Yahya

    2016-11-01

    We construct a reduced-order model (ROM) to study the Wall Shear Stress (WSS) distributions in image-based patient-specific aneurysms models. The magnitude of WSS has been shown to be a critical factor in growth and rupture of human aneurysms. We start the process by running a training case using Computational Fluid Dynamics (CFD) simulation with time-varying flow parameters, such that these parameters cover the range of parameters of interest. The method of snapshot Proper Orthogonal Decomposition (POD) is utilized to construct the reduced-order bases using the training CFD simulation. The resulting ROM enables us to study the flow patterns and the WSS distributions over a range of system parameters computationally very efficiently with a relatively small number of modes. This enables comprehensive analysis of the model system across a range of physiological conditions without the need to re-compute the simulation for small changes in the system parameters.

  13. Are patient-specific joint and inertial parameters necessary for accurate inverse dynamics analyses of gait?

    Science.gov (United States)

    Reinbolt, Jeffrey A; Haftka, Raphael T; Chmielewski, Terese L; Fregly, Benjamin J

    2007-05-01

    Variations in joint parameter (JP) values (axis positions and orientations in body segments) and inertial parameter (IP) values (segment masses, mass centers, and moments of inertia) as well as kinematic noise alter the results of inverse dynamics analyses of gait. Three-dimensional linkage models with joint constraints have been proposed as one way to minimize the effects of noisy kinematic data. Such models can also be used to perform gait optimizations to predict post-treatment function given pre-treatment gait data. This study evaluates whether accurate patient-specific JP and IP values are needed in three-dimensional linkage models to produce accurate inverse dynamics results for gait. The study was performed in two stages. First, we used optimization analyses to evaluate whether patient-specific JP and IP values can be calibrated accurately from noisy kinematic data, and second, we used Monte Carlo analyses to evaluate how errors in JP and IP values affect inverse dynamics calculations. Both stages were performed using a dynamic, 27 degrees-of-freedom, full-body linkage model and synthetic (i.e., computer generated) gait data corresponding to a nominal experimental gait motion. In general, JP but not IP values could be found accurately from noisy kinematic data. Root-mean-square (RMS) errors were 3 degrees and 4 mm for JP values and 1 kg, 22 mm, and 74 500 kg * mm2 for IP values. Furthermore, errors in JP but not IP values had a significant effect on calculated lower-extremity inverse dynamics joint torques. The worst RMS torque error averaged 4% bodyweight * height (BW * H) due to JP variations but less than 0.25% (BW * H) due to IP variations. These results suggest that inverse dynamics analyses of gait utilizing linkage models with joint constraints should calibrate the model's JP values to obtain accurate joint torques.

  14. Initial simulated FFR investigation using flow measurements in patient-specific 3D printed coronary phantoms

    Science.gov (United States)

    Shepard, Lauren; Sommer, Kelsey; Izzo, Richard; Podgorsak, Alexander; Wilson, Michael; Said, Zaid; Rybicki, Frank J.; Mitsouras, Dimitrios; Rudin, Stephen; Angel, Erin; Ionita, Ciprian N.

    2017-03-01

    Purpose: Accurate patient-specific phantoms for device testing or endovascular treatment planning can be 3D printed. We expand the applicability of this approach for cardiovascular disease, in particular, for CT-geometry derived benchtop measurements of Fractional Flow Reserve, the reference standard for determination of significant individual coronary artery atherosclerotic lesions. Materials and Methods: Coronary CT Angiography (CTA) images during a single heartbeat were acquired with a 320x0.5mm detector row scanner (Toshiba Aquilion ONE). These coronary CTA images were used to create 4 patientspecific cardiovascular models with various grades of stenosis: severe, <75% (n=1); moderate, 50-70% (n=1); and mild, <50% (n=2). DICOM volumetric images were segmented using a 3D workstation (Vitrea, Vital Images); the output was used to generate STL files (using AutoDesk Meshmixer), and further processed to create 3D printable geometries for flow experiments. Multi-material printed models (Stratasys Connex3) were connected to a programmable pulsatile pump, and the pressure was measured proximal and distal to the stenosis using pressure transducers. Compliance chambers were used before and after the model to modulate the pressure wave. A flow sensor was used to ensure flow rates within physiological reported values. Results: 3D model based FFR measurements correlated well with stenosis severity. FFR measurements for each stenosis grade were: 0.8 severe, 0.7 moderate and 0.88 mild. Conclusions: 3D printed models of patient-specific coronary arteries allows for accurate benchtop diagnosis of FFR. This approach can be used as a future diagnostic tool or for testing CT image-based FFR methods.

  15. Beyond finite elements: a comprehensive, patient-specific neurosurgical simulation utilizing a meshless method.

    Science.gov (United States)

    Miller, K; Horton, A; Joldes, G R; Wittek, A

    2012-10-11

    To be useful in clinical (surgical) simulations, a method must use fully nonlinear (both geometric and material) formulations to deal with large (finite) deformations of tissues. The method must produce meaningful results in a short time on consumer hardware and not require significant manual work while discretizing the problem domain. In this paper, we showcase the Meshless Total Lagrangian Explicit Dynamics Method (MTLED) which meets these requirements, and use it for computing brain deformations during surgery. The problem geometry is based on patient-specific MRI data and includes the parenchyma, tumor, ventricles and skull. Nodes are distributed automatically through the domain rendering the normally difficult problem of creating a patient-specific computational grid a trivial exercise. Integration is performed over a simple, regular background grid which does not need to conform to the geometry boundaries. Appropriate nonlinear material formulation is used. Loading is performed by displacing the parenchyma surface nodes near the craniotomy and a finite frictionless sliding contact is enforced between the skull (rigid) and parenchyma. The meshless simulation results are compared to both intraoperative MRIs and Finite Element Analysis results for multiple 2D sections. We also calculate Hausdorff distances between the computed deformed surfaces of the ventricles and those observed intraoperatively. The difference between previously validated Finite Element results and the meshless results presented here is less than 0.2mm. The results are within the limits of neurosurgical and imaging equipment accuracy (~1 mm) and demonstrate the method's ability to fulfill all of the important requirements for surgical simulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Haptic computer-assisted patient-specific preoperative planning for orthopedic fractures surgery.

    Science.gov (United States)

    Kovler, I; Joskowicz, L; Weil, Y A; Khoury, A; Kronman, A; Mosheiff, R; Liebergall, M; Salavarrieta, J

    2015-10-01

    The aim of orthopedic trauma surgery is to restore the anatomy and function of displaced bone fragments to support osteosynthesis. For complex cases, including pelvic bone and multi-fragment femoral neck and distal radius fractures, preoperative planning with a CT scan is indicated. The planning consists of (1) fracture reduction-determining the locations and anatomical sites of origin of the fractured bone fragments and (2) fracture fixation-selecting and placing fixation screws and plates. The current bone fragment manipulation, hardware selection, and positioning processes based on 2D slices and a computer mouse are time-consuming and require a technician. We present a novel 3D haptic-based system for patient-specific preoperative planning of orthopedic fracture surgery based on CT scans. The system provides the surgeon with an interactive, intuitive, and comprehensive, planning tool that supports fracture reduction and fixation. Its unique features include: (1) two-hand haptic manipulation of 3D bone fragments and fixation hardware models; (2) 3D stereoscopic visualization and multiple viewing modes; (3) ligaments and pivot motion constraints to facilitate fracture reduction; (4) semiautomatic and automatic fracture reduction modes; and (5) interactive custom fixation plate creation to fit the bone morphology. We evaluate our system with two experimental studies: (1) accuracy and repeatability of manual fracture reduction and (2) accuracy of our automatic virtual bone fracture reduction method. The surgeons achieved a mean accuracy of less than 1 mm for the manual reduction and 1.8 mm (std [Formula: see text] 1.1 mm) for the automatic reduction. 3D haptic-based patient-specific preoperative planning of orthopedic fracture surgery from CT scans is useful and accurate and may have significant advantages for evaluating and planning complex fractures surgery.

  17. Principal direction of inertia for 3D trajectories from patient-specific TMJ movement.

    Science.gov (United States)

    Kim, Dae-Seung; Choi, Soon-Chul; Lee, Sam-Sun; Heo, Min-Suk; Huh, Kyung-Hoe; Hwang, Soon-Jung; Kim, Seong-Ha; Yi, Won-Jin

    2013-03-01

    Accurate simulation and evaluation of mandibular movement is fundamental for the analysis of functional changes and effects of the mandible and maxilla before and after surgical treatments. We applied principal axes of inertia to the three-dimensional (3D) trajectories generated by patient-specific simulations of TMJ movements for the functional evaluations of mandible movement. Three-dimensional movements of the mandible and the maxilla were tracked based on a patient-specific splint and an optical tracking system. The dental occlusion recorded on the sprint provided synchronization for initial movement in the tracking and the simulation phases. The translation and rotation recorded during movement tracking was applied sequentially to the mandibular model in relation to a fixed maxilla model. The sequential 3D positions of selected landmarks on the mandible were calculated based on the reference coordinate system. The landmarks selected for analysis were bilateral condyles and pogonion points. The moment of inertia tensor was calculated with respect to the 3D trajectory points. Using the unit vectors along the principal axes derived from the tensor matrix, α, β and γ rotations around z-, y- and x-axes were determined to represent the principal directions as principal rotations respectively. The γ direction showed the higher standard deviation, variation of directions, than other directions at all the landmarks. The mandible movement has larger kinematic redundancy in the γ direction than α and β during mouth opening and closing. Principal directions of inertia would be applied to analyzing the changes in angular motion of trajectories introduced by mandibular shape changes from surgical treatments and also to the analysis of the influence of skeletal deformities on mandibular movement asymmetry. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Nanomedicine-Based Neuroprotective Strategies in Patient Specific-iPSC and Personalized Medicine

    Directory of Open Access Journals (Sweden)

    Shih-Fan Jang

    2014-03-01

    Full Text Available In recent decades, nanotechnology has attracted major interests in view of drug delivery systems and therapies against diseases, such as cancer, neurodegenerative diseases, and many others. Nanotechnology provides the opportunity for nanoscale particles or molecules (so called “Nanomedicine” to be delivered to the targeted sites, thereby, reducing toxicity (or side effects and improving drug bioavailability. Nowadays, a great deal of nano-structured particles/vehicles has been discovered, including polymeric nanoparticles, lipid-based nanoparticles, and mesoporous silica nanoparticles. Nanomedical utilizations have already been well developed in many different aspects, including disease treatment, diagnostic, medical devices designing, and visualization (i.e., cell trafficking. However, while quite a few successful progressions on chemotherapy using nanotechnology have been developed, the implementations of nanoparticles on stem cell research are still sparsely populated. Stem cell applications and therapies are being considered to offer an outstanding potential in the treatment for numbers of maladies. Human induced pluripotent stem cells (iPSCs are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state. Although the exact mechanisms underlying are still unclear, iPSCs are already being considered as useful tools for drug development/screening and modeling of diseases. Recently, personalized medicines have drawn great attentions in biological and pharmaceutical studies. Generally speaking, personalized medicine is a therapeutic model that offers a customized healthcare/cure being tailored to a specific patient based on his own genetic information. Consequently, the combination of nanomedicine and iPSCs could actually be the potent arms for remedies in transplantation medicine and personalized medicine. This review will focus on current use of nanoparticles on therapeutical applications, nanomedicine

  19. A validated disease specific prediction equation for resting metabolic rate in underweight patients with COPD

    Directory of Open Access Journals (Sweden)

    Anita Nordenson

    2010-09-01

    Full Text Available Anita Nordenson2, Anne Marie Grönberg1,2, Lena Hulthén1, Sven Larsson2, Frode Slinde11Department of Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden; 2Department of Internal Medicine/Respiratory Medicine and Allergology, Sahlgrenska Academy at University of Gothenburg, SwedenAbstract: Malnutrition is a serious condition in chronic obstructive pulmonary disease (COPD. Successful dietary intervention calls for calculations of resting metabolic rate (RMR. One disease-specific prediction equation for RMR exists based on mainly male patients. To construct a disease-specific equation for RMR based on measurements in underweight or weight-losing women and men with COPD, RMR was measured by indirect calorimetry in 30 women and 11 men with a diagnosis of COPD and body mass index <21 kg/m2. The following variables, possibly influencing RMR were measured: length, weight, middle upper arm circumference, triceps skinfold, body composition by dual energy x-ray absorptiometry and bioelectrical impedance, lung function, and markers of inflammation. Relations between RMR and measured variables were studied using univariate analysis according to Pearson. Gender and variables that were associated with RMR with a P value <0.15 were included in a forward multiple regression analysis. The best-fit multiple regression equation included only fat-free mass (FFM: RMR (kJ/day = 1856 + 76.0 FFM (kg. To conclude, FFM is the dominating factor influencing RMR. The developed equation can be used for prediction of RMR in underweight COPD patients.Keywords: pulmonary disease, chronic obstructive, basal metabolic rate, malnutrition, body composition

  20. Iterative robust adaptive beamforming

    Science.gov (United States)

    Li, Yang; Ma, Hong; Cheng, Li

    2017-12-01

    The minimum power distortionless response beamformer has a good interference rejection capability, but the desired signal will be suppressed if signal steering vector or data covariance matrix is not precise. The worst-case performance optimization-based robust adaptive beamformer (WCB) has been developed to solve this problem. However, the solution of WCB cannot be expressed in a closed form, and its performance is affected by a prior parameter, which is the steering vector error norm bound of the desired signal. In this paper, we derive an approximate diagonal loading expression of WCB. This expression reveals a feedback loop relationship between steering vector and weight vector. Then, a novel robust adaptive beamformer is developed based on the iterative implementation of this feedback loop. Theoretical analysis indicates that as the iterative step increases, the performance of the proposed beamformer gets better and the iteration converges. Furthermore, the proposed beamformer does not subject to the steering vector error norm bound constraint. Simulation examples show that the proposed beamformer has better performance than some classical and similar beamformers.

  1. Robust Cultural Pluralism

    Directory of Open Access Journals (Sweden)

    Richard A. Shweder

    2013-11-01

    Full Text Available In this wide ranging interview, Professor Richard A. Shweder from the Department of Comparative Human Development at the University of Chicago, discusses whether it is or is not possible to be a robust cultural pluralist and a dedicated political liberal at the same time. In this discussion, Professor Shweder offers his insights - based on over 40 years of research - on issues related to the history and re-emergence of cultural psychology; moral anthropology and psychology; the experimental method in psychological investigation and its philosophical basis; contemporary and historical cultural collisions – most notably conflicting representations of female genital surgeries; cultural diversity and inequality; and the dissemination of ideas through open access publishing and Twitter. Professor Shweder ends by offering valuable advice to young researchers in the field of cultural psychology as well as a glimpse into the larger themes of his forthcoming book, which seeks to provide answers to the question of what forms of political liberalism are most compatible with robust cultural pluralism and which are not.

  2. Association of IL-10 level and IL-10 promoter SNPs with specific antibodies in penicillin-allergic patients.

    Science.gov (United States)

    Qiao, Hai-Ling; Wen, Qiang; Gao, Na; Tian, Xin; Jia, Lin-Jing

    2007-03-01

    Our aim was to investigate the hypothesis that the sera interleukin-10 (IL-10) level and polymorphic nucleotides within the IL-10 gene promoters would link to specific IgE and IgG production and the expression of penicillin allergy. One hundred and two patients and 86 healthy subjects were chosen for assay of serum IL-10 level by enzyme-linked immunosorbent assay (ELISA) and type -1082 G/A and -819 C/T alleles by sequence-specific primer polymerase chain reaction (SSP-PCR). Radioallergosorbent test (RAST) and ELISA were used to examine eight types of specific immunoglobulin-E (IgE) and IgG antibodies, respectively, which included four types of antibodies to major and minor antigenic determinants. Compared with control subjects and patients with negative-specific IgE, there were significantly lower levels of IL-10 in patients with positive-specific IgE (P allergic patients with negative-specific IgG (P allergic-history group. Compared with controls and patients with negative antibodies, a significantly decreased frequency of the -1082 G allele was present in patients with positive antibodies (P allergic reaction to penicillins. The distributions of genotype and frequency of allele at the -1082 G/A position may be associated with the production of both specific IgE and IgG antibodies.

  3. Robustness Analysis and Tractability in Modeling

    NARCIS (Netherlands)

    Lisciandra, Chiara

    In the philosophy of science and epistemology literature, robustness analysis has become an umbrella term that refers to a variety of strategies. One of the main purposes of this paper is to argue that different strategies rely on different criteria for justifications. More specifically, I will

  4. Induced radioactivity in a patient-specific collimator used in proton therapy

    CERN Document Server

    Silari, M; Mauro, Egidio; Silari, Marco

    2010-01-01

    This paper discusses the activation of a patient-specific collimator, calculating dose rates, total activities and activities per unit mass of the mixture of radionuclides generated by proton irradiation in the energy range 100-250 MeV. Monte Carlo simulations were first performed for a generic case, using an approximate geometry and on the basis of assumptions on beam intensity and irradiation profile. A collimator used for a prostate cancer treatment was obtained from the MD Anderson Cancer Center (MDACC), Houston, USA, from which a number of samples were cut and analyzed by gamma spectrometry. The results of the gamma spectrometry are compared with the results of Monte Carlo simulations performed using geometrical and irradiation data specific to the unit. The assumptions made for the simulations and their impact on the results are discussed. Dose rate measurements performed in a low-background area at CERN and routine radiation protection measurements at the MDACC are also reported. It is shown that it sh...

  5. Planning acetabular fracture reduction using patient-specific multibody simulation of the hip

    Science.gov (United States)

    Oliveri, Hadrien; Boudissa, Mehdi; Tonetti, Jerome; Chabanas, Matthieu

    2017-03-01

    Acetabular fractures are a challenge in orthopedic surgery. Computer-aided solutions were proposed to segment bone fragments, simulate the fracture reduction or design the osteosynthesis fixation plates. This paper addresses the simulation part, which is usually carried out by freely moving bone fragments with six degrees of freedom to reproduce the pre-fracture state. Instead we propose a different paradigm, closer to actual surgeon's requirements: to simulate the surgical procedure itself rather than the desired result. A simple, patient-specific, biomechanical multibody model is proposed, integrating the main ligaments and muscles of the hip joint while accounting for contacts between bone fragments. Main surgical tools and actions can be simulated, such as clamps, Schanz screws or traction of the femur. Simulations are computed interactively, which enables clinicians to evaluate different strategies for an optimal surgical planning. Six retrospective cases were studied, with simple and complex fracture patterns. After interactively building the models from preoperative CT, gestures from the surgical reports were reproduced. Results of the simulations could then be compared with postoperative CT data. A qualitative study shows the model behavior is excellent and the simulated reductions fit the observed data. A more quantitative analysis is currently being completed. Two cases are particularly significant, for which the surgical reduction actually failed. Simulations show it was indeed not possible to reduce these fractures with the chosen approach. Had our simulator being used, a better planning may have avoided a second surgery to these patients.

  6. Remote ECG Monitoring Kit to Predict Patient-Specific Heart Abnormalities

    Directory of Open Access Journals (Sweden)

    Jiaming Chen

    2017-08-01

    Full Text Available Electrocardiogram (ECG signals are widely used to examine heart rhythms and general health conditions. However, the majority of commercial ECG kits are generic and their normal ranges are set based on the averages obtained from a large population of people with normal heart conditions. This averaging ignores the extreme inherent variability of normal heart signals. As such, many false alarms are generated if the thresholds are selected too strict and true alarms are missed if the thresholds are set too loose. Furthermore, false alarms may arise due to the high physical activity of the test person. In this paper, we developed a prototype for patient-specific heart monitoring kit, which learns the properties of a patient's normal ECG signal over time and reports significant deviations from this normal behavior, in addition to presenting significant violations from the global norms. Further, false alarms due to high physical activity levels are eliminated through processing the utilized accelerometer signal. This personalized remote heart monitoring kit with the proposed signal processing and self-tuning capabilities and wireless connectivity provides more detailed information and insightful interpretations of ECG signals compared to generic devices, therefore can be used for remote heart monitoring of high-risk people.

  7. An augmented reality system for patient-specific guidance of cardiac catheter ablation procedures.

    Science.gov (United States)

    De Buck, Stijn; Maes, Frederik; Ector, Joris; Bogaert, Jan; Dymarkowski, Steven; Heidbüchel, Hein; Suetens, Paul

    2005-11-01

    We present a system to assist in the treatment of cardiac arrhythmias by catheter ablation. A patient-specific three-dimensional (3-D) anatomical model, constructed from magnetic resonance images, is merged with fluoroscopic images in an augmented reality environment that enables the transfer of electrocardiography (ECG) measurements and cardiac activation times onto the model. Accurate mapping is realized through the combination of: a new calibration technique, adapted to catheter guided treatments; a visual matching registration technique, allowing the electrophysiologist to align the model with contrast-enhanced images; and the use of virtual catheters, which enable the annotation of multiple ECG measurements on the model. These annotations can be visualized by color coding on the patient model. We provide an accuracy analysis of each of these components independently. Based on simulation and experiments, we determined a segmentation error of 0.6 mm, a calibration error in the order of 1 mm and a target registration error of 1.04 +/- 0.45 mm. The system provides a 3-D visualization of the cardiac activation pattern which may facilitate and improve diagnosis and treatment of the arrhytmia. Because of its low cost and similar advantages we believe our approach can compete with existing commercial solutions, which rely on dedicated hardware and costly catheters. We provide qualitative results of the first clinical use of the system in 11 ablation procedures.

  8. Surgical guides (patient-specific instruments) for pediatric tibial bone sarcoma resection and allograft reconstruction.

    Science.gov (United States)

    Bellanova, Laura; Paul, Laurent; Docquier, Pierre-Louis

    2013-01-01

    To achieve local control of malignant pediatric bone tumors and to provide satisfactory oncological results, adequate resection margins are mandatory. The local recurrence rate is directly related to inappropriate excision margins. The present study describes a method for decreasing the resection margin width and ensuring that the margins are adequate. This method was developed in the tibia, which is a common site for the most frequent primary bone sarcomas in children. Magnetic resonance imaging (MRI) and computerized tomography (CT) were used for preoperative planning to define the cutting planes for the tumors: each tumor was segmented on MRI, and the volume of the tumor was coregistered with CT. After preoperative planning, a surgical guide (patient-specific instrument) that was fitted to a unique position on the tibia was manufactured by rapid prototyping. A second instrument was manufactured to adjust the bone allograft to fit the resection gap accurately. Pathologic evaluation of the resected specimens showed tumor-free resection margins in all four cases. The technologies described in this paper may improve the surgical accuracy and patient safety in surgical oncology. In addition, these techniques may decrease operating time and allow for reconstruction with a well-matched allograft to obtain stable osteosynthesis.

  9. Surgical Guides (Patient-Specific Instruments for Pediatric Tibial Bone Sarcoma Resection and Allograft Reconstruction

    Directory of Open Access Journals (Sweden)

    Laura Bellanova

    2013-01-01

    Full Text Available To achieve local control of malignant pediatric bone tumors and to provide satisfactory oncological results, adequate resection margins are mandatory. The local recurrence rate is directly related to inappropriate excision margins. The present study describes a method for decreasing the resection margin width and ensuring that the margins are adequate. This method was developed in the tibia, which is a common site for the most frequent primary bone sarcomas in children. Magnetic resonance imaging (MRI and computerized tomography (CT were used for preoperative planning to define the cutting planes for the tumors: each tumor was segmented on MRI, and the volume of the tumor was coregistered with CT. After preoperative planning, a surgical guide (patient-specific instrument that was fitted to a unique position on the tibia was manufactured by rapid prototyping. A second instrument was manufactured to adjust the bone allograft to fit the resection gap accurately. Pathologic evaluation of the resected specimens showed tumor-free resection margins in all four cases. The technologies described in this paper may improve the surgical accuracy and patient safety in surgical oncology. In addition, these techniques may decrease operating time and allow for reconstruction with a well-matched allograft to obtain stable osteosynthesis.

  10. Numerical simulations of the blood flow in the patient-specific arterial cerebral circle region.

    Science.gov (United States)

    Reorowicz, Piotr; Obidowski, Damian; Klosinski, Przemyslaw; Szubert, Wojciech; Stefanczyk, Ludomir; Jozwik, Krzysztof

    2014-05-07

    The Cerebral Circle Region, also known as the Circle of Willis (CoW), is a loop of arteries that form arterial connections between supply arteries to distribute blood throughout the cerebral mass. Among the population, only 25% to 50% have a complete system of arteries forming the CoW. 3D time-varying simulations for three different patient-specific artery anatomies of CoW were performed in order to gain a better insight into the phenomena existing in the cerebral blood flow. The models reconstructed on the basis of computer tomography images start from the aorta and include the largest arteries that supply the CoW and the arteries of CoW. Velocity values measured during the ultrasound examination have been compared with the results of simulations. It is shown that the flow in the right anterior artery in some cases may be supplied from the left internal carotid artery via the anterior communicating artery. The investigations conducted show that the computational fluid dynamic tool, which provides high resolution in both time and space domains, can be used to support physicians in diagnosing patients of different ages and various anatomical arterial structures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Reconstruction with a patient-specific titanium implant after a wide anterior chest wall resection

    Science.gov (United States)

    Turna, Akif; Kavakli, Kuthan; Sapmaz, Ersin; Arslan, Hakan; Caylak, Hasan; Gokce, Hasan Suat; Demirkaya, Ahmet

    2014-01-01

    The reconstruction of full-thickness chest wall defects is a challenging problem for thoracic surgeons, particularly after a wide resection of the chest wall that includes the sternum. The location and the size of the defect play a major role when selecting the method of reconstruction, while acceptable cosmetic and functional results remain the primary goal. Improvements in preoperative imaging techniques and reconstruction materials have an important role when planning and performing a wide chest wall resection with a low morbidity rate. In this report, we describe the reconstruction of a wide anterior chest wall defect with a patient-specific custom-made titanium implant. An infected mammary tumour recurrence in a 62-year old female, located at the anterior chest wall including the sternum, was resected, followed by a large custom-made titanium implant. Latissimus dorsi flap and split-thickness graft were also used for covering the implant successfully. A titanium custom-made chest wall implant could be a viable alternative for patients who had large chest wall tumours. PMID:24227881

  12. Patient Specific Seizure Prediction System Using Hilbert Spectrum and Bayesian Networks Classifiers

    Directory of Open Access Journals (Sweden)

    Nilufer Ozdemir

    2014-01-01

    Full Text Available The aim of this paper is to develop an automated system for epileptic seizure prediction from intracranial EEG signals based on Hilbert-Huang transform (HHT and Bayesian classifiers. Proposed system includes decomposition of the signals into intrinsic mode functions for obtaining features and use of Bayesian networks with correlation based feature selection for binary classification of preictal and interictal recordings. The system was trained and tested on Freiburg EEG database. 58 hours of preictal data, 40-minute data blocks prior to each of 87 seizures collected from 21 patients, and 503.1 hours of interictal data were examined resulting in 96.55% sensitivity with 0.21 false alarms per hour, 13.896% average proportion of time spent in warning, and 33.21 minutes of average detection latency using 30-second EEG segments with 50% overlap and a simple postprocessing technique resulting in a decision (a seizure is expected/not expected every 5 minutes. High sensitivity and low false positive rate with reasonable detection latency show that HHT based features are acceptable for patient specific seizure prediction from intracranial EEG data. Time spent for testing an EEG segment was 4.1451 seconds on average, which makes the system viable for use in real-time seizure control systems.

  13. Splintless orthognathic surgery: a novel technique using patient-specific implants (PSI).

    Science.gov (United States)

    Gander, Thomas; Bredell, Marius; Eliades, Theodore; Rücker, Martin; Essig, Harald

    2015-04-01

    In the past few years, advances in three-dimensional imaging have conducted to breakthrough in the diagnosis, treatment planning and result assessment in orthognathic surgery. Hereby error-prone and time-consuming planning steps, like model surgery and transfer of the face bow, can be eluded. Numerous positioning devices, in order to transfer the three-dimensional treatment plan to the intraoperative site, have been described. Nevertheless the use of positioning devices and intraoperative splints are failure-prone and time-consuming steps, which have to be performed during the operation and during general anesthesia of the patient. We describe a novel time-sparing and failsafe technique using patient-specific implants (PSI) as positioning guides and concurrently as rigid fixation of the maxilla in the planned position. This technique avoids elaborate positioning and removal of manufactured positioning devices and allows maxillary positioning without the use of occlusal splints. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  14. Robustness Metrics: Consolidating the multiple approaches to quantify Robustness

    DEFF Research Database (Denmark)

    Göhler, Simon Moritz; Eifler, Tobias; Howard, Thomas J.

    2016-01-01

    determined to be conceptually different from one another. The metrics were classified by their meaning and interpretation based on the types of information necessary to calculate the metrics. Four different classes were identified: 1) Sensitivity robustness metrics; 2) Size of feasible design space......, this ambiguity can have significant influence on the strategies used to combat variability, the way it is quantified and ultimately, the quality of the final design. In this contribution the literature for robustness metrics was systematically reviewed. From the 108 relevant publications found, 38 metrics were...... robustness metrics; 3) Functional expectancy and dispersion robustness metrics; and 4) Probability of conformance robustness metrics. The goal was to give a comprehensive overview of robustness metrics and guidance to scholars and practitioners to understand the different types of robustness metrics...

  15. More specific bands in the IgG western blot in sera from Scottish patients with suspected Lyme borreliosis.

    Science.gov (United States)

    Evans, Roger; Mavin, Sally; McDonagh, Susan; Chatterton, Jean M W; Milner, Rachel; Ho-Yen, Darrel O

    2010-08-01

    To identify further Western blot bands that may be specific in the diagnosis of Lyme borreliosis. The Borrelia burgdorferi antibody profiles of 270 western blot positive patients and 241 western blot negative patients from 2008 were examined. 27 different non-specific bands were detected in both groups. Six of 27 (22%) of the non-specific bands were detected significantly more in the western blot positive patients compared to the western blot negative patients (20 kDa, p<0.0001; 28 kDa, p<0.002; 36 kDa, p<0.002; 37 kDa, p<0.007; 48 kDa, p<0.023; 56 kDa, p<0.028; two-tailed F test). Results suggest that the 20, 28 and 48 kDa bands should be regarded as specific.

  16. Clinimetric evaluation of methods to measure muscle functioning in patients with non-specific neck pain: a systematic review

    National Research Council Canada - National Science Library

    Koning, C.H. de; Heuvel, SP van den; Staal, J.B; Smits-Engelsman, B.C.M; Heniks, E.J.M

    2008-01-01

    .... This article provides a critical analysis of the research literature on the clinimetric properties of tests to measure neck muscle strength or endurance in patients with non-specific neck pain, which...

  17. Factors associated with disease-specific survival of patients with non-small cell lung cancer.

    Science.gov (United States)

    Souza, Mirian Carvalho de; Cruz, Oswaldo Gonçalves; Vasconcelos, Ana Glória Godoi

    2016-01-01

    Lung cancer is a global public health problem and is associated with high mortality. Lung cancer could be largely avoided by reducing the prevalence of smoking. The objective of this study was to analyze the effects of social, behavioral, and clinical factors on the survival time of patients with non-small cell lung cancer treated at Cancer Hospital I of the José Alencar Gomes da Silva National Cancer Institute, located in the city of Rio de Janeiro, Brazil, between 2000 and 2003. This was a retrospective hospital cohort study involving 1,194 patients. The 60-month disease-specific survival probabilities were calculated with the Kaplan-Meier method for three stage groups. The importance of the studied factors was assessed with a hierarchical theoretical model after adjustment by Cox multiple regression. The estimated 60-month specific-disease lethality rate was 86.0%. The 60-month disease-specific survival probability ranged from 25.0% (stages I/II) to 2.5% (stage IV). The performance status, the intention to treat, and the initial treatment modality were the major prognostic factors identified in the study population. In this cohort of patients, the disease-specific survival probabilities were extremely low. We identified no factors that could be modified after the diagnosis in order to improve survival. Primary prevention, such as reducing the prevalence of smoking, is still the best method to reduce the number of people who will suffer the consequences of lung cancer. O câncer de pulmão é um problema de saúde pública global e é associado a elevada mortalidade. Ele poderia ser evitado em grande parte com a redução da prevalência do tabagismo. O objetivo deste estudo foi analisar os efeitos de fatores sociais, comportamentais e clínicos sobre o tempo de sobrevida de pacientes com câncer de pulmão de células não pequenas atendidos, entre 2000 e 2003, no Hospital do Câncer I do Instituto Nacional de Câncer José Alencar Gomes da Silva, localizado na

  18. Patient-specific 3D printed model in delineating brain glioma and surrounding structures in a pediatric patient

    Directory of Open Access Journals (Sweden)

    Ivan Lau

    2017-01-01

    Full Text Available Background and Objectives: Three-dimensional (3D printing has been increasingly used in medicine with applications in the diagnostic assessment of disease extent, medical education and training, preoperative planning, and surgical simulation. The use of 3D printing in brain tumors is very limited. In this study, we presented our preliminary experience of creating patient-specific 3D printed model of a brain tumor in a pediatric patient and demonstrated the feasibility of using 3D printing in delineating brain anatomy and tumor. Materials and Methods: A life-size 3D printed brain model of a 6-year-old girl, who was diagnosed with pilocytic astrocytoma, was generated. The model was created using high-resolution magnetic resonance images which were postprocessed and segmented to demonstrate normal anatomical structures and the tumor. The tumor was confirmed to be Grade I pilocytic astrocytoma after neurosurgery. Results: 3D printed model was found to provide realistic visualization of brain anatomical structures and tumor, and enhance understanding of pathology in relation to the surrounding structures. The mean difference in diameter measurements of the brain tumor was 0.53 mm (0.98% between the 3D printed model and computerized model. Conclusions: This study shows it is feasible to generate a 3D printed model of brain tumor with encouraging results achieved to replicate brain anatomy and tumor. 3D printed model of brain tumor could serve as an excellent tool for preoperative planning and simulation of surgical procedures, which deserve to be investigated in further studies.

  19. Cause-Specific Cardiovascular Risk Associated with Nonsteroidal Anti-Inflammatory Drugs among Myocardial Infarction Patients - A Nationwide Study

    DEFF Research Database (Denmark)

    Olsen, Anne-Marie Schjerning; Fosbøl, Emil L; Lindhardsen, Jesper

    2013-01-01

    Non steroidal anti-inflammatory drugs (NSAIDs) increase mortality and morbidity after myocardial infarction (MI). We examined cause-specific mortality and morbidity associated with NSAIDs in a nationwide cohort of MI patients.......Non steroidal anti-inflammatory drugs (NSAIDs) increase mortality and morbidity after myocardial infarction (MI). We examined cause-specific mortality and morbidity associated with NSAIDs in a nationwide cohort of MI patients....

  20. Dose-Specific Adverse Drug Reaction Identification in Electronic Patient Records: Temporal Data Mining in an Inpatient Psychiatric Population

    DEFF Research Database (Denmark)

    Eriksson, Robert; Werge, Thomas; Jensen, Lars Juhl

    2014-01-01

    all indication areas.The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner.We used a psychiatric hospital’s EPR system to investigate undesired drug effects. Within one workflow the method identified...... patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength.When applying the method to the 3,394 patients......Data collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across...

  1. International Conference on Robust Statistics

    CERN Document Server

    Filzmoser, Peter; Gather, Ursula; Rousseeuw, Peter

    2003-01-01

    Aspects of Robust Statistics are important in many areas. Based on the International Conference on Robust Statistics 2001 (ICORS 2001) in Vorau, Austria, this volume discusses future directions of the discipline, bringing together leading scientists, experienced researchers and practitioners, as well as younger researchers. The papers cover a multitude of different aspects of Robust Statistics. For instance, the fundamental problem of data summary (weights of evidence) is considered and its robustness properties are studied. Further theoretical subjects include e.g.: robust methods for skewness, time series, longitudinal data, multivariate methods, and tests. Some papers deal with computational aspects and algorithms. Finally, the aspects of application and programming tools complete the volume.

  2. A Randomized Clinical Trial Comparing the ELLIPTA and HandiHaler Dry Powder Inhalers in Patients With COPD: Inhaler-Specific Attributes and Overall Patient Preference.

    Science.gov (United States)

    Collison, Kathryn A; Patel, Pinal; Preece, Andrew F; Stanford, Richard H; Sharma, Raj K; Feldman, Gregory

    2017-12-11

    This randomised, open-label, cross-over, placebo-containing inhaler study assessed patient preference indicators for ELLIPTA and HandiHaler dry powder inhalers in patients with COPD (NCT02786927; GSK identifier: 204983). The primary objective of this study was to assess patient preference between ELLIPTA and HandiHaler based on the number of steps needed to use the inhaler. Eligible patients ≥40 years of age with COPD were randomised 1:1 to receive their current COPD medication plus a placebo-containing ELLIPTA or HandiHaler inhaler once daily for 7 ± 2 days (treatment period 1); this was followed by a 7 ± 2-day placebo treatment with the alternative inhaler. A 5-item questionnaire assessed inhaler-related patient preferences. A total of 212 patients (mean age, 65.1 years) were enrolled at 22 US sites; 73% had a COPD duration ≥5 years. Median (range) exposure was 8 ( 5 , 13 ) days for ELLIPTA and 8 ( 1 , 16) days for HandiHaler. Significantly more patients preferred ELLIPTA to HandiHaler in terms of the number of steps to use and all secondary attributes (size, comfort of the mouthpiece, remaining doses, and ease of use of the two inhalers; all p < 0.001). Similar results were observed irrespective of the order of inhaler use. Eighteen patients (8%) reported at least one AE and two (<1%) patients reported four non-fatal SAEs; none were related to the study treatment. Patient attitude toward a particular inhaler and their experiences in using it can affect adherence to therapy, which can in turn strongly influence effectiveness of inhaled medications. This study uses a robust methodology to assess patient preference.

  3. Robust procedures in chemometrics

    DEFF Research Database (Denmark)

    Kotwa, Ewelina

    and comparing the Partial Least Squares (PLS) regression technique with its multi-way alternative, N-PLS. Results of the analysis indicated superiority of the three-way frame-work, potentially constituting a novel assessment of the sea water measurements. Particularly in the case of regression models......The general aim of the thesis was to contribute to the improvement of data analytical techniques within the chemometric field. Regardless the multivariate structure of the data, it is still common in some fields to perform uni-variate data analysis using only simple statistics such as sample mean...... if contamination in the data is present. For this becoming a standard procedure, further work is required, aiming at implementing reliable robust algorithms into standard statistical programs....

  4. Robust Multimodal Dictionary Learning

    Science.gov (United States)

    Cao, Tian; Jojic, Vladimir; Modla, Shannon; Powell, Debbie; Czymmek, Kirk; Niethammer, Marc

    2014-01-01

    We propose a robust multimodal dictionary learning method for multimodal images. Joint dictionary learning for both modalities may be impaired by lack of correspondence between image modalities in training data, for example due to areas of low quality in one of the modalities. Dictionaries learned with such non-corresponding data will induce uncertainty about image representation. In this paper, we propose a probabilistic model that accounts for image areas that are poorly corresponding between the image modalities. We cast the problem of learning a dictionary in presence of problematic image patches as a likelihood maximization problem and solve it with a variant of the EM algorithm. Our algorithm iterates identification of poorly corresponding patches and re-finements of the dictionary. We tested our method on synthetic and real data. We show improvements in image prediction quality and alignment accuracy when using the method for multimodal image registration. PMID:24505674

  5. Passion, Robustness and Perseverance

    DEFF Research Database (Denmark)

    Lim, Miguel Antonio; Lund, Rebecca

    2016-01-01

    Evaluation and merit in the measured university are increasingly based on taken-for-granted assumptions about the “ideal academic”. We suggest that the scholar now needs to show that she is passionate about her work and that she gains pleasure from pursuing her craft. We suggest that passion...... passion and pleasure, in a twisted way, persist in the measured university and contribute to the increasing polarization between those who succeed and those who do not....... and pleasure achieve an exalted status as something compulsory. The scholar ought to feel passionate about her work and signal that she takes pleasure also in the difficult moments. Passion has become a signal of robustness and perseverance in a job market characterised by funding shortages, increased pressure...

  6. Robust Optical Flow Estimation

    Directory of Open Access Journals (Sweden)

    Javier Sánchez Pérez

    2013-10-01

    Full Text Available n this work, we describe an implementation of the variational method proposed by Brox etal. in 2004, which yields accurate optical flows with low running times. It has several benefitswith respect to the method of Horn and Schunck: it is more robust to the presence of outliers,produces piecewise-smooth flow fields and can cope with constant brightness changes. Thismethod relies on the brightness and gradient constancy assumptions, using the information ofthe image intensities and the image gradients to find correspondences. It also generalizes theuse of continuous L1 functionals, which help mitigate the effect of outliers and create a TotalVariation (TV regularization. Additionally, it introduces a simple temporal regularizationscheme that enforces a continuous temporal coherence of the flow fields.

  7. Robust automated knowledge capture.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens-Adams, Susan Marie; Abbott, Robert G.; Forsythe, James Chris; Trumbo, Michael Christopher Stefan; Haass, Michael Joseph; Hendrickson, Stacey M. Langfitt

    2011-10-01

    This report summarizes research conducted through the Sandia National Laboratories Robust Automated Knowledge Capture Laboratory Directed Research and Development project. The objective of this project was to advance scientific understanding of the influence of individual cognitive attributes on decision making. The project has developed a quantitative model known as RumRunner that has proven effective in predicting the propensity of an individual to shift strategies on the basis of task and experience related parameters. Three separate studies are described which have validated the basic RumRunner model. This work provides a basis for better understanding human decision making in high consequent national security applications, and in particular, the individual characteristics that underlie adaptive thinking.

  8. Specific serum IgE levels and FcepsilonRIbeta genetic polymorphism in patients with penicillins allergy.

    Science.gov (United States)

    Qiao, H-L; Yang, J; Zhang, Y-W

    2004-12-01

    Numerous studies have suggested that both genetic and environmental influences are involved in the pathogenesis of allergic disease and atopy. The objective of this investigation is to elucidate the underlying mechanism of penicillins allergy and improve the diagnostic methods. Radioallergosorbent test was used to examine eight kinds of specific IgE antibodies, which included four kinds of major and minor antigenic determinants, respectively, in the sera of 448 patients with penicillins allergy and 101 healthy subjects. A restriction endonuclease fragment length polymorphism of a polymerase chain reaction product was used for analysis of the FcepsilonRIbeta polymorphism. The positive rate of specific IgE in 448 patients was 58.26% (261), in which 37.28% (167) patients had positive IgE to major antigenic determinants and 47.09% (211) patients had positive IgE to minor antigenic determinants. Of the 179 patients with allergic history, 70.83% (17/24) patients had positive antibodies within 30 days, while 45.28% (24/53) had positive antibodies after 5 years. The positive reaction degree of skin test was absolutely correlated with specific IgE (P=0.047). Among patients with positive specific IgE, significant differences of E237G genotype were observed between patients with positive benzylpenicillanyl (BPA)-, phenoxomethylpenicilloyl (PVO)- or ampicilloyl (APO)-IgE and control group (P=0.015, 0.015, and 0.008, respectively). There were significant differences in E237G genotype between positive and negative BPA-, PVO- as well as APO-IgE patients (P = 0.014, 0.02, and 0.011, respectively). The patients with penicillins allergy have positive specific IgE not only to major antigenic determinants but also to minor antigenic determinants. The E237G variant of the FcepsilonRIbeta gene is involved in the development of penicillins allergy through the process for the production of specific IgE antibodies.

  9. Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

    Directory of Open Access Journals (Sweden)

    Mani Harika eVemula

    2016-03-01

    Full Text Available Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis (M.tb, the tuberculosis (TB causing bacilli in human is cleared by cell-mediated immunity (CMI with CD4+ T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches towards vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M.tb Zinc metalloprotease-1 (Zmp1, a secretory protein essential for intracellular survival and pathogenesis of M.tb. We observed that Zmp1 was secreted by in vitro grown M.tb under granuloma-like stress conditions (acidic, oxidative, iron deficiency and nutrient deprivation and generated Th2 cytokine microenvironment upon exogenous treatment of Peripheral Blood Mononulear Cells (PBMCs with recombinant Zmp1 (rZmp1. This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n=121 as against healthy control (n=62, household contacts (n=89 and non-specific infection controls (n=23. A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL to paucibacillary smear-negative pulmonary tuberculosis (PTB cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can be explored as antigen

  10. Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients

    DEFF Research Database (Denmark)

    Doherty, T Mark; Demissie, Abebech; Olobo, Joseph

    2002-01-01

    Diagnosis of latent Mycobacterium tuberculosis infection is considered essential for tuberculosis control but is hampered by the lack of specific reagents. We report that strong recognition of tuberculosis complex-specific antigen ESAT-6 by healthy household contacts of tuberculosis patients...... correlates with the subsequent development of active tuberculosis during a 2-year follow-up period....

  11. Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients

    DEFF Research Database (Denmark)

    Doherty, T Mark; Demissie, Abebech; Olobo, Joseph

    2002-01-01

    Diagnosis of latent Mycobacterium tuberculosis infection is considered essential for tuberculosis control but is hampered by the lack of specific reagents. We report that strong recognition of tuberculosis complex-specific antigen ESAT-6 by healthy household contacts of tuberculosis patients...

  12. The Streptococcus milleri population of a cystic fibrosis clinic reveals patient specificity and intraspecies diversity.

    Science.gov (United States)

    Sibley, Christopher D; Sibley, Kristen A; Leong, Tara A; Grinwis, Margot E; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2010-07-01

    The genetic relatedness of Streptococcus milleri group isolates from the airways of cystic fibrosis patients was determined by using pulsed-field gel electrophoresis. This study reveals no evidence for patient-to-patient transmission in our patient population; however, within individual patients, complex inter- and intraspecies diversity and dynamics can be observed.

  13. Prostate-specific antigen as an estimator of prostate volume in the management of patients with symptomatic benign prostatic hyperplasia

    NARCIS (Netherlands)

    Mochtar, CA; Kiemeney, LALM; van Riemsdijk, MM; Barnett, GS; Laguna, MP; Debruyne, FMJ; de la Rosette, JJMCH

    2003-01-01

    Objectives: To assess the ability of serum prostate specific antigen (PSA) to estimate prostate volume (PV) to aid in the management of patients with benign prostatic hyperplasia (BPH). Methods: From 1989 to 2002, data were collected from 2264 patients complaining of lower urinary tract symptoms

  14. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity

    NARCIS (Netherlands)

    Koraka, Penelopie; Murgue, Bernadette; Deparis, Xavier; Setiati, Tatty E.; Suharti, Catarina; van Gorp, Eric C. M.; Hack, C. E.; Osterhaus, Albert D. M. E.; Groen, Jan

    2003-01-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue

  15. Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: A prospective study

    Directory of Open Access Journals (Sweden)

    Storm Christian

    2012-01-01

    Full Text Available Abstract Background Neuron specific enolase (NSE has repeatedly been evaluated for neurological prognostication in patients after cardiac arrest. However, it is unclear whether current guidelines for NSE cutoff levels also apply to cardiac arrest patients treated with hypothermia. Thus, we investigated the prognostic significance of absolute NSE levels and NSE kinetics in cardiac arrest patients treated with hypothermia. Methods In a prospective study of 35 patients resuscitated from cardiac arrest, NSE was measured daily for four days following admission. Outcome was assessed at ICU discharge using the CPC score. All patients received hypothermia treatment for 24 hours at 33°C with a surface cooling device according to current guidelines. Results The cutoff for absolute NSE levels in patients with unfavourable outcome (CPC 3-5 72 hours after cardiac arrest was 57 μg/l with an area under the curve (AUC of 0.82 (sensitivity 47%, specificity 100%. The cutoff level for NSE kinetics in patients with unfavourable outcome (CPC 3-5 was an absolute increase of 7.9 μg/l (AUC 0.78, sensitivity 63%, specificity 100% and a relative increase of 33.1% (AUC 0.803, sensitivity 67%, specificity 100% at 48 hours compared to admission. Conclusion In cardiac arrest patients treated with hypothermia, prognostication of unfavourable outcome by NSE kinetics between admission and 48 hours after resuscitation may be superior to prognostication by absolute NSE levels.

  16. Melanoma patients' disease-specific knowledge, information preference, and appreciation of educational YouTube videos for self-inspection

    NARCIS (Netherlands)

    Damude, S.; Hoekstra-Weebers, J. E. H. M.; van Leeuwen, B. L.; Hoekstra, H. J.

    Background: Informing and educating melanoma patients is important for early detection of a recurrence or second primary. This study aimed to investigate Dutch melanoma patients' disease-specific knowledge, and their opinions on information provision and the value of e-Health videos. Methods: All

  17. Inter-tester reliability of a new diagnostic classification system for patients with non-specific low back pain

    DEFF Research Database (Denmark)

    Petersen, Tom Erik; Olsen, Steen; Laslett, Mark

    2004-01-01

    Most patients referred to physiotherapy with low back pain are without a precise medical diagnosis. Identification of subgroups of non-specific low back pain patients may improve clinical outcomes and research efficiency. A pathoanatomic classification system has been developed, classifying...

  18. Patient-specific core decompression surgery for early-stage ischemic necrosis of the femoral head.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available Core decompression is an efficient treatment for early stage ischemic necrosis of the femoral head. In conventional procedures, the pre-operative X-ray only shows one plane of the ischemic area, which often results in inaccurate drilling. This paper introduces a new method that uses computer-assisted technology and rapid prototyping to enhance drilling accuracy during core decompression surgeries and presents a validation study of cadaveric tests.Twelve cadaveric human femurs were used to simulate early-stage ischemic necrosis. The core decompression target at the anterolateral femoral head was simulated using an embedded glass ball (target. Three positioning Kirschner wires were drilled into the top and bottom of the large rotor. The specimen was then subjected to computed tomography (CT. A CT image of the specimen was imported into the Mimics software to construct a three-dimensional model including the target. The best core decompression channel was then designed using the 3D model. A navigational template for the specimen was designed using the Pro/E software and manufactured by rapid prototyping technology to guide the drilling channel. The specimen-specific navigation template was installed on the specimen using positioning Kirschner wires. Drilling was performed using a guide needle through the guiding hole on the templates. The distance between the end point of the guide needle and the target was measured to validate the patient-specific surgical accuracy.The average distance between the tip of the guide needle drilled through the guiding template and the target was 1.92±0.071 mm.Core decompression using a computer-rapid prototyping template is a reliable and accurate technique that could provide a new method of precision decompression for early-stage ischemic necrosis.

  19. CloudNeo: a cloud pipeline for identifying patient-specific tumor neoantigens.

    Science.gov (United States)

    Bais, Preeti; Namburi, Sandeep; Gatti, Daniel M; Zhang, Xinyu; Chuang, Jeffrey H

    2017-10-01

    We present CloudNeo, a cloud-based computational workflow for identifying patient-specific tumor neoantigens from next generation sequencing data. Tumor-specific mutant peptides can be detected by the immune system through their interactions with the human leukocyte antigen complex, and neoantigen presence has recently been shown to correlate with anti T-cell immunity and efficacy of checkpoint inhibitor therapy. However computing capabilities to identify neoantigens from genomic sequencing data are a limiting factor for understanding their role. This challenge has grown as cancer datasets become increasingly abundant, making them cumbersome to sto