Sample records for pca improves resolution

  1. [An improved low spectral distortion PCA fusion method].

    PubMed

    Peng, Shi; Zhang, Ai-Wu; Li, Han-Lun; Hu, Shao-Xing; Meng, Xian-Gang; Sun, Wei-Dong

    2013-10-01

    Aiming at the spectral distortion produced in PCA fusion process, the present paper proposes an improved low spectral distortion PCA fusion method. This method uses NCUT (normalized cut) image segmentation algorithm to make a complex hyperspectral remote sensing image into multiple sub-images for increasing the separability of samples, which can weaken the spectral distortions of traditional PCA fusion; Pixels similarity weighting matrix and masks were produced by using graph theory and clustering theory. These masks are used to cut the hyperspectral image and high-resolution image into some sub-region objects. All corresponding sub-region objects between the hyperspectral image and high-resolution image are fused by using PCA method, and all sub-regional integration results are spliced together to produce a new image. In the experiment, Hyperion hyperspectral data and Rapid Eye data were used. And the experiment result shows that the proposed method has the same ability to enhance spatial resolution and greater ability to improve spectral fidelity performance.

  2. A diffusion-matched principal component analysis (DM-PCA) based two-channel denoising procedure for high-resolution diffusion-weighted MRI

    PubMed Central

    Chang, Hing-Chiu; Bilgin, Ali; Bernstein, Adam; Trouard, Theodore P.

    2018-01-01

    Over the past several years, significant efforts have been made to improve the spatial resolution of diffusion-weighted imaging (DWI), aiming at better detecting subtle lesions and more reliably resolving white-matter fiber tracts. A major concern with high-resolution DWI is the limited signal-to-noise ratio (SNR), which may significantly offset the advantages of high spatial resolution. Although the SNR of DWI data can be improved by denoising in post-processing, existing denoising procedures may potentially reduce the anatomic resolvability of high-resolution imaging data. Additionally, non-Gaussian noise induced signal bias in low-SNR DWI data may not always be corrected with existing denoising approaches. Here we report an improved denoising procedure, termed diffusion-matched principal component analysis (DM-PCA), which comprises 1) identifying a group of (not necessarily neighboring) voxels that demonstrate very similar magnitude signal variation patterns along the diffusion dimension, 2) correcting low-frequency phase variations in complex-valued DWI data, 3) performing PCA along the diffusion dimension for real- and imaginary-components (in two separate channels) of phase-corrected DWI voxels with matched diffusion properties, 4) suppressing the noisy PCA components in real- and imaginary-components, separately, of phase-corrected DWI data, and 5) combining real- and imaginary-components of denoised DWI data. Our data show that the new two-channel (i.e., for real- and imaginary-components) DM-PCA denoising procedure performs reliably without noticeably compromising anatomic resolvability. Non-Gaussian noise induced signal bias could also be reduced with the new denoising method. The DM-PCA based denoising procedure should prove highly valuable for high-resolution DWI studies in research and clinical uses. PMID:29694400

  3. Energy resolution improvement of CdTe detectors by using the principal component analysis technique

    NASA Astrophysics Data System (ADS)

    Alharbi, T.

    2018-02-01

    In this paper, we report on the application of the Principal Component Analysis (PCA) technique for the improvement of the γ-ray energy resolution of CdTe detectors. The PCA technique is used to estimate the amount of charge-trapping effect which is reflected in the shape of each detector pulse, thereby correcting for the charge-trapping effect. The details of the method are described and the results obtained with a CdTe detector are shown. We have achieved an energy resolution of 1.8 % (FWHM) at 662 keV with full detection efficiency from a 1 mm thick CdTe detector which gives an energy resolution of 4.5 % (FWHM) by using the standard pulse processing method.

  4. Performance of Ultrafast DCE-MRI for Diagnosis of Prostate Cancer.

    PubMed

    Chatterjee, Aritrick; He, Dianning; Fan, Xiaobing; Wang, Shiyang; Szasz, Teodora; Yousuf, Ambereen; Pineda, Federico; Antic, Tatjana; Mathew, Melvy; Karczmar, Gregory S; Oto, Aytekin

    2018-03-01

    This study aimed to test high temporal resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for different zones of the prostate and evaluate its performance in the diagnosis of prostate cancer (PCa). Determine whether the addition of ultrafast DCE-MRI improves the performance of multiparametric MRI. Patients (n = 20) with pathologically confirmed PCa underwent preoperative 3T MRI with T2-weighted, diffusion-weighted, and high temporal resolution (~2.2 seconds) DCE-MRI using gadoterate meglumine (Guerbet, Bloomington, IN) without an endorectal coil. DCE-MRI data were analyzed by fitting signal intensity with an empirical mathematical model to obtain parameters: percent signal enhancement, enhancement rate (α), washout rate (β), initial enhancement slope, and enhancement start time along with apparent diffusion coefficient (ADC) and T2 values. Regions of interests were placed on sites of prostatectomy verified malignancy (n = 46) and normal tissue (n = 71) from different zones. Cancer (α = 6.45 ± 4.71 s -1 , β = 0.067 ± 0.042 s -1 , slope = 3.78 ± 1.90 s -1 ) showed significantly (P <.05) faster signal enhancement and washout rates than normal tissue (α = 3.0 ± 2.1 s -1 , β = 0.034 ± 0.050 s -1 , slope = 1.9 ± 1.4 s -1 ), but showed similar percentage signal enhancement and enhancement start time. Receiver operating characteristic analysis showed area under the curve for DCE parameters was comparable to ADC and T2 in the peripheral (DCE 0.67-0.82, ADC 0.80, T2 0.89) and transition zones (DCE 0.61-0.72, ADC 0.69, T2 0.75), but higher in the central zone (DCE 0.79-0.88, ADC 0.45, T2 0.45) and anterior fibromuscular stroma (DCE 0.86-0.89, ADC 0.35, T2 0.12). Importantly, combining DCE with ADC and T2 increased area under the curve by ~30%, further improving the diagnostic accuracy of PCa detection. Quantitative parameters from empirical mathematical model fits to ultrafast DCE-MRI improve diagnosis of PCa. DCE-MRI with higher temporal resolution may capture clinically useful information for PCa diagnosis that would be missed by low temporal resolution DCE-MRI. This new information could improve the performance of multiparametric MRI in PCa detection. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  5. Satellite image fusion based on principal component analysis and high-pass filtering.

    PubMed

    Metwalli, Mohamed R; Nasr, Ayman H; Allah, Osama S Farag; El-Rabaie, S; Abd El-Samie, Fathi E

    2010-06-01

    This paper presents an integrated method for the fusion of satellite images. Several commercial earth observation satellites carry dual-resolution sensors, which provide high spatial resolution or simply high-resolution (HR) panchromatic (pan) images and low-resolution (LR) multi-spectral (MS) images. Image fusion methods are therefore required to integrate a high-spectral-resolution MS image with a high-spatial-resolution pan image to produce a pan-sharpened image with high spectral and spatial resolutions. Some image fusion methods such as the intensity, hue, and saturation (IHS) method, the principal component analysis (PCA) method, and the Brovey transform (BT) method provide HR MS images, but with low spectral quality. Another family of image fusion methods, such as the high-pass-filtering (HPF) method, operates on the basis of the injection of high frequency components from the HR pan image into the MS image. This family of methods provides less spectral distortion. In this paper, we propose the integration of the PCA method and the HPF method to provide a pan-sharpened MS image with superior spatial resolution and less spectral distortion. The experimental results show that the proposed fusion method retains the spectral characteristics of the MS image and, at the same time, improves the spatial resolution of the pan-sharpened image.

  6. FFT-enhanced IHS transform method for fusing high-resolution satellite images

    USGS Publications Warehouse

    Ling, Y.; Ehlers, M.; Usery, E.L.; Madden, M.

    2007-01-01

    Existing image fusion techniques such as the intensity-hue-saturation (IHS) transform and principal components analysis (PCA) methods may not be optimal for fusing the new generation commercial high-resolution satellite images such as Ikonos and QuickBird. One problem is color distortion in the fused image, which causes visual changes as well as spectral differences between the original and fused images. In this paper, a fast Fourier transform (FFT)-enhanced IHS method is developed for fusing new generation high-resolution satellite images. This method combines a standard IHS transform with FFT filtering of both the panchromatic image and the intensity component of the original multispectral image. Ikonos and QuickBird data are used to assess the FFT-enhanced IHS transform method. Experimental results indicate that the FFT-enhanced IHS transform method may improve upon the standard IHS transform and the PCA methods in preserving spectral and spatial information. ?? 2006 International Society for Photogrammetry and Remote Sensing, Inc. (ISPRS).

  7. Impact of PCA Strategies on Pain Intensity and Functional Assessment Measures in Adults with Sickle Cell Disease during Hospitalized Vaso-Occlusive Episodes

    PubMed Central

    Dampier, Carlton D.; Wager, Carrie G.; Harrison, Ryan; Hsu, Lewis L.; Minniti, Caterina P.; Smith, Wally R.

    2012-01-01

    Clinical trials of sickle cell disease (SCD) pain treatment usually observe only small decrements in pain intensity during the course of hospitalization. Sub-optimal analgesic management and inadequate pain assessment methods are possible explanations for these findings. In a search for better methods for assessing inpatient SCD pain in adults, we examined several pain intensity and interference measures in both arms of a randomized controlled trial comparing two different opioid PCA therapies. Based upon longitudinal analysis of pain episodes, we found that scores from daily average Visual Analogue Scales (VAS) and several other measures, especially the Brief Pain Inventory (BPI), were sensitive to change in daily improvements in pain intensity associated with resolution of vaso-occlusive pain. In this preliminary trial, the low demand, high basal infusion (LDHI) strategy demonstrated faster, larger improvements in various measures of pain than the high demand, low basal infusion (HDLI) strategy for opioid PCA dosing, however, verification in larger studies is required. The measures and statistical approaches used in this analysis may facilitate design, reduce sample size, and improve analyses of treatment response in future SCD clinical trials of vaso-occlusive episodes. PMID:22886853

  8. Distribution of a low dose compound within pharmaceutical tablet by using multivariate curve resolution on Raman hyperspectral images.

    PubMed

    Boiret, Mathieu; de Juan, Anna; Gorretta, Nathalie; Ginot, Yves-Michel; Roger, Jean-Michel

    2015-01-25

    In this work, Raman hyperspectral images and multivariate curve resolution-alternating least squares (MCR-ALS) are used to study the distribution of actives and excipients within a pharmaceutical drug product. This article is mainly focused on the distribution of a low dose constituent. Different approaches are compared, using initially filtered or non-filtered data, or using a column-wise augmented dataset before starting the MCR-ALS iterative process including appended information on the low dose component. In the studied formulation, magnesium stearate is used as a lubricant to improve powder flowability. With a theoretical concentration of 0.5% (w/w) in the drug product, the spectral variance contained in the data is weak. By using a principal component analysis (PCA) filtered dataset as a first step of the MCR-ALS approach, the lubricant information is lost in the non-explained variance and its associated distribution in the tablet cannot be highlighted. A sufficient number of components to generate the PCA noise-filtered matrix has to be used in order to keep the lubricant variability within the data set analyzed or, otherwise, work with the raw non-filtered data. Different models are built using an increasing number of components to perform the PCA reduction. It is shown that the magnesium stearate information can be extracted from a PCA model using a minimum of 20 components. In the last part, a column-wise augmented matrix, including a reference spectrum of the lubricant, is used before starting MCR-ALS process. PCA reduction is performed on the augmented matrix, so the magnesium stearate contribution is included within the MCR-ALS calculations. By using an appropriate PCA reduction, with a sufficient number of components, or by using an augmented dataset including appended information on the low dose component, the distribution of the two actives, the two main excipients and the low dose lubricant are correctly recovered. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Object-based assessment of burn severity in diseased forests using high-spatial and high-spectral resolution MASTER airborne imagery

    NASA Astrophysics Data System (ADS)

    Chen, Gang; Metz, Margaret R.; Rizzo, David M.; Dillon, Whalen W.; Meentemeyer, Ross K.

    2015-04-01

    Forest ecosystems are subject to a variety of disturbances with increasing intensities and frequencies, which may permanently change the trajectories of forest recovery and disrupt the ecosystem services provided by trees. Fire and invasive species, especially exotic disease-causing pathogens and insects, are examples of disturbances that together could pose major threats to forest health. This study examines the impacts of fire and exotic disease (sudden oak death) on forests, with an emphasis on the assessment of post-fire burn severity in a forest where trees have experienced three stages of disease progression pre-fire: early-stage (trees retaining dried foliage and fine twigs), middle-stage (trees losing fine crown fuels), and late-stage (trees falling down). The research was conducted by applying Geographic Object-Based Image Analysis (GEOBIA) to MASTER airborne images that were acquired immediately following the fire for rapid assessment and contained both high-spatial (4 m) and high-spectral (50 bands) resolutions. Although GEOBIA has gradually become a standard tool for analyzing high-spatial resolution imagery, high-spectral resolution data (dozens to hundreds of bands) can dramatically reduce computation efficiency in the process of segmentation and object-based variable extraction, leading to complicated variable selection for succeeding modeling. Hence, we also assessed two widely used band reduction algorithms, PCA (principal component analysis) and MNF (minimum noise fraction), for the delineation of image objects and the subsequent performance of burn severity models using either PCA or MNF derived variables. To increase computation efficiency, only the top 5 PCA and MNF and top 10 PCA and MNF components were evaluated, which accounted for 10% and 20% of the total number of the original 50 spectral bands, respectively. Results show that if no band reduction was applied the models developed for the three stages of disease progression had relatively similar performance, where both spectral responses and texture contributed to burn assessments. However, the application of PCA and MNF introduced much greater variation among models across the three stages. For the early-stage disease progression, neither band reduction algorithms improved or retained the accuracy of burn severity modeling (except for the use of 10 MNF components). Compared to the no-band-reduction scenario, band reduction led to a greater level of overestimation of low-degree burns and underestimation of medium-degree burns, suggesting that the spectral variation removed by PCA and MNF was vital for distinguishing between the spectral reflectance from disease-induced dried crowns (still retaining high structural complexity) and fire ash. For the middle-stage, both algorithms improved the model R2 values by 2-37%, while the late-stage models had comparable or better performance to those using the original 50 spectral bands. This could be explained by the loss of tree crowns enabling better signal penetration, thus leading to reduced spectral variation from canopies. Hence, spectral bands containing a high degree of random noise were correctly removed by the band reduction algorithms. Compared to the middle-stage, the late-stage forest stands were covered by large piles of fallen trees and branches, resulting in higher variability of MASTER imagery. The ability of band reduction to improve the model performance for these late-stage forest stands was reduced, because the valuable spectral variation representing the actual late-stage forest status was partially removed by both algorithms as noise. Our results indicate that PCA and MNF are promising for balancing computation efficiency and the performance of burn severity models in forest stands subject to the middle and late stages of sudden oak death disease progression. Compared to PCA, MNF dramatically reduced image spectral variation, generating larger image objects with less complexity of object shapes. Whereas, PCA-based models delivered superior performance in most evaluated cases suggesting that some key spectral variability contributing to the accuracy of burn severity models in diseased forests may have been removed together with true spectral noise through MNF transformations.

  10. Performance evaluation of BPM system in SSRF using PCA method

    NASA Astrophysics Data System (ADS)

    Chen, Zhi-Chu; Leng, Yong-Bin; Yan, Ying-Bing; Yuan, Ren-Xian; Lai, Long-Wei

    2014-07-01

    The beam position monitor (BPM) system is of most importance in a light source. The capability of the BPM depends on the resolution of the system. The traditional standard deviation on the raw data method merely gives the upper limit of the resolution. Principal component analysis (PCA) had been introduced in the accelerator physics and it could be used to get rid of the actual signals. Beam related information was extracted before the evaluation of the BPM performance. A series of studies had been made in the Shanghai Synchrotron Radiation Facility (SSRF) and PCA was proved to be an effective and robust method in the performance evaluations of our BPM system.

  11. Improved accuracy of quantitative parameter estimates in dynamic contrast-enhanced CT study with low temporal resolution

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Sun Mo, E-mail: Sunmo.Kim@rmp.uhn.on.ca; Haider, Masoom A.; Jaffray, David A.

    Purpose: A previously proposed method to reduce radiation dose to patient in dynamic contrast-enhanced (DCE) CT is enhanced by principal component analysis (PCA) filtering which improves the signal-to-noise ratio (SNR) of time-concentration curves in the DCE-CT study. The efficacy of the combined method to maintain the accuracy of kinetic parameter estimates at low temporal resolution is investigated with pixel-by-pixel kinetic analysis of DCE-CT data. Methods: The method is based on DCE-CT scanning performed with low temporal resolution to reduce the radiation dose to the patient. The arterial input function (AIF) with high temporal resolution can be generated with a coarselymore » sampled AIF through a previously published method of AIF estimation. To increase the SNR of time-concentration curves (tissue curves), first, a region-of-interest is segmented into squares composed of 3 × 3 pixels in size. Subsequently, the PCA filtering combined with a fraction of residual information criterion is applied to all the segmented squares for further improvement of their SNRs. The proposed method was applied to each DCE-CT data set of a cohort of 14 patients at varying levels of down-sampling. The kinetic analyses using the modified Tofts’ model and singular value decomposition method, then, were carried out for each of the down-sampling schemes between the intervals from 2 to 15 s. The results were compared with analyses done with the measured data in high temporal resolution (i.e., original scanning frequency) as the reference. Results: The patients’ AIFs were estimated to high accuracy based on the 11 orthonormal bases of arterial impulse responses established in the previous paper. In addition, noise in the images was effectively reduced by using five principal components of the tissue curves for filtering. Kinetic analyses using the proposed method showed superior results compared to those with down-sampling alone; they were able to maintain the accuracy in the quantitative histogram parameters of volume transfer constant [standard deviation (SD), 98th percentile, and range], rate constant (SD), blood volume fraction (mean, SD, 98th percentile, and range), and blood flow (mean, SD, median, 98th percentile, and range) for sampling intervals between 10 and 15 s. Conclusions: The proposed method of PCA filtering combined with the AIF estimation technique allows low frequency scanning for DCE-CT study to reduce patient radiation dose. The results indicate that the method is useful in pixel-by-pixel kinetic analysis of DCE-CT data for patients with cervical cancer.« less

  12. Advances in the RXTE Proportional Counter Array Calibration: Nearing the Statistical Limit

    NASA Technical Reports Server (NTRS)

    Shaposhnikov, Nikolai; Jahoda, Keith; Markwardt, Craig; Swank, Jean; Strohmayer, Tod

    2012-01-01

    During its 16 years of service Rossi X-ray Timing Explorer (RXTE) mission has provided an extensive archive of data, which will serve as a primary source of high cadence observation of variable X-ray sources for fast timing studies. It is, therefore, very important to have the most reliable calibration of RXTE instruments. The Proportional Counter Array (PCA) is the primary instrument on-board RXTE which provides data in 2-50 keY with higher than millisecond time resolution in up to 256 energy channels. In 2009 RXTE team revised the response residual minimization method used to derive the parameters of the PCA physical model. The procedure is now based on the residual minimization between the model spectrum for Crab nebula emission and a calibration data set consisting of a number of spectra from the Crab and the on-board Am241 calibration source, uniformly covering a whole RXTE span. The new method led to a much more effective model convergence and allowed for better understanding of the behavior of the PCA energy-to-channel relationship. It greatly improved the response matrix performance. We describe the new version of the RXTE/PCA response generator PCARMF vll.7 along with the corresponding energy-to-channel conversion table (version e05v04) and their difference from the previous releases of PCA calibration. The new PCA response adequately represents the spectrum of the calibration sources and successfully predicts the energy of the narrow iron emission line in Cas-A throughout the RXTE mission.

  13. Transabdominal contrast-enhanced ultrasound imaging of the prostate.

    PubMed

    Mischi, Massimo; Demi, Libertario; Smeenge, Martijn; Kuenen, Maarten P J; Postema, Arnoud W; de la Rosette, Jean J M C H; Wijkstra, Hessel

    2015-04-01

    Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time-intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r(2) = 0.91 (r(2) > 0.75 for 78.6% of all prostate pixels) compared with r(2) = 0.91 (r(2) > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitoring. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. Does adding ketamine to morphine patient-controlled analgesia safely improve post-thoracotomy pain?

    PubMed

    Mathews, Timothy J; Churchhouse, Antonia M D; Housden, Tessa; Dunning, Joel

    2012-02-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'is the addition of ketamine to morphine patient-controlled analgesia (PCA) following thoracic surgery superior to morphine alone'. Altogether 201 papers were found using the reported search, of which nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This consisted of one systematic review of PCA morphine with ketamine (PCA-MK) trials, one meta-analysis of PCA-MK trials, four randomized controlled trials of PCA-MK, one meta-analysis of trials using a variety of peri-operative ketamine regimes and two cohort studies of PCA-MK. Main outcomes measured included pain score rated on visual analogue scale, morphine consumption and incidence of psychotomimetic side effects/hallucination. Two papers reported the measurements of respiratory function. This evidence shows that adding ketamine to morphine PCA is safe, with a reported incidence of hallucination requiring intervention of 2.9%, and a meta-analysis finding an incidence of all central nervous system side effects of 18% compared with 15% with morphine alone, P = 0.31, RR 1.27 with 95% CI (0.8-2.01). All randomized controlled trials of its use following thoracic surgery found no hallucination or psychological side effect. All five studies in thoracic surgery (n = 243) found reduced morphine requirements with PCA-MK. Pain scores were significantly lower in PCA-MK patients in thoracic surgery papers, with one paper additionally reporting increased patient satisfaction. However, no significant improvement was found in a meta-analysis of five papers studying PCA-MK in a variety of surgical settings. Both papers reporting respiratory outcomes found improved oxygen saturations and PaCO(2) levels in PCA-MK patients following thoracic surgery. We conclude that adding low-dose ketamine to morphine PCA is safe and post-thoracotomy may provide better pain control than PCA with morphine alone (PCA-MO), with reduced morphine consumption and possible improvement in respiratory function. These studies thus support the routine use of PCA-MK instead of PCA-MO to improve post-thoracotomy pain control.

  15. [Interest of evaluation of professional practice for the improvement of the management of postoperative pain with patient controlled analgesia (PCA)].

    PubMed

    Baumann, A; Cuignet-Royer, E; Cornet, C; Trueck, S; Heck, M; Taron, F; Peignier, C; Chastel, A; Gervais, P; Bouaziz, H; Audibert, G; Mertes, P-M

    2010-10-01

    To evaluate the daily practice of postoperative PCA in Nancy University Hospital, in continuity with a quality program of postoperative pain (POP) care conducted in 2003. A retrospective audit of patient medical records. A review of all the medical records of consecutive surgical patients managed by PCA over a 5-week period in six surgical services. Criteria studied: Evaluation of hospital means (eight criteria) and of medical and nursing staff practice (16 criteria). A second audit was conducted 6 months after the implementation of quality improvement measures. Assessment of the hospital means: temperature chart including pain scores and PCA drug consumption, patient information leaflet, PCA protocol, postoperative pre-filled prescription form (PFPF) for post-anaesthesia care including PCA, and optional training of nurses in postoperative pain management. EVALUATION OF PRACTICES: One hundred and fifty-nine files of a total of 176 patients were analyzed (88%). Improvements noted after 6 months: trace of POP evaluation progressed from 73 to 87%, advance prescription of PCA adjustment increased from 56 to 68% and of the treatment of adverse effects from 54 to 68%, trace of PCA adaptation by attending nurse from 15 to 43%, trace of the administration of the treatment of adverse effects by attending nurse from 24% to 64%, as did the use of PFPF from 59 to 70%. The usefulness of a pre-filled prescription form for post-anaesthesia care including PCA prescription is demonstrated. Quality improvement measures include: poster information and pocket guides on PCA for nurses, training of 3 nurses per service to act as "PCA advisers" who will in turn train their ward colleagues in PCA management and the use of equipment until an acute pain team is established. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  16. Cherenkov radiation-based three-dimensional position-sensitive PET detector: A Monte Carlo study.

    PubMed

    Ota, Ryosuke; Yamada, Ryoko; Moriya, Takahiro; Hasegawa, Tomoyuki

    2018-05-01

    Cherenkov radiation has recently received attention due to its prompt emission phenomenon, which has the potential to improve the timing performance of radiation detectors dedicated to positron emission tomography (PET). In this study, a Cherenkov-based three-dimensional (3D) position-sensitive radiation detector was proposed, which is composed of a monolithic lead fluoride (PbF 2 ) crystal and a photodetector array of which the signals can be readout independently. Monte Carlo simulations were performed to estimate the performance of the proposed detector. The position- and time resolution were evaluated under various practical conditions. The radiator size and various properties of the photodetector, e.g., readout pitch and single photon timing resolution (SPTR), were parameterized. The single photon time response of the photodetector was assumed to be a single Gaussian for the simplification. The photo detection efficiency of the photodetector was ideally 100% for all wavelengths. Compton scattering was included in simulations, but partly analyzed. To estimate the position at which a γ-ray interacted in the Cherenkov radiator, the center-of-gravity (COG) method was employed. In addition, to estimate the depth-of-interaction (DOI) principal component analysis (PCA), which is a multivariate analysis method and has been used to identify the patterns in data, was employed. The time-space distribution of Cherenkov photons was quantified to perform PCA. To evaluate coincidence time resolution (CTR), the time difference of two independent γ-ray events was calculated. The detection time was defined as the first photon time after the SPTR of the photodetector was taken into account. The position resolution on the photodetector plane could be estimated with high accuracy, by using a small number of Cherenkov photons. Moreover, PCA showed an ability to estimate the DOI. The position resolution heavily depends on the pitch of the photodetector array and the radiator thickness. If the readout pitch were ideally 0 and practically 3 mm, a full-width at half-maximum (FWHM) of 0.348 and 1.92 mm was achievable with a 10-mm-thick PbF 2 crystal, respectively. Furthermore, first-order correlation could be observed between the primary principal component and the true DOI. To obtain a coincidence timing resolution better than 100-ps FWHM with a 20-mm-thick PbF 2 crystal, a photodetector with SPTR of better than σ = 30 ps was necessary. From these results, the improvement of SPTR allows us to achieve CTR better than 100-ps FWHM, even in the case where a 20-mm-thick radiator is used. Our proposed detector has the potential to estimate the 3D interaction position of γ-rays in the radiator, using only time and space information of Cherenkov photons. © 2018 American Association of Physicists in Medicine.

  17. Structured Sparse Principal Components Analysis With the TV-Elastic Net Penalty.

    PubMed

    de Pierrefeu, Amicie; Lofstedt, Tommy; Hadj-Selem, Fouad; Dubois, Mathieu; Jardri, Renaud; Fovet, Thomas; Ciuciu, Philippe; Frouin, Vincent; Duchesnay, Edouard

    2018-02-01

    Principal component analysis (PCA) is an exploratory tool widely used in data analysis to uncover the dominant patterns of variability within a population. Despite its ability to represent a data set in a low-dimensional space, PCA's interpretability remains limited. Indeed, the components produced by PCA are often noisy or exhibit no visually meaningful patterns. Furthermore, the fact that the components are usually non-sparse may also impede interpretation, unless arbitrary thresholding is applied. However, in neuroimaging, it is essential to uncover clinically interpretable phenotypic markers that would account for the main variability in the brain images of a population. Recently, some alternatives to the standard PCA approach, such as sparse PCA (SPCA), have been proposed, their aim being to limit the density of the components. Nonetheless, sparsity alone does not entirely solve the interpretability problem in neuroimaging, since it may yield scattered and unstable components. We hypothesized that the incorporation of prior information regarding the structure of the data may lead to improved relevance and interpretability of brain patterns. We therefore present a simple extension of the popular PCA framework that adds structured sparsity penalties on the loading vectors in order to identify the few stable regions in the brain images that capture most of the variability. Such structured sparsity can be obtained by combining, e.g., and total variation (TV) penalties, where the TV regularization encodes information on the underlying structure of the data. This paper presents the structured SPCA (denoted SPCA-TV) optimization framework and its resolution. We demonstrate SPCA-TV's effectiveness and versatility on three different data sets. It can be applied to any kind of structured data, such as, e.g., -dimensional array images or meshes of cortical surfaces. The gains of SPCA-TV over unstructured approaches (such as SPCA and ElasticNet PCA) or structured approach (such as GraphNet PCA) are significant, since SPCA-TV reveals the variability within a data set in the form of intelligible brain patterns that are easier to interpret and more stable across different samples.

  18. Increasing patient knowledge on the proper usage of a PCA machine with the use of a post-operative instructional card.

    PubMed

    Shovel, Louisa; Max, Bryan; Correll, Darin J

    2016-01-01

    The purpose of this study was to see if an instructional card, attached to the PCA machine following total hip arthroplasty describing proper use of the device, would positively affect subjects' understanding of device usage, pain scores, pain medication consumption and satisfaction. Eighty adults undergoing total hip replacements who had been prescribed PCA were randomized into two study groups. Forty participants received the standard post-operative instruction on PCA device usage at our institution. The other 40 participants received the standard of care in addition to being given a typed instructional card immediately post-operatively, describing proper PCA device use. This card was attached to the PCA device during their recovery period. On post-operative day one, each patient completed a questionnaire on PCA usage, pain scores and satisfaction scores. The pain scores in the Instructional Card group were significantly lower than the Control group (p = 0.024). Subjects' understanding of PCA usage was also improved in the Instructional Card group for six of the seven questions asked. The findings from this study strongly support that postoperative patient information on proper PCA use by means of an instructional card improves pain control and hence the overall recovery for patients undergoing surgery. In addition, through improved understanding it adds an important safety feature in that patients and potentially their family members and/or friends may refrain from PCA-by-proxy. This article demonstrates that the simple intervention of adding an instructional card to a PCA machine is an effective method to improve patients' knowledge as well as pain control and potentially increase the safety of the device use.

  19. Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes.

    PubMed

    Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M; Aleixandre, Rosa N; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

    2016-01-01

    New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic.

  20. Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes

    PubMed Central

    Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M.; Aleixandre, Rosa N.; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

    2016-01-01

    New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic. PMID:27279911

  1. Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy.

    PubMed

    Perdonà, Sisto; Bruzzese, Dario; Ferro, Matteo; Autorino, Riccardo; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; Longo, Michele; Spinelli, Rosa; Di Lorenzo, Giuseppe; Oliva, Andrea; De Sio, Marco; Damiano, Rocco; Altieri, Vincenzo; Terracciano, Daniela

    2013-02-15

    Prostate health index (phi) and prostate cancer antigen 3 (PCA3) have been recently proposed as novel biomarkers for prostate cancer (PCa). We assessed the diagnostic performance of these biomarkers, alone or in combination, in men undergoing first prostate biopsy for suspicion of PCa. One hundred sixty male subjects were enrolled in this prospective observational study. PSA molecular forms, phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay), and other established biomarkers (tPSA, fPSA, and %fPSA) were assessed before patients underwent a 18-core first prostate biopsy. The discriminating ability between PCa-negative and PCa-positive biopsies of Beckman coulter phi and PCA3 score and other used biomarkers were determined. One hundred sixty patients met inclusion criteria. %p2PSA (p2PSA/fPSA × 100), phi and PCA3 were significantly higher in patients with PCa compared to PCa-negative group (median values: 1.92 vs. 1.55, 49.97 vs. 36.84, and 50 vs. 32, respectively, P ≤ 0.001). ROC curve analysis showed that %p2PSA, phi, and PCA3 are good indicator of malignancy (AUCs = 0.68, 0.71, and 0.66, respectively). A multivariable logistic regression model consisting of both the phi index and PCA3 score allowed to reach an overall diagnostic accuracy of 0.77. Decision curve analysis revealed that this "combined" marker achieved the highest net benefit over the examined range of the threshold probability. phi and PCA3 showed no significant difference in the ability to predict PCa diagnosis in men undergoing first prostate biopsy. However, diagnostic performance is significantly improved by combining phi and PCA3. Copyright © 2012 Wiley Periodicals, Inc.

  2. Facilitating text reading in posterior cortical atrophy.

    PubMed

    Yong, Keir X X; Rajdev, Kishan; Shakespeare, Timothy J; Leff, Alexander P; Crutch, Sebastian J

    2015-07-28

    We report (1) the quantitative investigation of text reading in posterior cortical atrophy (PCA), and (2) the effects of 2 novel software-based reading aids that result in dramatic improvements in the reading ability of patients with PCA. Reading performance, eye movements, and fixations were assessed in patients with PCA and typical Alzheimer disease and in healthy controls (experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (experiment 2). Mean reading accuracy in patients with PCA was significantly worse (57%) compared with both patients with typical Alzheimer disease (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%-270%) and self-rated measures of reading. Data suggest a greater efficiency of fixations and eye movements under the single-word reading aid in patients with PCA. These findings demonstrate how neurologic characterization of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. This study provides Class III evidence that for patients with PCA, 2 software-based reading aids (single-word and double-word) improve reading accuracy. © 2015 American Academy of Neurology.

  3. Facilitating text reading in posterior cortical atrophy

    PubMed Central

    Rajdev, Kishan; Shakespeare, Timothy J.; Leff, Alexander P.; Crutch, Sebastian J.

    2015-01-01

    Objective: We report (1) the quantitative investigation of text reading in posterior cortical atrophy (PCA), and (2) the effects of 2 novel software-based reading aids that result in dramatic improvements in the reading ability of patients with PCA. Methods: Reading performance, eye movements, and fixations were assessed in patients with PCA and typical Alzheimer disease and in healthy controls (experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (experiment 2). Results: Mean reading accuracy in patients with PCA was significantly worse (57%) compared with both patients with typical Alzheimer disease (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%–270%) and self-rated measures of reading. Data suggest a greater efficiency of fixations and eye movements under the single-word reading aid in patients with PCA. Conclusions: These findings demonstrate how neurologic characterization of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. Classification of evidence: This study provides Class III evidence that for patients with PCA, 2 software-based reading aids (single-word and double-word) improve reading accuracy. PMID:26138948

  4. Physicochemical and mechanical properties of paracetamol cocrystal with 5-nitroisophthalic acid.

    PubMed

    Hiendrawan, Stevanus; Veriansyah, Bambang; Widjojokusumo, Edward; Soewandhi, Sundani Nurono; Wikarsa, Saleh; Tjandrawinata, Raymond R

    2016-01-30

    We report novel pharmaceutical cocrystal of a popular antipyretic drug paracetamol (PCA) with coformer 5-nitroisophhthalic acid (5NIP) to improve its tabletability. The cocrystal (PCA-5NIP at molar ratio of 1:1) was synthesized by solvent evaporation technique using methanol as solvent. The physicochemical properties of cocrystal were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), fourier transform infrared spectroscopy (FTIR), hot stage polarized microscopy (HSPM) and scanning electron microscopy (SEM). Stability of the cocrystal was assessed by storing them at 40°C/75% RH for one month. Compared to PCA, the cocrystal displayed superior tableting performance. PCA-5NIP cocrystal showed a similar dissolution profile as compared to PCA and exhibited good stability. This study showed the utility of PCA-5NIP cocrystal for improving mechanical properties of PCA. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer

    PubMed Central

    Tonry, Claire L.; Leacy, Emma; Raso, Cinzia; Finn, Stephen P.; Armstrong, John; Pennington, Stephen R.

    2016-01-01

    Prostate Cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA) is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent research efforts in the field of PCa biomarkers have focused on the identification of tissue and fluid-based biomarkers that would be better able to stratify those individuals diagnosed with PCa who (i) might best receive no treatment (active surveillance of the disease); (ii) would benefit from existing treatments; or (iii) those who are likely to succumb to disease recurrence and/or have aggressive disease. The growing demand for better prostate cancer biomarkers has coincided with the development of improved discovery and evaluation technologies for multiplexed measurement of proteins in bio-fluids and tissues. This review aims to (i) provide an overview of these technologies as well as describe some of the candidate PCa protein biomarkers that have been discovered using them; (ii) address some of the general limitations in the clinical evaluation and validation of protein biomarkers; and (iii) make recommendations for strategies that could be adopted to improve the successful development of protein biomarkers to deliver improvements in personalized PCa patient decision making. PMID:27438858

  6. [Patient-controlled Analgesia (PCA): an Overview About Methods, Handling and New Modalities].

    PubMed

    Abrolat, Marie; Eberhart, Leopold H J; Kalmus, Gerald; Koch, Tilo; Nardi-Hiebl, Stefan

    2018-04-01

    Patient-controlled analgesia (PCA) is one of the well established methods for the treatment of postoperative pain. A cochrane-review concluded that PCA is associated with better postoperative pain ratings and improved patient-satifaction compared to traditional way of administering opioids. Some prerequisites concerning patient selection, education of the patient and the medical staff, and supervision during PCA therapy are mandatory for a safe use of PCA. Current PCA modalities (intravenous and epidural routes of application) are expanded by newer, less invasive routes of drug administration, e.g. by the iontophoretic transdermal and the sublingual route. Their role in improving safety and the quality of pain therapy on the one hand side, and costs on the other hand side are discussion. Georg Thieme Verlag KG Stuttgart · New York.

  7. Prostate-Specific Antigen (PSA) Screening and New Biomarkers for Prostate Cancer (PCa)

    PubMed Central

    Rittenhouse, Harry; Hu, Xinhai; Cammann, Henning; Jung, Klaus

    2014-01-01

    Abstract PSA screening reduces PCa-mortality but the disadvantages overdiagnosis and overtreatment require multivariable risk-prediction tools to select appropriate treatment or active surveillance. This review explains the differences between the two largest screening trials and discusses the drawbacks of screening and its meta-analysisxs. The current American and European screening strategies are described. Nonetheless, PSA is one of the most widely used tumor markers and strongly correlates with the risk of harboring PCa. However, while PSA has limitations for PCa detection with its low specificity there are several potential biomarkers presented in this review with utility for PCa currently being studied. There is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. From all PSA-based markers, the FDA-approved prostate health index (phi) shows improved specificity over percent free and total PSA. Another kallikrein panel, 4K, which includes KLK2 has recently shown promise in clinical research studies but has not yet undergone formal validation studies. In urine, prostate cancer gene 3 (PCA3) has also been validated and approved by the FDA for its utility to detect PCa. The potential correlation of PCA3 with cancer aggressiveness requires more clinical studies. The detection of the fusion of androgen-regulated genes with genes of the regulatory transcription factors in tissue of ~50% of all PCa-patients is a milestone in PCa research. A combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 shows an improved accuracy for PCa detection. Overall, the field of PCa biomarker discovery is very exciting and prospective. PMID:27683457

  8. Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer.

    PubMed

    Wang, Jing; Wu, Chen-Jiang; Bao, Mei-Ling; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong

    2017-10-01

    To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. • Machine-based analysis of MR radiomics outperformed in TZ cancer against PI-RADS. • Adding MR radiomics significantly improved the performance of PI-RADS. • DKI-derived Dapp and Kapp were two strong markers for the diagnosis of PCa.

  9. Informative Feature Selection for Object Recognition via Sparse PCA

    DTIC Science & Technology

    2011-04-07

    constraint on images collected from low-power camera net- works instead of high-end photography is that establishing wide-baseline feature correspondence of...variable selection tool for selecting informative features in the object images captured from low-resolution cam- era sensor networks. Firstly, we...More examples can be found in Figure 4 later. 3. Identifying Informative Features Classical PCA is a well established tool for the analysis of high

  10. Testing the impact of a multimedia video CD of patient-controlled analgesia on pain knowledge and pain relief in patients receiving surgery.

    PubMed

    Chen, Hsing-Hsia; Yeh, Mei-Ling; Yang, Hui-Ju

    2005-07-01

    This study aimed to develop a multimedia video CD (VCD) of patient-controlled analgesia (PCA) and test its effects on pain knowledge and pain relief in patients receiving surgery. This multimedia VCD of PCA was created to convey fundamental knowledge to both patients and their family members and help patients properly utilize PCA devices to relieve pain and improve recovery. The content of multimedia VCD of PCA included pre-admission pain education, introduction of PCA, nursing care procedures, and questions and answers. This study used a quasi-experimental research design to test effects of the multimedia education program in the experimental group of 30 subjects compared to the control subjects of equal number (without the multimedia VCD of PCA). (1) The intervention of multimedia VCD of PCA resulted in a statistically significant difference in pain knowledge between the experimental and control groups. (2) Subjects in the experimental group obtained a better outcome of pain relief compared to control subjects. (3) Subjects in the experimental group indicated that the multimedia VCD of PCA indeed helped them effectively operate their PCA devices to relieve surgery pain. The clinical application of the multimedia VCD of PCA could help patients improve knowledge on pain, learn how to use PCA devices, achieve proper pain relief, and increase effectiveness of recovery activities.

  11. Progress Towards Improved Analysis of TES X-ray Data Using Principal Component Analysis

    NASA Technical Reports Server (NTRS)

    Busch, S. E.; Adams, J. S.; Bandler, S. R.; Chervenak, J. A.; Eckart, M. E.; Finkbeiner, F. M.; Fixsen, D. J.; Kelley, R. L.; Kilbourne, C. A.; Lee, S.-J.; hide

    2015-01-01

    The traditional method of applying a digital optimal filter to measure X-ray pulses from transition-edge sensor (TES) devices does not achieve the best energy resolution when the signals have a highly non-linear response to energy, or the noise is non-stationary during the pulse. We present an implementation of a method to analyze X-ray data from TESs, which is based upon principal component analysis (PCA). Our method separates the X-ray signal pulse into orthogonal components that have the largest variance. We typically recover pulse height, arrival time, differences in pulse shape, and the variation of pulse height with detector temperature. These components can then be combined to form a representation of pulse energy. An added value of this method is that by reporting information on more descriptive parameters (as opposed to a single number representing energy), we generate a much more complete picture of the pulse received. Here we report on progress in developing this technique for future implementation on X-ray telescopes. We used an 55Fe source to characterize Mo/Au TESs. On the same dataset, the PCA method recovers a spectral resolution that is better by a factor of two than achievable with digital optimal filters.

  12. Predictive spectroscopy and chemical imaging based on novel optical systems

    NASA Astrophysics Data System (ADS)

    Nelson, Matthew Paul

    1998-10-01

    This thesis describes two futuristic optical systems designed to surpass contemporary spectroscopic methods for predictive spectroscopy and chemical imaging. These systems are advantageous to current techniques in a number of ways including lower cost, enhanced portability, shorter analysis time, and improved S/N. First, a novel optical approach to predicting chemical and physical properties based on principal component analysis (PCA) is proposed and evaluated. A regression vector produced by PCA is designed into the structure of a set of paired optical filters. Light passing through the paired filters produces an analog detector signal directly proportional to the chemical/physical property for which the regression vector was designed. Second, a novel optical system is described which takes a single-shot approach to chemical imaging with high spectroscopic resolution using a dimension-reduction fiber-optic array. Images are focused onto a two- dimensional matrix of optical fibers which are drawn into a linear distal array with specific ordering. The distal end is imaged with a spectrograph equipped with an ICCD camera for spectral analysis. Software is used to extract the spatial/spectral information contained in the ICCD images and deconvolute them into wave length-specific reconstructed images or position-specific spectra which span a multi-wavelength space. This thesis includes a description of the fabrication of two dimension-reduction arrays as well as an evaluation of the system for spatial and spectral resolution, throughput, image brightness, resolving power, depth of focus, and channel cross-talk. PCA is performed on the images by treating rows of the ICCD images as spectra and plotting the scores of each PC as a function of reconstruction position. In addition, iterative target transformation factor analysis (ITTFA) is performed on the spectroscopic images to generate ``true'' chemical maps of samples. Univariate zero-order images, univariate first-order spectroscopic images, bivariate first-order spectroscopic images, and multivariate first-order spectroscopic images of the temporal development of laser-induced plumes are presented and interpreted. Reconstructed chemical images generated using bivariate and trivariate wavelength techniques, bimodal and trimodal PCA methods, and bimodal and trimodal ITTFA approaches are also included.

  13. Application of principal component analysis for improvement of X-ray fluorescence images obtained by polycapillary-based micro-XRF technique

    NASA Astrophysics Data System (ADS)

    Aida, S.; Matsuno, T.; Hasegawa, T.; Tsuji, K.

    2017-07-01

    Micro X-ray fluorescence (micro-XRF) analysis is repeated as a means of producing elemental maps. In some cases, however, the XRF images of trace elements that are obtained are not clear due to high background intensity. To solve this problem, we applied principal component analysis (PCA) to XRF spectra. We focused on improving the quality of XRF images by applying PCA. XRF images of the dried residue of standard solution on the glass substrate were taken. The XRF intensities for the dried residue were analyzed before and after PCA. Standard deviations of XRF intensities in the PCA-filtered images were improved, leading to clear contrast of the images. This improvement of the XRF images was effective in cases where the XRF intensity was weak.

  14. Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report.

    PubMed

    Francio, Vinicius T; Boesch, Ron; Tunning, Michael

    2015-03-01

    Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient's perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option.

  15. Simple motion correction strategy reduces respiratory-induced motion artifacts for k-t accelerated and compressed-sensing cardiovascular magnetic resonance perfusion imaging.

    PubMed

    Zhou, Ruixi; Huang, Wei; Yang, Yang; Chen, Xiao; Weller, Daniel S; Kramer, Christopher M; Kozerke, Sebastian; Salerno, Michael

    2018-02-01

    Cardiovascular magnetic resonance (CMR) stress perfusion imaging provides important diagnostic and prognostic information in coronary artery disease (CAD). Current clinical sequences have limited temporal and/or spatial resolution, and incomplete heart coverage. Techniques such as k-t principal component analysis (PCA) or k-t sparcity and low rank structure (SLR), which rely on the high degree of spatiotemporal correlation in first-pass perfusion data, can significantly accelerate image acquisition mitigating these problems. However, in the presence of respiratory motion, these techniques can suffer from significant degradation of image quality. A number of techniques based on non-rigid registration have been developed. However, to first approximation, breathing motion predominantly results in rigid motion of the heart. To this end, a simple robust motion correction strategy is proposed for k-t accelerated and compressed sensing (CS) perfusion imaging. A simple respiratory motion compensation (MC) strategy for k-t accelerated and compressed-sensing CMR perfusion imaging to selectively correct respiratory motion of the heart was implemented based on linear k-space phase shifts derived from rigid motion registration of a region-of-interest (ROI) encompassing the heart. A variable density Poisson disk acquisition strategy was used to minimize coherent aliasing in the presence of respiratory motion, and images were reconstructed using k-t PCA and k-t SLR with or without motion correction. The strategy was evaluated in a CMR-extended cardiac torso digital (XCAT) phantom and in prospectively acquired first-pass perfusion studies in 12 subjects undergoing clinically ordered CMR studies. Phantom studies were assessed using the Structural Similarity Index (SSIM) and Root Mean Square Error (RMSE). In patient studies, image quality was scored in a blinded fashion by two experienced cardiologists. In the phantom experiments, images reconstructed with the MC strategy had higher SSIM (p < 0.01) and lower RMSE (p < 0.01) in the presence of respiratory motion. For patient studies, the MC strategy improved k-t PCA and k-t SLR reconstruction image quality (p < 0.01). The performance of k-t SLR without motion correction demonstrated improved image quality as compared to k-t PCA in the setting of respiratory motion (p < 0.01), while with motion correction there is a trend of better performance in k-t SLR as compared with motion corrected k-t PCA. Our simple and robust rigid motion compensation strategy greatly reduces motion artifacts and improves image quality for standard k-t PCA and k-t SLR techniques in setting of respiratory motion due to imperfect breath-holding.

  16. Imaging of prostate cancer with PET/CT using 18F-Fluorocholine

    PubMed Central

    Vali, Reza; Loidl, Wolfgang; Pirich, Christian; Langesteger, Werner; Beheshti, Mohsen

    2015-01-01

    While 18F-Fluorodeoxyglucose (18F-FDG) Positron-Emission Tomography (PET) has limited value in prostate cancer (PCa), it may be useful for specific subgroups of PCa patients with hormone-resistant poorly differentiated cell types. 18F-Fluorocholine (18F-FCH) PET/CT has been increasingly used in primary and recurrent PCa and has been shown to add valuable information. Although there is a correlation between the foci of activity and the areas of malignancy in the prostate gland, the clinical value of 18F-FCH is still controversial for detection of the malignant focus in the prostate. For the T-staging of PCa at diagnosis the value of 18F-FCH is limited. This is probably due to limited resolution of PET system and positive findings in benign prostate diseases. Conversely, 18F-FCH PET/CT is a promising imaging modality for the delineation of local and distant nodal recurrence and bone metastases and is poised to have an impact on therapy management. In this review, recent studies of 18F-FCH PET/CT in PCa are summarized. PMID:25973332

  17. Using pan-sharpened high resolution satellite data to improve impervious surfaces estimation

    NASA Astrophysics Data System (ADS)

    Xu, Ru; Zhang, Hongsheng; Wang, Ting; Lin, Hui

    2017-05-01

    Impervious surface is an important environmental and socio-economic indicator for numerous urban studies. While a large number of researches have been conducted to estimate the area and distribution of impervious surface from satellite data, the accuracy for impervious surface estimation (ISE) is insufficient due to high diversity of urban land cover types. This study evaluated the use of panchromatic (PAN) data in very high resolution satellite image for improving the accuracy of ISE by various pan-sharpening approaches, with a further comprehensive analysis of its scale effects. Three benchmark pan-sharpening approaches, Gram-Schmidt (GS), PANSHARP and principal component analysis (PCA) were applied to WorldView-2 in three spots of Hong Kong. The on-screen digitization were carried out based on Google Map and the results were viewed as referenced impervious surfaces. The referenced impervious surfaces and the ISE results were then re-scaled to various spatial resolutions to obtain the percentage of impervious surfaces. The correlation coefficient (CC) and root mean square error (RMSE) were adopted as the quantitative indicator to assess the accuracy. The accuracy differences between three research areas were further illustrated by the average local variance (ALV) which was used for landscape pattern analysis. The experimental results suggested that 1) three research regions have various landscape patterns; 2) ISE accuracy extracted from pan-sharpened data was better than ISE from original multispectral (MS) data; and 3) this improvement has a noticeable scale effects with various resolutions. The improvement was reduced slightly as the resolution became coarser.

  18. Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2–10 ng/ml

    PubMed Central

    Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D’Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K.; Terracciano, Daniela

    2013-01-01

    Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2–10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2–10 ng/ml at initial biopsy, outperforming currently used %fPSA. PMID:23861782

  19. Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) significantly improve prostate cancer detection at initial biopsy in a total PSA range of 2-10 ng/ml.

    PubMed

    Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D'Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K; Terracciano, Daniela

    2013-01-01

    Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA.

  20. Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report

    PubMed Central

    Francio, Vinicius T.; Boesch, Ron; Tunning, Michael

    2015-01-01

    Objective: Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. Clinical features: A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Intervention and Outcome: Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient’s perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. Conclusion: PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option. PMID:25729084

  1. Contact- and distance-based principal component analysis of protein dynamics.

    PubMed

    Ernst, Matthias; Sittel, Florian; Stock, Gerhard

    2015-12-28

    To interpret molecular dynamics simulations of complex systems, systematic dimensionality reduction methods such as principal component analysis (PCA) represent a well-established and popular approach. Apart from Cartesian coordinates, internal coordinates, e.g., backbone dihedral angles or various kinds of distances, may be used as input data in a PCA. Adopting two well-known model problems, folding of villin headpiece and the functional dynamics of BPTI, a systematic study of PCA using distance-based measures is presented which employs distances between Cα-atoms as well as distances between inter-residue contacts including side chains. While this approach seems prohibitive for larger systems due to the quadratic scaling of the number of distances with the size of the molecule, it is shown that it is sufficient (and sometimes even better) to include only relatively few selected distances in the analysis. The quality of the PCA is assessed by considering the resolution of the resulting free energy landscape (to identify metastable conformational states and barriers) and the decay behavior of the corresponding autocorrelation functions (to test the time scale separation of the PCA). By comparing results obtained with distance-based, dihedral angle, and Cartesian coordinates, the study shows that the choice of input variables may drastically influence the outcome of a PCA.

  2. Contact- and distance-based principal component analysis of protein dynamics

    NASA Astrophysics Data System (ADS)

    Ernst, Matthias; Sittel, Florian; Stock, Gerhard

    2015-12-01

    To interpret molecular dynamics simulations of complex systems, systematic dimensionality reduction methods such as principal component analysis (PCA) represent a well-established and popular approach. Apart from Cartesian coordinates, internal coordinates, e.g., backbone dihedral angles or various kinds of distances, may be used as input data in a PCA. Adopting two well-known model problems, folding of villin headpiece and the functional dynamics of BPTI, a systematic study of PCA using distance-based measures is presented which employs distances between Cα-atoms as well as distances between inter-residue contacts including side chains. While this approach seems prohibitive for larger systems due to the quadratic scaling of the number of distances with the size of the molecule, it is shown that it is sufficient (and sometimes even better) to include only relatively few selected distances in the analysis. The quality of the PCA is assessed by considering the resolution of the resulting free energy landscape (to identify metastable conformational states and barriers) and the decay behavior of the corresponding autocorrelation functions (to test the time scale separation of the PCA). By comparing results obtained with distance-based, dihedral angle, and Cartesian coordinates, the study shows that the choice of input variables may drastically influence the outcome of a PCA.

  3. Incorporating biological information in sparse principal component analysis with application to genomic data.

    PubMed

    Li, Ziyi; Safo, Sandra E; Long, Qi

    2017-07-11

    Sparse principal component analysis (PCA) is a popular tool for dimensionality reduction, pattern recognition, and visualization of high dimensional data. It has been recognized that complex biological mechanisms occur through concerted relationships of multiple genes working in networks that are often represented by graphs. Recent work has shown that incorporating such biological information improves feature selection and prediction performance in regression analysis, but there has been limited work on extending this approach to PCA. In this article, we propose two new sparse PCA methods called Fused and Grouped sparse PCA that enable incorporation of prior biological information in variable selection. Our simulation studies suggest that, compared to existing sparse PCA methods, the proposed methods achieve higher sensitivity and specificity when the graph structure is correctly specified, and are fairly robust to misspecified graph structures. Application to a glioblastoma gene expression dataset identified pathways that are suggested in the literature to be related with glioblastoma. The proposed sparse PCA methods Fused and Grouped sparse PCA can effectively incorporate prior biological information in variable selection, leading to improved feature selection and more interpretable principal component loadings and potentially providing insights on molecular underpinnings of complex diseases.

  4. Electric Power Engineering Cost Predicting Model Based on the PCA-GA-BP

    NASA Astrophysics Data System (ADS)

    Wen, Lei; Yu, Jiake; Zhao, Xin

    2017-10-01

    In this paper a hybrid prediction algorithm: PCA-GA-BP model is proposed. PCA algorithm is established to reduce the correlation between indicators of original data and decrease difficulty of BP neural network in complex dimensional calculation. The BP neural network is established to estimate the cost of power transmission project. The results show that PCA-GA-BP algorithm can improve result of prediction of electric power engineering cost.

  5. Performance assessment of automated tissue characterization for prostate H and E stained histopathology

    NASA Astrophysics Data System (ADS)

    DiFranco, Matthew D.; Reynolds, Hayley M.; Mitchell, Catherine; Williams, Scott; Allan, Prue; Haworth, Annette

    2015-03-01

    Reliable automated prostate tumor detection and characterization in whole-mount histology images is sought in many applications, including post-resection tumor staging and as ground-truth data for multi-parametric MRI interpretation. In this study, an ensemble-based supervised classification algorithm for high-resolution histology images was trained on tile-based image features including histogram and gray-level co-occurrence statistics. The algorithm was assessed using different combinations of H and E prostate slides from two separate medical centers and at two different magnifications (400x and 200x), with the aim of applying tumor classification models to new data. Slides from both datasets were annotated by expert pathologists in order to identify homogeneous cancerous and non-cancerous tissue regions of interest, which were then categorized as (1) low-grade tumor (LG-PCa), including Gleason 3 and high-grade prostatic intraepithelial neoplasia (HG-PIN), (2) high-grade tumor (HG-PCa), including various Gleason 4 and 5 patterns, or (3) non-cancerous, including benign stroma and benign prostatic hyperplasia (BPH). Classification models for both LG-PCa and HG-PCa were separately trained using a support vector machine (SVM) approach, and per-tile tumor prediction maps were generated from the resulting ensembles. Results showed high sensitivity for predicting HG-PCa with an AUC up to 0.822 using training data from both medical centres, while LG-PCa showed a lower sensitivity of 0.763 with the same training data. Visual inspection of cancer probability heatmaps from 9 patients showed that 17/19 tumors were detected, and HG-PCa generally reported less false positives than LG-PCa.

  6. Insights on the Spectral Signatures of Stellar Activity and Planets from PCA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Davis, Allen B.; Fischer, Debra A.; Cisewski, Jessi

    Photospheric velocities and stellar activity features such as spots and faculae produce measurable radial velocity signals that currently obscure the detection of sub-meter-per-second planetary signals. However, photospheric velocities are imprinted differently in a high-resolution spectrum than are Keplerian Doppler shifts. Photospheric activity produces subtle differences in the shapes of absorption lines due to differences in how temperature or pressure affects the atomic transitions. In contrast, Keplerian Doppler shifts affect every spectral line in the same way. With a high enough signal-to-noise (S/N) and resolution, statistical techniques can exploit differences in spectra to disentangle the photospheric velocities and detect lower-amplitude exoplanetmore » signals. We use simulated disk-integrated time-series spectra and principal component analysis (PCA) to show that photospheric signals introduce spectral line variability that is distinct from that of Doppler shifts. We quantify the impact of instrumental resolution and S/N for this work.« less

  7. The effects of Doppler broadening and detector resolution on the performance of three-stage Compton cameras

    PubMed Central

    Mackin, Dennis; Polf, Jerimy; Peterson, Steve; Beddar, Sam

    2013-01-01

    Purpose: The authors investigated how the characteristics of the detectors used in a three-stage Compton camera (CC) affect the CC's ability to accurately measure the emission distribution and energy spectrum of prompt gammas (PG) emitted by nuclear de-excitations during proton therapy. The detector characteristics they studied included the material (high-purity germanium [HPGe] and cadmium zinc telluride [CZT]), Doppler broadening (DB), and resolution (lateral, depth, and energy). Methods: The authors simulated three-stage HPGe and CZT CCs of various configurations, detecting gammas from point sources with energies ranging from 0.511 to 7.12 MeV. They also simulated a proton pencil beam irradiating a tissue target to study how the detector characteristics affect the PG data measured by CCs in a clinical proton therapy setting. They used three figures of merit: the distance of closest approach (DCA) and the point of closest approach (PCA) between the measured and actual position of the PG emission origin, and the calculated energy resolution. Results: For CCs with HPGe detectors, DB caused the DCA to be greater than 3 mm for 14% of the 6.13 MeV gammas and 20% of the 0.511 MeV gammas. For CCs with CZT detectors, DB caused the DCA to be greater than 3 mm for 18% of the 6.13 MeV gammas and 25% of the 0.511 MeV gammas. The full width at half maximum (FWHM) of the PCA in the \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}\\hat z\\end{equation*} \\end{document}z^ direction for HPGe and CZT detectors ranged from 1.3 to 0.4 mm for gammas with incident energy ranging from 0.511 to 7.12 MeV. For CCs composed of HPGe detectors, the resolution of incident gamma energy calculated by the CC ranged from 6% to 1% for gammas with true incident energies from 0.511 to 7.12 MeV. For CCs composed of CZT detectors, the resolution of gamma energy calculated by the CC ranged from 10% to 1% for gammas with true incident energies from 0.511 to 7.12 MeV. For HPGe and CZT CCs in which all detector effect were included, the DCA was less than 3 mm for 75% and 68% of the detected gammas, respectively, and restricting gammas to those having energy greater than 2.0 MeV increased these percentages to 83% and 77% for HPGe and CZT, respectively. Distributions of the true gamma origins and the PCA after detector characteristics had been included showed good agreement on beam range and some loss of resolution for the lateral profile of the PG emission. Characteristic energy lines were evident in the calculated gamma energy spectrum. Conclusions: The authors found the following: (1) DB is the dominant source of spatial and energy resolution loss in the CCs at all energy levels; (2) the largest difference in the spatial resolution of HPGe and CZT CCs is that the spatial resolution distributions of CZT have broader tails. The differences in the FWHM of these distributions are small; (3) the energy resolution of both HPGe and CZT three-stage CCs is adequate for PG spectroscopy; and (4) restricting the gammas to those having energy greater than 2.0 MeV can improve the achievable image resolution. PMID:23298111

  8. Performance of In-Pixel Circuits for Photon Counting Arrays (PCAs) Based on Polycrystalline Silicon TFTs

    PubMed Central

    Liang, Albert K.; Koniczek, Martin; Antonuk, Larry E.; El-Mohri, Youcef; Zhao, Qihua; Street, Robert A.; Lu, Jeng Ping

    2017-01-01

    Photon counting arrays (PCAs), defined as pixelated imagers which measure the absorbed energy of x-ray photons individually and record this information digitally, are of increasing clinical interest. A number of PCA prototypes with a 1 mm pixel-to-pixel pitch have recently been fabricated with polycrystalline silicon (poly-Si) — a thin-film technology capable of creating monolithic imagers of a size commensurate with human anatomy. In this study, analog and digital simulation frameworks were developed to provide insight into the influence of individual poly-Si transistors on pixel circuit performance — information that is not readily available through empirical means. The simulation frameworks were used to characterize the circuit designs employed in the prototypes. The analog framework, which determines the noise produced by individual transistors, was used to estimate energy resolution, as well as to identify which transistors contribute the most noise. The digital framework, which analyzes how well circuits function in the presence of significant variations in transistor properties, was used to estimate how fast a circuit can produce an output (referred to as output count rate). In addition, an algorithm was developed and used to estimate the minimum pixel pitch that could be achieved for the pixel circuits of the current prototypes. The simulation frameworks predict that the analog component of the PCA prototypes could have energy resolution as low as 8.9% FWHM at 70 keV; and the digital components should work well even in the presence of significant TFT variations, with the fastest component having output count rates as high as 3 MHz. Finally, based on conceivable improvements in the underlying fabrication process, the algorithm predicts that the 1 mm pitch of the current PCA prototypes could be reduced significantly, potentially to between ~240 and 290 μm. PMID:26878107

  9. Performance of in-pixel circuits for photon counting arrays (PCAs) based on polycrystalline silicon TFTs.

    PubMed

    Liang, Albert K; Koniczek, Martin; Antonuk, Larry E; El-Mohri, Youcef; Zhao, Qihua; Street, Robert A; Lu, Jeng Ping

    2016-03-07

    Photon counting arrays (PCAs), defined as pixelated imagers which measure the absorbed energy of x-ray photons individually and record this information digitally, are of increasing clinical interest. A number of PCA prototypes with a 1 mm pixel-to-pixel pitch have recently been fabricated with polycrystalline silicon (poly-Si)-a thin-film technology capable of creating monolithic imagers of a size commensurate with human anatomy. In this study, analog and digital simulation frameworks were developed to provide insight into the influence of individual poly-Si transistors on pixel circuit performance-information that is not readily available through empirical means. The simulation frameworks were used to characterize the circuit designs employed in the prototypes. The analog framework, which determines the noise produced by individual transistors, was used to estimate energy resolution, as well as to identify which transistors contribute the most noise. The digital framework, which analyzes how well circuits function in the presence of significant variations in transistor properties, was used to estimate how fast a circuit can produce an output (referred to as output count rate). In addition, an algorithm was developed and used to estimate the minimum pixel pitch that could be achieved for the pixel circuits of the current prototypes. The simulation frameworks predict that the analog component of the PCA prototypes could have energy resolution as low as 8.9% full width at half maximum (FWHM) at 70 keV; and the digital components should work well even in the presence of significant thin-film transistor (TFT) variations, with the fastest component having output count rates as high as 3 MHz. Finally, based on conceivable improvements in the underlying fabrication process, the algorithm predicts that the 1 mm pitch of the current PCA prototypes could be reduced significantly, potentially to between ~240 and 290 μm.

  10. PHI and PCA3 improve the prognostic performance of PRIAS and Epstein criteria in predicting insignificant prostate cancer in men eligible for active surveillance.

    PubMed

    Cantiello, Francesco; Russo, Giorgio Ivan; Cicione, Antonio; Ferro, Matteo; Cimino, Sebastiano; Favilla, Vincenzo; Perdonà, Sisto; De Cobelli, Ottavio; Magno, Carlo; Morgia, Giuseppe; Damiano, Rocco

    2016-04-01

    To assess the performance of prostate health index (PHI) and prostate cancer antigen 3 (PCA3) when added to the PRIAS or Epstein criteria in predicting the presence of pathologically insignificant prostate cancer (IPCa) in patients who underwent radical prostatectomy (RP) but eligible for active surveillance (AS). An observational retrospective study was performed in 188 PCa patients treated with laparoscopic or robot-assisted RP but eligible for AS according to Epstein or PRIAS criteria. Blood and urinary specimens were collected before initial prostate biopsy for PHI and PCA3 measurements. Multivariate logistic regression analyses and decision curve analysis were carried out to identify predictors of IPCa using the updated ERSPC definition. At the multivariate analyses, the inclusion of both PCA3 and PHI significantly increased the accuracy of the Epstein multivariate model in predicting IPCa with an increase of 17 % (AUC = 0.77) and of 32 % (AUC = 0.92), respectively. The inclusion of both PCA3 and PHI also increased the predictive accuracy of the PRIAS multivariate model with an increase of 29 % (AUC = 0.87) and of 39 % (AUC = 0.97), respectively. DCA revealed that the multivariable models with the addition of PHI or PCA3 showed a greater net benefit and performed better than the reference models. In a direct comparison, PHI outperformed PCA3 performance resulting in higher net benefit. In a same cohort of patients eligible for AS, the addition of PHI and PCA3 to Epstein or PRIAS models improved their prognostic performance. PHI resulted in greater net benefit in predicting IPCa compared to PCA3.

  11. Predicting prostate biopsy outcome: prostate health index (phi) and prostate cancer antigen 3 (PCA3) are useful biomarkers.

    PubMed

    Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Marino, Ada; Sorrentino, Alessandra; Di Carlo, Angelina; Autorino, Riccardo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Altieri, Vincenzo; Mariano, Angela; Macchia, Vincenzo; Terracciano, Daniela

    2012-08-16

    Indication for prostate biopsy is presently mainly based on prostate-specific antigen (PSA) serum levels and digital-rectal examination (DRE). In view of the unsatisfactory accuracy of these two diagnostic exams, research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as phi and PCA3. The purpose of this prospective study was to assess the diagnostic accuracy of phi and PCA3 for prostate cancer using biopsy as gold standard. Phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay) and other established biomarkers (tPSA, fPSA and %fPSA) were assessed before a 18-core prostate biopsy in a group of 251 subjects at their first biopsy. Values of %p2PSA and phi were significantly higher in patients with PCa compared with PCa-negative group (p<0.001) and also compared with high grade prostatic intraepithelial neoplasia (HGPIN) (p<0.001). PCA3 score values were significantly higher in PCa compared with PCa-negative subjects (p<0.001) and in HGPIN vs PCa-negative patients (p<0.001). ROC curve analysis showed that %p2PSA, phi and PCA3 are predictive of malignancy. In conclusion, %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men undergoing their first prostate biopsy. PCA3 score is more useful in discriminating between HGPIN and non-cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Successor to the RXTE PCA based upon focusing optics

    NASA Astrophysics Data System (ADS)

    Gorenstein, Paul

    2002-01-01

    There is broad interest in a next generation timing mission to succeed the PCA of RXTE which will provide more effective area than its 0.6 square meters and much better energy resolution. Currently prospective missions are, like the PCA, based upon large area detectors. Serious consideration should also be given to a focusing system. The focusing system would be a modular array of relatively small diameter imaging telescopes or concentrators with solid state detectors in their focal planes. For areas exceeding a square meter a focusing system could actually be less complex, more reliable, and for one particular optical design perhaps not much more massive. The total detector area would be only a few percent of the telescope aperture, which makes the acquisition of detectors much less challenging. Today it is possible to obtain commercially a sufficient number of detectors with good energy resolution for all the focal planes of the focusing array. They require only modest cooling and that could be accomplished passively in space. Several optical designs are possible. The disadvantages of an optical system are larger mass, more difficultly obtaining broad bandwidth, smaller field of view, and larger volume to accommodate the focal length distance and a larger diameter. On the other hand, the focusing system is more sensitive to fainter sources, is much more efficient below 2 keV, is less sensitive to background and is likely to be less costly overall than an array of solid state area detectors with equally good energy resolution.

  13. SU-D-207A-07: The Effects of Inter-Cycle Respiratory Motion Variation On Dose Accumulation in Single Fraction MR-Guided SBRT Treatment of Renal Cell Carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stemkens, B; Glitzner, M; Kontaxis, C

    Purpose: To assess the dose deposition in simulated single-fraction MR-Linac treatments of renal cell carcinoma, when inter-cycle respiratory motion variation is taken into account using online MRI. Methods: Three motion characterization methods, with increasing complexity, were compared to evaluate the effect of inter-cycle motion variation and drifts on the accumulated dose for an SBRT kidney MR-Linac treatment: 1) STATIC, in which static anatomy was assumed, 2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, based on the respiratory phase and 3) PCA, in which 3D volumes were generated using a PCA-model, enabling the detection of inter-cycle variations and drifts. An experimentalmore » ITV-based kidney treatment was simulated in a 1.5T magnetic field on three volunteer datasets. For each volunteer a retrospectively sorted 4D-MRI (ten respiratory phases) and fast 2D cine-MR images (temporal resolution = 476ms) were acquired to simulate MR-imaging during radiation. For each method, the high spatio-temporal resolution 3D volumes were non-rigidly registered to obtain deformation vector fields (DVFs). Using the DVFs, pseudo-CTs (generated from the 4D-MRI) were deformed and the dose was accumulated for the entire treatment. The accuracies of all methods were independently determined using an additional, orthogonal 2D-MRI slice. Results: Motion was most accurately estimated using the PCA method, which correctly estimated drifts and inter-cycle variations (RMSE=3.2, 2.2, 1.1mm on average for STATIC, AVG-RESP and PCA, compared to the 2DMRI slice). Dose-volume parameters on the ITV showed moderate changes (D99=35.2, 32.5, 33.8Gy for STATIC, AVG-RESP and PCA). AVG-RESP showed distinct hot/cold spots outside the ITV margin, which were more distributed for the PCA scenario, since inter-cycle variations were not modeled by the AVG-RESP method. Conclusion: Dose differences were observed when inter-cycle variations were taken into account. The increased inter-cycle randomness in motion as captured by the PCA model mitigates the local (erroneous) hotspots estimated by the AVG-RESP method.« less

  14. Antagonistic Activity and Mode of Action of Phenazine-1-Carboxylic Acid, Produced by Marine Bacterium Pseudomonas aeruginosa PA31x, Against Vibrio anguillarum In vitro and in a Zebrafish In vivo Model

    PubMed Central

    Zhang, Linlin; Tian, Xueying; Kuang, Shan; Liu, Ge; Zhang, Chengsheng; Sun, Chaomin

    2017-01-01

    Phenazine and its derivatives are very important secondary metabolites produced from Pseudomonas spp. and have exhibited broad-spectrum antifungal and antibacterial activities. However, till date, there are few reports about marine derived Pseudomonas and its production of phenazine metabolites. In this study, we isolated a marine Pseudomonas aeruginosa strain PA31x which produced natural product inhibiting the growth of Vibrio anguillarum C312, one of the most serious bacterial pathogens in marine aquaculture. Combining high-resolution electro-spray-ionization mass spectroscopy and nuclear magnetic resonance spectroscopy analyses, the functional compound against V. anguillarum was demonstrated to be phenazine-1-carboxylic acid (PCA), an important phenazine derivative. Molecular studies indicated that the production of PCA by P. aeruginosa PA31x was determined by gene clusters phz1 and phz2 in its genome. Electron microscopic results showed that treatment of V. anguillarum with PCA developed complete lysis of bacterial cells with fragmented cytoplasm being released to the surrounding environment. Additional evidence indicated that reactive oxygen species generation preceded PCA-induced microbe and cancer cell death. Notably, treatment with PCA gave highly significant protective activities against the development of V. anguillarum C312 on zebrafish. Additionally, the marine derived PCA was further found to effectively inhibit the growth of agricultural pathogens, Acidovorax citrulli NP1 and Phytophthora nicotianae JM1. Taken together, this study reveals that marine Pseudomonas derived PCA carries antagonistic activities against both aquacultural and agricultural pathogens, which broadens the application fields of PCA. PMID:28289406

  15. Genetic variants in RNA-induced silencing complex genes and prostate cancer.

    PubMed

    Nikolić, Z; Savić Pavićević, D; Vučić, N; Cerović, S; Vukotić, V; Brajušković, G

    2017-04-01

    The purpose of this study is to evaluate the potential association between genetic variants in genes encoding the components of RNA-induced silencing complex and prostate cancer (PCa) risk. Genetic variants chosen for this study are rs3742330 in DICER1, rs4961280 in AGO2, rs784567 in TARBP2, rs7813 in GEMIN4 and rs197414 in GEMIN3. The study involved 355 PCa patients, 360 patients with benign prostatic hyperplasia and 318 healthy controls. For individuals diagnosed with PCa, clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotyping was performed using high-resolution melting analysis, PCR-RFLP, TaqMan SNP Genotyping Assay and real-time PCR-based genotyping assay using specific probes. Allelic and genotypic associations were evaluated by unconditional linear and logistic regression methods. The study provided no evidence of association between the analyzed genetic variants and PCa risk. Nevertheless, allele A of rs784567 was found to confer the reduced risk of higher serum PSA level at diagnosis (P = 0.046; Difference = -66.64, 95 % CI -131.93 to 1.35, for log-additive model). Furthermore, rs4961280, as well as rs3742330, were shown to be associated with GS. These variants, together with rs7813, were found to be associated with the lower clinical stage of PCa. Also, rs3742330 minor allele G was found to be associated with lower PCa aggressiveness (P = 0.036; OR 0.14, 95 % CI 0.023-1.22, for recessive model). According to our data, rs3742330, rs4961280 and rs7813 qualify for potentially protective genetic variants against PCa progression. These variants were not shown to be associated with PCa risk.

  16. Super-resolution method for face recognition using nonlinear mappings on coherent features.

    PubMed

    Huang, Hua; He, Huiting

    2011-01-01

    Low-resolution (LR) of face images significantly decreases the performance of face recognition. To address this problem, we present a super-resolution method that uses nonlinear mappings to infer coherent features that favor higher recognition of the nearest neighbor (NN) classifiers for recognition of single LR face image. Canonical correlation analysis is applied to establish the coherent subspaces between the principal component analysis (PCA) based features of high-resolution (HR) and LR face images. Then, a nonlinear mapping between HR/LR features can be built by radial basis functions (RBFs) with lower regression errors in the coherent feature space than in the PCA feature space. Thus, we can compute super-resolved coherent features corresponding to an input LR image according to the trained RBF model efficiently and accurately. And, face identity can be obtained by feeding these super-resolved features to a simple NN classifier. Extensive experiments on the Facial Recognition Technology, University of Manchester Institute of Science and Technology, and Olivetti Research Laboratory databases show that the proposed method outperforms the state-of-the-art face recognition algorithms for single LR image in terms of both recognition rate and robustness to facial variations of pose and expression.

  17. PEM-PCA: a parallel expectation-maximization PCA face recognition architecture.

    PubMed

    Rujirakul, Kanokmon; So-In, Chakchai; Arnonkijpanich, Banchar

    2014-01-01

    Principal component analysis or PCA has been traditionally used as one of the feature extraction techniques in face recognition systems yielding high accuracy when requiring a small number of features. However, the covariance matrix and eigenvalue decomposition stages cause high computational complexity, especially for a large database. Thus, this research presents an alternative approach utilizing an Expectation-Maximization algorithm to reduce the determinant matrix manipulation resulting in the reduction of the stages' complexity. To improve the computational time, a novel parallel architecture was employed to utilize the benefits of parallelization of matrix computation during feature extraction and classification stages including parallel preprocessing, and their combinations, so-called a Parallel Expectation-Maximization PCA architecture. Comparing to a traditional PCA and its derivatives, the results indicate lower complexity with an insignificant difference in recognition precision leading to high speed face recognition systems, that is, the speed-up over nine and three times over PCA and Parallel PCA.

  18. Exercise and prostate cancer: From basic science to clinical applications.

    PubMed

    Campos, Christian; Sotomayor, Paula; Jerez, Daniel; González, Javier; Schmidt, Camila B; Schmidt, Katharina; Banzer, Winfried; Godoy, Alejandro S

    2018-06-01

    Prostate cancer (PCa) is a disease of increasing medical significance worldwide. In developed countries, PCa is the most common non-skin cancer in men, and one of the leading causes of cancer-related deaths. Exercise is one of the environmental factors that have been shown to influence cancer risk. Moreover, systemic reviews and meta-analysis have suggested that total physical activity is related to a decrease in the risk of developing PCa. In addition, epidemiological studies have shown that exercise, after diagnosis, has benefits regarding PCa development, and positive outcome in patients under treatment. The standard treatment for locally advanced or metastatic PCa is Androgen deprivation therapy (ADT). ADT produces diverse side effects, including loss of libido, changes in body composition (increase abdominal fat), and reduced muscle mass, and muscle tone. Analysis of numerous research publications showed that aerobic and/or resistance training improve patient's physical condition, such us, cardiorespiratory fitness, muscle strength, physical function, body composition, and fatigue. Therefore, exercise might counteract several ADT treatment-induced side effects. In addition of the aforementioned benefits, epidemiological, and in vitro studies have shown that exercise might decrease PCa development. Thus, physical activity might attenuate the risk of PCa and supervised exercise intervention might improve deleterious effects of cancer treatment, such as ADT side effects. This review article provides evidence indicating that exercise could complement, and potentiate, the current standard treatments for advanced PCa, probably by creating an unfavorable microenvironment that can negatively affect tumor development, and progression. © 2018 Wiley Periodicals, Inc.

  19. Cluster analysis of commercial samples of Bauhinia spp. using HPLC-UV/PDA and MCR-ALS/PCA without peak alignment procedure.

    PubMed

    Ardila, Jorge Armando; Funari, Cristiano Soleo; Andrade, André Marques; Cavalheiro, Alberto José; Carneiro, Renato Lajarim

    2015-01-01

    Bauhinia forficata Link. is recognised by the Brazilian Health Ministry as a treatment of hypoglycemia and diabetes. Analytical methods are useful to assess the plant identity due the similarities found in plants from Bauhinia spp. HPLC-UV/PDA in combination with chemometric tools is an alternative widely used and suitable for authentication of plant material, however, the shifts of retention times for similar compounds in different samples is a problem. To perform comparisons between the authentic medicinal plant (Bauhinia forficata Link.) and samples commercially available in drugstores claiming to be "Bauhinia spp. to treat diabetes" and to evaluate the performance of multivariate curve resolution - alternating least squares (MCR-ALS) associated to principal component analysis (PCA) when compared to pure PCA. HPLC-UV/PDA data obtained from extracts of leaves were evaluated employing a combination of MCR-ALS and PCA, which allowed the use of the full chromatographic and spectrometric information without the need of peak alignment procedures. The use of MCR-ALS/PCA showed better results than the conventional PCA using only one wavelength. Only two of nine commercial samples presented characteristics similar to the authentic Bauhinia forficata spp., considering the full HPLC-UV/PDA data. The combination of MCR-ALS and PCA is very useful when applied to a group of samples where a general alignment procedure could not be applied due to the different chromatographic profiles. This work also demonstrates the need of more strict control from the health authorities regarding herbal products available on the market. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Consensus classification of posterior cortical atrophy

    PubMed Central

    Crutch, Sebastian J.; Schott, Jonathan M.; Rabinovici, Gil D.; Murray, Melissa; Snowden, Julie S.; van der Flier, Wiesje M.; Dickerson, Bradford C.; Vandenberghe, Rik; Ahmed, Samrah; Bak, Thomas H.; Boeve, Bradley F.; Butler, Christopher; Cappa, Stefano F.; Ceccaldi, Mathieu; de Souza, Leonardo Cruz; Dubois, Bruno; Felician, Olivier; Galasko, Douglas; Graff-Radford, Jonathan; Graff-Radford, Neill R.; Hof, Patrick R.; Krolak-Salmon, Pierre; Lehmann, Manja; Magnin, Eloi; Mendez, Mario F.; Nestor, Peter J.; Onyike, Chiadi U.; Pelak, Victoria S.; Pijnenburg, Yolande; Primativo, Silvia; Rossor, Martin N.; Ryan, Natalie S.; Scheltens, Philip; Shakespeare, Timothy J.; González, Aida Suárez; Tang-Wai, David F.; Yong, Keir X. X.; Carrillo, Maria; Fox, Nick C.

    2017-01-01

    Introduction A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Methods Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. Results A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. Discussion There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work. PMID:28259709

  1. Consensus classification of posterior cortical atrophy.

    PubMed

    Crutch, Sebastian J; Schott, Jonathan M; Rabinovici, Gil D; Murray, Melissa; Snowden, Julie S; van der Flier, Wiesje M; Dickerson, Bradford C; Vandenberghe, Rik; Ahmed, Samrah; Bak, Thomas H; Boeve, Bradley F; Butler, Christopher; Cappa, Stefano F; Ceccaldi, Mathieu; de Souza, Leonardo Cruz; Dubois, Bruno; Felician, Olivier; Galasko, Douglas; Graff-Radford, Jonathan; Graff-Radford, Neill R; Hof, Patrick R; Krolak-Salmon, Pierre; Lehmann, Manja; Magnin, Eloi; Mendez, Mario F; Nestor, Peter J; Onyike, Chiadi U; Pelak, Victoria S; Pijnenburg, Yolande; Primativo, Silvia; Rossor, Martin N; Ryan, Natalie S; Scheltens, Philip; Shakespeare, Timothy J; Suárez González, Aida; Tang-Wai, David F; Yong, Keir X X; Carrillo, Maria; Fox, Nick C

    2017-08-01

    A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Exploring high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for metabonomic analysis of apples.

    PubMed

    Vermathen, Martina; Marzorati, Mattia; Vermathen, Peter

    2012-01-01

    Classical liquid-state high-resolution (HR) NMR spectroscopy has proved a powerful tool in the metabonomic analysis of liquid food samples like fruit juices. In this paper the application of (1)H high-resolution magic angle spinning (HR-MAS) NMR spectroscopy to apple tissue is presented probing its potential for metabonomic studies. The (1)H HR-MAS NMR spectra are discussed in terms of the chemical composition of apple tissue and compared to liquid-state NMR spectra of apple juice. Differences indicate that specific metabolic changes are induced by juice preparation. The feasibility of HR-MAS NMR-based multivariate analysis is demonstrated by a study distinguishing three different apple cultivars by principal component analysis (PCA). Preliminary results are shown from subsequent studies comparing three different cultivation methods by means of PCA and partial least squares discriminant analysis (PLS-DA) of the HR-MAS NMR data. The compounds responsible for discriminating organically grown apples are discussed. Finally, an outlook of our ongoing work is given including a longitudinal study on apples.

  3. Ice Mass Change in Greenland and Antarctica Between 1993 and 2013 from Satellite Gravity Measurements

    NASA Technical Reports Server (NTRS)

    Talpe, Matthieu J.; Nerem, R. Steven; Forootan, Ehsan; Schmidt, Michael; Lemoine, Frank G.; Enderlin, Ellyn M.; Landerer, Felix W.

    2017-01-01

    We construct long-term time series of Greenland and Antarctic ice sheet mass change from satellite gravity measurements. A statistical reconstruction approach is developed based on a principal component analysis (PCA) to combine high-resolution spatial modes from the Gravity Recovery and Climate Experiment (GRACE) mission with the gravity information from conventional satellite tracking data. Uncertainties of this reconstruction are rigorously assessed; they include temporal limitations for short GRACE measurements, spatial limitations for the low-resolution conventional tracking data measurements, and limitations of the estimated statistical relationships between low- and high-degree potential coefficients reflected in the PCA modes. Trends of mass variations in Greenland and Antarctica are assessed against a number of previous studies. The resulting time series for Greenland show a higher rate of mass loss than other methods before 2000, while the Antarctic ice sheet appears heavily influenced by interannual variations.

  4. Genome Sequence of Sphingomonas wittichii DP58, the First Reported Phenazine-1-Carboxylic Acid-Degrading Strain

    PubMed Central

    Ma, Zhiwei; Shen, Xuemei; Wang, Wei; Peng, Huasong; Xu, Ping; Zhang, Xuehong

    2012-01-01

    Sphingomonas wittichii DP58 (CCTCC M 2012027), the first reported phenazine-1-carboxylic acid (PCA)-degrading strain, was isolated from pimiento rhizosphere soils. Here we present a 5.6-Mb assembly of its genome. This sequence would contribute to the elucidation of the molecular mechanism of PCA degradation to improve the antifungal's effectiveness or remove superfluous PCA. PMID:22689229

  5. Guided filter and principal component analysis hybrid method for hyperspectral pansharpening

    NASA Astrophysics Data System (ADS)

    Qu, Jiahui; Li, Yunsong; Dong, Wenqian

    2018-01-01

    Hyperspectral (HS) pansharpening aims to generate a fused HS image with high spectral and spatial resolution through integrating an HS image with a panchromatic (PAN) image. A guided filter (GF) and principal component analysis (PCA) hybrid HS pansharpening method is proposed. First, the HS image is interpolated and the PCA transformation is performed on the interpolated HS image. The first principal component (PC1) channel concentrates on the spatial information of the HS image. Different from the traditional PCA method, the proposed method sharpens the PAN image and utilizes the GF to obtain the spatial information difference between the HS image and the enhanced PAN image. Then, in order to reduce spectral and spatial distortion, an appropriate tradeoff parameter is defined and the spatial information difference is injected into the PC1 channel through multiplying by this tradeoff parameter. Once the new PC1 channel is obtained, the fused image is finally generated by the inverse PCA transformation. Experiments performed on both synthetic and real datasets show that the proposed method outperforms other several state-of-the-art HS pansharpening methods in both subjective and objective evaluations.

  6. PCA-HOG symmetrical feature based diseased cell detection

    NASA Astrophysics Data System (ADS)

    Wan, Min-jie

    2016-04-01

    A histogram of oriented gradient (HOG) feature is applied to the field of diseased cell detection, which can detect diseased cells in high resolution tissue images rapidly, accurately and efficiently. Firstly, motivated by symmetrical cellular forms, a new HOG symmetrical feature based on the traditional HOG feature is proposed to meet the condition of cell detection. Secondly, considering the high feature dimension of traditional HOG feature leads to plenty of memory resources and long runtime in practical applications, a classical dimension reduction method called principal component analysis (PCA) is used to reduce the dimension of high-dimensional HOG descriptor. Because of that, computational speed is increased greatly, and the accuracy of detection can be controlled in a proper range at the same time. Thirdly, support vector machine (SVM) classifier is trained with PCA-HOG symmetrical features proposed above. At last, practical tissue images is detected and analyzed by SVM classifier. In order to verify the effectiveness of this new algorithm, it is practically applied to conduct diseased cell detection which takes 200 pieces of H&E (hematoxylin & eosin) high resolution staining histopathological images collected from 20 breast cancer patients as a sample. The experiment shows that the average processing rate can be 25 frames per second and the detection accuracy can be 92.1%.

  7. Improving the detection of cocoa bean fermentation-related changes using image fusion

    NASA Astrophysics Data System (ADS)

    Ochoa, Daniel; Criollo, Ronald; Liao, Wenzhi; Cevallos-Cevallos, Juan; Castro, Rodrigo; Bayona, Oswaldo

    2017-05-01

    Complex chemical processes occur in during cocoa bean fermentation. To select well-fermented beans, experts take a sample of beans, cut them in half and visually check its color. Often farmers mix high and low quality beans therefore, chocolate properties are difficult to control. In this paper, we explore how close-range hyper- spectral (HS) data can be used to characterize the fermentation process of two types of cocoa beans (CCN51 and National). Our aim is to find spectral differences to allow bean classification. The main issue is to extract reliable spectral data as openings resulting from the loss of water during fermentation, can cover up to 40% of the bean surface. We exploit HS pan-sharpening techniques to increase the spatial resolution of HS images and filter out uneven surface regions. In particular, the guided filter PCA approach which has proved suitable to use high-resolution RGB data as guide image. Our preliminary results show that this pre-processing step improves the separability of classes corresponding to each fermentation stage compared to using the average spectrum of the bean surface.

  8. Quantitative assessment of the mechanical properties of prostate tissue with optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Ling, Yuting; Li, Chunhui; Zhou, Kanheng; Guan, Guangying; Lang, Stephen; McGloin, David; Nabi, Ghulam; Huang, Zhihong

    2018-02-01

    Prostate cancer (PCa) is a heterogeneous disease with multifocal origin. In current clinical care, the Gleason scoring system is the well-established diagnosis by microscopic evaluation of the tissue from trans-rectal ultrasound (TRUS) guided biopsies. Nevertheless, the sensitivity and specificity in detecting PCa can range from 40 to 50% for conventional TRUS B-mode imaging. Tissue elasticity is associated with the disease progression and elastography technique has recently shown promise in aiding PCa diagnosis. However, many cancer foci in the prostate gland has very small size less than 1 mm and those detected by medical elastography were larger than 2 mm. Hereby, we introduce optical coherence elastography (OCE) to quantify the prostate stiffness with high resolution in the magnitude of 10 µm. Following our feasibility study of 10 patients reported previously, we recruited 60 more patients undergoing 12-core TRUS guided biopsies for suspected PCa with a total of 720 biopsies. The stiffness of cancer tissue was approximately 57.63% higher than that of benign ones. Using histology as reference standard and cut-off threshold of 600kPa, the data analysis showed sensitivity and specificity of 89.6% and 99.8% respectively. The method also demonstrated potential in characterising different grades of PCa based on the change of tissue morphology and quantitative mechanical properties. In conclusion, quantitative OCE can be a reliable technique to identify PCa lesion and differentiate indolent from aggressive cancer.

  9. Watching a signaling protein function in real time via 100-ps time-resolved Laue crystallography

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schotte, Friedrich; Cho, Hyun Sun; Kaila, Ville R.I.

    2012-11-06

    To understand how signaling proteins function, it is necessary to know the time-ordered sequence of events that lead to the signaling state. We recently developed on the BioCARS 14-IDB beamline at the Advanced Photon Source the infrastructure required to characterize structural changes in protein crystals with near-atomic spatial resolution and 150-ps time resolution, and have used this capability to track the reversible photocycle of photoactive yellow protein (PYP) following trans-to-cis photoisomerization of its p-coumaric acid (pCA) chromophore over 10 decades of time. The first of four major intermediates characterized in this study is highly contorted, with the pCA carbonyl rotatedmore » nearly 90° out of the plane of the phenolate. A hydrogen bond between the pCA carbonyl and the Cys69 backbone constrains the chromophore in this unusual twisted conformation. Density functional theory calculations confirm that this structure is chemically plausible and corresponds to a strained cis intermediate. This unique structure is short-lived (~600 ps), has not been observed in prior cryocrystallography experiments, and is the progenitor of intermediates characterized in previous nanosecond time-resolved Laue crystallography studies. The structural transitions unveiled during the PYP photocycle include trans/cis isomerization, the breaking and making of hydrogen bonds, formation/relaxation of strain, and gated water penetration into the interior of the protein. This mechanistically detailed, near-atomic resolution description of the complete PYP photocycle provides a framework for understanding signal transduction in proteins, and for assessing and validating theoretical/computational approaches in protein biophysics.« less

  10. An improved PCA method with application to boiler leak detection.

    PubMed

    Sun, Xi; Marquez, Horacio J; Chen, Tongwen; Riaz, Muhammad

    2005-07-01

    Principal component analysis (PCA) is a popular fault detection technique. It has been widely used in process industries, especially in the chemical industry. In industrial applications, achieving a sensitive system capable of detecting incipient faults, which maintains the false alarm rate to a minimum, is a crucial issue. Although a lot of research has been focused on these issues for PCA-based fault detection and diagnosis methods, sensitivity of the fault detection scheme versus false alarm rate continues to be an important issue. In this paper, an improved PCA method is proposed to address this problem. In this method, a new data preprocessing scheme and a new fault detection scheme designed for Hotelling's T2 as well as the squared prediction error are developed. A dynamic PCA model is also developed for boiler leak detection. This new method is applied to boiler water/steam leak detection with real data from Syncrude Canada's utility plant in Fort McMurray, Canada. Our results demonstrate that the proposed method can effectively reduce false alarm rate, provide effective and correct leak alarms, and give early warning to operators.

  11. Multiresolution generalized N dimension PCA for ultrasound image denoising

    PubMed Central

    2014-01-01

    Background Ultrasound images are usually affected by speckle noise, which is a type of random multiplicative noise. Thus, reducing speckle and improving image visual quality are vital to obtaining better diagnosis. Method In this paper, a novel noise reduction method for medical ultrasound images, called multiresolution generalized N dimension PCA (MR-GND-PCA), is presented. In this method, the Gaussian pyramid and multiscale image stacks on each level are built first. GND-PCA as a multilinear subspace learning method is used for denoising. Each level is combined to achieve the final denoised image based on Laplacian pyramids. Results The proposed method is tested with synthetically speckled and real ultrasound images, and quality evaluation metrics, including MSE, SNR and PSNR, are used to evaluate its performance. Conclusion Experimental results show that the proposed method achieved the lowest noise interference and improved image quality by reducing noise and preserving the structure. Our method is also robust for the image with a much higher level of speckle noise. For clinical images, the results show that MR-GND-PCA can reduce speckle and preserve resolvable details. PMID:25096917

  12. The Present and Future of Prostate Cancer Urine Biomarkers

    PubMed Central

    Rigau, Marina; Olivan, Mireia; Garcia, Marta; Sequeiros, Tamara; Montes, Melania; Colás, Eva; Llauradó, Marta; Planas, Jacques; de Torres, Inés; Morote, Juan; Cooper, Colin; Reventós, Jaume; Clark, Jeremy; Doll, Andreas

    2013-01-01

    In order to successfully cure patients with prostate cancer (PCa), it is important to detect the disease at an early stage. The existing clinical biomarkers for PCa are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid over-treatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two thirds of the biopsies performed are still unnecessary. Thus the discovery of non-invasive PCa biomarkers remains urgent. In recent years, the utilization of urine has emerged as an attractive option for the non-invasive detection of PCa. Moreover, a great improvement in high-throughput “omic” techniques has presented considerable opportunities for the identification of new biomarkers. Herein, we will review the most significant urine biomarkers described in recent years, as well as some future prospects in that field. PMID:23774836

  13. Antifouling polyethersulfone hemodialysis membranes incorporated with poly (citric acid) polymerized multi-walled carbon nanotubes.

    PubMed

    Abidin, Muhammad Nidzhom Zainol; Goh, Pei Sean; Ismail, Ahmad Fauzi; Othman, Mohd Hafiz Dzarfan; Hasbullah, Hasrinah; Said, Noresah; Kadir, Siti Hamimah Sheikh Abdul; Kamal, Fatmawati; Abdullah, Mohd Sohaimi; Ng, Be Cheer

    2016-11-01

    Poly (citric acid)-grafted-MWCNT (PCA-g-MWCNT) was incorporated as nanofiller in polyethersulfone (PES) to produce hemodialysis mixed matrix membrane (MMM). Citric acid monohydrate was polymerized onto the surface of MWCNTs by polycondensation. Neat PES membrane and PES/MWCNTs MMMs were fabricated by dry-wet spinning technique. The membranes were characterized in terms of morphology, pure water flux (PWF) and bovine serum albumin (BSA) protein rejection. The grafting yield of PCA onto MWCNTs was calculated as 149.2%. The decrease of contact angle from 77.56° to 56.06° for PES/PCA-g-MWCNTs membrane indicated the increase in surface hydrophilicity, which rendered positive impacts on the PWF and BSA rejection of the membrane. The PWF increased from 15.8Lm(-2)h(-1) to 95.36Lm(-2)h(-1) upon the incorporation of PCA-g-MWCNTs due to the attachment of abundant hydrophilic groups that present on the MWCNTs, which have improved the affinity of membrane towards the water molecules. For protein rejection, the PES/PCA-g-MWCNTs MMM rejected 95.2% of BSA whereas neat PES membrane demonstrated protein rejection of 90.2%. Compared to commercial PES hemodialysis membrane, the PES/PCA-g-MWCNTs MMMs showed less flux decline behavior and better PWF recovery ratio, suggesting that the membrane antifouling performance was improved. The incorporation of PCA-g-MWCNTs enhanced the separation features and antifouling capabilities of the PES membrane for hemodialysis application. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

    PubMed Central

    Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

    2011-01-01

    Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

  15. Improving couples' quality of life through a Web-based prostate cancer education intervention.

    PubMed

    Song, Lixin; Rini, Christine; Deal, Allison M; Nielsen, Matthew E; Chang, Hao; Kinneer, Patty; Teal, Randall; Johnson, David C; Dunn, Mary W; Mark, Barbara; Palmer, Mary H

    2015-03-01

    To evaluate the feasibility and acceptability of a newly developed web-based, couple-oriented intervention called Prostate Cancer Education and Resources for Couples (PERC). Quantitative, qualitative, mixed-methods approach. Oncology outpatient clinics at the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center at UNC–Chapel Hill. 26 patients with localized prostate cancer (PCa) and their partners. Pre- and postpilot quantitative assessments and a postpilot qualitative interview were conducted. General and PCa-specific symptoms, quality of life, psychosocial factors, PERC’s ease of use, and web activities. Improvement was shown in some PCa-specific and general symptoms (small effect sizes for patients and small-to-medium effect sizes for partners), overall quality of life, and physical and social domains of quality of life for patients (small effect sizes). Web activity data indicated high PERC use. Qualitative and quantitative analyses indicated that participants found PERC easy to use and understand,as well as engaging, of high quality, and relevant. Overall, participants were satisfied with PERC and reported that PERC improved their knowledge about symptom management and communication as a couple. PERC was a feasible, acceptable method of reducing the side effects of PCa treatment–related symptoms and improving quality of life. PERC has the potential to reduce the negative impacts of symptoms and enhance quality of life for patients with localized PCa and their partners, particularly for those who live in rural areas and have limited access to post-treatment supportive care.

  16. Association of THADA, FOXP4, GPRC6A/RFX6 genes and 8q24 risk alleles with prostate cancer in Northern Chinese men.

    PubMed

    Li, Xing-Hui; Xu, Yong; Yang, Kuo; Shi, Jian-Jian; Zhang, Xiao; Yang, Fang; Yuan, Huiping; Zhu, Xiaoquan; Zhang, Yu-Hong; Wang, Jian-Ye; Yang, Ze

    2015-01-01

    Prostate cancer (PCa) is one of the most common malignancies in males, and multiple genetic studies have confirmed association with susceptibility to PCa. However, the risk conferred in men living in China is unkown. We selected 6 previously identified variants as candidates to define their association with PCa in Chinese men. We genotyped 6 single nucleotide polymorphisms (SNPs) (rs1465618, rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) using high resolution melting (HRM) analysis and assessed their association with PCa risk in a case-control study of 481 patients and 480 controls in a Chinese population. In addition, the individual and cumulative contribution for the risk of PCa and clinical covariates were analysed. We found that 5 of the 6 genetic variants were associated with PCa risk. The T allele of rs339331 and the G allele of rs16901966 showed a significant association with PCa susceptibility: OR (95%CI)= 0.78 (0.64-0.94), p<0.009 and OR (95%CI)= 0.66 (0.54-0.81), p<0.0001, as well as A allele of rs1447295 (OR [95%CI]=1.46 (1.17-1.84), p<0.001) and T allele of rs10090154 (OR [95%CI]= 0.58 (0.46-0.74), p<0.0001). rs339331(T) was associated with a 0.71-fold and 1.42-fold increase of PCa risk by dominant model (p=0.007) and recessive model (p=0.007). rs16901966 (G) was associated with a 0.51-fold and 1.98-fold increase of PCa risk by dominant model (p=0.006) and recessive model (p=0.0058). rs10090154 (T) was associated with a 1.89-fold and 0.53-fold increase of PCa risk by dominant model (p=0.000006) and recessive model (p=0.000006). And, rs1983891(C) was associated with a 0.77-fold increase of PCa risk by recessive model (p=0.045). rs1447295 was associated with a 1.57-fold increase of PCa risk by dominant model (p=0.008). rs1465618 showed no significant association with PCa. The cumulative effects test of risk alleles (rs rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) showed an increasing risk to PCa in a frequency-dependent manner (ptrend=0.001), and men with more than 3 risk alleles had the most significant susceptibility to PCa (OR=1.99, p=0.001), compared with those who had one risk allele (OR=1.17, p=0.486). Our results provide further support for association of the THADA, FOXP4, GPRC6A/RFX6 and 8q24 genes with Pca in Asian populations. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms.

  17. Silymarin improves the behavioural, biochemical and histoarchitecture alterations in focal ischemic rats: a comparative evaluation with piracetam and protocatachuic acid.

    PubMed

    Muley, Milind M; Thakare, Vishnu N; Patil, Rajesh R; Kshirsagar, Ajay D; Naik, Suresh R

    2012-08-01

    Comparative neuroprotective potential of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) was evaluated in focal ischemic rats. Various pharmacological, biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite content, brain water content) and behavioural (memory impairment, motor control, neurological score) including infarct size and histopathological alterations were evaluated. Silymarin (200mg/kg) and PCA treatment significantly improved behavioural, biochemical and histopathological changes, and reduced water content and infarct size. However, piracetam only improved behavioural and histopathological changes, reduced water content and infarct size. The findings indicate that silymarin exhibits neuroprotective activity better than PCA and piracetam in focal ischemia/reperfusion reflected by its better restoration of behavioural and antioxidant profile. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

    PubMed

    Gold, Samuel A; Hale, Graham R; Bloom, Jonathan B; Smith, Clayton P; Rayn, Kareem N; Valera, Vladimir; Wood, Bradford J; Choyke, Peter L; Turkbey, Baris; Pinto, Peter A

    2018-05-21

    Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

  19. 68Ga-HBED-CC-PSMA PET/CT Versus Histopathology in Primary Localized Prostate Cancer: A Voxel-Wise Comparison

    PubMed Central

    Zamboglou, Constantinos; Schiller, Florian; Fechter, Tobias; Wieser, Gesche; Jilg, Cordula Annette; Chirindel, Alin; Salman, Nasr; Drendel, Vanessa; Werner, Martin; Mix, Michael; Meyer, Philipp Tobias; Grosu, Anca Ligia

    2016-01-01

    Purpose: We performed a voxel-wise comparison of 68Ga-HBED-CC-PSMA PET/CT with prostate histopathology to evaluate the performance of 68Ga-HBED-CC-PSMA for the detection and delineation of primary prostate cancer (PCa). Methodology: Nine patients with histopathological proven primary PCa underwent 68Ga-HBED-CC-PSMA PET/CT followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and histopathologically prepared. Histopathological information was matched to ex-vivo CT. PCa volume (PCa-histo) and non-PCa tissue in the prostate (NPCa-histo) were processed to obtain a PCa-model, which was adjusted to PET-resolution (histo-PET). Each histo-PET was coregistered to in-vivo PSMA-PET/CT data. Results: Analysis of spatial overlap between histo-PET and PSMA PET revealed highly significant correlations (p < 10-5) in nine patients and moderate to high coefficients of determination (R²) from 42 to 82 % with an average of 60 ± 14 % in eight patients (in one patient R2 = 7 %). Mean SUVmean in PCa-histo and NPCa-histo was 5.6 ± 6.1 and 3.3 ± 2.5 (p = 0.012). Voxel-wise receiver-operating characteristic (ROC) analyses comparing the prediction by PSMA-PET with the non-smoothed tumor distribution from histopathology yielded an average area under the curve of 0.83 ± 0.12. Absolute and relative SUV (normalized to SUVmax) thresholds for achieving at least 90 % sensitivity were 3.19 ± 3.35 and 0.28 ± 0.09, respectively. Conclusions: Voxel-wise analyses revealed good correlations of 68Ga-HBED-CC-PSMA PET/CT and histopathology in eight out of nine patients. Thus, PSMA-PET allows a reliable detection and delineation of PCa as basis for PET-guided focal therapies. PMID:27446496

  20. Prostate-specific membrane antigen targeted imaging and therapy of prostate cancer using a PSMA inhibitor as a homing ligand.

    PubMed

    Kularatne, Sumith A; Wang, Kevin; Santhapuram, Hari-Krishna R; Low, Philip S

    2009-01-01

    Prostate cancer (PCa) is a major cause of mortality and morbidity in Western society today. Current methods for detecting PCa are limited, leaving most early malignancies undiagnosed and sites of metastasis in advanced disease undetected. Major deficiencies also exist in the treatment of PCa, especially metastatic disease. In an effort to improve both detection and therapy of PCa, we have developed a PSMA-targeted ligand that delivers attached imaging and therapeutic agents selectively to PCa cells without targeting normal cells. The PSMA-targeted radioimaging agent (DUPA-(99m)Tc) was found to bind PSMA-positive human PCa cells (LNCaP cell line) with nanomolar affinity (K(D) = 14 nM). Imaging and biodistribution studies revealed that DUPA-(99m)Tc localizes primarily to LNCaP cell tumor xenografts in nu/nu mice (% injected dose/gram = 11.3 at 4 h postinjection; tumor-to-muscle ratio = 75:1). Two PSMA-targeted optical imaging agents (DUPA-FITC and DUPA-rhodamine B) were also shown to efficiently label PCa cells and to internalize and traffic to intracellular endosomes. A PSMA-targeted chemotherapeutic agent (DUPA-TubH) was demonstrated to kill PSMA-positive LNCaP cells in culture (IC(50) = 3 nM) and to eliminate established tumor xenografts in nu/nu mice with no detectable weight loss. Blockade of tumor targeting upon administration of excess PSMA inhibitor (PMPA) and the absence of targeting to PSMA-negative tumors confirmed the specificity of each of the above targeted reagents for PSMA. Tandem use of the imaging and therapeutic agents targeted to the same receptor could allow detection, staging, monitoring, and treatment of PCa with improved accuracy and efficacy.

  1. Differentiation of neuropsychological features between posterior cortical atrophy and early onset Alzheimer's disease.

    PubMed

    Li, Jieying; Wu, Liyong; Tang, Yi; Zhou, Aihong; Wang, Fen; Xing, Yi; Jia, Jianping

    2018-05-10

    Posterior cortical atrophy (PCA) is a group of clinical syndromes characterized by visuospatial and visuoperceptual impairment, with memory relatively preserved. Although PCA is pathologically almost identical to Alzheimer's disease (AD), they have different cognitive features. Those differences have only rarely been reported in any Chinese population. The purpose of the study is to establish neuropsychological tests that distinguish the clinical features of PCA from early onset AD (EOAD). Twenty-one PCA patients, 20 EOAD patients, and 20 healthy controls participated in this study. Patients had disease duration of ≤4 years. All participants completed a series of neuropsychological tests to evaluate their visuospatial, visuoperceptual, visuo-constructive, language, executive function, memory, calculation, writing, and reading abilities. The cognitive features of PCA and EOAD were compared. All the neuropsychological test scores showed that both the PCA and EOAD patients were significantly more impaired than people in the control group. However, PCA patients were significantly more impaired than EOAD patients in visuospatial, visuoperceptual, and visuo-constructive function, as well as in handwriting, and reading Chinese characters. The profile of neuropsychological test results highlights cognitive features that differ between PCA and EOAD. One surprising result is that the two syndromes could be distinguished by patients' ability to read and write Chinese characters. Tests based on these characteristics could therefore form a brief PCA neuropsychological examination that would improve the diagnosis of PCA.

  2. Fast and Accurate Radiative Transfer Calculations Using Principal Component Analysis for (Exo-)Planetary Retrieval Models

    NASA Astrophysics Data System (ADS)

    Kopparla, P.; Natraj, V.; Shia, R. L.; Spurr, R. J. D.; Crisp, D.; Yung, Y. L.

    2015-12-01

    Radiative transfer (RT) computations form the engine of atmospheric retrieval codes. However, full treatment of RT processes is computationally expensive, prompting usage of two-stream approximations in current exoplanetary atmospheric retrieval codes [Line et al., 2013]. Natraj et al. [2005, 2010] and Spurr and Natraj [2013] demonstrated the ability of a technique using principal component analysis (PCA) to speed up RT computations. In the PCA method for RT performance enhancement, empirical orthogonal functions are developed for binned sets of inherent optical properties that possess some redundancy; costly multiple-scattering RT calculations are only done for those few optical states corresponding to the most important principal components, and correction factors are applied to approximate radiation fields. Kopparla et al. [2015, in preparation] extended the PCA method to a broadband spectral region from the ultraviolet to the shortwave infrared (0.3-3 micron), accounting for major gas absorptions in this region. Here, we apply the PCA method to a some typical (exo-)planetary retrieval problems. Comparisons between the new model, called Universal Principal Component Analysis Radiative Transfer (UPCART) model, two-stream models and line-by-line RT models are performed, for spectral radiances, spectral fluxes and broadband fluxes. Each of these are calculated at the top of the atmosphere for several scenarios with varying aerosol types, extinction and scattering optical depth profiles, and stellar and viewing geometries. We demonstrate that very accurate radiance and flux estimates can be obtained, with better than 1% accuracy in all spectral regions and better than 0.1% in most cases, as compared to a numerically exact line-by-line RT model. The accuracy is enhanced when the results are convolved to typical instrument resolutions. The operational speed and accuracy of UPCART can be further improved by optimizing binning schemes and parallelizing the codes, work on which is under way.

  3. 2L-PCA: a two-level principal component analyzer for quantitative drug design and its applications.

    PubMed

    Du, Qi-Shi; Wang, Shu-Qing; Xie, Neng-Zhong; Wang, Qing-Yan; Huang, Ri-Bo; Chou, Kuo-Chen

    2017-09-19

    A two-level principal component predictor (2L-PCA) was proposed based on the principal component analysis (PCA) approach. It can be used to quantitatively analyze various compounds and peptides about their functions or potentials to become useful drugs. One level is for dealing with the physicochemical properties of drug molecules, while the other level is for dealing with their structural fragments. The predictor has the self-learning and feedback features to automatically improve its accuracy. It is anticipated that 2L-PCA will become a very useful tool for timely providing various useful clues during the process of drug development.

  4. Energetics of short hydrogen bonds in photoactive yellow protein.

    PubMed

    Saito, Keisuke; Ishikita, Hiroshi

    2012-01-03

    Recent neutron diffraction studies of photoactive yellow protein (PYP) proposed that the H bond between protonated Glu46 and the chromophore [ionized p-coumaric acid (pCA)] was a low-barrier H bond (LBHB). Using the atomic coordinates of the high-resolution crystal structure, we analyzed the energetics of the short H bond by two independent methods: electrostatic pK(a) calculations and a quantum mechanical/molecular mechanical (QM/MM) approach. (i) In the QM/MM optimized geometry, we reproduced the two short H-bond distances of the crystal structure: Tyr42-pCA (2.50 Å) and Glu46-pCA (2.57 Å). However, the H atoms obviously belonged to the Tyr or Glu moieties, and were not near the midpoint of the donor and acceptor atoms. (ii) The potential-energy curves of the two H bonds resembled those of standard asymmetric double-well potentials, which differ from those of LBHB. (iii) The calculated pK(a) values for Glu46 and pCA were 8.6 and 5.4, respectively. The pK(a) difference was unlikely to satisfy the prerequisite for LBHB. (iv) The LBHB in PYP was originally proposed to stabilize the ionized pCA because deprotonated Arg52 cannot stabilize it. However, the calculated pK(a) of Arg52 and QM/MM optimized geometry suggested that Arg52 was protonated on the protein surface. The short H bond between Glu46 and ionized pCA in the PYP ground state could be simply explained by electrostatic stabilization without invoking LBHB.

  5. Health status monitoring for ICU patients based on locally weighted principal component analysis.

    PubMed

    Ding, Yangyang; Ma, Xin; Wang, Youqing

    2018-03-01

    Intelligent status monitoring for critically ill patients can help medical stuff quickly discover and assess the changes of disease and then make appropriate treatment strategy. However, general-type monitoring model now widely used is difficult to adapt the changes of intensive care unit (ICU) patients' status due to its fixed pattern, and a more robust, efficient and fast monitoring model should be developed to the individual. A data-driven learning approach combining locally weighted projection regression (LWPR) and principal component analysis (PCA) is firstly proposed and applied to monitor the nonlinear process of patients' health status in ICU. LWPR is used to approximate the complex nonlinear process with local linear models, in which PCA could be further applied to status monitoring, and finally a global weighted statistic will be acquired for detecting the possible abnormalities. Moreover, some improved versions are developed, such as LWPR-MPCA and LWPR-JPCA, which also have superior performance. Eighteen subjects were selected from the Physiobank's Multi-parameter Intelligent Monitoring for Intensive Care II (MIMIC II) database, and two vital signs of each subject were chosen for online monitoring. The proposed method was compared with several existing methods including traditional PCA, Partial least squares (PLS), just in time learning combined with modified PCA (L-PCA), and Kernel PCA (KPCA). The experimental results demonstrated that the mean fault detection rate (FDR) of PCA can be improved by 41.7% after adding LWPR. The mean FDR of LWPR-MPCA was increased by 8.3%, compared with the latest reported method L-PCA. Meanwhile, LWPR spent less training time than others, especially KPCA. LWPR is first introduced into ICU patients monitoring and achieves the best monitoring performance including adaptability to changes in patient status, sensitivity for abnormality detection as well as its fast learning speed and low computational complexity. The algorithm is an excellent approach to establishing a personalized model for patients, which is the mainstream direction of modern medicine in the following development, as well as improving the global monitoring performance. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  6. Time-dependent analysis of dosage delivery information for patient-controlled analgesia services.

    PubMed

    Kuo, I-Ting; Chang, Kuang-Yi; Juan, De-Fong; Hsu, Steen J; Chan, Chia-Tai; Tsou, Mei-Yung

    2018-01-01

    Pain relief always plays the essential part of perioperative care and an important role of medical quality improvement. Patient-controlled analgesia (PCA) is a method that allows a patient to self-administer small boluses of analgesic to relieve the subjective pain. PCA logs from the infusion pump consisted of a lot of text messages which record all events during the therapies. The dosage information can be extracted from PCA logs to provide easily understanding features. The analysis of dosage information with time has great help to figure out the variance of a patient's pain relief condition. To explore the trend of pain relief requirement, we developed a PCA dosage information generator (PCA DIG) to extract meaningful messages from PCA logs during the first 48 hours of therapies. PCA dosage information including consumption, delivery, infusion rate, and the ratio between demand and delivery is presented with corresponding values in 4 successive time frames. Time-dependent statistical analysis demonstrated the trends of analgesia requirements decreased gradually along with time. These findings are compatible with clinical observations and further provide valuable information about the strategy to customize postoperative pain management.

  7. Comprehensive analysis of commercial willow bark extracts by new technology platform: combined use of metabolomics, high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy and high-resolution radical scavenging assay.

    PubMed

    Agnolet, Sara; Wiese, Stefanie; Verpoorte, Robert; Staerk, Dan

    2012-11-02

    Here, proof-of-concept of a new analytical platform used for the comprehensive analysis of a small set of commercial willow bark products is presented, and compared with a traditional standardization solely based on analysis of salicin and salicin derivatives. The platform combines principal component analysis (PCA) of two chemical fingerprints, i.e., HPLC and (1)H NMR data, and a pharmacological fingerprint, i.e., high-resolution 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS(+)) reduction profile, with targeted identification of constituents of interest by hyphenated HPLC-solid-phase extraction-tube transfer NMR, i.e., HPLC-SPE-ttNMR. Score plots from PCA of HPLC and (1)H NMR fingerprints showed the same distinct grouping of preparations formulated as capsules of Salix alba bark and separation of S. alba cortex. Loading plots revealed this to be due to high amount of salicin in capsules and ampelopsin, taxifolin, 7-O-methyltaxifolin-3'-O-glucoside, and 7-O-methyltaxifolin in S. alba cortex, respectively. PCA of high-resolution radical scavenging profiles revealed clear separation of preparations along principal component 1 due to the major radical scavengers (+)-catechin and ampelopsin. The new analytical platform allowed identification of 16 compounds in commercial willow bark extracts, and identification of ampelopsin, taxifolin, 7-O-methyltaxifolin-3'-O-glucoside, and 7-O-methyltaxifolin in S. alba bark extract is reported for the first time. The detection of the novel compound, ethyl 1-hydroxy-6-oxocyclohex-2-enecarboxylate, is also described. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription.

    PubMed

    Liu, Youhong; Liu, Yijun; Yuan, Bowen; Yin, Linglong; Peng, Yuchong; Yu, Xiaohui; Zhou, Weibing; Gong, Zhicheng; Liu, Jianye; He, Leye; Li, Xiong

    2017-03-07

    Androgen/AR is the primary contributor to prostate cancer (PCa) progression by regulating Prostate Specific Antigen (PSA) gene transcription. The disease inevitably evolves to androgen-independent (AI) status. Other mechanisms by which PSA is regulated and develops to AI have not yet been fully determined. FOXM1 is a cell proliferation-specific transcription factor highly expressed in PCa cells compared to non-malignant prostate epithelial cells, suggesting that the aberrant overexpression of FOXM1 contributes to PCa development. In addition to regulating AR gene transcription and cell cycle-regulatory genes, FOXM1 selectively regulates the gene transcription of KLK2 and PSA, typical androgen responsive genes. Screening the potential FOXM1-binding sites by ChIP-PCR, we found that FOXM1 directly binds to the FHK binding motifs in the PSA promoter/enhancer regions. AI C4-2 cells have more FOXM1 binding sites than androgen dependent LNCaP cells. The depletion of FOXM1 by small molecular inhibitors significantly improves the suppression of PSA gene transcription by the anti-AR agent Cadosax. This is the first report showing that FOXM1 promotes PCa progression by regulating PSA gene transcription, particularly in AI PCa cells. The combination of anti-AR agents and FOXM1 inhibitors has the potential to greatly improve therapy for late-stage PCa patients by suppressing PSA levels.

  9. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    PubMed Central

    Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  10. Substantial Family History of Prostate Cancer in Black Men Recruited for Prostate Cancer Screening

    PubMed Central

    Mastalski, Kathleen; Coups, Elliot J.; Ruth, Karen; Raysor, Susan; Giri, Veda N.

    2008-01-01

    Background Black men are at increased risk for prostate cancer (PCA), particularly with a family history (FH) of the disease. Previous reports have raised concern for suboptimal screening of Black men with a FH of PCA. We report on the extent of FH of PCA from a prospective, longitudinal PCA screening program for high-risk men. Methods Black men ages 35-69 are eligible for PCA screening through the Prostate Cancer Risk Assessment Program (PRAP) regardless of FH. Rates of self-reported FH of PCA, breast, and colon cancer at baseline were compared with an age-matched sample of Black men from the 2005 National Health Interview Survey (NHIS) using standard statistical methods. Results As of January 2007, 332 Black men with pedigree information were enrolled in PRAP and FH of PCA was compared to 838 Black men from the 2005 NHIS. Black men in PRAP reported significantly more first-degree relatives with PCA compared to Black men in the 2005 NHIS (34.3%, 95% CI 29.2-39.7 vs. 5.7%, 95% CI 3.9-7.4). Black men in PRAP also had more FH of breast cancer compared to the 2005 NHIS (11.5%, 95% CI 8.2-15.4 vs 6.3%, 95% CI 4.6-8.0). Conclusions FH of PCA appears to be a motivating factor for Black men seeking PCA screening. Targeted recruitment and education among Black families should improve PCA screening rates. Efforts to recruit Black men without a FH of PCA are also needed. Condensed Abstract Black men seeking prostate cancer screening have a substantial burden of family history of prostate cancer. Targeted education and enhancing discussion in Black families should increase prostate cancer screening and adherence. PMID:18816608

  11. PSMA PET and radionuclide therapy in prostate cancer

    PubMed Central

    Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter L.

    2016-01-01

    Prostate cancer (Pca) is the most common malignancy in men and a major cause of cancer death. Accurate imaging plays an important role in diagnosis, staging, restaging, detection of biochemical recurrence, and for therapy of PCa patients. Since no effective treatment is available for advanced PCa, there is an urgent need to develop new and more effective therapeutic strategies. In order to optimize treatment outcome, especially in high risk PCa patients, therapy of PCa is moving rapidly towards personalization. Medical imaging, including positron emission tomography (PET)/computed tomography (CT), plays an important role in personalized medicine in oncology. In the recent years, much focus has been on prostate specific membrane antigen (PSMA) as a promising target for imaging and therapy with radionuclides, since it is upregulated in most PCa. In the prostate, one potential role for PSMA PET imaging is to help guiding focal therapy. Several studies have shown great potential of PSMA PET/CT for initial staging, lymph node staging, and detection of recurrence of PCa, even at very low PSA values after primary therapy. Furthermore, studies have shown that PSMA PET/CT has a higher detection rate than choline PET/CT. Radiolabeled PSMA ligands for therapy show promise in several studies with metastatic PCa, and is an area of active investigation. The “Image and treat” strategy, with radiolabeled PSMA ligands, has the potential to improve the treatment outcome of PCa patients, and is paving the way for precision medicine in PCa. The aim of this review is to give an overview of recent advancement in PSMA PET and radionuclide therapy of PCa. PMID:27825432

  12. Prostate cancer characterization by optical contrast enhanced photoacoustics

    NASA Astrophysics Data System (ADS)

    Xu, Guan; Qin, Ming; Mukundan, Ananya; Siddiqui, Javed; Takada, Marilia; Vilar-Saavedra, Paulo; Tomlins, Scott A.; Kopelman, Raoul; Wang, Xueding

    2016-03-01

    During the past decades, prostate cancer (PCa), with an annual incident rate much higher than any other cancer, is the most commonly diagnosed cancer in American men. PCa has a relatively low progression rate yet the survival percentage decreases dramatically once the cancer has metastasized. Identifying aggressive from indolent PCa to prevent metastasis and death is critical to improving outcomes for patients with PCa. Standard procedure for assessing the aggressiveness of PCa involves the removal of tumor tissues by transrectal (TR) ultrasound (US) guided needle biopsy. The microscopic architecture of the biopsied tissue is visualized by histological or immunohistochemical staining procedures. The heterogeneity of the microscopic architecture is characterized by a Gleason score, a quantitative description of the aggressiveness of PCa. Due to the inability to identify the cancer cells, most noninvasive imaging modalities can only provide diagnosis of PCa at limited accuracy. This study investigates the feasibility of identifying PCa tumors and characterizing the aggressiveness of PCa by photoacoustic imaging assisted by cancer targeting polyacrylamide (PAA) nanoparticles (NPs). PAA is a biocompatible material used in clinics for the past 20 years. PAA NPs can protect capsulated optical contrast agents from interference by enzymes and enable prolonged systematic circulation in the living biological environment. The cancer targeting mechanism is achieved by conjugating the NPs to F3 peptides, which trace nucleolin overexpressed on the surface of cancer cells. Preliminary studies have shown that the NPs are capable of staining the PCa cells in vivo.

  13. Opioid Patient Controlled Analgesia (PCA) use during the Initial Experience with the IMPROVE PCA Trial: A Phase III Analgesic Trial for Hospitalized Sickle Cell Patients with Painful Episodes

    PubMed Central

    Dampier, Carlton D.; Smith, Wally R.; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C.; Minniti, Caterina P.; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A. Kyle; McClish, Donna; McKinlay, Sonja M.; Miller, Scott T.; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J.; Weiner, Debra L.

    2015-01-01

    Opioid analgesics administered by patient-controlled analgesia (PCA) are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations, a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents, mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI and in the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI 0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage. PMID:21953763

  14. Integration of lipidomics and transcriptomics unravels aberrant lipid metabolism and defines cholesteryl oleate as potential biomarker of prostate cancer

    NASA Astrophysics Data System (ADS)

    Li, Jia; Ren, Shancheng; Piao, Hai-Long; Wang, Fubo; Yin, Peiyuan; Xu, Chuanliang; Lu, Xin; Ye, Guozhu; Shao, Yaping; Yan, Min; Zhao, Xinjie; Sun, Yinghao; Xu, Guowang

    2016-02-01

    In-depth delineation of lipid metabolism in prostate cancer (PCa) is significant to open new insights into prostate tumorigenesis and progression, and provide potential biomarkers with greater accuracy for improved diagnosis. Here, we performed lipidomics and transcriptomics in paired prostate cancer tumor (PCT) and adjacent nontumor (ANT) tissues, followed by external validation of biomarker candidates. We identified major dysregulated pathways involving lipogenesis, lipid uptake and phospholipids remodeling, correlated with widespread lipid accumulation and lipid compositional reprogramming in PCa. Specifically, cholesteryl esters (CEs) were most prominently accumulated in PCa, and significantly associated with cancer progression and metastasis. We showed that overexpressed scavenger receptor class B type I (SR-BI) may contribute to CEs accumulation. In discovery set, CEs robustly differentiated PCa from nontumor (area under curve (AUC) of receiver operating characteristics (ROC), 0.90-0.94). In validation set, CEs potently distinguished PCa and non-malignance (AUC, 0.84-0.91), and discriminated PCa and benign prostatic hyperplasia (BPH) (AUC, 0.90-0.96), superior to serum prostate-specific antigen (PSA) (AUC = 0.83). Cholesteryl oleate showed highest AUCs in distinguishing PCa from non-malignance or BPH (AUC = 0.91 and 0.96). Collectively, our results unravel the major lipid metabolic aberrations in PCa and imply the potential role of CEs, particularly, cholesteryl oleate, as molecular biomarker for PCa detection.

  15. Lifestyle interventions to improve the quality of life of men with prostate cancer: A systematic review of randomized controlled trials.

    PubMed

    Menichetti, Julia; Villa, Silvia; Magnani, Tiziana; Avuzzi, Barbara; Bosetti, Davide; Marenghi, Cristina; Morlino, Sara; Rancati, Tiziana; Van Poppel, Hein; Salvioni, Roberto; Valdagni, Riccardo; Bellardita, Lara

    2016-12-01

    Improving quality of life is a key issue for patients with prostate cancer (PCa). Lifestyle interventions could positively impact the quality of life of patients. However, there is no clear-cut understanding of the role of diet, exercise and risky behaviour reduction in improving the quality of life of men with PCa. The aim of this review was to systematically summarize randomized controlled trials on lifestyle in PCa patients with quality of life as main outcome. 17 trials were included. Most of them referred to exercise interventions (71%) and involved men undergoing androgen deprivation therapy (47%). Exercise studies yielded the greater amount of positive results on quality of life outcomes (67%), followed by dietary interventions (50%) and combined lifestyle interventions (33%). In particular, supervised exercise programs with resistance training sessions were the ones producing greater convincing evidence for benefits on quality of life. Further studies with high methodological quality providing adequate information to develop evidence-based, personalized lifestyle interventions that can effectively ameliorate PCa-related quality of life are needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Facilitating Neuronal Connectivity Analysis of Evoked Responses by Exposing Local Activity with Principal Component Analysis Preprocessing: Simulation of Evoked MEG

    PubMed Central

    Gao, Lin; Zhang, Tongsheng; Wang, Jue; Stephen, Julia

    2014-01-01

    When connectivity analysis is carried out for event related EEG and MEG, the presence of strong spatial correlations from spontaneous activity in background may mask the local neuronal evoked activity and lead to spurious connections. In this paper, we hypothesized PCA decomposition could be used to diminish the background activity and further improve the performance of connectivity analysis in event related experiments. The idea was tested using simulation, where we found that for the 306-channel Elekta Neuromag system, the first 4 PCs represent the dominant background activity, and the source connectivity pattern after preprocessing is consistent with the true connectivity pattern designed in the simulation. Improving signal to noise of the evoked responses by discarding the first few PCs demonstrates increased coherences at major physiological frequency bands when removing the first few PCs. Furthermore, the evoked information was maintained after PCA preprocessing. In conclusion, it is demonstrated that the first few PCs represent background activity, and PCA decomposition can be employed to remove it to expose the evoked activity for the channels under investigation. Therefore, PCA can be applied as a preprocessing approach to improve neuronal connectivity analysis for event related data. PMID:22918837

  17. Facilitating neuronal connectivity analysis of evoked responses by exposing local activity with principal component analysis preprocessing: simulation of evoked MEG.

    PubMed

    Gao, Lin; Zhang, Tongsheng; Wang, Jue; Stephen, Julia

    2013-04-01

    When connectivity analysis is carried out for event related EEG and MEG, the presence of strong spatial correlations from spontaneous activity in background may mask the local neuronal evoked activity and lead to spurious connections. In this paper, we hypothesized PCA decomposition could be used to diminish the background activity and further improve the performance of connectivity analysis in event related experiments. The idea was tested using simulation, where we found that for the 306-channel Elekta Neuromag system, the first 4 PCs represent the dominant background activity, and the source connectivity pattern after preprocessing is consistent with the true connectivity pattern designed in the simulation. Improving signal to noise of the evoked responses by discarding the first few PCs demonstrates increased coherences at major physiological frequency bands when removing the first few PCs. Furthermore, the evoked information was maintained after PCA preprocessing. In conclusion, it is demonstrated that the first few PCs represent background activity, and PCA decomposition can be employed to remove it to expose the evoked activity for the channels under investigation. Therefore, PCA can be applied as a preprocessing approach to improve neuronal connectivity analysis for event related data.

  18. Innovative Comparison of Transient Ignition Temperature at the Booster Interface, New Stainless Steel Pyrovalve Primer Chamber Assembly "V" (PCA) Design Versus the Current Aluminum "Y" PCA Design

    NASA Technical Reports Server (NTRS)

    Saulsberry, Regor L.; McDougle, Stephen H.; Garcia,Roberto; Johnson, Kenneth L.; Sipes, William; Rickman, Steven; Hosangadi, Ashvin

    2011-01-01

    An assessment of four spacecraft pyrovalve anomalies that occurred during ground testing was conducted by the NASA Engineering & Safety Center (NESC) in 2008. In all four cases, a common aluminum (Al) primer chamber assembly (PCA) was used with dual NASA Standard Initiators (NSIs) and the nearly simultaneous (separated by less than 80 microseconds) firing of both initiators failed to ignite the booster charge. The results of the assessment and associated test program were reported in AIAA Paper AIAA-2008-4798, NESC Independent Assessment of Pyrovalve Ground Test Anomalies. As a result of the four Al PCA anomalies, and the test results and findings of the NESC assessment, the Mars Science Laboratory (MSL) project team decided to make changes to the PCA. The material for the PCA body was changed from aluminum (Al) to stainless steel (SS) to avoid melting, distortion, and potential leakage of the NSI flow passages when the device functioned. The flow passages, which were interconnected in a Y-shaped configuration (Y-PCA) in the original design, were changed to a V-shaped configuration (V-PCA). The V-shape was used to more efficiently transfer energy from the NSIs to the booster. Development and qualification testing of the new design clearly demonstrated faster booster ignition times compared to the legacy AL Y-PCA design. However, the final NESC assessment report recommended that the SS V-PCA be experimentally characterized and quantitatively compared to the Al Y-PCA design. This data was deemed important for properly evaluating the design options for future NASA projects. This test program has successfully quantified the improvement of the SS V-PCA over the Al Y-PCA. A phase B of the project was also conducted and evaluated the effect of firing command skew and enlargement of flame channels to further assist spacecraft applications.

  19. PCA3-based nomogram for predicting prostate cancer and high grade cancer on initial transrectal guided biopsy.

    PubMed

    Elshafei, Ahmed; Chevli, K Kent; Moussa, Ayman S; Kara, Onder; Chueh, Shih-Chieh; Walter, Peter; Hatem, Asmaa; Gao, Tianming; Jones, J Stephen; Duff, Michael

    2015-12-01

    To develop a validated prostate cancer antigen 3 (PCA3) based nomogram that predicts likelihood of overall prostate cancer (PCa) and intermediate/high grade prostate cancer (HGPCa) in men pursuing initial transrectal prostate biopsy (TRUS-PBx). Data were collected on 3,675 men with serum prostate specific antigen level (PSA) ≤ 20 ng/ml who underwent initial prostate biopsy with at least 10 cores sampling at time of the biopsy. Two logistic regression models were constructed to predict overall PCa and HGPCa incorporating age, race, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and digital rectal exam (DRE). One thousand six hundred twenty (44%) patients had biopsy confirmed PCa with 701 men (19.1%) showing HGPCa. Statistically significant predictors of overall PCa were age (P < 0.0001, OR. 1.51), PSA at diagnosis (P < 0.0001, OR.1.95), PCA3 (P < 0.0001, OR.3.06), TPV (P < 0.0001, OR.0.47), FH (P = 0.003, OR.1.32), and abnormal DRE (P = 0.001, OR. 1.32). While for HGPCa, predictors were age (P < 0.0001, OR.1.77), PSA (P < 0.0001, OR.2.73), PCA3 (P < 0.0001, OR.2.26), TPV (P < 0.0001, OR.0.4), and DRE (P < 0.0001, OR.1.53). Two nomograms were reconstructed for predicted overall PCa probability at time of initial biopsy with a concordance index of 0.742 (Fig. 1), and HGPCa with a concordance index of 0.768 (Fig. 2). Our internally validated initial biopsy PCA3 based nomogram is reconstructed based on a large dataset. The c-index indicates high predictive accuracy, especially for high grade PCa and improves the ability to predict biopsy outcomes. © 2015 Wiley Periodicals, Inc.

  20. Hyperspectral-stimulated Raman scattering imaging of cholesteryl ester accumulation: new avenue to diagnosis of human prostate cancer

    NASA Astrophysics Data System (ADS)

    Du, Jun; Wang, Ping; Yue, Shuhua

    2016-10-01

    Most prostate cancers (PCa) are slowly growing, and only the aggressive ones require early diagnosis and effective treatment. The current standard for PCa diagnosis remains histopathology. Nonetheless, for the differentiation between Gleason score 6 (low-risk PCa), which can be left without treatment, and Gleason score 7 (high-risk PCa), which requires active treatment, the inter-observer discordance can be up to 40%. Our previous study reveals that cholesteryl ester (CE) accumulation induced by PI3K/AKT activation underlies human PCa aggressiveness. However, Raman spectromicroscopy used in this study could only provide compositional information of certain lipid droplets (LDs) selected by the observer, which overlooked cell-to-cell variation and hindered translation to accurate automated diagnosis. Here, we demonstrated quantitative mapping of CE level in human prostate tissues using hyperspectral stimulated Raman scattering (SRS) microscopy that renders compositional information for every pixel in the image. Specifically, hundreds of SRS images at Raman shift between 1620-1800 cm-1 were taken, and multivariate curve resolution algorism was used to retrieve concentration images of acyl C=C bond, sterol C=C bond, and ester C=O bond. Given that the ratio between images of sterol C=C and ester C=O (sterol C=C/C=O) is nonlinearly proportional to CE percentage out of total lipid, we were able to quantitatively map CE level. Our data showed that CE level was significantly greater in high Gleason grade compared to low Gleason grade, and could be a factor that significantly contributed to cancer recurrence. Our study provides an opportunity towards more accurate PCa diagnosis and prediction of aggressiveness.

  1. Ionospheric total electron content anomalies due to Typhoon Nakri on 29 May 2008: A nonlinear principal component analysis

    NASA Astrophysics Data System (ADS)

    Lin, Jyh-Woei

    2012-09-01

    This paper uses Nonlinear Principal Component Analysis (NLPCA) and Principal Component Analysis (PCA) to determine Total Electron Content (TEC) anomalies in the ionosphere for the Nakri Typhoon on 29 May, 2008 (UTC). NLPCA, PCA and image processing are applied to the global ionospheric map (GIM) with transforms conducted for the time period 12:00-14:00 UT on 29 May 2008 when the wind was most intense. Results show that at a height of approximately 150-200 km the TEC anomaly using NLPCA is more localized; however its intensity increases with height and becomes more widespread. The TEC anomalies are not found by PCA. Potential causes of the results are discussed with emphasis given to vertical acoustic gravity waves. The approximate position of the typhoon's eye can be detected if the GIM is divided into fine enough maps with adequate spatial-resolution at GPS-TEC receivers. This implies that the trace of the typhoon in the regional GIM is caught using NLPCA.

  2. Transrectal real-time tissue elastography targeted biopsy coupled with peak strain index improves the detection of clinically important prostate cancer.

    PubMed

    Ma, Qi; Yang, Dong-Rong; Xue, Bo-Xin; Wang, Cheng; Chen, Han-Bin; Dong, Yun; Wang, Cai-Shan; Shan, Yu-Xi

    2017-07-01

    The focus of the present study was to evaluate transrectal real-time tissue elastography (RTE)-targeted two-core biopsy coupled with peak strain index for the detection of prostate cancer (PCa) and to compare this method with 10-core systematic biopsy. A total of 141 patients were enrolled for evaluation. The diagnostic value of peak strain index was assessed using a receiver operating characteristic curve. The cancer detection rates of the two approaches and corresponding positive cores and Gleason score were compared. The cancer detection rate per core in the RTE-targeted biopsy (44%) was higher compared with that in systematic biopsy (30%). The peak strain index value of PCa was higher compared with that of the benign lesion. PCa was detected with the highest sensitivity (87.5%) and specificity (85.5%) using the threshold value of a peak strain index of ≥5.97 with an area under the curve value of 0.95. When the Gleason score was ≥7, RTE-targeted biopsy coupled with peak strain index detected 95.6% of PCa cases, but 84.4% were detected using systematic biopsy. Peak strain index as a quantitative parameter may improve the differentiation of PCa from benign lesions in the prostate peripheral zone. Transrectal RTE-targeted biopsy coupled with peak strain index may enhance the detection of clinically significant PCa, particularly when combined with systematic biopsy.

  3. Competing-risks mortality after radiotherapy vs. observation for localized prostate cancer: a population-based study.

    PubMed

    Abdollah, Firas; Sun, Maxine; Schmitges, Jan; Thuret, Rodolphe; Tian, Zhe; Shariat, Shahrokh F; Briganti, Alberto; Jeldres, Claudio; Perrotte, Paul; Montorsi, Francesco; Karakiewicz, Pierre I

    2012-09-01

    Contemporary patients with localized prostate cancer (PCa) are more frequently treated with radiotherapy. However, there are limited data on the effect of this treatment on cancer-specific mortality (CSM). Our objective was to test the relationship between radiotherapy and survival in men with localized PCa and compare it with those treated with observation. A population-based cohort identified 68,797 men with cT1-T2 PCa treated with radiotherapy or observation between the years 1992 and 2005. Propensity-score matching was used to minimize potential bias related to treatment assignment. Competing-risks analyses tested the effect of treatment type (radiotherapy vs. observation) on CSM, after accounting to other-cause mortality. All analyses were carried out within PCa risk, baseline comorbidity status, and age groups. Radiotherapy was associated with more favorable 10-year CSM rates than observation in patients with high-risk PCa (8.8 vs. 14.4%, hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50-0.68). Conversely, the beneficial effect of radiotherapy on CSM was not evident in patients with low-intermediate risk PCa (3.7 vs. 4.1%, HR: 0.91, 95% CI: 0.80-1.04). Radiotherapy was beneficial in elderly patients (5.6 vs. 7.3%, HR: 0.70, 95% CI: 0.59-0.80). Moreover, it was associated with improved CSM rates among patients with no comorbidities (5.7 vs. 6.5%, HR: 0.81, 95% CI: 0.67-0.98), one comorbidity (4.6 vs. 6.0%, HR: 0.87, 95% CI: 0.75-0.99), and more than two comorbidities (4.2 vs. 5.0%, HR: 0.79, 95% CI: 0.65-0.96). Radiotherapy substantially improves CSM in patients with high-risk PCa, with little or no benefit in patients with low-/intermediate-risk PCa relative to observation. These findings must be interpreted within the context of the limitations of observational data. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. [Analyzing and modeling methods of near infrared spectroscopy for in-situ prediction of oil yield from oil shale].

    PubMed

    Liu, Jie; Zhang, Fu-Dong; Teng, Fei; Li, Jun; Wang, Zhi-Hong

    2014-10-01

    In order to in-situ detect the oil yield of oil shale, based on portable near infrared spectroscopy analytical technology, with 66 rock core samples from No. 2 well drilling of Fuyu oil shale base in Jilin, the modeling and analyzing methods for in-situ detection were researched. By the developed portable spectrometer, 3 data formats (reflectance, absorbance and K-M function) spectra were acquired. With 4 different modeling data optimization methods: principal component-mahalanobis distance (PCA-MD) for eliminating abnormal samples, uninformative variables elimination (UVE) for wavelength selection and their combina- tions: PCA-MD + UVE and UVE + PCA-MD, 2 modeling methods: partial least square (PLS) and back propagation artificial neural network (BPANN), and the same data pre-processing, the modeling and analyzing experiment were performed to determine the optimum analysis model and method. The results show that the data format, modeling data optimization method and modeling method all affect the analysis precision of model. Results show that whether or not using the optimization method, reflectance or K-M function is the proper spectrum format of the modeling database for two modeling methods. Using two different modeling methods and four different data optimization methods, the model precisions of the same modeling database are different. For PLS modeling method, the PCA-MD and UVE + PCA-MD data optimization methods can improve the modeling precision of database using K-M function spectrum data format. For BPANN modeling method, UVE, UVE + PCA-MD and PCA- MD + UVE data optimization methods can improve the modeling precision of database using any of the 3 spectrum data formats. In addition to using the reflectance spectra and PCA-MD data optimization method, modeling precision by BPANN method is better than that by PLS method. And modeling with reflectance spectra, UVE optimization method and BPANN modeling method, the model gets the highest analysis precision, its correlation coefficient (Rp) is 0.92, and its standard error of prediction (SEP) is 0.69%.

  5. Classification of high-resolution multispectral satellite remote sensing images using extended morphological attribute profiles and independent component analysis

    NASA Astrophysics Data System (ADS)

    Wu, Yu; Zheng, Lijuan; Xie, Donghai; Zhong, Ruofei

    2017-07-01

    In this study, the extended morphological attribute profiles (EAPs) and independent component analysis (ICA) were combined for feature extraction of high-resolution multispectral satellite remote sensing images and the regularized least squares (RLS) approach with the radial basis function (RBF) kernel was further applied for the classification. Based on the major two independent components, the geometrical features were extracted using the EAPs method. In this study, three morphological attributes were calculated and extracted for each independent component, including area, standard deviation, and moment of inertia. The extracted geometrical features classified results using RLS approach and the commonly used LIB-SVM library of support vector machines method. The Worldview-3 and Chinese GF-2 multispectral images were tested, and the results showed that the features extracted by EAPs and ICA can effectively improve the accuracy of the high-resolution multispectral image classification, 2% larger than EAPs and principal component analysis (PCA) method, and 6% larger than APs and original high-resolution multispectral data. Moreover, it is also suggested that both the GURLS and LIB-SVM libraries are well suited for the multispectral remote sensing image classification. The GURLS library is easy to be used with automatic parameter selection but its computation time may be larger than the LIB-SVM library. This study would be helpful for the classification application of high-resolution multispectral satellite remote sensing images.

  6. The willingness of patients to pay for intravenous patient-controlled analgesia in Korea.

    PubMed

    Lim, Hyungsun; Lee, Duck-Hyoung; Lee, Jeongwoo; Han, Young Jin; Choe, Huhn; Son, Ji-Seon

    2012-06-01

    The use of intravenous patient-controlled analgesia (IV-PCA) has been increasing because it has advantages such as improved pain relief, greater patient satisfaction, and fewer postoperative complications. However, current research has not considered the patients' thoughts about IV-PCA's cost-effectiveness. The purpose of this study was to investigate the willingness to pay (WTP) for IV-PCA and the relationship between patients' characteristics and WTP in Korea. We enrolled 400 adult patients who were scheduled for elective surgery. The patient was requested to indicate a series of predefined amounts of money (Korean won; 30,000/50,000/100,000/150,000/200,000/300,000/500,000). We also recorded patient characteristics, such as age, sex, type of surgery, IV-PCA history, education level, the person responsible for medical expenses, type of insurance, net annual income, and residential area. Three days after surgery, we asked about the degree of satisfaction and the WTP for IV-PCA. For IV-PCA, the median WTP was 100,000 won (25-75%; 50,000-200,000 won: US$1 = W1078.04; July 19, 2011) before surgery. All patients' characteristics were not related to preoperative WTP for IV-PCA, whereas the increase in WTP after surgery showed a tendency correlated to higher IV-PCA satisfaction. The median WTP was 100,000 won. The satisfaction of IV-PCA increased patients' WTP after surgery, but the WTP may be independent of patient characteristics in Korea.

  7. Patient-controlled hospital admission for patients with severe mental disorders: a nationwide prospective multicentre study.

    PubMed

    Thomsen, C T; Benros, M E; Maltesen, T; Hastrup, L H; Andersen, P K; Giacco, D; Nordentoft, M

    2018-04-01

    To assess whether implementing patient-controlled admission (PCA) can reduce coercion and improve other clinical outcomes for psychiatric in-patients. During 2013-2016, 422 patients in the PCA group were propensity score matched 1:5 with a control group (n = 2110) that received treatment as usual (TAU). Patients were followed up for at least one year using the intention to treat principle utilising nationwide registers. In a paired design, the outcomes of PCA patients during the year after signing a contract were compared with the year before. No reduction in coercion (risk difference = 0.001; 95% CI: -0.038; 0.040) or self-harming behaviour (risk difference = 0.005; 95% CI: -0.008; 0.018) was observed in the PCA group compared with the TAU group. The PCA group had more in-patient bed days (mean difference = 28.4; 95% CI: 21.3; 35.5) and more medication use (P < 0.0001) than the TAU group. Before and after analyses showed reduction in coercion (P = 0.0001) and in-patient bed days (P = 0.0003). Implementing PCA did not reduce coercion, service use or self-harm behaviour when compared with TAU. Beneficial effects of PCA were observed only in the before and after PCA comparisons. Further research should investigate whether PCA affects other outcomes to better establish its clinical value. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Synthesis and antifungal evaluation of PCA amide analogues.

    PubMed

    Qin, Chuan; Yu, Di-Ya; Zhou, Xu-Dong; Zhang, Min; Wu, Qing-Lai; Li, Jun-Kai

    2018-04-18

    To improve the physical and chemical properties of phenazine-1-carboxylic acid (PCA) and find higher antifungal compounds, a series of PCA amide analogues were designed and synthesized and their structures were confirmed by 1 H NMR, HRMS, and X-ray. Most compounds showed some antifungal activities in vitro. Particularly, compound 3d exhibited inhibition effect against Pyriculariaoryzac Cavgra with EC 50 value of 28.7 μM and compound 3q exhibited effect against Rhizoctonia solani with EC 50 value of 24.5 μM, more potently active than that of the positive control PCA with its EC 50 values of 37.3 μM (Pyriculariaoryzac Cavgra) and 33.2 μM (Rhizoctonia solani), respectively.

  9. Study of support vector machine and serum surface-enhanced Raman spectroscopy for noninvasive esophageal cancer detection

    NASA Astrophysics Data System (ADS)

    Li, Shao-Xin; Zeng, Qiu-Yao; Li, Lin-Fang; Zhang, Yan-Jiao; Wan, Ming-Ming; Liu, Zhi-Ming; Xiong, Hong-Lian; Guo, Zhou-Yi; Liu, Song-Hao

    2013-02-01

    The ability of combining serum surface-enhanced Raman spectroscopy (SERS) with support vector machine (SVM) for improving classification esophageal cancer patients from normal volunteers is investigated. Two groups of serum SERS spectra based on silver nanoparticles (AgNPs) are obtained: one group from patients with pathologically confirmed esophageal cancer (n=30) and the other group from healthy volunteers (n=31). Principal components analysis (PCA), conventional SVM (C-SVM) and conventional SVM combination with PCA (PCA-SVM) methods are implemented to classify the same spectral dataset. Results show that a diagnostic accuracy of 77.0% is acquired for PCA technique, while diagnostic accuracies of 83.6% and 85.2% are obtained for C-SVM and PCA-SVM methods based on radial basis functions (RBF) models. The results prove that RBF SVM models are superior to PCA algorithm in classification serum SERS spectra. The study demonstrates that serum SERS in combination with SVM technique has great potential to provide an effective and accurate diagnostic schema for noninvasive detection of esophageal cancer.

  10. Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

    PubMed

    Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

    2015-02-01

    Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. [The value of PHI/PCA3 in the early diagnosis of prostate cancer].

    PubMed

    Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P

    2016-01-12

    To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

  12. Waist-hip Ratio (WHR), a Better Predictor for Prostate Cancer than Body Mass Index (BMI): Results from a Chinese Hospital-based Biopsy Cohort.

    PubMed

    Tang, Bo; Han, Cheng-Tao; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Vidal, Adriana C; Freedland, Stephen J; Zhu, Yao; Ye, Ding-Wei

    2017-03-08

    To investigate whether waist-hip ratio (WHR) is a better predictor of prostate cancer (PCa) incidence than body mass index (BMI) in Chinese men. Of consecutive patients who underwent prostate biopsies in one tertiary center between 2013 and 2015, we examined data on 1018 with PSA ≤20 ng/ml. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the associations between BMI, WHR and PCa incidence. Area under the ROC (AUC) was used to evaluate the accuracy of different prognostic models. A total of 255 men and 103 men were diagnosed with PCa and high grade PCa (HGPCa, Gleason score ≥8). WHR was an independent risk factor for both PCa (OR = 1.07 95%Cl 1.03-1.11) and HGPCa (OR = 1.14 95%Cl 1.09-1.19) detection, while BMI had no relationship with either PCa or HGPCa detection. Adding WHR to a multivariable model increased the AUC for detecting HGPCa from 0.66 (95%Cl 0.60-0.72) to 0.71 (95%Cl 0.65-0.76). In this Chinese cohort, WHR was significantly predictive of PCa and HGPCa. Adding WHR to a multivariable model increased the diagnostic accuracy for detecting HGPCa. If confirmed, including WHR measurement may improve PCa and HGPCa detection.

  13. Waist-hip Ratio (WHR), a Better Predictor for Prostate Cancer than Body Mass Index (BMI): Results from a Chinese Hospital-based Biopsy Cohort

    PubMed Central

    Tang, Bo; Han, Cheng-Tao; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Vidal, Adriana C.; Freedland, Stephen J.; Zhu, Yao; Ye, Ding-Wei

    2017-01-01

    To investigate whether waist-hip ratio (WHR) is a better predictor of prostate cancer (PCa) incidence than body mass index (BMI) in Chinese men. Of consecutive patients who underwent prostate biopsies in one tertiary center between 2013 and 2015, we examined data on 1018 with PSA ≤20 ng/ml. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the associations between BMI, WHR and PCa incidence. Area under the ROC (AUC) was used to evaluate the accuracy of different prognostic models. A total of 255 men and 103 men were diagnosed with PCa and high grade PCa (HGPCa, Gleason score ≥8). WHR was an independent risk factor for both PCa (OR = 1.07 95%Cl 1.03–1.11) and HGPCa (OR = 1.14 95%Cl 1.09–1.19) detection, while BMI had no relationship with either PCa or HGPCa detection. Adding WHR to a multivariable model increased the AUC for detecting HGPCa from 0.66 (95%Cl 0.60–0.72) to 0.71 (95%Cl 0.65–0.76). In this Chinese cohort, WHR was significantly predictive of PCa and HGPCa. Adding WHR to a multivariable model increased the diagnostic accuracy for detecting HGPCa. If confirmed, including WHR measurement may improve PCa and HGPCa detection. PMID:28272469

  14. Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes.

    PubMed

    Dampier, Carlton D; Smith, Wally R; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C; Minniti, Caterina P; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A Kyle; McClish, Donna; McKinlay, Sonja M; Miller, Scott T; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J; Weiner, Debra L

    2011-12-01

    Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI andin the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.

  15. Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters.

    PubMed

    Sitter, Beathe; Lundgren, Steinar; Bathen, Tone F; Halgunset, Jostein; Fjosne, Hans E; Gribbestad, Ingrid S

    2006-02-01

    Breast cancer is the most frequent form of cancer in women and improved diagnostic methods are desirable. Malignant cells have altered metabolism and metabolic mapping might become a tool in cancer diagnostics. High-resolution magic angle spinning (HR MAS) MR spectroscopy of tissue biopsies provides detailed information on metabolic composition. The 600 MHz 1H HR MAS spectra were acquired of breast cancer tissue from 85 patients and adjacent non-involved tissue from 18 of these patients. Tissue specimens were investigated by microscopy after MR analysis. The resulting spectra were examined by three different approaches. Relative intensities of glycerophosphocholine (GPC), phosphocholine (PC) and choline were compared for cancerous and non-involved specimens. Eight metabolites, choline, creatine, beta-glucose, GPC, glycine, myo-inositol, PC and taurine, were quantified from the recorded spectra and compared with tumor histological type and size, patient's lymph node status and tissue composition of sample. The spectra were also compared with tumor histological type and size, lymph node status and tissue composition of samples using principal component analysis (PCA). Tumor samples could be distinguished from non-involved samples (82% sensitivity, 100% specificity) based on relative intensities of signals from GPC, PC and choline in 1H HR MAS spectra. Tissue concentrations of metabolites showed few differences between groups of samples, which can be caused by limitations in the quantification procedure. Choline and glycine concentrations were found to be significantly higher in tumors larger than 2 cm compared with smaller tumors. PCA of MAS spectra from patients with invasive ductal carcinomas indicated a possible prediction of spread to axillary lymph nodes. Metabolite estimates and PCA of MAS spectra were influenced by the percentage of tumor cells in the investigated specimens. 2006 John Wiley & Sons, Ltd.

  16. Near-field photothermal microspectroscopy for adult stem-cell identification and characterization.

    PubMed

    Grude, Olaug; Hammiche, Azzedine; Pollock, Hubert; Bentley, Adam J; Walsh, Michael J; Martin, Francis L; Fullwood, Nigel J

    2007-12-01

    The identification of stem cells in adult tissue is a challenging problem in biomedicine. Currently, stem cells are identified by individual epitopes, which are generally tissue specific. The discovery of a stem-cell marker common to other adult tissue types could open avenues in the development of therapeutic stem-cell strategies. We report the use of the novel technique of Fourier transform infrared near-field photothermal microspectroscopy (FTIR-PTMS) for the characterization of stem cells, transit amplifying (TA) cells and terminally differentiated (TD) cells in the corneal epithelium. Principal component analysis (PCA) data demonstrate excellent discrimination of cell type by spectra. PCA in combination with linear discriminant analysis (PCA-LDA) shows that FTIR-PTMS very effectively discriminates between the three cell populations. Statistically significant differences above the 99% confidence level between IR spectra from stem cells and TA cells suggest that nucleic acid conformational changes are an important component of the differences between spectral data from the two cell types. FTIR-PTMS is a new addition to existing spectroscopy methods based on the concept of interfacing a conventional FTIR spectrometer with an atomic force microscope equipped with a near-field thermal sensing probe. FTIR-PTMS spectroscopy currently has spatial resolution that is similar to that of diffraction-limited optical detection FTIR spectroscopy techniques, but as a near-field probing technique has considerable potential for further improvement. Our work also suggests that FTIR-PTMS is potentially more sensitive than synchrotron radiation FTIR spectroscopy for some applications. Microspectroscopy techniques like FTIR-PTMS provide information about the entire molecular composition of cells, in contrast to epitope recognition that only considers the presence or absence of individual molecules. Our results with FTIR-PTMS on corneal stem cells are promising for the potential development of an IR spectral fingerprint for stem cells.

  17. Geological and Structural Patterns on Titan Enhanced Through Cassini's SAR PCA and High-Resolution Radiometry

    NASA Astrophysics Data System (ADS)

    Paganelli, F.; Schubert, G.; Lopes, R. M. C.; Malaska, M.; Le Gall, A. A.; Kirk, R. L.

    2016-12-01

    The current SAR data coverage on Titan encompasses several areas in which multiple radar passes are present and overlapping, providing additional information to aid the interpretation of geological and structural features. We exploit the different combinations of look direction and variable incidence angle to examine Cassini Synthetic Aperture RADAR (SAR) data using the Principal Component Analysis (PCA) technique and high-resolution radiometry, as a tool to aid in the interpretation of geological and structural features. Look direction and variable incidence angle is of particular importance in the analysis of variance in the images, which aid in the perception and identification of geological and structural features, as extensively demonstrated in Earth and planetary examples. The PCA enhancement technique uses projected non-ortho-rectified SAR imagery in order to maintain the inherent differences in scattering and geometric properties due to the different look directions, while enhancing the geometry of surface features. The PC2 component provides a stereo view of the areas in which complex surface features and structural patterns can be enhanced and outlined. We focus on several areas of interest, in older and recently acquired flybys, in which evidence of geological and structural features can be enhanced and outlined in the PC1 and PC2 components. Results of this technique provide enhanced geometry and insights into the interpretation of the observed geological and structural features, thus allowing a better understanding towards the geology and tectonics on Titan.

  18. PCA determination of the radiometric noise of high spectral resolution infrared observations from spectral residuals: Application to IASI

    NASA Astrophysics Data System (ADS)

    Serio, C.; Masiello, G.; Camy-Peyret, C.; Jacquette, E.; Vandermarcq, O.; Bermudo, F.; Coppens, D.; Tobin, D.

    2018-02-01

    The problem of characterizing and estimating the instrumental or radiometric noise of satellite high spectral resolution infrared spectrometers directly from Earth observations is addressed in this paper. An approach has been developed, which relies on the Principal Component Analysis (PCA) with a suitable criterion to select the optimal number of PC scores. Different selection criteria have been set up and analysed, which is based on the estimation theory of Least Squares and/or Maximum Likelihood Principle. The approach is independent of any forward model and/or radiative transfer calculations. The PCA is used to define an orthogonal basis, which, in turn, is used to derive an optimal linear reconstruction of the observations. The residual vector that is the observation vector minus the calculated or reconstructed one is then used to estimate the instrumental noise. It will be shown that the use of the spectral residuals to assess the radiometric instrumental noise leads to efficient estimators, which are largely independent of possible departures of the true noise from that assumed a priori to model the observational covariance matrix. Application to the Infrared Atmospheric Sounder Interferometer (IASI) has been considered. A series of case studies has been set up, which make use of IASI observations. As a major result, the analysis confirms the high stability and radiometric performance of IASI. The approach also proved to be efficient in characterizing noise features due to mechanical micro-vibrations of the beam splitter of the IASI instrument.

  19. Automated multivariate analysis of multi-sensor data submitted online: Real-time environmental monitoring.

    PubMed

    Eide, Ingvar; Westad, Frank

    2018-01-01

    A pilot study demonstrating real-time environmental monitoring with automated multivariate analysis of multi-sensor data submitted online has been performed at the cabled LoVe Ocean Observatory located at 258 m depth 20 km off the coast of Lofoten-Vesterålen, Norway. The major purpose was efficient monitoring of many variables simultaneously and early detection of changes and time-trends in the overall response pattern before changes were evident in individual variables. The pilot study was performed with 12 sensors from May 16 to August 31, 2015. The sensors provided data for chlorophyll, turbidity, conductivity, temperature (three sensors), salinity (calculated from temperature and conductivity), biomass at three different depth intervals (5-50, 50-120, 120-250 m), and current speed measured in two directions (east and north) using two sensors covering different depths with overlap. A total of 88 variables were monitored, 78 from the two current speed sensors. The time-resolution varied, thus the data had to be aligned to a common time resolution. After alignment, the data were interpreted using principal component analysis (PCA). Initially, a calibration model was established using data from May 16 to July 31. The data on current speed from two sensors were subject to two separate PCA models and the score vectors from these two models were combined with the other 10 variables in a multi-block PCA model. The observations from August were projected on the calibration model consecutively one at a time and the result was visualized in a score plot. Automated PCA of multi-sensor data submitted online is illustrated with an attached time-lapse video covering the relative short time period used in the pilot study. Methods for statistical validation, and warning and alarm limits are described. Redundant sensors enable sensor diagnostics and quality assurance. In a future perspective, the concept may be used in integrated environmental monitoring.

  20. Quorum sensing systems differentially regulate the production of phenazine-1-carboxylic acid in the rhizobacterium Pseudomonas aeruginosa PA1201

    PubMed Central

    Sun, Shuang; Zhou, Lian; Jin, Kaiming; Jiang, Haixia; He, Ya-Wen

    2016-01-01

    Pseudomonas aeruginosa strain PA1201 is a newly identified rhizobacterium that produces high levels of the secondary metabolite phenazine-1-carboxylic acid (PCA), the newly registered biopesticide Shenqinmycin. PCA production in liquid batch cultures utilizing a specialized PCA-promoting medium (PPM) typically occurs after the period of most rapid growth, and production is regulated in a quorum sensing (QS)-dependent manner. PA1201 contains two PCA biosynthetic gene clusters phz1 and phz2; both clusters contribute to PCA production, with phz2 making a greater contribution. PA1201 also contains a complete set of genes for four QS systems (LasI/LasR, RhlI/RhlR, PQS/MvfR, and IQS). By using several methods including gene deletion, the construction of promoter-lacZ fusion reporter strains, and RNA-Seq analysis, this study investigated the effects of the four QS systems on bacterial growth, QS signal production, the expression of phz1 and phz2, and PCA production. The possible mechanisms for the strain- and condition-dependent expression of phz1 and phz2 were discussed, and a schematic model was proposed. These findings provide a basis for further genetic engineering of the QS systems to improve PCA production. PMID:27456813

  1. Efficacy and tolerability of intravenous morphine patient-controlled analgesia (PCA) in women undergoing cesarean delivery.

    PubMed

    Andziak, Marta; Beta, Jarosław; Barwijuk, Michal; Issat, Tadeusz; Jakimiuk, Artur J

    2015-06-01

    The aim of the study was to evaluate analgesic efficacy and tolerability of patient-controlled analgesia (PCA) with intravenous morphine. Our observational study included 50 women who underwent a Misgav-Ladach or modified Misgav-Ladach cesarean section. Automated PCA infusion device (Medima S-PCA Syringe Pump, Medima, Krakow, Poland) was used for postoperative pain control. Time of morphine administration or initiation of intravenous patient-controlled analgesia (IV PCA) with morphine was recorded, as well as post-operative pain at rest assessed by a visual analogue scale (VAS). All patients were followed up for 24 hours after discharge from the operating room, taking into account patient records, worst pain score at rest, number of IV PCA attempts, and drug consumption. Median of total morphine doses used during the postoperative period was 42.9mg (IQR 35.6-48.5), with median infusion time of 687.0 min. (IQR 531.0-757.5). Pain severity and total drug consumption improved after the first 3 hours following cesarean delivery (p < 0.01). Mean number of PCA attempts per patient was 33 (IQR: 24-37), with median of 11 placebo attempts (IQR: 3-27). Patient-controlled analgesia with morphine is an efficient and acceptable analgesic method in women undergoing cesarean section.

  2. Impervious surfaces mapping using high resolution satellite imagery

    NASA Astrophysics Data System (ADS)

    Shirmeen, Tahmina

    In recent years, impervious surfaces have emerged not only as an indicator of the degree of urbanization, but also as an indicator of environmental quality. As impervious surface area increases, storm water runoff increases in velocity, quantity, temperature and pollution load. Any of these attributes can contribute to the degradation of natural hydrology and water quality. Various image processing techniques have been used to identify the impervious surfaces, however, most of the existing impervious surface mapping tools used moderate resolution imagery. In this project, the potential of standard image processing techniques to generate impervious surface data for change detection analysis using high-resolution satellite imagery was evaluated. The city of Oxford, MS was selected as the study site for this project. Standard image processing techniques, including Normalized Difference Vegetation Index (NDVI), Principal Component Analysis (PCA), a combination of NDVI and PCA, and image classification algorithms, were used to generate impervious surfaces from multispectral IKONOS and QuickBird imagery acquired in both leaf-on and leaf-off conditions. Accuracy assessments were performed, using truth data generated by manual classification, with Kappa statistics and Zonal statistics to select the most appropriate image processing techniques for impervious surface mapping. The performance of selected image processing techniques was enhanced by incorporating Soil Brightness Index (SBI) and Greenness Index (GI) derived from Tasseled Cap Transformed (TCT) IKONOS and QuickBird imagery. A time series of impervious surfaces for the time frame between 2001 and 2007 was made using the refined image processing techniques to analyze the changes in IS in Oxford. It was found that NDVI and the combined NDVI--PCA methods are the most suitable image processing techniques for mapping impervious surfaces in leaf-off and leaf-on conditions respectively, using high resolution multispectral imagery. It was also found that IS data generated by these techniques can be refined by removing the conflicting dry soil patches using SBI and GI obtained from TCT of the same imagery used for IS data generation. The change detection analysis of the IS time series shows that Oxford experienced the major changes in IS from the year 2001 to 2004 and 2006 to 2007.

  3. AXIN2 expression predicts prostate cancer recurrence and regulates invasion and tumor growth.

    PubMed

    Hu, Brian R; Fairey, Adrian S; Madhav, Anisha; Yang, Dongyun; Li, Meng; Groshen, Susan; Stephens, Craig; Kim, Philip H; Virk, Navneet; Wang, Lina; Martin, Sue Ellen; Erho, Nicholas; Davicioni, Elai; Jenkins, Robert B; Den, Robert B; Xu, Tong; Xu, Yucheng; Gill, Inderbir S; Quinn, David I; Goldkorn, Amir

    2016-05-01

    Treatment of prostate cancer (PCa) may be improved by identifying biological mechanisms of tumor growth that directly impact clinical disease progression. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor phenotype impact PCa biology and recurrence. Radical prostatectomy (RP) specimens (±disease recurrence, N = 276) were analyzed by qRT-PCR to quantify expression of genes associated with self-renewal, drug resistance, and tumorigenicity in prior studies. Associations between gene expression and PCa recurrence were confirmed by bootstrap internal validation and by external validation in independent cohorts (total N = 675) and in silico. siRNA knockdown and lentiviral overexpression were used to determine the effect of gene expression on PCa invasion, proliferation, and tumor growth. Four candidate genes were differentially expressed in PCa recurrence. Of these, low AXIN2 expression was internally validated in the discovery cohort. Validation in external cohorts and in silico demonstrated that low AXIN2 was independently associated with more aggressive PCa, biochemical recurrence, and metastasis-free survival after RP. Functionally, siRNA-mediated depletion of AXIN2 significantly increased invasiveness, proliferation, and tumor growth. Conversely, ectopic overexpression of AXIN2 significantly reduced invasiveness, proliferation, and tumor growth. Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts, and its expression levels in PCa cells significantly impacted invasiveness, proliferation, and tumor growth. Given these novel roles, further study of AXIN2 in PCa may yield promising new predictive and therapeutic strategies. © 2016 Wiley Periodicals, Inc.

  4. Temporal Processing of Dynamic Positron Emission Tomography via Principal Component Analysis in the Sinogram Domain

    NASA Astrophysics Data System (ADS)

    Chen, Zhe; Parker, B. J.; Feng, D. D.; Fulton, R.

    2004-10-01

    In this paper, we compare various temporal analysis schemes applied to dynamic PET for improved quantification, image quality and temporal compression purposes. We compare an optimal sampling schedule (OSS) design, principal component analysis (PCA) applied in the image domain, and principal component analysis applied in the sinogram domain; for region-of-interest quantification, sinogram-domain PCA is combined with the Huesman algorithm to quantify from the sinograms directly without requiring reconstruction of all PCA channels. Using a simulated phantom FDG brain study and three clinical studies, we evaluate the fidelity of the compressed data for estimation of local cerebral metabolic rate of glucose by a four-compartment model. Our results show that using a noise-normalized PCA in the sinogram domain gives similar compression ratio and quantitative accuracy to OSS, but with substantially better precision. These results indicate that sinogram-domain PCA for dynamic PET can be a useful preprocessing stage for PET compression and quantification applications.

  5. Prostate Cancer Cell–Stromal Cell Cross-Talk via FGFR1 Mediates Antitumor Activity of Dovitinib in Bone Metastases

    PubMed Central

    Wan, Xinhai; Corn, Paul G.; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W.; Efstathiou, Eleni; Li-Ning Tapia, Elsa M.; Zurita, Amado J.; Aparicio, Ana; Ravoori, Murali K.; Vazquez, Elba S.; Robinson, Dan R.; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K.; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M.; Logothetis, Christopher J.; Navone, Nora M.

    2015-01-01

    Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell–bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. PMID:25186177

  6. Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases.

    PubMed

    Wan, Xinhai; Corn, Paul G; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W; Efstathiou, Eleni; Li Ning Tapia, Elsa M; Tapia, Elsa M Li-Ning; Zurita, Amado J; Aparicio, Ana; Ravoori, Murali K; Vazquez, Elba S; Robinson, Dan R; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M; Logothetis, Christopher J; Navone, Nora M

    2014-09-03

    Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell-bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in serum prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. Copyright © 2014, American Association for the Advancement of Science.

  7. An application of principal component analysis to the clavicle and clavicle fixation devices.

    PubMed

    Daruwalla, Zubin J; Courtis, Patrick; Fitzpatrick, Clare; Fitzpatrick, David; Mullett, Hannan

    2010-03-26

    Principal component analysis (PCA) enables the building of statistical shape models of bones and joints. This has been used in conjunction with computer assisted surgery in the past. However, PCA of the clavicle has not been performed. Using PCA, we present a novel method that examines the major modes of size and three-dimensional shape variation in male and female clavicles and suggests a method of grouping the clavicle into size and shape categories. Twenty-one high-resolution computerized tomography scans of the clavicle were reconstructed and analyzed using a specifically developed statistical software package. After performing statistical shape analysis, PCA was applied to study the factors that account for anatomical variation. The first principal component representing size accounted for 70.5 percent of anatomical variation. The addition of a further three principal components accounted for almost 87 percent. Using statistical shape analysis, clavicles in males have a greater lateral depth and are longer, wider and thicker than in females. However, the sternal angle in females is larger than in males. PCA confirmed these differences between genders but also noted that men exhibit greater variance and classified clavicles into five morphological groups. This unique approach is the first that standardizes a clavicular orientation. It provides information that is useful to both, the biomedical engineer and clinician. Other applications include implant design with regard to modifying current or designing future clavicle fixation devices. Our findings support the need for further development of clavicle fixation devices and the questioning of whether gender-specific devices are necessary.

  8. Spin-labeling of Dexamethasone: Radical Stability vs. Temporal Resolution of EPR-Spectroscopy on Biological Samples

    NASA Astrophysics Data System (ADS)

    Walker, Karolina A.; Unbehauen, Michael L.; Lohan, Silke B.; Saeidpour, Siavash; Meinke, Martina C.; Zimmer, Reinhold; Haag, Rainer

    2018-05-01

    Spin-labeling active compounds is a convenient way to prepare them for EPR spectroscopy with minimal alteration of the target molecule. In this study we present the labeling reaction of dexamethasone (Dx) with either TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) or PCA (3-(carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy) with high yields. According to NMR data, both labels are attached at the primary hydroxy group of the steroid. In subsequent spin-stability measurements both compounds were applied onto HaCaT cells. When the signal of Dx-TEMPO decreased below the detection limit within 3 h, the signal of Dx-PCA remained stable for the same period of time.

  9. PCA3 Reference Set Application: T2-Erg-Martin Sanda-Emory (2014) — EDRN Public Portal

    Cancer.gov

    We hypothesize that combining T2:erg (T2:erg) fusion and PCA3 detection in urine collected after digital rectal exam can improve the specificity of identifying clinically significant prostate cancer presence over the standard PSA and DRE. To address this hypothesis we propose to validate the performance of the urinary T2:erg in a multiplex model predicting the diagnosis of clinically significant prostate cancer on subsequent prostate biopsy using post-DRE pre biopsy urine specimens from a cohort of 900 men on the EDRN’s PCA3 trial.

  10. Prostate cancer gene 3 and multiparametric magnetic resonance can reduce unnecessary biopsies: decision curve analysis to evaluate predictive models.

    PubMed

    Busetto, Gian Maria; De Berardinis, Ettore; Sciarra, Alessandro; Panebianco, Valeria; Giovannone, Riccardo; Rosato, Stefano; D'Errigo, Paola; Di Silverio, Franco; Gentile, Vincenzo; Salciccia, Stefano

    2013-12-01

    To overcome the well-known prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasound-guided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Antidiabetic and antihyperlipidemic activity of p-coumaric acid in diabetic rats, role of pancreatic GLUT 2: In vivo approach.

    PubMed

    Amalan, Venkatesan; Vijayakumar, Natesan; Indumathi, Dhananjayan; Ramakrishnan, Arumugam

    2016-12-01

    P-coumaric acid (p-CA, 3-[4-hydroxyphenyl]-2-propenoic acid), the major component widely found in nutritious plant foods, has various antioxidant, antiinflammatory and anticancer property. To evaluate the antidiabetic and antihyperlipidemic mechanisms, via the effects on carbohydrate, lipids and lipoproteins responses in adult male albino Wistar rats were examined by treated with p-CA. Rats were injected with streptozotocin (STZ, 40mg/kg b.w.) by intraperitonially (i.p.) 30days for the induction of experimental diabetes mellitus. Diabetic rats were treated with p-CA orally at a dose of 100mg/kg b.w. The potential defending character of p-CA against diabetic rats was evaluated by performing the various biochemical parameters and glucose transporter such as GLUT2 mRNA expression of pancreas. Administration of p-CA significantly lowers the blood glucose level, gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase whereas increases the activities of hexokinase, glucose-6 phosphatase dehydrogenase and GSH via by increasing level of insulin. p-CA reduces the total cholesterol and triglycerides in both plasma and tissues i.e. liver and kidney. p-CA also decreases the LDL-C, VLDL-C and it considerably increase the level of HDL-C. A significant decreased expression of GLUT 2 mRNA in the pancreas was recorded in the supplementation of p-CA treated groups. Taken together, these results suggest that p-CA modulates glucose and lipid metabolism via GLUT 2 activation in the pancreatic and has potentially beneficial effects in improving or treating metabolic disorders. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers.

    PubMed

    Duscharla, Divya; Bhumireddy, Sudarshana Reddy; Lakshetti, Sridhar; Pospisil, Heike; Murthy, P V L N; Walther, Reinhard; Sripadi, Prabhakar; Ummanni, Ramesh

    2016-01-01

    Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient's serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet's serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10-6 in Fischer's exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis.

  13. Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers

    PubMed Central

    Duscharla, Divya; Bhumireddy, Sudarshana Reddy; Lakshetti, Sridhar; Pospisil, Heike; Murthy, P. V. L. N.; Walther, Reinhard; Sripadi, Prabhakar; Ummanni, Ramesh

    2016-01-01

    Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient’s serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet’s serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10−6 in Fischer’s exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis. PMID:26958841

  14. A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.

    PubMed

    Rigau, Marina; Ortega, Israel; Mir, Maria Carmen; Ballesteros, Carlos; Garcia, Marta; Llauradó, Marta; Colás, Eva; Pedrola, Núria; Montes, Melania; Sequeiros, Tamara; Ertekin, Tugce; Majem, Blanca; Planas, Jacques; Ruiz, Anna; Abal, Miguel; Sánchez, Alex; Morote, Juan; Reventós, Jaume; Doll, Andreas

    2011-12-01

    Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Copyright © 2011 Wiley Periodicals, Inc.

  15. An Estimate of the Incidence of Prostate Cancer in Africa: A Systematic Review and Meta-Analysis

    PubMed Central

    Aderemi, Adewale Victor; Iseolorunkanmi, Alexander; Oyedokun, Ayo; Ayo, Charles K.

    2016-01-01

    Background Prostate cancer (PCa) is rated the second most common cancer and sixth leading cause of cancer deaths among men globally. Reports show that African men suffer disproportionately from PCa compared to men from other parts of the world. It is still quite difficult to accurately describe the burden of PCa in Africa due to poor cancer registration systems. We systematically reviewed the literature on prostate cancer in Africa and provided a continent-wide incidence rate of PCa based on available data in the region. Methods A systematic literature search of Medline, EMBASE and Global Health from January 1980 to June 2015 was conducted, with additional search of Google Scholar, International Association of Cancer Registries (IACR), International Agency for Research on Cancer (IARC), and WHO African region websites, for studies that estimated incidence rate of PCa in any African location. Having assessed quality and consistency across selected studies, we extracted incidence rates of PCa and conducted a random effects meta-analysis. Results Our search returned 9766 records, with 40 studies spreading across 16 African countries meeting our selection criteria. We estimated a pooled PCa incidence rate of 22.0 (95% CI: 19.93–23.97) per 100,000 population, and also reported a median incidence rate of 19.5 per 100,000 population. We observed an increasing trend in PCa incidence with advancing age, and over the main years covered. Conclusion Effective cancer registration and extensive research are vital to appropriately quantifying PCa burden in Africa. We hope our findings may further assist at identifying relevant gaps, and contribute to improving knowledge, research, and interventions targeted at prostate cancer in Africa. PMID:27073921

  16. Transcatheter Arterial Embolization with a Mixture of Absolute Ethanol and Iodized Oil for Poorly Visualized Endophytic Renal Masses Prior to CT-Guided Percutaneous Cryoablation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Michimoto, Kenkichi, E-mail: michikoo@jikei.ac.jp; Shimizu, Kanichiro; Kameoka, Yoshihiko

    PurposeTo retrospectively evaluate the feasibility of transcatheter arterial embolization (TAE) using a mixture of absolute ethanol and iodized oil to improve localization of endophytic renal masses on unenhanced computed tomography (CT) prior to CT-guided percutaneous cryoablation (PCA).Materials and MethodsOur institutional review board approved this retrospective study. From September 2011 to June 2015, 17 patients (mean age, 66.8 years) with stage T1a endophytic renal masses (mean diameter, 26.5 mm) underwent TAE using a mixture of absolute ethanol and iodized oil to improve visualization of small and endophytic renal masses on unenhanced CT prior to CT-guided PCA. TAE was considered successful that accumulated iodizedmore » oil depicted whole of the tumor edge on CT. PCA was considered successful when the iceball covered the entire tumor with over a 5 mm margin. Oncological and renal functional outcomes and complications were also evaluated.ResultsTAE was successfully performed in 16 of 17 endophytic tumors. The 16 tumors were performed under CT-guided PCA with their distinct visualization of localization and safe ablated margin. During the mean follow-up period of 15.4 ± 5.1 months, one patient developed local recurrence. Estimated glomerular filtration rate declined by 8 % with statistical significance (P = 0.01). There was no procedure-related significant complication.ConclusionTAE using a mixture of absolute ethanol and iodized oil to improve visualization of endophytic renal masses facilitated tumor localization on unenhanced CT, permitting depiction of the tumor edge as well as a safe margin for ablation during CT-guided PCA, with an acceptable decline in renal function.« less

  17. Liposome bupivacaine for improvement in economic outcomes and opioid burden in GI surgery: IMPROVE Study pooled analysis.

    PubMed

    Cohen, Stephen M; Vogel, Jon D; Marcet, Jorge E; Candiotti, Keith A

    2014-01-01

    Postsurgical pain management remains a significant challenge. Liposome bupivacaine, as part of a multimodal analgesic regimen, has been shown to significantly reduce postsurgical opioid consumption, hospital length of stay (LOS), and hospitalization costs in gastrointestinal (GI) surgery, compared with intravenous (IV) opioid-based patient-controlled analgesia (PCA). Pooled results from open-label studies comparing a liposome bupivacaine-based multimodal analgesic regimen with IV opioid PCA were analyzed. Patients (n=191) who underwent planned surgery and received study drug (IV opioid PCA, n=105; multimodal analgesia, n=86) were included. Liposome bupivacaine-based multimodal analgesia compared with IV opioid PCA significantly reduced mean (standard deviation [SD]) postsurgical opioid consumption (38 [55] mg versus [vs] 96 [85] mg; P<0.0001), postsurgical LOS (median 2.9 vs 4.3 days; P<0.0001), and mean hospitalization costs (US$8,271 vs US$10,726; P=0.0109). The multimodal analgesia group reported significantly fewer patients with opioid-related adverse events (AEs) than the IV opioid PCA group (P=0.0027); there were no significant between-group differences in patient satisfaction scores at 30 days. A liposome bupivacaine-based multimodal analgesic regimen was associated with significantly less opioid consumption, opioid-related AEs, and better health economic outcomes compared with an IV opioid PCA-based regimen in patients undergoing GI surgery. This pooled analysis is based on data from Phase IV clinical trials registered on the US National Institutes of Health www.ClinicalTrials.gov database under study identifiers NCT01460485, NCT01507220, NCT01507233, NCT01509638, NCT01509807, NCT01509820, NCT01461122, NCT01461135, NCT01534988, and NCT01507246.

  18. Application of multi-scale wavelet entropy and multi-resolution Volterra models for climatic downscaling

    NASA Astrophysics Data System (ADS)

    Sehgal, V.; Lakhanpal, A.; Maheswaran, R.; Khosa, R.; Sridhar, Venkataramana

    2018-01-01

    This study proposes a wavelet-based multi-resolution modeling approach for statistical downscaling of GCM variables to mean monthly precipitation for five locations at Krishna Basin, India. Climatic dataset from NCEP is used for training the proposed models (Jan.'69 to Dec.'94) and are applied to corresponding CanCM4 GCM variables to simulate precipitation for the validation (Jan.'95-Dec.'05) and forecast (Jan.'06-Dec.'35) periods. The observed precipitation data is obtained from the India Meteorological Department (IMD) gridded precipitation product at 0.25 degree spatial resolution. This paper proposes a novel Multi-Scale Wavelet Entropy (MWE) based approach for clustering climatic variables into suitable clusters using k-means methodology. Principal Component Analysis (PCA) is used to obtain the representative Principal Components (PC) explaining 90-95% variance for each cluster. A multi-resolution non-linear approach combining Discrete Wavelet Transform (DWT) and Second Order Volterra (SoV) is used to model the representative PCs to obtain the downscaled precipitation for each downscaling location (W-P-SoV model). The results establish that wavelet-based multi-resolution SoV models perform significantly better compared to the traditional Multiple Linear Regression (MLR) and Artificial Neural Networks (ANN) based frameworks. It is observed that the proposed MWE-based clustering and subsequent PCA, helps reduce the dimensionality of the input climatic variables, while capturing more variability compared to stand-alone k-means (no MWE). The proposed models perform better in estimating the number of precipitation events during the non-monsoon periods whereas the models with clustering without MWE over-estimate the rainfall during the dry season.

  19. Benchmarking of data fusion algorithms in support of earth observation based Antarctic wildlife monitoring

    NASA Astrophysics Data System (ADS)

    Witharana, Chandi; LaRue, Michelle A.; Lynch, Heather J.

    2016-03-01

    Remote sensing is a rapidly developing tool for mapping the abundance and distribution of Antarctic wildlife. While both panchromatic and multispectral imagery have been used in this context, image fusion techniques have received little attention. We tasked seven widely-used fusion algorithms: Ehlers fusion, hyperspherical color space fusion, high-pass fusion, principal component analysis (PCA) fusion, University of New Brunswick fusion, and wavelet-PCA fusion to resolution enhance a series of single-date QuickBird-2 and Worldview-2 image scenes comprising penguin guano, seals, and vegetation. Fused images were assessed for spectral and spatial fidelity using a variety of quantitative quality indicators and visual inspection methods. Our visual evaluation elected the high-pass fusion algorithm and the University of New Brunswick fusion algorithm as best for manual wildlife detection while the quantitative assessment suggested the Gram-Schmidt fusion algorithm and the University of New Brunswick fusion algorithm as best for automated classification. The hyperspherical color space fusion algorithm exhibited mediocre results in terms of spectral and spatial fidelities. The PCA fusion algorithm showed spatial superiority at the expense of spectral inconsistencies. The Ehlers fusion algorithm and the wavelet-PCA algorithm showed the weakest performances. As remote sensing becomes a more routine method of surveying Antarctic wildlife, these benchmarks will provide guidance for image fusion and pave the way for more standardized products for specific types of wildlife surveys.

  20. Study of recognizing multiple persons' complicated hand gestures from the video sequence acquired by a moving camera

    NASA Astrophysics Data System (ADS)

    Dan, Luo; Ohya, Jun

    2010-02-01

    Recognizing hand gestures from the video sequence acquired by a dynamic camera could be a useful interface between humans and mobile robots. We develop a state based approach to extract and recognize hand gestures from moving camera images. We improved Human-Following Local Coordinate (HFLC) System, a very simple and stable method for extracting hand motion trajectories, which is obtained from the located human face, body part and hand blob changing factor. Condensation algorithm and PCA-based algorithm was performed to recognize extracted hand trajectories. In last research, this Condensation Algorithm based method only applied for one person's hand gestures. In this paper, we propose a principal component analysis (PCA) based approach to improve the recognition accuracy. For further improvement, temporal changes in the observed hand area changing factor are utilized as new image features to be stored in the database after being analyzed by PCA. Every hand gesture trajectory in the database is classified into either one hand gesture categories, two hand gesture categories, or temporal changes in hand blob changes. We demonstrate the effectiveness of the proposed method by conducting experiments on 45 kinds of sign language based Japanese and American Sign Language gestures obtained from 5 people. Our experimental recognition results show better performance is obtained by PCA based approach than the Condensation algorithm based method.

  1. Sparse PCA corrects for cell type heterogeneity in epigenome-wide association studies.

    PubMed

    Rahmani, Elior; Zaitlen, Noah; Baran, Yael; Eng, Celeste; Hu, Donglei; Galanter, Joshua; Oh, Sam; Burchard, Esteban G; Eskin, Eleazar; Zou, James; Halperin, Eran

    2016-05-01

    In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) and designed for the correction of cell type heterogeneity in EWAS. ReFACTor does not require knowledge of cell counts, and it provides improved estimates of cell type composition, resulting in improved power and control for false positives in EWAS. Corresponding software is available at http://www.cs.tau.ac.il/~heran/cozygene/software/refactor.html.

  2. Empirical downscaling of daily minimum air temperature at very fine resolutions in complex terrain

    Treesearch

    Zachary A. Holden; John T. Abatzoglou; Charles H. Luce; L. Scott Baggett

    2011-01-01

    Available air temperature models do not adequately account for the influence of terrain on nocturnal air temperatures. An empirical model for night time air temperatures was developed using a network of one hundred and forty inexpensive temperature sensors deployed across the Bitterroot National Forest, Montana. A principle component analysis (PCA) on minimum...

  3. Metabolomics by Proton High-Resolution Magic-Angle-Spinning Nuclear Magnetic Resonance of Tomato Plants Treated with Two Secondary Metabolites Isolated from Trichoderma.

    PubMed

    Mazzei, Pierluigi; Vinale, Francesco; Woo, Sheridan Lois; Pascale, Alberto; Lorito, Matteo; Piccolo, Alessandro

    2016-05-11

    Trichoderma fungi release 6-pentyl-2H-pyran-2-one (1) and harzianic acid (2) secondary metabolites to improve plant growth and health protection. We isolated metabolites 1 and 2 from Trichoderma strains, whose different concentrations were used to treat seeds of Solanum lycopersicum. The metabolic profile in the resulting 15 day old tomato leaves was studied by high-resolution magic-angle-spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy directly on the whole samples without any preliminary extraction. Principal component analysis (PCA) of HRMAS NMR showed significantly enhanced acetylcholine and γ-aminobutyric acid (GABA) content accompanied by variable amount of amino acids in samples treated with both Trichoderma secondary metabolites. Seed germination rates, seedling fresh weight, and the metabolome of tomato leaves were also dependent upon doses of metabolites 1 and 2 treatments. HRMAS NMR spectroscopy was proven to represent a rapid and reliable technique for evaluating specific changes in the metabolome of plant leaves and calibrating the best concentration of bioactive compounds required to stimulate plant growth.

  4. Reaction Kinetics for the Biocatalytic Conversion of Phenazine-1-Carboxylic Acid to 2-Hydroxyphenazine

    PubMed Central

    Chen, Mingmin; Cao, Hongxia; Peng, Huasong; Hu, Hongbo; Wang, Wei; Zhang, Xuehong

    2014-01-01

    The phenazine derivative 2-hydroxyphenazine (2-OH-PHZ) plays an important role in the biocontrol of plant diseases, and exhibits stronger bacteriostatic and fungistatic activity than phenazine-1-carboxylic acid (PCA) toward some pathogens. PhzO has been shown to be responsible for the conversion of PCA to 2-OH-PHZ, however the kinetics of the reaction have not been systematically studied. Further, the yield of 2-OH-PHZ in fermentation culture is quite low and enhancement in our understanding of the reaction kinetics may contribute to improvements in large-scale, high-yield production of 2-OH-PHZ for biological control and other applications. In this study we confirmed previous reports that free PCA is converted to 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the action of a single enzyme PhzO, and particularly demonstrate that this reaction is dependent on NADP(H) and Fe3+. Fe3+ enhanced the conversion from PCA to 2-OH-PHZ and 28°C was a optimum temperature for the conversion. However, PCA added in excess to the culture inhibited the production of 2-OH-PHZ. 2-OH-PCA was extracted and purified from the broth, and it was confirmed that the decarboxylation of 2-OH-PCA could occur without the involvement of any enzyme. A kinetic analysis of the conversion of 2-OH-PCA to 2-OH-PHZ in the absence of enzyme and under different temperatures and pHs in vitro, revealed that the conversion followed first-order reaction kinetics. In the fermentation, the concentration of 2-OH-PCA increased to about 90 mg/L within a red precipitate fraction, as compared to 37 mg/L within the supernatant. The results of this study elucidate the reaction kinetics involved in the biosynthesis of 2-OH-PHZ and provide insights into in vitro methods to enhance yields of 2-OH-PHZ. PMID:24905009

  5. Combined serum and EPS-urine proteomic analysis using iTRAQ technology for discovery of potential prostate cancer biomarkers.

    PubMed

    Zhang, Mo; Chen, Lizhu; Yuan, Zhengwei; Yang, Zeyu; Li, Yue; Shan, Liping; Yin, Bo; Fei, Xiang; Miao, Jianing; Song, Yongsheng

    2016-11-01

    Prostate cancer (PCa) is one of the most common malignant tumors and a major cause of cancer-related death for men worldwide. The aim of our study was to identify potential non-invasive serum and expressed prostatic secretion (EPS)-urine biomarkers for accurate diagnosis of PCa. Here, we performed a combined isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to compare protein profiles using pooled serum and EPS-urine samples from 4 groups of patients: benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), localized PCa and metastatic PCa. The differentially expressed proteins were rigorously selected and further validated in a large and independent cohort using classical ELISA and Western blot assays. Finally, we established a multiplex biomarker panel consisting of 3 proteins (serum PF4V1, PSA, and urinary CRISP3) with an excellent diagnostic capacity to differentiate PCa from BPH [area under the receiver operating characteristic curve (AUC) of 0.941], which showed an evidently greater discriminatory ability than PSA alone (AUC, 0.757) (P<0.001). Importantly, even when PSA level was in the gray zone (4-10 ng/mL), a combination of PF4V1 and CRISP3 could achieve a relatively high diagnostic efficacy (AUC, 0.895). Furthermore, their combination also had the potential to distinguish PCa from HGPIN (AUC, 0.934). Our results demonstrated that the combined application of serum and EPS-urine biomarkers can improve the diagnosis of PCa and provide a new prospect for non-invasive PCa detection.

  6. Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses.

    PubMed

    Ferraro, Bernadette; Cisper, Neil J; Talbott, Kendra T; Philipson-Weiner, Lindsey; Lucke, Colleen E; Khan, Amir S; Sardesai, Niranjan Y; Weiner, David B

    2011-01-01

    Prostate cancer (PCa) remains a significant public health problem. Current treatment modalities for PCa can be useful, but may be accompanied by deleterious side effects and often do not confer long-term control. Accordingly, additional modalities, such as immunotherapy, may represent an important approach for PCa treatment. The identification of tissue-specific antigens engenders PCa an attractive target for immunotherapeutic approaches. Delivery of DNA vaccines with electroporation has shown promising results for prophylactic and therapeutic targets in a variety of species including humans. Application of this technology for PCa immunotherapy strategies has been limited to single antigen and epitope targets. We sought to test the hypothesis that a broader collection of antigens would improve the breadth and effectiveness of a PCa immune therapy approach. We therefore developed highly optimized DNA vaccines encoding prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) as a dual antigen approach to immune therapy of PCa. PSA-and PSMA-specific cellular immunogenicity was evaluated in a mouse model for co-delivery and single antigen vaccination. Mice received 2 immunizations spaced 2 weeks apart and immunogenicity was evaluated 1 week after the second vaccination. Both the PSA and PSMA vaccines induced robust antigen-specific IFNγ responses by ELISpot. Further characterization of cellular immunogenicity by flow cytometry indicated strong antigen-specific TNFα production by CD4+ T cells and IFNγ and IL-2 secretion by both CD4+ and CD8+ T cells. There was also a strong humoral response as determined by PSA-specific seroconversion. These data support further study of this novel approach to immune therapy of PCa.

  7. Multiscale 3D Shape Analysis using Spherical Wavelets

    PubMed Central

    Nain, Delphine; Haker, Steven; Bobick, Aaron; Tannenbaum, Allen

    2013-01-01

    Shape priors attempt to represent biological variations within a population. When variations are global, Principal Component Analysis (PCA) can be used to learn major modes of variation, even from a limited training set. However, when significant local variations exist, PCA typically cannot represent such variations from a small training set. To address this issue, we present a novel algorithm that learns shape variations from data at multiple scales and locations using spherical wavelets and spectral graph partitioning. Our results show that when the training set is small, our algorithm significantly improves the approximation of shapes in a testing set over PCA, which tends to oversmooth data. PMID:16685992

  8. Multiscale 3D shape analysis using spherical wavelets.

    PubMed

    Nain, Delphine; Haker, Steven; Bobick, Aaron; Tannenbaum, Allen R

    2005-01-01

    Shape priors attempt to represent biological variations within a population. When variations are global, Principal Component Analysis (PCA) can be used to learn major modes of variation, even from a limited training set. However, when significant local variations exist, PCA typically cannot represent such variations from a small training set. To address this issue, we present a novel algorithm that learns shape variations from data at multiple scales and locations using spherical wavelets and spectral graph partitioning. Our results show that when the training set is small, our algorithm significantly improves the approximation of shapes in a testing set over PCA, which tends to oversmooth data.

  9. Rectus sheath catheter infusions for post-operative pain management.

    PubMed

    Layzell, Mandy

    2014-06-24

    Managing pain following major abdominal surgery remains a challenge. Traditionally, patient-controlled analgesia (PCA) or epidural analgesia have been used, which have improved post-operative pain and the patient experience, but have presented some problems in recovery. PCA can cause adverse effects, including sedation, nausea, vomiting, and prolonged gastric ileus. While epidurals do have some advantages over PCA, there are risks involved related to catheter insertion and adverse effects, such as hypotension and motor blocks which limit mobility. This article examines rectus sheath catheter infusions, a relatively new and alternative technique to epidural analgesia, and presents some early audit data related to pain scores, analgesic use and mobility.

  10. Age-related changes in with-the-rule and oblique corneal astigmatism.

    PubMed

    Naeser, Kristian; Savini, Giacomo; Bregnhøj, Jesper Flethøj

    2018-01-25

    To describe the age-related changes in with-the-rule (WTR) and oblique keratometric astigmatism (KA), posterior corneal astigmatism (PCA) and total corneal astigmatism (TCA). We used a Pentacam HR (high-resolution) rotating Scheimpflug camera to determine the KA, PCA and TCA in the right eyes of 710 patients, aged from 20 to 88 years. The age-related changes along the vertical, horizontal and oblique meridians were analyzed with Naeser's polar value method in a cross-sectional study. In the whole group, all meridional astigmatic powers and polar values were stable in the age groups from 20 to 49 years, followed by a 1.0 dioptre (D) against-the-rule (ATR) change in KA and TCA, and a 0.12 D reduction in against-the-rule PCA. A nasal rotation of the steep meridian in KA and TCA was noted in the 70-88 years old. The PCA averaged approximately 0.25 D ATR in all age groups. Females displayed the same early astigmatic stability as in the whole group, while male eyes demonstrated a linear decay from 1.5 D WTR at 20 years to 0.5 D ATR astigmatism for the oldest patients. Corneal astigmatism is stable until the age of 50 years; thereafter both keratometric and total corneal astigmatism show a 0.25 D ATR change per 10 years. The average 0.25 D ATR PCA compensates the predominant keratometric WTR astigmatism in the younger patients and increases the TCA in the elderly with keratometric ATR astigmatism. The gender-based differences in age-related astigmatism require further studies. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Chemometric Methods to Quantify 1D and 2D NMR Spectral Differences Among Similar Protein Therapeutics.

    PubMed

    Chen, Kang; Park, Junyong; Li, Feng; Patil, Sharadrao M; Keire, David A

    2018-04-01

    NMR spectroscopy is an emerging analytical tool for measuring complex drug product qualities, e.g., protein higher order structure (HOS) or heparin chemical composition. Most drug NMR spectra have been visually analyzed; however, NMR spectra are inherently quantitative and multivariate and thus suitable for chemometric analysis. Therefore, quantitative measurements derived from chemometric comparisons between spectra could be a key step in establishing acceptance criteria for a new generic drug or a new batch after manufacture change. To measure the capability of chemometric methods to differentiate comparator NMR spectra, we calculated inter-spectra difference metrics on 1D/2D spectra of two insulin drugs, Humulin R® and Novolin R®, from different manufacturers. Both insulin drugs have an identical drug substance but differ in formulation. Chemometric methods (i.e., principal component analysis (PCA), 3-way Tucker3 or graph invariant (GI)) were performed to calculate Mahalanobis distance (D M ) between the two brands (inter-brand) and distance ratio (D R ) among the different lots (intra-brand). The PCA on 1D inter-brand spectral comparison yielded a D M value of 213. In comparing 2D spectra, the Tucker3 analysis yielded the highest differentiability value (D M  = 305) in the comparisons made followed by PCA (D M  = 255) then the GI method (D M  = 40). In conclusion, drug quality comparisons among different lots might benefit from PCA on 1D spectra for rapidly comparing many samples, while higher resolution but more time-consuming 2D-NMR-data-based comparisons using Tucker3 analysis or PCA provide a greater level of assurance for drug structural similarity evaluation between drug brands.

  12. Network intrusion detection based on a general regression neural network optimized by an improved artificial immune algorithm.

    PubMed

    Wu, Jianfa; Peng, Dahao; Li, Zhuping; Zhao, Li; Ling, Huanzhang

    2015-01-01

    To effectively and accurately detect and classify network intrusion data, this paper introduces a general regression neural network (GRNN) based on the artificial immune algorithm with elitist strategies (AIAE). The elitist archive and elitist crossover were combined with the artificial immune algorithm (AIA) to produce the AIAE-GRNN algorithm, with the aim of improving its adaptivity and accuracy. In this paper, the mean square errors (MSEs) were considered the affinity function. The AIAE was used to optimize the smooth factors of the GRNN; then, the optimal smooth factor was solved and substituted into the trained GRNN. Thus, the intrusive data were classified. The paper selected a GRNN that was separately optimized using a genetic algorithm (GA), particle swarm optimization (PSO), and fuzzy C-mean clustering (FCM) to enable a comparison of these approaches. As shown in the results, the AIAE-GRNN achieves a higher classification accuracy than PSO-GRNN, but the running time of AIAE-GRNN is long, which was proved first. FCM and GA-GRNN were eliminated because of their deficiencies in terms of accuracy and convergence. To improve the running speed, the paper adopted principal component analysis (PCA) to reduce the dimensions of the intrusive data. With the reduction in dimensionality, the PCA-AIAE-GRNN decreases in accuracy less and has better convergence than the PCA-PSO-GRNN, and the running speed of the PCA-AIAE-GRNN was relatively improved. The experimental results show that the AIAE-GRNN has a higher robustness and accuracy than the other algorithms considered and can thus be used to classify the intrusive data.

  13. Assessing signal-to-noise in quantitative proteomics: multivariate statistical analysis in DIGE experiments.

    PubMed

    Friedman, David B

    2012-01-01

    All quantitative proteomics experiments measure variation between samples. When performing large-scale experiments that involve multiple conditions or treatments, the experimental design should include the appropriate number of individual biological replicates from each condition to enable the distinction between a relevant biological signal from technical noise. Multivariate statistical analyses, such as principal component analysis (PCA), provide a global perspective on experimental variation, thereby enabling the assessment of whether the variation describes the expected biological signal or the unanticipated technical/biological noise inherent in the system. Examples will be shown from high-resolution multivariable DIGE experiments where PCA was instrumental in demonstrating biologically significant variation as well as sample outliers, fouled samples, and overriding technical variation that would not be readily observed using standard univariate tests.

  14. Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells.

    PubMed

    Muniyan, Sakthivel; Chou, Yu-Wei; Ingersoll, Matthew A; Devine, Alexus; Morris, Marisha; Odero-Marah, Valerie A; Khan, Shafiq A; Chaney, William G; Bu, Xiu R; Lin, Ming-Fong

    2014-10-10

    Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells

    PubMed Central

    Muniyan, Sakthivel; Chou, Yu-Wei; Ingersoll, Matthew A.; Devine, Alexus; Morris, Marisha; Odero-Marah, Valerie A.; Khan, Shafiq A.; Chaney, William G.; Bu, Xiu R.; Lin, Ming-Fong

    2014-01-01

    Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa. PMID:25050738

  16. Genome-wide copy number analysis reveals candidate gene loci that confer susceptibility to high-grade prostate cancer.

    PubMed

    Poniah, Prevathe; Mohd Zain, Shamsul; Abdul Razack, Azad Hassan; Kuppusamy, Shanggar; Karuppayah, Shankar; Sian Eng, Hooi; Mohamed, Zahurin

    2017-09-01

    Two key issues in prostate cancer (PCa) that demand attention currently are the need for a more precise and minimally invasive screening test owing to the inaccuracy of prostate-specific antigen and differential diagnosis to distinguish advanced vs. indolent cancers. This continues to pose a tremendous challenge in diagnosis and prognosis of PCa and could potentially lead to overdiagnosis and overtreatment complications. Copy number variations (CNVs) in the human genome have been linked to various carcinomas including PCa. Detection of these variants may improve clinical treatment as well as an understanding of the pathobiology underlying this complex disease. To this end, we undertook a pilot genome-wide CNV analysis approach in 36 subjects (18 patients with high-grade PCa and 18 controls that were matched by age and ethnicity) in search of more accurate biomarkers that could potentially explain susceptibility toward high-grade PCa. We conducted this study using the array comparative genomic hybridization technique. Array results were validated in 92 independent samples (46 high-grade PCa, 23 benign prostatic hyperplasia, and 23 healthy controls) using polymerase chain reaction-based copy number counting method. A total of 314 CNV regions were found to be unique to PCa subjects in this cohort (P<0.05). A log 2 ratio-based copy number analysis revealed 5 putative rare or novel CNV loci or both associated with susceptibility to PCa. The CNV gain regions were 1q21.3, 15q15, 7p12.1, and a novel CNV in PCa 12q23.1, harboring ARNT, THBS1, SLC5A8, and DDC genes that are crucial in the p53 and cancer pathways. A CNV loss and deletion event was observed at 8p11.21, which contains the SFRP1 gene from the Wnt signaling pathway. Cross-comparison analysis with genes associated to PCa revealed significant CNVs involved in biological processes that elicit cancer pathogenesis via cytokine production and endothelial cell proliferation. In conclusion, we postulated that the CNVs identified in this study could provide an insight into the development of advanced PCa. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Urinary microRNAs for prostate cancer diagnosis, prognosis, and treatment response: are we there yet?

    PubMed

    Balacescu, Ovidiu; Petrut, Bogdan; Tudoran, Oana; Feflea, Dragos; Balacescu, Loredana; Anghel, Andrei; Sirbu, Ioan O; Seclaman, Edward; Marian, Catalin

    2017-11-01

    Prostate cancer (PCa) remains one of the leading causes of cancer-related deaths in men. Despite the tremendous progress in research over the years, a suitable minimally invasive PCa biomarker is yet to be discovered. The recent advances regarding the roles of microRNAs as biomarkers has allowed for their study in PCa as well, especially as blood-based markers. However, there are several studies that used urine as biological sample to evaluate microRNAs as biomarkers for PCa diagnosis, prognosis, and treatment response, which were reviewed herein. A high degree of inconsistency among reports has been observed, which could be due to several analytical aspects, starting with different urinary fractions used for analysis and continuing with the employment of various analytical platforms and methods of statistical analysis. However, a few microRNAs were found to be dysregulated in the urine of PCa patients, which alone or together with serum prostate-specific antigen seem to improve diagnostic power even in the gray zone of PCa. These results warrant further confirmation by larger prospective studies, preferably using a standardized protocol for analysis. WIREs RNA 2017, 8:e1438. doi: 10.1002/wrna.1438 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  18. Image restoration for three-dimensional fluorescence microscopy using an orthonormal basis for efficient representation of depth-variant point-spread functions

    PubMed Central

    Patwary, Nurmohammed; Preza, Chrysanthe

    2015-01-01

    A depth-variant (DV) image restoration algorithm for wide field fluorescence microscopy, using an orthonormal basis decomposition of DV point-spread functions (PSFs), is investigated in this study. The efficient PSF representation is based on a previously developed principal component analysis (PCA), which is computationally intensive. We present an approach developed to reduce the number of DV PSFs required for the PCA computation, thereby making the PCA-based approach computationally tractable for thick samples. Restoration results from both synthetic and experimental images show consistency and that the proposed algorithm addresses efficiently depth-induced aberration using a small number of principal components. Comparison of the PCA-based algorithm with a previously-developed strata-based DV restoration algorithm demonstrates that the proposed method improves performance by 50% in terms of accuracy and simultaneously reduces the processing time by 64% using comparable computational resources. PMID:26504634

  19. Comparative Study of Blood-Based Biomarkers, α2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection.

    PubMed

    Ferrer-Batallé, Montserrat; Llop, Esther; Ramírez, Manel; Aleixandre, Rosa Núria; Saez, Marc; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

    2017-04-17

    Prostate Specific Antigen (PSA) is the most commonly used serum marker for prostate cancer (PCa), although it is not specific and sensitive enough to allow the differential diagnosis of the more aggressive tumors. For that, new diagnostic methods are being developed, such as PCA-3, PSA isoforms that have resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms. In the present study, we have compared the PHI with our recently developed PSA glycoform assay, based on the determination of the α2,3-sialic acid percentage of serum PSA (% α2,3-SA), in a cohort of 79 patients, which include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH) patients. The % α2,3-SA could distinguish high-risk PCa patients from the rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs. 0.840), although the PHI correlated better with the Gleason score than the % α2,3-SA. The combination of both markers increased the AUC up to 0.985 resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk PCa from the other low and intermediate-risk PCa and BPH patients. These results suggest that both serum markers complement each other and offer an improved diagnostic tool to identify high-risk PCa, which is an important requirement for guiding treatment decisions.

  20. IMPROVED SEARCH OF PRINCIPAL COMPONENT ANALYSIS DATABASES FOR SPECTRO-POLARIMETRIC INVERSION

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Casini, R.; Lites, B. W.; Ramos, A. Asensio

    2013-08-20

    We describe a simple technique for the acceleration of spectro-polarimetric inversions based on principal component analysis (PCA) of Stokes profiles. This technique involves the indexing of the database models based on the sign of the projections (PCA coefficients) of the first few relevant orders of principal components of the four Stokes parameters. In this way, each model in the database can be attributed a distinctive binary number of 2{sup 4n} bits, where n is the number of PCA orders used for the indexing. Each of these binary numbers (indices) identifies a group of ''compatible'' models for the inversion of amore » given set of observed Stokes profiles sharing the same index. The complete set of the binary numbers so constructed evidently determines a partition of the database. The search of the database for the PCA inversion of spectro-polarimetric data can profit greatly from this indexing. In practical cases it becomes possible to approach the ideal acceleration factor of 2{sup 4n} as compared to the systematic search of a non-indexed database for a traditional PCA inversion. This indexing method relies on the existence of a physical meaning in the sign of the PCA coefficients of a model. For this reason, the presence of model ambiguities and of spectro-polarimetric noise in the observations limits in practice the number n of relevant PCA orders that can be used for the indexing.« less

  1. Racial Differences in the Diagnosis and Treatment of Prostate Cancer.

    PubMed

    Pietro, Giuliano Di; Chornokur, Ganna; Kumar, Nagi B; Davis, Chemar; Park, Jong Y

    2016-11-01

    Disparities between African American and Caucasian men in prostate cancer (PCa) diagnosis and treatment in the United States have been well established, with significant racial disparities documented at all stages of PCa management, from differences in the type of treatment offered to progression-free survival or death. These disparities appear to be complex in nature, involving biological determinants as well as socioeconomic and cultural aspects. We present a review of the literature on racial disparities in the diagnosis of PCa, treatment, survival, and genetic susceptibility. Significant differences were found among African Americans and whites in the incidence and mortality rates; namely, African Americans are diagnosed with PCa at younger ages than whites and usually with more advanced stages of the disease, and also undergo prostate-specific antigen testing less frequently. However, the determinants of the high rate of incidence and aggressiveness of PCa in African Americans remain unresolved. This pattern can be attributed to socioeconomic status, detection occurring at advanced stages of the disease, biological aggressiveness, family history, and differences in genetic susceptibility. Another risk factor for PCa is obesity. We found many discrepancies regarding treatment, including a tendency for more African American patients to be in watchful waiting than whites. Many factors are responsible for the higher incidence and mortality rates in African Americans. Better screening, improved access to health insurance and clinics, and more homogeneous forms of treatment will contribute to the reduction of disparities between African Americans and white men in PCa incidence and mortality.

  2. Prostate-Specific Membrane Antigen Targeted Therapy of Prostate Cancer Using a DUPA-Paclitaxel Conjugate.

    PubMed

    Lv, Qingzhi; Yang, Jincheng; Zhang, Ruoshi; Yang, Zimeng; Yang, Zhengtao; Wang, Yongjun; Xu, Youjun; He, Zhonggui

    2018-05-07

    Prostate cancer (PCa) is the most prevalent cancer among men in the United States and remains the second-leading cause of cancer mortality in men. Paclitaxel (PTX) is the first line chemotherapy for PCa treatment, but its therapeutic efficacy is greatly restricted by the nonspecific distribution in vivo. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of most PCa cells, and its expression level increases with cancer aggressiveness, while being present at low levels in normal cells. The high expression level of PSMA in PCa cells offers an opportunity for target delivery of nonspecific cytotoxic drugs to PCa cells, thus improving therapeutic efficacy and reducing toxicity. PSMA has high affinity for DUPA, a glutamate urea ligand. Herein, a novel DUPA-PTX conjugate is developed using DUPA as the targeting ligand to deliver PTX specifically for treatment of PSMA expressing PCa. The targeting ligand DUPA enhances the transport capability and selectivity of PTX to tumor cells via PSMA mediated endocytosis. Besides, DUPA is conjugated with PTX via a disulfide bond, which facilitates the rapid and differential drug release in tumor cells. The DUPA-PTX conjugate exhibits potent cytotoxicity in PSMA expressing cell lines and induces a complete cessation of tumor growth with no obvious toxicity. Our findings give new insight into the PSMA-targeted delivery of chemotherapeutics and provide an opportunity for the development of novel active targeting drug delivery systems for PCa therapy.

  3. Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis in Biopsy-naive Men with Suspected Prostate Cancer Based on Elevated Prostate-specific Antigen Values: Results from a Randomized Prospective Blinded Controlled Trial.

    PubMed

    Tonttila, Panu P; Lantto, Juha; Pääkkö, Eija; Piippo, Ulla; Kauppila, Saila; Lammentausta, Eveliina; Ohtonen, Pasi; Vaarala, Markku H

    2016-03-01

    Multiparametric magnetic resonance imaging (MP-MRI) may improve the detection of clinically significant prostate cancer (PCa). To compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided random biopsy for overall and clinically significant PCa detection among patients with suspected PCa based on prostate-specific antigen (PSA) values. This institutional review board-approved, single-center, prospective, randomized controlled trial (April 2011 to December 2014) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values (PSA <20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA <10 ng/ml). Patients were randomized 1:1 to the MP-MRI or control group. Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided random biopsy and cognitive MRI/TRUS fusion targeted biopsy. The control group underwent TRUS-guided random biopsy alone. MP-MRI 3-T phased-array surface coil. The primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups. Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinically significant PCa in the MP-MRI and control groups. Between-group analyses were performed. Overall, 53 and 60 patients were evaluable in the MP-MRI and control groups, respectively. The overall PCa detection rate and the clinically significant cancer detection rate were similar between the MP-MRI and control groups, respectively (64% [34 of 53] vs 57% [34 of 60]; 7.5% difference [95% confidence interval (CI), -10 to 25], p=0.5, and 55% [29 of 53] vs 45% [27 of 60]; 9.7% difference [95% CI, -8.5 to 27], p=0.8). The PCa detection rate was higher than assumed during the planning of this single-center trial. MP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values. In this randomized clinical trial, additional prostate magnetic resonance imaging (MRI) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound-guided random biopsy in the diagnosis of prostate cancer. Similar numbers of cancers were detected with and without MRI. ClinicalTrials.gov identifier: NCT01357512. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  4. Empirical modeling of spatial and temporal variation in warm season nocturnal air temperatures in two North Idaho mountain ranges, USA

    Treesearch

    Zachery A. Holden; Michael A. Crimmins; Samuel A. Cushman; Jeremy S. Littell

    2010-01-01

    Accurate, fine spatial resolution predictions of surface air temperatures are critical for understanding many hydrologic and ecological processes. This study examines the spatial and temporal variability in nocturnal air temperatures across a mountainous region of Northern Idaho. Principal components analysis (PCA) was applied to a network of 70 Hobo temperature...

  5. Contribution made by multivariate curve resolution applied to gel permeation chromatography-Fourier transform infrared data for an in-depth characterization of styrene-butadiene rubber blends.

    PubMed

    Ruckebusch, C; Vilmin, F; Coste, N; Huvenne, J P

    2008-07-01

    We evaluate the contribution made by multivariate curve resolution-alternating least squares (MCR-ALS) for resolving gel permeation chromatography-Fourier transform infrared (GPC-FT-IR) data collected on butadiene rubber (BR) and styrene butadiene rubber (SBR) blends in order to access in-depth knowledge of polymers along the molecular weight distribution (MWD). In the BR-SBR case, individual polymers differ in chemical composition but share almost the same MWD. Principal component analysis (PCA) gives a general overview of the data structure and attests to the feasibility of modeling blends as a binary system. MCR-ALS is then performed. It allows resolving the chromatographic coelution and validates the chosen methodology. For SBR-SBR blends, the problem is more challenging since the individual elastomers present the same chemical composition. Rank deficiency is detected from the PCA data structure analysis. MCR-ALS is thus performed on column-wise augmented matrices. It brings very useful insight into the composition of the analyzed blends. In particular, a weak change in the composition of individual SBR in the MWD's lowest mass region is revealed.

  6. High-resolution face verification using pore-scale facial features.

    PubMed

    Li, Dong; Zhou, Huiling; Lam, Kin-Man

    2015-08-01

    Face recognition methods, which usually represent face images using holistic or local facial features, rely heavily on alignment. Their performances also suffer a severe degradation under variations in expressions or poses, especially when there is one gallery per subject only. With the easy access to high-resolution (HR) face images nowadays, some HR face databases have recently been developed. However, few studies have tackled the use of HR information for face recognition or verification. In this paper, we propose a pose-invariant face-verification method, which is robust to alignment errors, using the HR information based on pore-scale facial features. A new keypoint descriptor, namely, pore-Principal Component Analysis (PCA)-Scale Invariant Feature Transform (PPCASIFT)-adapted from PCA-SIFT-is devised for the extraction of a compact set of distinctive pore-scale facial features. Having matched the pore-scale features of two-face regions, an effective robust-fitting scheme is proposed for the face-verification task. Experiments show that, with one frontal-view gallery only per subject, our proposed method outperforms a number of standard verification methods, and can achieve excellent accuracy even the faces are under large variations in expression and pose.

  7. An Evaluation of Feature Learning Methods for High Resolution Image Classification

    NASA Astrophysics Data System (ADS)

    Tokarczyk, P.; Montoya, J.; Schindler, K.

    2012-07-01

    Automatic image classification is one of the fundamental problems of remote sensing research. The classification problem is even more challenging in high-resolution images of urban areas, where the objects are small and heterogeneous. Two questions arise, namely which features to extract from the raw sensor data to capture the local radiometry and image structure at each pixel or segment, and which classification method to apply to the feature vectors. While classifiers are nowadays well understood, selecting the right features remains a largely empirical process. Here we concentrate on the features. Several methods are evaluated which allow one to learn suitable features from unlabelled image data by analysing the image statistics. In a comparative study, we evaluate unsupervised feature learning with different linear and non-linear learning methods, including principal component analysis (PCA) and deep belief networks (DBN). We also compare these automatically learned features with popular choices of ad-hoc features including raw intensity values, standard combinations like the NDVI, a few PCA channels, and texture filters. The comparison is done in a unified framework using the same images, the target classes, reference data and a Random Forest classifier.

  8. New algorithm for toric intraocular lens power calculation considering the posterior corneal astigmatism.

    PubMed

    Canovas, Carmen; Alarcon, Aixa; Rosén, Robert; Kasthurirangan, Sanjeev; Ma, Joseph J K; Koch, Douglas D; Piers, Patricia

    2018-02-01

    To assess the accuracy of toric intraocular lens (IOL) power calculations of a new algorithm that incorporates the effect of posterior corneal astigmatism (PCA). Abbott Medical Optics, Inc., Groningen, the Netherlands. Retrospective case report. In eyes implanted with toric IOLs, the exact vergence formula of the Tecnis toric calculator was used to predict refractive astigmatism from preoperative biometry, surgeon-estimated surgically induced astigmatism (SIA), and implanted IOL power, with and without including the new PCA algorithm. For each calculation method, the error in predicted refractive astigmatism was calculated as the vector difference between the prediction and the actual refraction. Calculations were also made using postoperative keratometry (K) values to eliminate the potential effect of incorrect SIA estimates. The study comprised 274 eyes. The PCA algorithm significantly reduced the centroid error in predicted refractive astigmatism (P < .001). With the PCA algorithm, the centroid error reduced from 0.50 @ 1 to 0.19 @ 3 when using preoperative K values and from 0.30 @ 0 to 0.02 @ 84 when using postoperative K values. Patients who had anterior corneal against-the-rule, with-the-rule, and oblique astigmatism had improvement with the PCA algorithm. In addition, the PCA algorithm reduced the median absolute error in all groups (P < .001). The use of the new PCA algorithm decreased the error in the prediction of residual refractive astigmatism in eyes implanted with toric IOLs. Therefore, the new PCA algorithm, in combination with an exact vergence IOL power calculation formula, led to an increased predictability of toric IOL power. Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  9. Clinical performance of serum [-2]proPSA derivatives, %p2PSA and PHI, in the detection and management of prostate cancer.

    PubMed

    Huang, Ya-Qiang; Sun, Tong; Zhong, Wei-De; Wu, Chin-Lee

    2014-01-01

    Prostate-specific antigen (PSA) has been widely used as a serum marker for prostate cancer (PCa) screening or progression monitoring, which dramatically increased rate of early detection while significantly reduced PCa-specific mortality. However, a number of limitations of PSA have been noticed. Low specificity of PSA may lead to overtreatment in men who presenting with a total PSA (tPSA) level of < 10 ng/mL. As a type of free PSA (fPSA), [-2]proPSA is differentially expressed in peripheral zone of prostate gland and found to be elevated in serum of men with PCa. Two p2PSA-based derivatives, prostate health index (PHI) and %p2PSA, which were defined as [(p2PSA/fPSA) × √ tPSA] and [(p2PSA/fPSA) × 100] respectively, have been suggested to be increased in PCa and can better distinguish PCa from benign prostatic diseases than tPSA or fPSA. We performed a systematic review of the available scientific evidences to evaluate the potentials of %p2PSA and PHI in clinical application. Mounting evidences suggested that both %p2PSA and PHI possess higher area under the ROC curve (AUC) and better specificity at a high sensitivity for PCa detection when compare with tPSA and %fPSA. It indicated that measurements of %p2PSA and PHI significantly improved the accuracy of PCa detection and diminished unnecessary biopsies. Furthermore, elevations of %p2PSA and PHI are related to more aggressive diseases. %p2PSA and PHI might be helpful in reducing overtreatment on indolent cases or assessing the progression of PCa in men who undergo active surveillance. Further studies are needed before being applied in routine clinical practice.

  10. A Systematic Review and Meta-analysis of the Diagnostic Accuracy of Prostate Health Index and 4-Kallikrein Panel Score in Predicting Overall and High-grade Prostate Cancer.

    PubMed

    Russo, Giorgio Ivan; Regis, Federica; Castelli, Tommaso; Favilla, Vincenzo; Privitera, Salvatore; Giardina, Raimondo; Cimino, Sebastiano; Morgia, Giuseppe

    2017-08-01

    Markers for prostate cancer (PCa) have progressed over recent years. In particular, the prostate health index (PHI) and the 4-kallikrein (4K) panel have been demonstrated to improve the diagnosis of PCa. We aimed to review the diagnostic accuracy of PHI and the 4K panel for PCa detection. We performed a systematic literature search of PubMed, EMBASE, Cochrane, and Academic One File databases until July 2016. We included diagnostic accuracy studies that used PHI or 4K panel for the diagnosis of PCa or high-grade PCa. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Twenty-eight studies including 16,762 patients have been included for the analysis. The pooled data showed a sensitivity of 0.89 and 0.74 for PHI and 4K panel, respectively, for PCa detection and a pooled specificity of 0.34 and 0.60 for PHI and 4K panel, respectively. The derived area under the curve (AUC) from the hierarchical summary receiver operating characteristic (HSROC) showed an accuracy of 0.76 and 0.72 for PHI and 4K panel respectively. For high-grade PCa detection, the pooled sensitivity was 0.93 and 0.87 for PHI and 4K panel, respectively, whereas the pooled specificity was 0.34 and 0.61 for PHI and 4K panel, respectively. The derived AUC from the HSROC showed an accuracy of 0.82 and 0.81 for PHI and 4K panel, respectively. Both PHI and the 4K panel provided good diagnostic accuracy in detecting overall and high-grade PCa. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. CscoreTool: fast Hi-C compartment analysis at high resolution.

    PubMed

    Zheng, Xiaobin; Zheng, Yixian

    2018-05-01

    The genome-wide chromosome conformation capture (Hi-C) has revealed that the eukaryotic genome can be partitioned into A and B compartments that have distinctive chromatin and transcription features. Current Principle Component Analyses (PCA)-based method for the A/B compartment prediction based on Hi-C data requires substantial CPU time and memory. We report the development of a method, CscoreTool, which enables fast and memory-efficient determination of A/B compartments at high resolution even in datasets with low sequencing depth. https://github.com/scoutzxb/CscoreTool. xzheng@carnegiescience.edu. Supplementary data are available at Bioinformatics online.

  12. Joint Bayesian Estimation of Quasar Continua and the Lyα Forest Flux Probability Distribution Function

    NASA Astrophysics Data System (ADS)

    Eilers, Anna-Christina; Hennawi, Joseph F.; Lee, Khee-Gan

    2017-08-01

    We present a new Bayesian algorithm making use of Markov Chain Monte Carlo sampling that allows us to simultaneously estimate the unknown continuum level of each quasar in an ensemble of high-resolution spectra, as well as their common probability distribution function (PDF) for the transmitted Lyα forest flux. This fully automated PDF regulated continuum fitting method models the unknown quasar continuum with a linear principal component analysis (PCA) basis, with the PCA coefficients treated as nuisance parameters. The method allows one to estimate parameters governing the thermal state of the intergalactic medium (IGM), such as the slope of the temperature-density relation γ -1, while marginalizing out continuum uncertainties in a fully Bayesian way. Using realistic mock quasar spectra created from a simplified semi-numerical model of the IGM, we show that this method recovers the underlying quasar continua to a precision of ≃ 7 % and ≃ 10 % at z = 3 and z = 5, respectively. Given the number of principal component spectra, this is comparable to the underlying accuracy of the PCA model itself. Most importantly, we show that we can achieve a nearly unbiased estimate of the slope γ -1 of the IGM temperature-density relation with a precision of +/- 8.6 % at z = 3 and +/- 6.1 % at z = 5, for an ensemble of ten mock high-resolution quasar spectra. Applying this method to real quasar spectra and comparing to a more realistic IGM model from hydrodynamical simulations would enable precise measurements of the thermal and cosmological parameters governing the IGM, albeit with somewhat larger uncertainties, given the increased flexibility of the model.

  13. ToF-SIMS and principal component analysis of lipids and amino acids from inflamed and dysplastic human colonic mucosa.

    PubMed

    Urbini, Marco; Petito, Valentina; de Notaristefani, Francesco; Scaldaferri, Franco; Gasbarrini, Antonio; Tortora, Luca

    2017-10-01

    Here, time of flight secondary ion mass spectrometry (ToF-SIMS) and multivariate analysis were combined to study the role of ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), in the colon cancer progression. ToF-SIMS was used to obtain mass spectra and chemical maps from the mucosal surface of human normal (NC), inflamed (IC), and dysplastic (DC) colon tissues. Chemical mapping with a lateral resolution of ≈ 1 μm allowed to evaluate zonation of fatty acids and amino acids as well as the morphological condition of the intestinal glands. High mass resolution ToF-SIMS spectra showed chemical differences in lipid and amino acid composition as a function of pathological state. In positive ion mode, mono- (MAG), di- (DAG), and triacylglycerol (TAG) signals were detected in NC tissues, while in IC and DC tissues, the only cholesterol was present as lipid class representative. Signals from fatty acids, collected in negative ion mode, were subjected to principal component analysis (PCA). PCA showed a strict correlation between IC and DC samples, due to an increase of stearic, arachidonic, and linoleic acid. In the same way, differences in the amino acid composition were highlighted through multivariate analysis. PCA revealed that glutamic acid, leucine/isoleucine, and valine fragments are related to IC tissues. On the other hand, tyrosine, methionine, and tryptophan peaks contributed highly to the separation of DC tissues. Finally, a classification of NC, IC, and DC patients was also achieved through hierarchical cluster analysis of amino acid fragments. In this case, human colonic inflammation showed a stronger relationship with normal than dysplastic condition. Graphical Abstract ᅟ.

  14. ENSO-driven nutrient variability recorded by central equatorial Pacific corals

    NASA Astrophysics Data System (ADS)

    LaVigne, M.; Nurhati, I. S.; Cobb, K. M.; McGregor, H. V.; Sinclair, D. J.; Sherrell, R. M.

    2012-12-01

    Recent evidence for shifts in global ocean primary productivity suggests that surface ocean nutrient availability is a key link between global climate and ocean carbon cycling. Time-series records from satellite, in situ buoy sensors, and bottle sampling have documented the impact of the El Niño Southern Oscillation (ENSO) on equatorial Pacific hydrography and broad changes in biogeochemistry since the late 1990's, however, data are sparse prior to this. Here we use a new paleoceanographic nutrient proxy, coral P/Ca, to explore the impact of ENSO on nutrient availability in the central equatorial Pacific at higher-resolution than available from in situ nutrient data. Corals from Christmas (157°W 2°N) and Fanning (159°W 4°N) Islands recorded a well-documented decrease in equatorial upwelling as a ~40% decrease in P/Ca during the 1997-98 ENSO cycle, validating the application of this proxy to Pacific Porites corals. We compare the biogeochemical shifts observed through the 1997-98 event with two pre-TOGA-TAO ENSO cycles (1982-83 and 1986-87) reconstructed from a longer Christmas Island core. All three corals revealed ~30-40% P/Ca depletions during ENSO warming as a result of decreased regional wind stress, thermocline depth, and equatorial upwelling velocity. However, at the termination of each El Niño event, surface nutrients did not return to pre-ENSO levels for ~4-12 months after, SST as a result of increased biological draw down of surface nutrients. These records demonstrate the utility of high-resolution coral nutrient archives for understanding the impact of tropical Pacific climate on the nutrient and carbon cycling of this key region.

  15. Investigation of gastric cancers in nude mice using X-ray in-line phase contrast imaging.

    PubMed

    Tao, Qiang; Luo, Shuqian

    2014-07-24

    This paper is to report the new imaging of gastric cancers without the use of imaging agents. Both gastric normal regions and gastric cancer regions can be distinguished by using the principal component analysis (PCA) based on the gray level co-occurrence matrix (GLCM). Human gastric cancer BGC823 cells were implanted into the stomachs of nude mice. Then, 3, 5, 7, 9 or 11 days after cancer cells implantation, the nude mice were sacrificed and their stomachs were removed. X-ray in-line phase contrast imaging (XILPCI), an X-ray phase contrast imaging method, has greater soft tissue contrast than traditional absorption radiography and generates higher-resolution images. The gastric specimens were imaged by an XILPCIs' charge coupled device (CCD) of 9 μm image resolution. The PCA of the projective images' region of interests (ROIs) based on GLCM were extracted to discriminate gastric normal regions and gastric cancer regions. Different stages of gastric cancers were classified by using support vector machines (SVMs). The X-ray in-line phase contrast images of nude mice gastric specimens clearly show the gastric architectures and the details of the early gastric cancers. The phase contrast computed tomography (CT) images of nude mice gastric cancer specimens are better than the traditional absorption CT images without the use of imaging agents. The results of the PCA of the texture parameters based on GLCM of normal regions is (F1+F2) >8.5, but those of cancer regions is (F1+F2) <8.5. The classification accuracy is 83.3% that classifying gastric specimens into different stages using SVMs. This is a very preliminary feasibility study. With further researches, XILPCI could become a noninvasive method for future the early detection of gastric cancers or medical researches.

  16. Prostate cancer invasion and metastasis: Insights from mining genomic data

    DOE PAGES

    Hudson, Bryan D.; Kulp, Kristen S.; Loots, Gabriela G.

    2013-07-22

    Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men in the Western world and the second leading cause of cancer-related deaths among men worldwide. Although most cancers have the potential to metastasize under appropriate conditions, PCa favors the skeleton as a primary site of metastasis, suggesting that the bone microenvironment is conducive to its growth. PCa metastasis proceeds through a complex series of molecular events that include angiogenesis at the site of the original tumor, local migration within the primary site, intravasation into the blood stream, survival within the circulation, extravasation of the tumor cells to themore » target organ and colonization of those cells within the new site. In turn, each one of these steps involves a complicated chain of events that utilize multiple protein–protein interactions, protein signaling cascades and transcriptional changes. Despite the urgent need to improve current biomarkers for diagnosis, prognosis and drug resistance, advances have been slow. Global gene expression methods such as gene microarrays and RNA sequencing enable the study of thousands of genes simultaneously and allow scientists to examine molecular pathways of cancer pathogenesis. In this review, we summarize the current literature that explored high-throughput transcriptome analysis toward the advancement of biomarker discovery for PCa. Novel biomarkers are strongly needed to enable more accurate detection of PCa, improve prediction of tumor aggressiveness and facilitate the discovery of new therapeutic targets for tailored medicine. Furthermore, promising molecular markers identified from gene expression profiling studies include HPN, CLU1, WT1, WNT5A, AURKA and SPARC.« less

  17. Fisetin enhances chemotherapeutic effect of cabazitaxel against human prostate cancer cells

    PubMed Central

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Siddiqui, Imtiaz Ahmad; Verma, Ajit Kumar; Mukhtar, Hasan

    2016-01-01

    Although treatment of prostate cancer (PCa) has improved over the past several years, taxanes such as cabazitaxel remain the only form of effective chemotherapy that improves survival in patients with metastatic castration-resistant PCa. However, the effectiveness of this class of drugs has been associated with various side effects and drug resistance. We previously reported that fisetin, a hydroxyflavone, is a microtubule stabilizing agent and inhibits PCa cell proliferation, migration, and invasion and suggested its use as an adjuvant for treatment of prostate and other cancer types. In this study, we investigated the effect of fisetin in combination with cabazitaxel with the objective to achieve maximum therapeutic benefit, reduce dose and toxicity and minimize or delay the induction of drug resistance and metastasis. Our data show for the first time that a combination of fisetin (20 μM) enhances cabazitaxel (5nM) and synergistically reduces 22Rν1, PC-3M-luc-6, and C4-2 cell viability and metastatic properties with minimal adverse effects on normal prostate epithelial cells. In addition, the combination of fisetin with cabazitaxel was associated with inhibition of proliferation and enhancement of apoptosis. Furthermore, combination treatment resulted in inhibition of tumor growth, invasion and metastasis when assessed in two in-vivo xenograft mouse models. These results provide evidence that fisetin may have therapeutic benefit for patients with advanced PCa through enhancing the efficacy of cabazitaxel under both androgen-dependent and androgen-independent conditions. This study underscores the benefit of the combination of fisetin with cabazitaxel for the treatment of advanced and resistant PCa and possibly other cancer types. PMID:27765854

  18. Prostate cancer invasion and metastasis: Insights from mining genomic data

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hudson, Bryan D.; Kulp, Kristen S.; Loots, Gabriela G.

    Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men in the Western world and the second leading cause of cancer-related deaths among men worldwide. Although most cancers have the potential to metastasize under appropriate conditions, PCa favors the skeleton as a primary site of metastasis, suggesting that the bone microenvironment is conducive to its growth. PCa metastasis proceeds through a complex series of molecular events that include angiogenesis at the site of the original tumor, local migration within the primary site, intravasation into the blood stream, survival within the circulation, extravasation of the tumor cells to themore » target organ and colonization of those cells within the new site. In turn, each one of these steps involves a complicated chain of events that utilize multiple protein–protein interactions, protein signaling cascades and transcriptional changes. Despite the urgent need to improve current biomarkers for diagnosis, prognosis and drug resistance, advances have been slow. Global gene expression methods such as gene microarrays and RNA sequencing enable the study of thousands of genes simultaneously and allow scientists to examine molecular pathways of cancer pathogenesis. In this review, we summarize the current literature that explored high-throughput transcriptome analysis toward the advancement of biomarker discovery for PCa. Novel biomarkers are strongly needed to enable more accurate detection of PCa, improve prediction of tumor aggressiveness and facilitate the discovery of new therapeutic targets for tailored medicine. Furthermore, promising molecular markers identified from gene expression profiling studies include HPN, CLU1, WT1, WNT5A, AURKA and SPARC.« less

  19. Contrast-Enhanced Ultrasound Angiogenesis Imaging by Mutual Information Analysis for Prostate Cancer Localization.

    PubMed

    Schalk, Stefan G; Demi, Libertario; Bouhouch, Nabil; Kuenen, Maarten P J; Postema, Arnoud W; de la Rosette, Jean J M C H; Wijkstra, Hessel; Tjalkens, Tjalling J; Mischi, Massimo

    2017-03-01

    The role of angiogenesis in cancer growth has stimulated research aimed at noninvasive cancer detection by blood perfusion imaging. Recently, contrast ultrasound dispersion imaging was proposed as an alternative method for angiogenesis imaging. After the intravenous injection of an ultrasound-contrast-agent bolus, dispersion can be indirectly estimated from the local similarity between neighboring time-intensity curves (TICs) measured by ultrasound imaging. Up until now, only linear similarity measures have been investigated. Motivated by the promising results of this approach in prostate cancer (PCa), we developed a novel dispersion estimation method based on mutual information, thus including nonlinear similarity, to further improve its ability to localize PCa. First, a simulation study was performed to establish the theoretical link between dispersion and mutual information. Next, the method's ability to localize PCa was validated in vivo in 23 patients (58 datasets) referred for radical prostatectomy by comparison with histology. A monotonic relationship between dispersion and mutual information was demonstrated. The in vivo study resulted in a receiver operating characteristic (ROC) curve area equal to 0.77, which was superior (p = 0.21-0.24) to that obtained by linear similarity measures (0.74-0.75) and (p <; 0.05) to that by conventional perfusion parameters (≤0.70). Mutual information between neighboring time-intensity curves can be used to indirectly estimate contrast dispersion and can lead to more accurate PCa localization. An improved PCa localization method can possibly lead to better grading and staging of tumors, and support focal-treatment guidance. Moreover, future employment of the method in other types of angiogenic cancer can be considered.

  20. Hyperspectral image visualization based on a human visual model

    NASA Astrophysics Data System (ADS)

    Zhang, Hongqin; Peng, Honghong; Fairchild, Mark D.; Montag, Ethan D.

    2008-02-01

    Hyperspectral image data can provide very fine spectral resolution with more than 200 bands, yet presents challenges for visualization techniques for displaying such rich information on a tristimulus monitor. This study developed a visualization technique by taking advantage of both the consistent natural appearance of a true color image and the feature separation of a PCA image based on a biologically inspired visual attention model. The key part is to extract the informative regions in the scene. The model takes into account human contrast sensitivity functions and generates a topographic saliency map for both images. This is accomplished using a set of linear "center-surround" operations simulating visual receptive fields as the difference between fine and coarse scales. A difference map between the saliency map of the true color image and that of the PCA image is derived and used as a mask on the true color image to select a small number of interesting locations where the PCA image has more salient features than available in the visible bands. The resulting representations preserve hue for vegetation, water, road etc., while the selected attentional locations may be analyzed by more advanced algorithms.

  1. Improved Maturity and Ripeness Classifications of Magnifera Indica cv. Harumanis Mangoes through Sensor Fusion of an Electronic Nose and Acoustic Sensor

    PubMed Central

    Zakaria, Ammar; Shakaff, Ali Yeon Md; Masnan, Maz Jamilah; Saad, Fathinul Syahir Ahmad; Adom, Abdul Hamid; Ahmad, Mohd Noor; Jaafar, Mahmad Nor; Abdullah, Abu Hassan; Kamarudin, Latifah Munirah

    2012-01-01

    In recent years, there have been a number of reported studies on the use of non-destructive techniques to evaluate and determine mango maturity and ripeness levels. However, most of these reported works were conducted using single-modality sensing systems, either using an electronic nose, acoustics or other non-destructive measurements. This paper presents the work on the classification of mangoes (Magnifera Indica cv. Harumanis) maturity and ripeness levels using fusion of the data of an electronic nose and an acoustic sensor. Three groups of samples each from two different harvesting times (week 7 and week 8) were evaluated by the e-nose and then followed by the acoustic sensor. Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were able to discriminate the mango harvested at week 7 and week 8 based solely on the aroma and volatile gases released from the mangoes. However, when six different groups of different maturity and ripeness levels were combined in one classification analysis, both PCA and LDA were unable to discriminate the age difference of the Harumanis mangoes. Instead of six different groups, only four were observed using the LDA, while PCA showed only two distinct groups. By applying a low level data fusion technique on the e-nose and acoustic data, the classification for maturity and ripeness levels using LDA was improved. However, no significant improvement was observed using PCA with data fusion technique. Further work using a hybrid LDA-Competitive Learning Neural Network was performed to validate the fusion technique and classify the samples. It was found that the LDA-CLNN was also improved significantly when data fusion was applied. PMID:22778629

  2. Network Intrusion Detection Based on a General Regression Neural Network Optimized by an Improved Artificial Immune Algorithm

    PubMed Central

    Wu, Jianfa; Peng, Dahao; Li, Zhuping; Zhao, Li; Ling, Huanzhang

    2015-01-01

    To effectively and accurately detect and classify network intrusion data, this paper introduces a general regression neural network (GRNN) based on the artificial immune algorithm with elitist strategies (AIAE). The elitist archive and elitist crossover were combined with the artificial immune algorithm (AIA) to produce the AIAE-GRNN algorithm, with the aim of improving its adaptivity and accuracy. In this paper, the mean square errors (MSEs) were considered the affinity function. The AIAE was used to optimize the smooth factors of the GRNN; then, the optimal smooth factor was solved and substituted into the trained GRNN. Thus, the intrusive data were classified. The paper selected a GRNN that was separately optimized using a genetic algorithm (GA), particle swarm optimization (PSO), and fuzzy C-mean clustering (FCM) to enable a comparison of these approaches. As shown in the results, the AIAE-GRNN achieves a higher classification accuracy than PSO-GRNN, but the running time of AIAE-GRNN is long, which was proved first. FCM and GA-GRNN were eliminated because of their deficiencies in terms of accuracy and convergence. To improve the running speed, the paper adopted principal component analysis (PCA) to reduce the dimensions of the intrusive data. With the reduction in dimensionality, the PCA-AIAE-GRNN decreases in accuracy less and has better convergence than the PCA-PSO-GRNN, and the running speed of the PCA-AIAE-GRNN was relatively improved. The experimental results show that the AIAE-GRNN has a higher robustness and accuracy than the other algorithms considered and can thus be used to classify the intrusive data. PMID:25807466

  3. Improved maturity and ripeness classifications of Magnifera Indica cv. Harumanis mangoes through sensor fusion of an electronic nose and acoustic sensor.

    PubMed

    Zakaria, Ammar; Shakaff, Ali Yeon Md; Masnan, Maz Jamilah; Saad, Fathinul Syahir Ahmad; Adom, Abdul Hamid; Ahmad, Mohd Noor; Jaafar, Mahmad Nor; Abdullah, Abu Hassan; Kamarudin, Latifah Munirah

    2012-01-01

    In recent years, there have been a number of reported studies on the use of non-destructive techniques to evaluate and determine mango maturity and ripeness levels. However, most of these reported works were conducted using single-modality sensing systems, either using an electronic nose, acoustics or other non-destructive measurements. This paper presents the work on the classification of mangoes (Magnifera Indica cv. Harumanis) maturity and ripeness levels using fusion of the data of an electronic nose and an acoustic sensor. Three groups of samples each from two different harvesting times (week 7 and week 8) were evaluated by the e-nose and then followed by the acoustic sensor. Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were able to discriminate the mango harvested at week 7 and week 8 based solely on the aroma and volatile gases released from the mangoes. However, when six different groups of different maturity and ripeness levels were combined in one classification analysis, both PCA and LDA were unable to discriminate the age difference of the Harumanis mangoes. Instead of six different groups, only four were observed using the LDA, while PCA showed only two distinct groups. By applying a low level data fusion technique on the e-nose and acoustic data, the classification for maturity and ripeness levels using LDA was improved. However, no significant improvement was observed using PCA with data fusion technique. Further work using a hybrid LDA-Competitive Learning Neural Network was performed to validate the fusion technique and classify the samples. It was found that the LDA-CLNN was also improved significantly when data fusion was applied.

  4. Quantitative analysis of NMR spectra with chemometrics

    NASA Astrophysics Data System (ADS)

    Winning, H.; Larsen, F. H.; Bro, R.; Engelsen, S. B.

    2008-01-01

    The number of applications of chemometrics to series of NMR spectra is rapidly increasing due to an emerging interest for quantitative NMR spectroscopy e.g. in the pharmaceutical and food industries. This paper gives an analysis of advantages and limitations of applying the two most common chemometric procedures, Principal Component Analysis (PCA) and Multivariate Curve Resolution (MCR), to a designed set of 231 simple alcohol mixture (propanol, butanol and pentanol) 1H 400 MHz spectra. The study clearly demonstrates that the major advantage of chemometrics is the visualisation of larger data structures which adds a new exploratory dimension to NMR research. While robustness and powerful data visualisation and exploration are the main qualities of the PCA method, the study demonstrates that the bilinear MCR method is an even more powerful method for resolving pure component NMR spectra from mixtures when certain conditions are met.

  5. Biparametric MRI of the prostate.

    PubMed

    Scialpi, Michele; D'Andrea, Alfredo; Martorana, Eugenio; Malaspina, Corrado Maria; Aisa, Maria Cristina; Napoletano, Maria; Orlandi, Emanuele; Rondoni, Valeria; Scialpi, Pietro; Pacchiarini, Diamante; Palladino, Diego; Dragone, Michele; Di Renzo, Giancarlo; Simeone, Annalisa; Bianchi, Giampaolo; Brunese, Luca

    2017-12-01

    Biparametric Magnetic Resonance Imaging (bpMRI) of the prostate combining both morphologic T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) is emerging as an alternative to multiparametric MRI (mpMRI) to detect, to localize and to guide prostatic targeted biopsy in patients with suspicious prostate cancer (PCa). BpMRI overcomes some limitations of mpMRI such as the costs, the time required to perform the study, the use of gadolinium-based contrast agents and the lack of a guidance for management of score 3 lesions equivocal for significant PCa. In our experience the optimal and similar clinical results of the bpMRI in comparison to mpMRI are essentially related to the DWI that we consider the dominant sequence for detection suspicious PCa both in transition and in peripheral zone. In clinical practice, the adoption of bpMRI standardized scoring system, indicating the likelihood to diagnose a clinically significant PCa and establishing the management of each suspicious category (from 1 to 4), could represent the rationale to simplify and to improve the current interpretation of mpMRI based on Prostate Imaging and Reporting Archiving Data System version 2 (PI-RADS v2). In this review article we report and describe the current knowledge about bpMRI in the detection of suspicious PCa and a simplified PI-RADS based on bpMRI for management of each suspicious PCa categories to facilitate the communication between radiologists and urologists.

  6. Biparametric MRI of the prostate

    PubMed Central

    Scialpi, Michele; D’Andrea, Alfredo; Martorana, Eugenio; Malaspina, Corrado Maria; Aisa, Maria Cristina; Napoletano, Maria; Orlandi, Emanuele; Rondoni, Valeria; Scialpi, Pietro; Pacchiarini, Diamante; Palladino, Diego; Dragone, Michele; Di Renzo, Giancarlo; Simeone, Annalisa; Bianchi, Giampaolo; Brunese, Luca

    2017-01-01

    Biparametric Magnetic Resonance Imaging (bpMRI) of the prostate combining both morphologic T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) is emerging as an alternative to multiparametric MRI (mpMRI) to detect, to localize and to guide prostatic targeted biopsy in patients with suspicious prostate cancer (PCa). BpMRI overcomes some limitations of mpMRI such as the costs, the time required to perform the study, the use of gadolinium-based contrast agents and the lack of a guidance for management of score 3 lesions equivocal for significant PCa. In our experience the optimal and similar clinical results of the bpMRI in comparison to mpMRI are essentially related to the DWI that we consider the dominant sequence for detection suspicious PCa both in transition and in peripheral zone. In clinical practice, the adoption of bpMRI standardized scoring system, indicating the likelihood to diagnose a clinically significant PCa and establishing the management of each suspicious category (from 1 to 4), could represent the rationale to simplify and to improve the current interpretation of mpMRI based on Prostate Imaging and Reporting Archiving Data System version 2 (PI-RADS v2). In this review article we report and describe the current knowledge about bpMRI in the detection of suspicious PCa and a simplified PI-RADS based on bpMRI for management of each suspicious PCa categories to facilitate the communication between radiologists and urologists. PMID:29201499

  7. Prostate-specific membrane antigen for prostate cancer theranostics: from imaging to targeted therapy.

    PubMed

    Arsenault, Frédéric; Beauregard, Jean-Mathieu; Pouliot, Frédéric

    2018-06-22

    In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i.e. theranostic) PSMA tracers. Development in small PSMA-targeted molecules labeled with gallium-68 and fluorine-18 show promising results for primary staging and detection of disease at biochemical recurrence using PET/computed tomography (PET/CT). Studies show a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and bone scan) or choline PET tracers, especially for restaging after prostate-specific antigen failure following loco-regional therapy. In addition, some PSMA tracers can be labeled with beta-minus and alpha particle emitters, yielding encouraging response rates and low toxicity, and potentially offering a new line of targeted therapy for metastatic castration-resistant PCa. PSMA-targeted tracers have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given their specific biodistribution toward PCa tissue, PSMA RLT now offers new therapeutic possibilities to target metastatic PCa. Prospective multicenter randomized studies investigating the clinical impact management impacts of PSMA-targeted molecules are urgently needed.

  8. Characteristics and sensitivity analysis of multiple-time-resolved source patterns of PM2.5 with real time data using Multilinear Engine 2

    NASA Astrophysics Data System (ADS)

    Peng, Xing; Shi, Guo-Liang; Gao, Jian; Liu, Jia-Yuan; HuangFu, Yan-Qi; Ma, Tong; Wang, Hai-Ting; Zhang, Yue-Chong; Wang, Han; Li, Hui; Ivey, Cesunica E.; Feng, Yin-Chang

    2016-08-01

    With real time resolved data of Particulate matter (PM) and chemical species, understanding the source patterns and chemical characteristics is critical to establish controlling of PM. In this work, PM2.5 and chemical species were measured by corresponding online instruments with 1-h time resolution in Beijing. Multilinear Engine 2 (ME2) model was applied to explore the sources, and four sources (vehicle emission, crustal dust, secondary formation and coal combustion) were identified. To investigate the sensitivity of time resolution on the source contributions and chemical characteristics, ME2 was conducted with four time resolution runs (1-h, 2-h, 4-h, and 8-h). Crustal dust and coal combustion display large variation in the four time resolutions runs, with their contributions ranging from 6.7 to 10.4 μg m-3 and from 6.4 to 12.2 μg m-3, respectively. The contributions of vehicle emission and secondary formation range from 7.5 to 10.5 and from 14.7 to 16.7 μg m-3, respectively. The sensitivity analyses were conducted by principal component analysis-plot (PCA-plot), coefficient of divergence (CD), average absolute error (AAE) and correlation coefficients. For the four time resolution runs, the source contributions and profiles of crustal dust and coal combustion were more unstable than other source categories, possibly due to the lack of key markers of crustal dust and coal combustion (e.g. Si, Al). On the other hand, vehicle emission and crustal dust were more sensitive to time series of source contributions at different time resolutions. Findings in this study can improve our knowledge of source contributions and chemical characteristics at different time solutions.

  9. Increased resource use in men with metastatic prostate cancer does not result in improved survival or quality of care at the end of life.

    PubMed

    Golan, Ron; Bernstein, Adrien N; Gu, Xiangmei; Dinerman, Brian F; Sedrakyan, Art; Hu, Jim C

    2018-05-15

    Cancer care and end-of-life (EOL) care contribute substantially to health care expenditures. Outside of clinical trials, to our knowledge there exists no standardized protocol to monitor disease progression in men with metastatic prostate cancer (mPCa). The objective of the current study was to evaluate the factors and outcomes associated with increased imaging and serum prostate-specific antigen use in men with mPCa. Using Surveillance, Epidemiology, and End Results-Medicare data from 2004 to 2012, the authors identified men diagnosed with mPCa with at least 6 months of follow-up. Extreme users were classified as those who had either received prostate-specific antigen testing greater than once per month, or who underwent cross-sectional imaging or bone scan more frequently than every 2 months over a 6-month period. Associations between extreme use and survival outcomes, costs, and quality of care at EOL, as measured by timing of hospice referral, frequency of emergency department visits, length of stay, and intensive care unit or hospital admissions, were examined. Overall, a total of 3026 men with mPCa were identified, 791 of whom (26%) were defined as extreme users. Extreme users were more commonly young, white/non-Hispanic, married, higher earning, and more educated (P<.001, respectively). Extreme use was not associated with improved quality of care at EOL. Yearly health care costs after diagnosis were 36.4% higher among extreme users (95% confidence interval, 27.4%-45.3%; P<.001). Increased monitoring among men with mPCa significantly increases health care costs, without a definitive improvement in survival nor quality of care at EOL noted. Monitoring for disease progression outside of clinical trials should be reserved for those in whom findings will change management. Cancer 2018;124:2212-9. © 2018 American Cancer Society. © 2018 American Cancer Society.

  10. Effect of scalp blocks with levobupivacaine on recovery profiles after craniotomy for aneurysm clipping: a randomized, double-blind, and controlled study.

    PubMed

    Hwang, Jin-Young; Bang, Jae-Seung; Oh, Chang-Wan; Joo, Jin-Deok; Park, Seong-Joo; Do, Sang-Hwan; Yoo, Yong-Jae; Ryu, Jung-Hee

    2015-01-01

    This study was conducted to evaluate the effect of scalp blocks using levobupivacaine on recovery profiles including postoperative pain, patient-controlled analgesia (PCA) consumption, postoperative nausea and vomiting (PONV), and other adverse events in patients undergoing frontoparietal craniotomy for aneurysm clipping. Fifty-two patients scheduled for elective frontoparietal craniotomy for unruptured aneurysm clipping were enrolled. After surgery, scalp blocks were performed using normal saline (group C, n = 26) or 0.75% levobupivacaine (group L, n = 26). Postoperative pain scores and PCA consumption were recorded for 72 hours after recovery of consciousness. The time from patient recovery to the first use of PCA drug and rescue analgesics, the requirement for vasoactive agents, and adverse effects related to PCA and local anesthetics also were recorded. Postoperative pain scores and PCA consumption in group L were lower than in group C (P < .05). The time intervals from patient recovery to the first use of PCA drug (P < .001) and rescue analgesics (P = .038) was longer in group L than in group C. Additionally, less antihypertensive agent was required (P = .017), and PONV occurred less frequently (P = .039) in group L than in group C. Scalp blocks with 0.75% levobupivacaine improved recovery profiles in that it effectively lowered postoperative pain and PCA consumption without severe adverse events and also reduced the requirement for a postoperative antihypertensive agent and the incidence of PONV in patients who underwent frontoparietal craniotomy for aneurysm clipping. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study.

    PubMed

    Larkin, S E T; Johnston, H E; Jackson, T R; Jamieson, D G; Roumeliotis, T I; Mockridge, C I; Michael, A; Manousopoulou, A; Papachristou, E K; Brown, M D; Clarke, N W; Pandha, H; Aukim-Hastie, C L; Cragg, M S; Garbis, S D; Townsend, P A

    2016-10-25

    Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease. We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa. We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6. Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker.

  12. Effect of process control agent on the structural and magnetic properties of nano/amorphous Fe0.7Nb0.1Zr0.1Ti0.1 powders prepared by high energy ball milling

    NASA Astrophysics Data System (ADS)

    Khazaei Feizabad, Mohammad Hossein; Sharafi, Shahriar; Khayati, Gholam Reza; Ranjbar, Mohammad

    2018-03-01

    In this study, amorphous Fe0.7Nb0.1Zr0.1Ti0.1 alloy without metalloids was produced by mechanical alloying of pure mixture elements. Miedema's semi-empirical model was employed to predict the possibility of amorphous phase formation in proposed alloying system. The effect of Hexane as process control agent (PCA) on the structural, magnetic, morphological and thermal properties of the products was investigated. The results showed that the presence of PCA was necessary for the formation of amorphous phase as well as improved its soft magnetic properties. The PCA addition causes an increase of the saturation magnetization (about 43%) and decrease of the coercivity (about 50%). Moreover, the sample milled without PCA, showed a wide particle size distribution as well as relatively spherical geometry. While, in the presence of PCA the powders were aspherical and Polygon. In addition, the crystallization and Curie temperatures were found to be around 800 °C and 650 °C, respectively which are relatively high values for these kinds of alloys.

  13. Echo-Planar Imaging-Based, J-Resolved Spectroscopic Imaging for Improved Metabolite Detection in Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    Imaging (EP-JRESI); Citrate, Choline, Creatine , Spermine, 3Tesla MRI scanner, Endo-rectal MR coil, WET Water Suppression, prostate cancer (PCa...spectroscopic imaging are due to the overlap of metabolite resonances, quantifying few metabolites only (citrate (Cit), choline (Ch), creatine (Cr...concentrations of citrate (Cit), creatine (Cr), choline (Ch) and polyamines that are used to detect and diagnose PCa (2). The challenging task in 1D MRS

  14. Vocal fold paralysis: improved adductor recovery by vincristine blockade of posterior cricoarytenoid.

    PubMed

    Paniello, Randal C

    2015-03-01

    A new treatment for acute unilateral vocal-fold paralysis (UVFP) was proposed in which a drug is injected into the posterior cricoarytenoid muscle (PCA) shortly after nerve injury, before the degree of natural recovery is known, to prevent antagonistic synkinetic reinnervation. This concept was tested in a series of canine experiments using vincristine as the blocking agent. Animal experiments. Laryngeal adductor function was measured at baseline and at 6 months following experimental recurrent laryngeal nerve (RLN) injuries, including complete transection, crush injury, and cautery. In the treatment animals, the PCA was injected with vincristine at the time of RLN injury. Adductor function in the vincristine-treated hemilarynges was significantly improved compared with injury-matched noninjected controls (total n = 43). Transection/repair controls recovered 56.1% of original adductor strength; vincristine-treated hemilarynges recovered to 73.1% (P = 0.002). Cautery injuries also improved with vincristine block (60.7% vs. 88.7%; P = 0.031). Crush injuries recovered well even without vincristine (104.8% vs. 111.2%; P = 0.35). These findings support a new paradigm of early, preemptive blockade of the antagonist muscle (PCA) to improve ultimate net adductor strength, which could potentially improve functional recovery in many UVFP patients and avoid the need for medialization procedures. Possible clinical aspects of this new approach are discussed. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  15. Performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches in VQ codebook generation for image compression

    NASA Astrophysics Data System (ADS)

    Tsai, Jinn-Tsong; Chou, Ping-Yi; Chou, Jyh-Horng

    2015-11-01

    The aim of this study is to generate vector quantisation (VQ) codebooks by integrating principle component analysis (PCA) algorithm, Linde-Buzo-Gray (LBG) algorithm, and evolutionary algorithms (EAs). The EAs include genetic algorithm (GA), particle swarm optimisation (PSO), honey bee mating optimisation (HBMO), and firefly algorithm (FF). The study is to provide performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches. The PCA-EA-LBG approaches contain PCA-GA-LBG, PCA-PSO-LBG, PCA-HBMO-LBG, and PCA-FF-LBG, while the PCA-LBG-EA approaches contain PCA-LBG, PCA-LBG-GA, PCA-LBG-PSO, PCA-LBG-HBMO, and PCA-LBG-FF. All training vectors of test images are grouped according to PCA. The PCA-EA-LBG used the vectors grouped by PCA as initial individuals, and the best solution gained by the EAs was given for LBG to discover a codebook. The PCA-LBG approach is to use the PCA to select vectors as initial individuals for LBG to find a codebook. The PCA-LBG-EA used the final result of PCA-LBG as an initial individual for EAs to find a codebook. The search schemes in PCA-EA-LBG first used global search and then applied local search skill, while in PCA-LBG-EA first used local search and then employed global search skill. The results verify that the PCA-EA-LBG indeed gain superior results compared to the PCA-LBG-EA, because the PCA-EA-LBG explores a global area to find a solution, and then exploits a better one from the local area of the solution. Furthermore the proposed PCA-EA-LBG approaches in designing VQ codebooks outperform existing approaches shown in the literature.

  16. [Combined use of ECK-triggered 2D-phase contrast MR angiography and 2D-time-of-flight MR angiography for planning and follow up before and after vascular intervention of pelvic and leg arteries].

    PubMed

    Reimer, P; Wilhelm, M; Lentschig, M; Wörtler, K; Marx, C; Allkemper, T; Boettger, U; Heinecke, A; Rummeny, E J; Peters, P E

    1998-03-01

    To develop a strategy for the complete work-up of vessel lumen and vessel wall for planning and follow-up of radiological interventions of lower extremity arteries. A total of 36 patients (21 pre-, 8 post- and 7 pre- and postinterventional) were studied. MRA studies were performed using an ECG-triggered phase contrast technique for the demonstration of intraluminal flow and an axial high resolution time-of-flight technique to assess the vascular wall. All MRA studies were analysed by intraindividual DSA comparison for the assessment of flow and wall structures. Combined MRA techniques provided a good correlation with DSA for the assessment of vascular flow. The kappa test revealed a value of greater than 0.61 for most on the vessel segments proving a good correlation of both methods. Orthogonal high-resolution TOF-MRA provided additional information for the assessment postinterventional wall haematomas and hard plaques. Combination of PCA to study flow and axial TOF to study wall pathology improves the usefulness of peripheral MRA.

  17. Local Treatment of Metastatic Prostate Cancer: What is the Evidence So Far?

    PubMed

    Leonel Almeida, Pedro; Jorge Pereira, Bruno

    2018-01-01

    Advances in technological, laboratorial, and imaging studies and new treatments available in the last decades significantly improved prostate cancer survival rates. However, this did not occur in metastatic prostate cancer (mPCa) at diagnosis which, in young and fit patients, will become invariably resistant to the established treatments. Progression will lead to an impairment in patients' quality of life and disease-related death. The authors intend to perform a literature review of the advantages of primary treatment of mPCa. Articles were retrieved and filtered for relevance from PubMed, SciELO, and ScienceDirect until March 2017. Primary treatment is currently indicated only in cases of nonmetastatic PCa. Nonetheless, there might be some benefits in doing local treatment in mPCa in order to control local disease, prevent new metastasis, and improve the efficacy of chemotherapy and hormonotherapy with similar complications rate when compared to locally confined cancer. Independent factors that have a negative influence are age above 70 years, cT4 stage or high-grade disease, PSA ≥ 20 ng/ml, and pelvic lymphadenopathies. The presence of 3 or more of these factors conditions CSS and OS is the same between patients who performed local treatment and those who did not. Metastasis degree and location number can also influence outcome. Meanwhile, patients with visceral metastases have worse results. There is growing evidence supporting local treatment in cases of metastatic prostate cancer at diagnosis in the context of a multimodal approach. However, it should be kept in mind that most of the existing studies are retrospective and it would be important to make consistent prospective studies with well-defined patient selection criteria in order to sustain the existing data and understand the main indications to select patients and perform primary treatment in mPCa.

  18. Fish oil slows prostate cancer xenograft growth relative to other dietary fats and is associated with decreased mitochondrial and insulin pathway gene expression.

    PubMed

    Lloyd, J C; Masko, E M; Wu, C; Keenan, M M; Pilla, D M; Aronson, W J; Chi, J-Ta; Freedland, S J

    2013-12-01

    Previous mouse studies suggest that decreasing dietary fat content can slow prostate cancer (PCa) growth. To our knowledge, no study has yet compared the effect of multiple different fats on PCa progression. We sought to systematically compare the effect of fish oil, olive oil, corn oil and animal fat on PCa progression. A total of 96 male severe combined immunodeficient mice were injected with LAPC-4 human PCa cells. Two weeks following injection, mice were randomized to a Western diet based on fish oil, olive oil, corn oil or animal fat (35% kilocalories from fat). Animals were euthanized when tumor volumes reached 1000 mm(3). Serum was collected at death and assayed for PSA, insulin, insulin-like growth factor-1 (IGF-1), IGF-1-binding protein-3 and prostaglandin E-2 (PGE-2) levels. Tumors were also assayed for PGE-2 and cyclooxygenase-2 levels, and global gene expression was analyzed using Affymetrix microarrays. Mice weights and tumor volumes were equivalent across groups at randomization. Overall, fish oil consumption was associated with improved survival relative to other dietary groups (P=0.014). On gene expression analyses, the fish oil group had decreased signal in pathways related to mitochondrial physiology and insulin synthesis/secretion. In this xenograft model, we found that consuming a diet in which fish oil was the only fat source slowed tumor growth and improved survival compared with that in mice consuming diets composed of olive oil, corn oil or animal fat. Although prior studies showed that the amount of fat is important for PCa growth, this study suggests that the type of dietary fat consumed may also be important.

  19. Origin of fecal contamination in waters from contrasted areas: stanols as Microbial Source Tracking markers.

    PubMed

    Derrien, M; Jardé, E; Gruau, G; Pourcher, A M; Gourmelon, M; Jadas-Hécart, A; Pierson Wickmann, A C

    2012-09-01

    Improving the microbiological quality of coastal and river waters relies on the development of reliable markers that are capable of determining sources of fecal pollution. Recently, a principal component analysis (PCA) method based on six stanol compounds (i.e. 5β-cholestan-3β-ol (coprostanol), 5β-cholestan-3α-ol (epicoprostanol), 24-methyl-5α-cholestan-3β-ol (campestanol), 24-ethyl-5α-cholestan-3β-ol (sitostanol), 24-ethyl-5β-cholestan-3β-ol (24-ethylcoprostanol) and 24-ethyl-5β-cholestan-3α-ol (24-ethylepicoprostanol)) was shown to be suitable for distinguishing between porcine and bovine feces. In this study, we tested if this PCA method, using the above six stanols, could be used as a tool in "Microbial Source Tracking (MST)" methods in water from areas of intensive agriculture where diffuse fecal contamination is often marked by the co-existence of human and animal sources. In particular, well-defined and stable clusters were found in PCA score plots clustering samples of "pure" human, bovine and porcine feces along with runoff and diluted waters in which the source of contamination is known. A good consistency was also observed between the source assignments made by the 6-stanol-based PCA method and the microbial markers for river waters contaminated by fecal matter of unknown origin. More generally, the tests conducted in this study argue for the addition of the PCA method based on six stanols in the MST toolbox to help identify fecal contamination sources. The data presented in this study show that this addition would improve the determination of fecal contamination sources when the contamination levels are low to moderate. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Fish Oil Slows Prostate Cancer Xenograft Growth Relative to Other Dietary Fats and is Associated with Decreased Mitochondrial and Insulin Pathway Gene Expression

    PubMed Central

    Lloyd, Jessica C.; Masko, Elizabeth M.; Wu, Chenwei; Keenan, Melissa M.; Pilla, Danielle M.; Aronson, William J.; Chi, Jen-Tsan A.; Freedland, Stephen J.

    2013-01-01

    Background Previous mouse studies suggest that decreasing dietary fat content can slow prostate cancer (PCa) growth. To our knowledge, no study has yet compared the effect of multiple different fats on PCa progression. We sought to systematically compare the effect of fish oil, olive oil, corn oil, and animal fat on PCa progression. Methods A total of 96 male SCID mice were injected with LAPC-4 human PCa cells. Two weeks following injection, mice were randomized to a fish oil, olive oil, corn oil, or animal fat-based Western diet (35% kcals from fat). Animals were euthanized when tumors reached 1,000mm3. Serum was collected at sacrifice and assayed for PSA, insulin, IGF-1, IGFBP-3, and PGE-2 levels. Tumors were also assayed for PGE-2 and COX-2 levels and global gene expression analyzed using Affymetrix microarrays. Results Mice weights and tumor volumes were equivalent across groups at randomization. Overall, fish oil consumption was associated with improved survival, relative to other dietary groups (p=0.014). On gene expression analyses, the fish oil group had decreased signal in pathways related to mitochondrial physiology and insulin synthesis/secretion. Conclusions In this xenograft model, we found that consuming a diet in which fish oil was the only fat source slowed tumor growth and improved survival, compared to mice consuming diets composed of olive oil, corn oil, or animal fat. While prior studies showed that the amount of fat is important for PCa growth, the current study suggests that type of dietary fat consumed may also be important. PMID:23877027

  1. Improved medical image fusion based on cascaded PCA and shift invariant wavelet transforms.

    PubMed

    Reena Benjamin, J; Jayasree, T

    2018-02-01

    In the medical field, radiologists need more informative and high-quality medical images to diagnose diseases. Image fusion plays a vital role in the field of biomedical image analysis. It aims to integrate the complementary information from multimodal images, producing a new composite image which is expected to be more informative for visual perception than any of the individual input images. The main objective of this paper is to improve the information, to preserve the edges and to enhance the quality of the fused image using cascaded principal component analysis (PCA) and shift invariant wavelet transforms. A novel image fusion technique based on cascaded PCA and shift invariant wavelet transforms is proposed in this paper. PCA in spatial domain extracts relevant information from the large dataset based on eigenvalue decomposition, and the wavelet transform operating in the complex domain with shift invariant properties brings out more directional and phase details of the image. The significance of maximum fusion rule applied in dual-tree complex wavelet transform domain enhances the average information and morphological details. The input images of the human brain of two different modalities (MRI and CT) are collected from whole brain atlas data distributed by Harvard University. Both MRI and CT images are fused using cascaded PCA and shift invariant wavelet transform method. The proposed method is evaluated based on three main key factors, namely structure preservation, edge preservation, contrast preservation. The experimental results and comparison with other existing fusion methods show the superior performance of the proposed image fusion framework in terms of visual and quantitative evaluations. In this paper, a complex wavelet-based image fusion has been discussed. The experimental results demonstrate that the proposed method enhances the directional features as well as fine edge details. Also, it reduces the redundant details, artifacts, distortions.

  2. eGSM: A extended Sky Model of Diffuse Radio Emission

    NASA Astrophysics Data System (ADS)

    Kim, Doyeon; Liu, Adrian; Switzer, Eric

    2018-01-01

    Both cosmic microwave background and 21cm cosmology observations must contend with astrophysical foreground contaminants in the form of diffuse radio emission. For precise cosmological measurements, these foregrounds must be accurately modeled over the entire sky Ideally, such full-sky models ought to be primarily motivated by observations. Yet in practice, these observations are limited, with data sets that are observed not only in a heterogenous fashion, but also over limited frequency ranges. Previously, the Global Sky Model (GSM) took some steps towards solving the problem of incomplete observational data by interpolating over multi-frequency maps using principal component analysis (PCA).In this poster, we present an extended version of GSM (called eGSM) that includes the following improvements: 1) better zero-level calibration 2) incorporation of non-uniform survey resolutions and sky coverage 3) the ability to quantify uncertainties in sky models 4) the ability to optimally select spectral models using Bayesian Evidence techniques.

  3. Fingerprinting Breast Cancer vs. Normal Mammary Cells by Mass Spectrometric Analysis of Volatiles

    NASA Astrophysics Data System (ADS)

    He, Jingjing; Sinues, Pablo Martinez-Lozano; Hollmén, Maija; Li, Xue; Detmar, Michael; Zenobi, Renato

    2014-06-01

    There is increasing interest in the development of noninvasive diagnostic methods for early cancer detection, to improve the survival rate and quality of life of cancer patients. Identification of volatile metabolic compounds may provide an approach for noninvasive early diagnosis of malignant diseases. Here we analyzed the volatile metabolic signature of human breast cancer cell lines versus normal human mammary cells. Volatile compounds in the headspace of conditioned culture medium were directly fingerprinted by secondary electrospray ionization-mass spectrometry. The mass spectra were subsequently treated statistically to identify discriminating features between normal vs. cancerous cell types. We were able to classify different samples by using feature selection followed by principal component analysis (PCA). Additionally, high-resolution mass spectrometry allowed us to propose their chemical structures for some of the most discriminating molecules. We conclude that cancerous cells can release a characteristic odor whose constituents may be used as disease markers.

  4. Evaluation of polygenic risk scores for predicting breast and prostate cancer risk.

    PubMed

    Machiela, Mitchell J; Chen, Chia-Yen; Chen, Constance; Chanock, Stephen J; Hunter, David J; Kraft, Peter

    2011-09-01

    Recently, polygenic risk scores (PRS) have been shown to be associated with certain complex diseases. The approach has been based on the contribution of counting multiple alleles associated with disease across independent loci, without requiring compelling evidence that every locus had already achieved definitive genome-wide statistical significance. Whether PRS assist in the prediction of risk of common cancers is unknown. We built PRS from lists of genetic markers prioritized by their association with breast cancer (BCa) or prostate cancer (PCa) in a training data set and evaluated whether these scores could improve current genetic prediction of these specific cancers in independent test samples. We used genome-wide association data on 1,145 BCa cases and 1,142 controls from the Nurses' Health Study and 1,164 PCa cases and 1,113 controls from the Prostate Lung Colorectal and Ovarian Cancer Screening Trial. Ten-fold cross validation was used to build and evaluate PRS with 10 to 60,000 independent single nucleotide polymorphisms (SNPs). For both BCa and PCa, the models that included only published risk alleles maximized the cross-validation estimate of the area under the ROC curve (0.53 for breast and 0.57 for prostate). We found no significant evidence that PRS using common variants improved risk prediction for BCa and PCa over replicated SNP scores. © 2011 Wiley-Liss, Inc.

  5. Using artificial intelligence to improve identification of nanofluid gas-liquid two-phase flow pattern in mini-channel

    NASA Astrophysics Data System (ADS)

    Xiao, Jian; Luo, Xiaoping; Feng, Zhenfei; Zhang, Jinxin

    2018-01-01

    This work combines fuzzy logic and a support vector machine (SVM) with a principal component analysis (PCA) to create an artificial-intelligence system that identifies nanofluid gas-liquid two-phase flow states in a vertical mini-channel. Flow-pattern recognition requires finding the operational details of the process and doing computer simulations and image processing can be used to automate the description of flow patterns in nanofluid gas-liquid two-phase flow. This work uses fuzzy logic and a SVM with PCA to improve the accuracy with which the flow pattern of a nanofluid gas-liquid two-phase flow is identified. To acquire images of nanofluid gas-liquid two-phase flow patterns of flow boiling, a high-speed digital camera was used to record four different types of flow-pattern images, namely annular flow, bubbly flow, churn flow, and slug flow. The textural features extracted by processing the images of nanofluid gas-liquid two-phase flow patterns are used as inputs to various identification schemes such as fuzzy logic, SVM, and SVM with PCA to identify the type of flow pattern. The results indicate that the SVM with reduced characteristics of PCA provides the best identification accuracy and requires less calculation time than the other two schemes. The data reported herein should be very useful for the design and operation of industrial applications.

  6. Online Educational Tool to Promote Bone Health in Cancer Survivors.

    PubMed

    des Bordes, Jude K A; Suarez-Almazor, Maria E; Volk, Robert J; Lu, Huifang; Edwards, Beatrice; Lopez-Olivo, Maria A

    2017-10-01

    Osteoporosis burden is significant in cancer survivors. Websites providing health information abound, but their development, quality, and source of information remain unclear. Our aim was to use a systematic and transparent approach to create an educational website on bone health, and to evaluate its potential to improve knowledge, self-management, and awareness in prostate cancer (PCa) and breast cancer (BCa) survivors. Guided by the Health Belief Model, we created a website using international standards and evaluated it in 10 PCa and 10 BCa survivors with self-administered questionnaire before, after, and 1 month after navigating the website. The mean scores on the knowledge questionnaire at baseline, postintervention and 1 month were, respectively, 5.1 (±2.0), 6.9 (±2.5), and 6.7 (±2.4), p < .008, in PCa and 3.4 (±2.7), 7.6 (±3.0), and 6.5 (±3.8), p  = .016, in BCa survivors. Acceptability ratings ranged from 60% to 100%. Participants found the website useful, helpful, and able to raise bone health awareness. Our website improved bone health knowledge in both PCa and BCa survivors. A systematic and transparent approach to the development of online educational websites could result in a tool capable of meeting the educational needs of targeted consumers. Cancer survivors could benefit from proven online educational tools.

  7. Spatiotemporal Filtering Using Principal Component Analysis and Karhunen-Loeve Expansion Approaches for Regional GPS Network Analysis

    NASA Technical Reports Server (NTRS)

    Dong, D.; Fang, P.; Bock, F.; Webb, F.; Prawirondirdjo, L.; Kedar, S.; Jamason, P.

    2006-01-01

    Spatial filtering is an effective way to improve the precision of coordinate time series for regional GPS networks by reducing so-called common mode errors, thereby providing better resolution for detecting weak or transient deformation signals. The commonly used approach to regional filtering assumes that the common mode error is spatially uniform, which is a good approximation for networks of hundreds of kilometers extent, but breaks down as the spatial extent increases. A more rigorous approach should remove the assumption of spatially uniform distribution and let the data themselves reveal the spatial distribution of the common mode error. The principal component analysis (PCA) and the Karhunen-Loeve expansion (KLE) both decompose network time series into a set of temporally varying modes and their spatial responses. Therefore they provide a mathematical framework to perform spatiotemporal filtering.We apply the combination of PCA and KLE to daily station coordinate time series of the Southern California Integrated GPS Network (SCIGN) for the period 2000 to 2004. We demonstrate that spatially and temporally correlated common mode errors are the dominant error source in daily GPS solutions. The spatial characteristics of the common mode errors are close to uniform for all east, north, and vertical components, which implies a very long wavelength source for the common mode errors, compared to the spatial extent of the GPS network in southern California. Furthermore, the common mode errors exhibit temporally nonrandom patterns.

  8. Spectral identification of melon seeds variety based on k-nearest neighbor and Fisher discriminant analysis

    NASA Astrophysics Data System (ADS)

    Li, Cuiling; Jiang, Kai; Zhao, Xueguan; Fan, Pengfei; Wang, Xiu; Liu, Chuan

    2017-10-01

    Impurity of melon seeds variety will cause reductions of melon production and economic benefits of farmers, this research aimed to adopt spectral technology combined with chemometrics methods to identify melon seeds variety. Melon seeds whose varieties were "Yi Te Bai", "Yi Te Jin", "Jing Mi NO.7", "Jing Mi NO.11" and " Yi Li Sha Bai "were used as research samples. A simple spectral system was developed to collect reflective spectral data of melon seeds, including a light source unit, a spectral data acquisition unit and a data processing unit, the detection wavelength range of this system was 200-1100nm with spectral resolution of 0.14 7.7nm. The original reflective spectral data was pre-treated with de-trend (DT), multiple scattering correction (MSC), first derivative (FD), normalization (NOR) and Savitzky-Golay (SG) convolution smoothing methods. Principal Component Analysis (PCA) method was adopted to reduce the dimensions of reflective spectral data and extract principal components. K-nearest neighbour (KNN) and Fisher discriminant analysis (FDA) methods were used to develop discriminant models of melon seeds variety based on PCA. Spectral data pretreatments improved the discriminant effects of KNN and FDA, FDA generated better discriminant results than KNN, both KNN and FDA methods produced discriminant accuracies reaching to 90.0% for validation set. Research results showed that using spectral technology in combination with KNN and FDA modelling methods to identify melon seeds variety was feasible.

  9. Ketamine added to morphine or hydromorphone patient-controlled analgesia for acute postoperative pain in adults: a systematic review and meta-analysis of randomized trials.

    PubMed

    Wang, Li; Johnston, Bradley; Kaushal, Alka; Cheng, Davy; Zhu, Fang; Martin, Janet

    2016-03-01

    To determine whether ketamine added to morphine or hydromorphone patient-controlled analgesia (PCA) provides clinically relevant reductions in postoperative pain, opioid requirements, and adverse events when compared with morphine or hydromorphone PCA in adults undergoing surgery. We systematically searched six databases up to June 2, 2015 for randomized controlled trials (RCTs) comparing ketamine plus morphine/hydromorphone PCA vs morphine/hydromorphone PCA for postoperative pain in adults. Thirty-six RCTs including 2,502 patients proved eligible, and 22 of these were at low risk of bias. The addition of ketamine to morphine/hydromorphone PCA decreased postoperative pain intensity at six to 72 hr when measured at rest (weighted mean difference [WMD] on a 10-cm visual analogue scale ranged from -0.4 to -1.3 cm) and during mobilization (WMD ranged from -0.4 to -0.5 cm). Adjunctive ketamine also significantly reduced cumulative morphine consumption at 24-72 hr by approximately 5-20 mg. Predefined subgroup analyses and meta-regression did not detect significant differences across subgroups, including a dose-response relationship. There was no significant difference in patient satisfaction scores at 24 and 48 hr. Nevertheless, the addition of ketamine to morphine/hydromorphone PCA significantly reduced postoperative nausea and vomiting (relative risk, 0.71; 95% confidence interval [CI], 0.60 to 0.85; absolute risk reduction, 8.9%; 95% CI, 4.6 to 12.2). Significant effects on other adverse events (e.g., hallucinations, vivid dreams) were not detected, though only a few studies reported on them. Adding ketamine to morphine/hydromorphone PCA provides a small improvement in postoperative analgesia while reducing opioid requirements. Adjunctive ketamine also reduces postoperative nausea and vomiting without a detected increase in other adverse effects; however, adverse events were probably underreported.

  10. Recruitment Methods and Show Rates to a Prostate Cancer Early Detection Program for High-Risk Men: A Comprehensive Analysis

    PubMed Central

    Giri, Veda N.; Coups, Elliot J.; Ruth, Karen; Goplerud, Julia; Raysor, Susan; Kim, Taylor Y.; Bagden, Loretta; Mastalski, Kathleen; Zakrzewski, Debra; Leimkuhler, Suzanne; Watkins-Bruner, Deborah

    2009-01-01

    Purpose Men with a family history (FH) of prostate cancer (PCA) and African American (AA) men are at higher risk for PCA. Recruitment and retention of these high-risk men into early detection programs has been challenging. We report a comprehensive analysis on recruitment methods, show rates, and participant factors from the Prostate Cancer Risk Assessment Program (PRAP), which is a prospective, longitudinal PCA screening study. Materials and Methods Men 35–69 years are eligible if they have a FH of PCA, are AA, or have a BRCA1/2 mutation. Recruitment methods were analyzed with respect to participant demographics and show to the first PRAP appointment using standard statistical methods Results Out of 707 men recruited, 64.9% showed to the initial PRAP appointment. More individuals were recruited via radio than from referral or other methods (χ2 = 298.13, p < .0001). Men recruited via radio were more likely to be AA (p<0.001), less educated (p=0.003), not married or partnered (p=0.007), and have no FH of PCA (p<0.001). Men recruited via referrals had higher incomes (p=0.007). Men recruited via referral were more likely to attend their initial PRAP visit than those recruited by radio or other methods (χ2 = 27.08, p < .0001). Conclusions This comprehensive analysis finds that radio leads to higher recruitment of AA men with lower socioeconomic status. However, these are the high-risk men that have lower show rates for PCA screening. Targeted motivational measures need to be studied to improve show rates for PCA risk assessment for these high-risk men. PMID:19758657

  11. A prospective cohort study of treatment decision-making for prostate cancer following participation in a multidisciplinary clinic.

    PubMed

    Hurwitz, Lauren M; Cullen, Jennifer; Elsamanoudi, Sally; Kim, Daniel J; Hudak, Jane; Colston, Maryellen; Travis, Judith; Kuo, Huai-Ching; Porter, Christopher R; Rosner, Inger L

    2016-05-01

    Patients diagnosed with prostate cancer (PCa) are presented with several treatment options of similar efficacy but varying side effects. Understanding how and why patients make their treatment decisions, as well as the effect of treatment choice on long-term outcomes, is critical to ensuring effective, patient-centered care. This study examined treatment decision-making in a racially diverse, equal-access, contemporary cohort of patients with PCa counseled on treatment options at a multidisciplinary clinic. A prospective cohort study was initiated at the Walter Reed National Military Medical Center (formerly Walter Reed Army Medical Center) in 2006. Newly diagnosed patients with PCa were enrolled before attending a multidisciplinary clinic. Patients completed surveys preclinic and postclinic to assess treatment preferences, reasons for treatment choice, and decisional regret. As of January 2014, 925 patients with PCa enrolled in this study. Surgery (54%), external radiation (20%), and active surveillance (12%) were the most common primary treatments for patients with low- and intermediate-risk PCa, whereas patients with high-risk PCa chose surgery (34%) or external radiation with neoadjuvant hormones (57%). Treatment choice differed by age at diagnosis, race, comorbidity status, and calendar year in both univariable and multivariable analyses. Patients preferred to play an active role in the decision-making process and cited doctors at the clinic as the most helpful source of treatment-related information. Almost all patients reported satisfaction with their decision. This is one of the first prospective cohort studies to examine treatment decision-making in an equal-access, multidisciplinary clinic setting. Studies of this cohort would aid in understanding and improving the PCa decision-making process. Published by Elsevier Inc.

  12. Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

    PubMed

    Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

    2017-12-01

    The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

  13. Serum markers for prostate cancer: a rational approach to the literature.

    PubMed

    Steuber, Thomas; O'Brien, Matthew Frank; Lilja, Hans

    2008-07-01

    Due to its universal applicability for early detection and prediction of cancer stage and disease recurrence, widespread implementation of serum-based prostate-specific antigen (PSA) measurements has a significant influence on current treatment strategies for men with prostate cancer (PCa). However, over-detection and the resultant over-treatment of indolent cancers have been strongly implicated to occur. Using current recommended guidelines, the PSA test suffers from both limited sensitivity and specificity to enable efficacious population-based cancer detection. Therefore, novel biomarkers are much needed to complement PSA by enhancing its diagnostic and prognostic performance. The present literature on serum markers for PCa was reviewed. PSA derivatives, molecular PSA isoforms, and novel molecular targets in blood were summarized and weighted against their potential to improve decision-making of men with PCa. Current evidence suggests that no single analyte is likely to achieve the desired level of diagnostic and prognostic accuracy for PCa. However, the combination of biomarkers with clinical and demographic data, for example, using established standard nomograms, has produced progress toward the goal of both optimal screening and risk assessment. Furthermore, potential candidate molecular markers for PCa can be derived from high-throughput technologies. Current studies demonstrate that understanding dynamic PSA changes over time may offer diagnostic and prognostic information. Bridging the gap between basic science and clinical practice represents the main goal in the near future to enable physicians to tailor risk-adjusted screening and treatment strategies for current patients with PCa.

  14. Absolute Quantitation of DNA Methylation of 28 Candidate Genes in Prostate Cancer Using Pyrosequencing

    PubMed Central

    Vasiljeviš, Nataڑa; Wu, Keqiang; Brentnall, Adam R.; Kim, Dae Cheol; Thorat, Mangesh A.; Kudahetti, Sakunthala C.; Mao, Xueying; Xue, Liyan; Yu, Yongwei; Shaw, Greg L.; Beltran, Luis; Lu, Yong-Jie; Berney, Daniel M.; Cuzick, Jack; Lorincz, Attila T.

    2011-01-01

    Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.001), while SERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2a and SFN were not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level of SFN, SLIT2 and SERPINB5 distinguished low and high Gleason score cancers, e.g. SFN and SERPINB5 together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes including CDH1 previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001). Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes like RARB, HIN1, BCL2, APC and GSTP1 is warranted for diagnostic potential and SFN, SLIT2 and SERPINB5 for prognostic potential. PMID:21694441

  15. Landslides Identification Using Airborne Laser Scanning Data Derived Topographic Terrain Attributes and Support Vector Machine Classification

    NASA Astrophysics Data System (ADS)

    Pawłuszek, Kamila; Borkowski, Andrzej

    2016-06-01

    Since the availability of high-resolution Airborne Laser Scanning (ALS) data, substantial progress in geomorphological research, especially in landslide analysis, has been carried out. First and second order derivatives of Digital Terrain Model (DTM) have become a popular and powerful tool in landslide inventory mapping. Nevertheless, an automatic landslide mapping based on sophisticated classifiers including Support Vector Machine (SVM), Artificial Neural Network or Random Forests is often computationally time consuming. The objective of this research is to deeply explore topographic information provided by ALS data and overcome computational time limitation. For this reason, an extended set of topographic features and the Principal Component Analysis (PCA) were used to reduce redundant information. The proposed novel approach was tested on a susceptible area affected by more than 50 landslides located on Rożnów Lake in Carpathian Mountains, Poland. The initial seven PCA components with 90% of the total variability in the original topographic attributes were used for SVM classification. Comparing results with landslide inventory map, the average user's accuracy (UA), producer's accuracy (PA), and overall accuracy (OA) were calculated for two models according to the classification results. Thereby, for the PCA-feature-reduced model UA, PA, and OA were found to be 72%, 76%, and 72%, respectively. Similarly, UA, PA, and OA in the non-reduced original topographic model, was 74%, 77% and 74%, respectively. Using the initial seven PCA components instead of the twenty original topographic attributes does not significantly change identification accuracy but reduce computational time.

  16. Using principal component analysis and annual seasonal trend analysis to assess karst rocky desertification in southwestern China.

    PubMed

    Zhang, Zhiming; Ouyang, Zhiyun; Xiao, Yi; Xiao, Yang; Xu, Weihua

    2017-06-01

    Increasing exploitation of karst resources is causing severe environmental degradation because of the fragility and vulnerability of karst areas. By integrating principal component analysis (PCA) with annual seasonal trend analysis (ASTA), this study assessed karst rocky desertification (KRD) within a spatial context. We first produced fractional vegetation cover (FVC) data from a moderate-resolution imaging spectroradiometer normalized difference vegetation index using a dimidiate pixel model. Then, we generated three main components of the annual FVC data using PCA. Subsequently, we generated the slope image of the annual seasonal trends of FVC using median trend analysis. Finally, we combined the three PCA components and annual seasonal trends of FVC with the incidence of KRD for each type of carbonate rock to classify KRD into one of four categories based on K-means cluster analysis: high, moderate, low, and none. The results of accuracy assessments indicated that this combination approach produced greater accuracy and more reasonable KRD mapping than the average FVC based on the vegetation coverage standard. The KRD map for 2010 indicated that the total area of KRD was 78.76 × 10 3  km 2 , which constitutes about 4.06% of the eight southwest provinces of China. The largest KRD areas were found in Yunnan province. The combined PCA and ASTA approach was demonstrated to be an easily implemented, robust, and flexible method for the mapping and assessment of KRD, which can be used to enhance regional KRD management schemes or to address assessment of other environmental issues.

  17. Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways.

    PubMed

    Ward, Ashley B; Mir, Hina; Kapur, Neeraj; Gales, Dominique N; Carriere, Patrick P; Singh, Shailesh

    2018-06-14

    Despite recent advances in diagnosis and treatment, prostate cancer (PCa) remains the leading cause of cancer-related deaths in men. Current treatments offered in the clinics are often toxic and have severe side effects. Hence, to treat and manage PCa, new agents with fewer side effects or having potential to reduce side effects of conventional therapy are needed. In this study, we show anti-cancer effects of quercetin, an abundant bioflavonoid commonly used to treat prostatitis, and defined quercetin-induced cellular and molecular changes leading to PCa cell death. Cell viability was assessed using MTT. Cell death mode, mitochondrial outer membrane potential, and oxidative stress levels were determined by flow cytometry using Annexin V-7 AAD dual staining kit, JC-1 dye, and ROS detection kit, respectively. Antibody microarray and western blot were used to delineate the molecular changes induced by quercetin. PCa cells treated with various concentrations of quercetin showed time- and dose-dependent decrease in cell viability compared to controls, without affecting normal prostate epithelial cells. Quercetin led to apoptotic and necrotic cell death in PCa cells by affecting the mitochondrial integrity and disturbing the ROS homeostasis depending upon the genetic makeup and oxidative status of the cells. LNCaP and PC-3 cells that have an oxidative cellular environment showed ROS quenching after quercetin treatment while DU-145 showed rise in ROS levels despite having a highly reductive environment. Opposing effects of quercetin were also observed on the pro-survival pathways of PCa cells. PCa cells with mutated p53 (DU-145) and increased ROS showed significant reduction in the activation of pro-survival Akt pathway while Raf/MEK were activated in response to quercetin. PC-3 cells lacking p53 and PTEN with reduced ROS levels showed significant activation of Akt and NF-κB pathway. Although some of these changes are commonly associated with oncogenic response, the cumulative effect of these alterations is PCa cell death. Our results demonstrated quercetin exerts its anti-cancer effects by modulating ROS, Akt, and NF-κB pathways. Quercetin could be used as a chemopreventive option as well as in combination with chemotherapeutic drugs to improve clinical outcomes of PCa patients.

  18. Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial.

    PubMed

    Johnston, Thomas J; Shaw, Greg L; Lamb, Alastair D; Parashar, Deepak; Greenberg, David; Xiong, Tengbin; Edwards, Alison L; Gnanapragasam, Vincent; Holding, Peter; Herbert, Phillipa; Davis, Michael; Mizielinsk, Elizabeth; Lane, J Athene; Oxley, Jon; Robinson, Mary; Mason, Malcolm; Staffurth, John; Bollina, Prasad; Catto, James; Doble, Andrew; Doherty, Alan; Gillatt, David; Kockelbergh, Roger; Kynaston, Howard; Prescott, Steve; Paul, Alan; Powell, Philip; Rosario, Derek; Rowe, Edward; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E

    2017-03-01

    Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17μg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  19. A perspective on two chemometrics tools: PCA and MCR, and introduction of a new one: Pattern recognition entropy (PRE), as applied to XPS and ToF-SIMS depth profiles of organic and inorganic materials

    NASA Astrophysics Data System (ADS)

    Chatterjee, Shiladitya; Singh, Bhupinder; Diwan, Anubhav; Lee, Zheng Rong; Engelhard, Mark H.; Terry, Jeff; Tolley, H. Dennis; Gallagher, Neal B.; Linford, Matthew R.

    2018-03-01

    X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) are much used analytical techniques that provide information about the outermost atomic and molecular layers of materials. In this work, we discuss the application of multivariate spectral techniques, including principal component analysis (PCA) and multivariate curve resolution (MCR), to the analysis of XPS and ToF-SIMS depth profiles. Multivariate analyses often provide insight into data sets that is not easily obtained in a univariate fashion. Pattern recognition entropy (PRE), which has its roots in Shannon's information theory, is also introduced. This approach is not the same as the mutual information/entropy approaches sometimes used in data processing. A discussion of the theory of each technique is presented. PCA, MCR, and PRE are applied to four different data sets obtained from: a ToF-SIMS depth profile through ca. 100 nm of plasma polymerized C3F6 on Si, a ToF-SIMS depth profile through ca. 100 nm of plasma polymerized PNIPAM (poly (N-isopropylacrylamide)) on Si, an XPS depth profile through a film of SiO2 on Si, and an XPS depth profile through a film of Ta2O5 on Ta. PCA, MCR, and PRE reveal the presence of interfaces in the films, and often indicate that the first few scans in the depth profiles are different from those that follow. PRE and backward difference PRE provide this information in a straightforward fashion. Rises in the PRE signals at interfaces suggest greater complexity to the corresponding spectra. Results from PCA, especially for the higher principal components, were sometimes difficult to understand. MCR analyses were generally more interpretable.

  20. Identification and visualization of dominant patterns and anomalies in remotely sensed vegetation phenology using a parallel tool for principal components analysis

    Treesearch

    Richard Tran Mills; Jitendra Kumar; Forrest M. Hoffman; William W. Hargrove; Joseph P. Spruce; Steven P. Norman

    2013-01-01

    We investigated the use of principal components analysis (PCA) to visualize dominant patterns and identify anomalies in a multi-year land surface phenology data set (231 m × 231 m normalized difference vegetation index (NDVI) values derived from the Moderate Resolution Imaging Spectroradiometer (MODIS)) used for detecting threats to forest health in the conterminous...

  1. Characterization of the lateral distribution of fluorescent lipid in binary-constituent lipid monolayers by principal component analysis.

    PubMed

    Sugár, István P; Zhai, Xiuhong; Boldyrev, Ivan A; Molotkovsky, Julian G; Brockman, Howard L; Brown, Rhoderick E

    2010-01-01

    Lipid lateral organization in binary-constituent monolayers consisting of fluorescent and nonfluorescent lipids has been investigated by acquiring multiple emission spectra during measurement of each force-area isotherm. The emission spectra reflect BODIPY-labeled lipid surface concentration and lateral mixing with different nonfluorescent lipid species. Using principal component analysis (PCA) each spectrum could be approximated as the linear combination of only two principal vectors. One point on a plane could be associated with each spectrum, where the coordinates of the point are the coefficients of the linear combination. Points belonging to the same lipid constituents and experimental conditions form a curve on the plane, where each point belongs to a different mole fraction. The location and shape of the curve reflects the lateral organization of the fluorescent lipid mixed with a specific nonfluorescent lipid. The method provides massive data compression that preserves and emphasizes key information pertaining to lipid distribution in different lipid monolayer phases. Collectively, the capacity of PCA for handling large spectral data sets, the nanoscale resolution afforded by the fluorescence signal, and the inherent versatility of monolayers for characterization of lipid lateral interactions enable significantly enhanced resolution of lipid lateral organizational changes induced by different lipid compositions.

  2. MetMSLine: an automated and fully integrated pipeline for rapid processing of high-resolution LC-MS metabolomic datasets.

    PubMed

    Edmands, William M B; Barupal, Dinesh K; Scalbert, Augustin

    2015-03-01

    MetMSLine represents a complete collection of functions in the R programming language as an accessible GUI for biomarker discovery in large-scale liquid-chromatography high-resolution mass spectral datasets from acquisition through to final metabolite identification forming a backend to output from any peak-picking software such as XCMS. MetMSLine automatically creates subdirectories, data tables and relevant figures at the following steps: (i) signal smoothing, normalization, filtration and noise transformation (PreProc.QC.LSC.R); (ii) PCA and automatic outlier removal (Auto.PCA.R); (iii) automatic regression, biomarker selection, hierarchical clustering and cluster ion/artefact identification (Auto.MV.Regress.R); (iv) Biomarker-MS/MS fragmentation spectra matching and fragment/neutral loss annotation (Auto.MS.MS.match.R) and (v) semi-targeted metabolite identification based on a list of theoretical masses obtained from public databases (DBAnnotate.R). All source code and suggested parameters are available in an un-encapsulated layout on http://wmbedmands.github.io/MetMSLine/. Readme files and a synthetic dataset of both X-variables (simulated LC-MS data), Y-variables (simulated continuous variables) and metabolite theoretical masses are also available on our GitHub repository. © The Author 2014. Published by Oxford University Press.

  3. MetMSLine: an automated and fully integrated pipeline for rapid processing of high-resolution LC–MS metabolomic datasets

    PubMed Central

    Edmands, William M. B.; Barupal, Dinesh K.; Scalbert, Augustin

    2015-01-01

    Summary: MetMSLine represents a complete collection of functions in the R programming language as an accessible GUI for biomarker discovery in large-scale liquid-chromatography high-resolution mass spectral datasets from acquisition through to final metabolite identification forming a backend to output from any peak-picking software such as XCMS. MetMSLine automatically creates subdirectories, data tables and relevant figures at the following steps: (i) signal smoothing, normalization, filtration and noise transformation (PreProc.QC.LSC.R); (ii) PCA and automatic outlier removal (Auto.PCA.R); (iii) automatic regression, biomarker selection, hierarchical clustering and cluster ion/artefact identification (Auto.MV.Regress.R); (iv) Biomarker—MS/MS fragmentation spectra matching and fragment/neutral loss annotation (Auto.MS.MS.match.R) and (v) semi-targeted metabolite identification based on a list of theoretical masses obtained from public databases (DBAnnotate.R). Availability and implementation: All source code and suggested parameters are available in an un-encapsulated layout on http://wmbedmands.github.io/MetMSLine/. Readme files and a synthetic dataset of both X-variables (simulated LC–MS data), Y-variables (simulated continuous variables) and metabolite theoretical masses are also available on our GitHub repository. Contact: ScalbertA@iarc.fr PMID:25348215

  4. High-Resolution Magic-Angle-Spinning NMR and Magnetic Resonance Imaging Spectroscopies Distinguish Metabolome and Structural Properties of Maize Seeds from Plants Treated with Different Fertilizers and Arbuscular mycorrhizal fungi.

    PubMed

    Mazzei, Pierluigi; Cozzolino, Vincenza; Piccolo, Alessandro

    2018-03-21

    Both high-resolution magic-angle-spinning (HRMAS) and magnetic resonance imaging (MRI) NMR spectroscopies were applied here to identify the changes of metabolome, morphology, and structural properties induced in seeds (caryopses) of maize plants grown at field level under either mineral or compost fertilization in combination with the inoculation by arbuscular mycorrhizal fungi (AMF). The metabolome of intact caryopses was examined by HRMAS-NMR, while the morphological aspects, endosperm properties and seed water distribution were investigated by MRI. Principal component analysis (PCA) was applied to evaluate 1 H CPMG (Carr-Purcel-Meiboom-Gill) HRMAS spectra as well as several MRI-derived parameters ( T 1 , T 2 , and self-diffusion coefficients) of intact maize caryopses. PCA score-plots from spectral results indicated that both seeds metabolome and structural properties depended on the specific field treatment undergone by maize plants. Our findings show that a combination of multivariate statistical analyses with advanced and nondestructive NMR techniques, such as HRMAS and MRI, enables the evaluation of the effects induced on maize caryopses by different fertilization and management practices at field level. The spectroscopic approach adopted here may become useful for the objective appraisal of the quality of seeds produced under a sustainable agriculture.

  5. Street conflict mediation to prevent youth violence: conflict characteristics and outcomes.

    PubMed

    Whitehill, Jennifer M; Webster, Daniel W; Vernick, Jon S

    2013-06-01

    Mediation of potentially violent conflicts is a key component of CeaseFire, an effective gun violence-prevention programme. To describe conflicts mediated by outreach workers (OW) in Baltimore's CeaseFire replication, examine neighbourhood variation, and measure associations between conflict risk factors and successful nonviolent resolution. A cross-sectional study was conducted using records for 158 conflicts mediated between 2007 and 2009. Involvement of youth, gangs, retaliation, weapons and other risk factors were described. Principal component analysis (PCA) was used for data-reduction purposes before the relationship between conflict risk components and mediation success was assessed with multivariate logistic regression. Most conflicts involved 2-3 individuals. Youth, persons with a history of violence, gang members and weapons were commonly present. OWs reported immediate, nonviolent resolution for 65% of mediated conflicts; an additional 23% were at least temporarily resolved without violence. PCA identified four dimensions of conflict risk: the risk-level of individuals involved; whether the incident was related to retaliation; the number of people involved; and shooting likelihood. However, these factors were not related to the OW's ability to resolve the conflict. Neighbourhoods with programme-associated reductions in homicides mediated more gang-related conflicts; neighbourhoods without programme-related homicide reductions encountered more retaliatory conflicts and more weapons.

  6. Improved method for fluorescence cytometric immunohematology testing.

    PubMed

    Roback, John D; Barclay, Sheilagh; Hillyer, Christopher D

    2004-02-01

    A method for accurate immunohematology testing by fluorescence cytometry (FC) was previously described. Nevertheless, the use of vacuum filtration to wash RBCs and a standard-flow cytometer for data acquisition hindered efforts to incorporate this method into an automated platform. A modified procedure was developed that used low-speed centrifugation of 96-well filter plates for RBC staining. Small-footprint benchtop capillary cytometers (PCA and PCA-96, Guava Technologies, Inc.) were used for data acquisition. Authentic clinical samples from hospitalized patients were tested for ABO group and the presence of D antigen (n = 749) as well as for the presence of RBC alloantibodies (n = 428). Challenging samples with mixed-field reactions and weak antibodies were included. Results were compared to those obtained by column agglutination technology (CAT), and discrepancies were resolved by standard tube methods. Detailed investigations of FC sensitivity and reproducibility were also performed. The modified FC method with the PCA determined the correct ABO group and D type for 98.7 percent of 520 samples, compared to 98.8 percent for CAT (p > 0.05). No-type-determined (NTD) rates were 1.2 percent for both methods. In testing for unexpected alloantibodies, FC determined the correct result for 98.6 percent of 215 samples, compared to 96.3 percent for CAT (p > 0.05). When samples were automatically acquired in the 96-well plate format with the PCA-96, 98.7 percent of 229 samples had correct ABO group and D type determined by FC, compared to 97.4 percent for CAT (p > 0.05). NTD rates were 0.9 and 2.6 percent, respectively. Antibody screens were accurate for 99.1 percent of 213 samples with the PCA-96, compared to 99.5 percent for CAT (p > 0.05). Further investigations demonstrated that FC with the PCA-96 was better than CAT at detecting weak anti-A (p < 0.0001) and alloantibodies. An improved method for FC immunohematology testing has been described. This assay was comparable in accuracy to standard CAT techniques, but had better sensitivity for detecting weak antibodies and was superior in detecting mixed-field reactions (p < 0.005). The FC method demonstrated excellent reproducibility. The compatibility of this assay with the PCA-96 capillary cytometer with plate-handling capabilities should simplify development of a completely automated platform.

  7. Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice.

    PubMed

    Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M

    2017-04-01

    Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice. Swiss albino mice subjected to ARS exhibited an increased immobility time in forced swim test, elevated serum corticosterone and produced oxidative stress dependent alterations in cerebral cortex and hippocampus mainly increased thiobarbituric acid reactive substances and reduced catalase (CAT), superoxide dismutase (SOD) activity. Treatment with PCA was able to prevent stress induced immobility time in forced swim test without altering locomotor activity in mice. Further, PCA treatment attenuated the elevation of serum corticosterone, lipid peroxidation and restored enzymatic antioxidants in cerebral cortex and hippocampus in ARS mice. Altogether, the experimental findings demonstrate the notion that PCA exhibit antidepressant like activity might be related, at least in part, to its capability of modulating antioxidant defense system and oxidative damage induced by ARS in cerebral cortex and hippocampus in mice and thus maintain the pro-/anti-oxidative homeostasis.

  8. The synergy between ionizing radiation and immunotherapy in the treatment of prostate cancer.

    PubMed

    Sathianathen, Niranjan J; Krishna, Suprita; Konety, Badrinath R; Griffith, Thomas S

    2017-09-01

    There has been a surge in the use of immunotherapy for genitourinary malignancies. Immunotherapy is an established treatment for metastatic renal cell carcinoma and nonmuscle invasive bladder cancer, but its potential for treating prostate cancer (PCa) remains under investigation. Despite reported survival benefits, no published Phase III PCa trials using immunotherapy only as a treatment has demonstrated direct antitumor effects by reducing prostate-specific antigen levels. Subsequently, the thought of combining immunotherapy with other treatment modalities has gained traction as a way to achieving optimal results. Based on data from other malignancies, it is hypothesized that radiotherapy and immunotherapy can act synergistically to improve outcomes. We will discuss the clinical potential of combining immune-based treatments with radiotherapy as a treatment for advanced PCa.

  9. Multiparametric prostate MRI: technical conduct, standardized report and clinical use.

    PubMed

    Manfredi, Matteo; Mele, Fabrizio; Garrou, Diletta; Walz, Jochen; Fütterer, Jurgen J; Russo, Filippo; Vassallo, Lorenzo; Villers, Arnauld; Emberton, Mark; Valerio, Massimo

    2018-02-01

    Multiparametric prostate MRI (mp-MRI) is an emerging imaging modality for diagnosis, characterization, staging, and treatment planning of prostate cancer (PCa). The technique, results reporting, and its role in clinical practice have been the subject of significant development over the last decade. Although mp-MRI is not yet routinely used in the diagnostic pathway, almost all urological guidelines have emphasized the potential role of mp-MRI in several aspects of PCa management. Moreover, new MRI sequences and scanning techniques are currently under evaluation to improve the diagnostic accuracy of mp-MRI. This review presents an overview of mp-MRI, summarizing the technical applications, the standardized reporting systems used, and their current roles in various stages of PCa management. Finally, this critical review also reports the main limitations and future perspectives of the technique.

  10. Kernel-PCA data integration with enhanced interpretability

    PubMed Central

    2014-01-01

    Background Nowadays, combining the different sources of information to improve the biological knowledge available is a challenge in bioinformatics. One of the most powerful methods for integrating heterogeneous data types are kernel-based methods. Kernel-based data integration approaches consist of two basic steps: firstly the right kernel is chosen for each data set; secondly the kernels from the different data sources are combined to give a complete representation of the available data for a given statistical task. Results We analyze the integration of data from several sources of information using kernel PCA, from the point of view of reducing dimensionality. Moreover, we improve the interpretability of kernel PCA by adding to the plot the representation of the input variables that belong to any dataset. In particular, for each input variable or linear combination of input variables, we can represent the direction of maximum growth locally, which allows us to identify those samples with higher/lower values of the variables analyzed. Conclusions The integration of different datasets and the simultaneous representation of samples and variables together give us a better understanding of biological knowledge. PMID:25032747

  11. Amelioration of cognitive, motor and endogenous defense functions with silymarin, piracetam and protocatechuic acid in the cerebral global ischemic rat model.

    PubMed

    Muley, Milind M; Thakare, Vishnu N; Patil, Rajesh R; Bafna, Pallavi A; Naik, Suresh R

    2013-07-19

    The neuroprotective activities of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) on cerebral global ischemic/reperfusion were evaluated in a rat model. A midline ventral incision was made in the throat region. The right and left common carotid arteries were located and a bilateral common carotid artery occlusion (BCCAO) was performed for 30min using atraumatic clamps followed by a 24h period of reperfusion. Neurological/behavioral functions (cognitive and motor), endogenous defense systems (lipid peroxidation, glutathione, catalase, and superoxide dismutase), reduced water content and infarct size and histopathological alterations were then studied. Silymarin and PCA treatments significantly improved cognitive, motor and endogenous defense functions, histopathological alterations, and, reduced both water content and infarct size compared to the vehicle-treated ischemic control group. Piracetam treatment improved neurological and histopathological alterations, reduced water content and infarct size, but failed to restore/prevent the impaired endogenous defense functions significantly. Silymarin showed better neuroprotection than piracetam and PCA in experimentally induced global ischemic/reperfusion and was able to facilitate mnemonic performance. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Physical vs. photolithographic patterning of plasma polymers: an investigation by ToF-SSIMS and multivariate analysis

    PubMed Central

    Mishra, Gautam; Easton, Christopher D.; McArthur, Sally L.

    2009-01-01

    Physical and photolithographic techniques are commonly used to create chemical patterns for a range of technologies including cell culture studies, bioarrays and other biomedical applications. In this paper, we describe the fabrication of chemical micropatterns from commonly used plasma polymers. Atomic force microcopy (AFM) imaging, Time-of-Flight Static Secondary Ion Mass Spectrometry (ToF-SSIMS) imaging and multivariate analysis have been employed to visualize the chemical boundaries created by these patterning techniques and assess the spatial and chemical resolution of the patterns. ToF-SSIMS analysis demonstrated that well defined chemical and spatial boundaries were obtained from photolithographic patterning, while the resolution of physical patterning via a transmission electron microscopy (TEM) grid varied depending on the properties of the plasma system including the substrate material. In general, physical masking allowed diffusion of the plasma species below the mask and bleeding of the surface chemistries. Multivariate analysis techniques including Principal Component Analysis (PCA) and Region of Interest (ROI) assessment were used to investigate the ToF-SSIMS images of a range of different plasma polymer patterns. In the most challenging case, where two strongly reacting polymers, allylamine and acrylic acid were deposited, PCA confirmed the fabrication of micropatterns with defined spatial resolution. ROI analysis allowed for the identification of an interface between the two plasma polymers for patterns fabricated using the photolithographic technique which has been previously overlooked. This study clearly demonstrated the versatility of photolithographic patterning for the production of multichemistry plasma polymer arrays and highlighted the need for complimentary characterization and analytical techniques during the fabrication plasma polymer micropatterns. PMID:19950941

  13. Fusion of shallow and deep features for classification of high-resolution remote sensing images

    NASA Astrophysics Data System (ADS)

    Gao, Lang; Tian, Tian; Sun, Xiao; Li, Hang

    2018-02-01

    Effective spectral and spatial pixel description plays a significant role for the classification of high resolution remote sensing images. Current approaches of pixel-based feature extraction are of two main kinds: one includes the widelyused principal component analysis (PCA) and gray level co-occurrence matrix (GLCM) as the representative of the shallow spectral and shape features, and the other refers to the deep learning-based methods which employ deep neural networks and have made great promotion on classification accuracy. However, the former traditional features are insufficient to depict complex distribution of high resolution images, while the deep features demand plenty of samples to train the network otherwise over fitting easily occurs if only limited samples are involved in the training. In view of the above, we propose a GLCM-based convolution neural network (CNN) approach to extract features and implement classification for high resolution remote sensing images. The employment of GLCM is able to represent the original images and eliminate redundant information and undesired noises. Meanwhile, taking shallow features as the input of deep network will contribute to a better guidance and interpretability. In consideration of the amount of samples, some strategies such as L2 regularization and dropout methods are used to prevent over-fitting. The fine-tuning strategy is also used in our study to reduce training time and further enhance the generalization performance of the network. Experiments with popular data sets such as PaviaU data validate that our proposed method leads to a performance improvement compared to individual involved approaches.

  14. An Automated Micro-Total Immunoassay System for Measuring Cancer-Associated α2,3-linked Sialyl N-Glycan-Carrying Prostate-Specific Antigen May Improve the Accuracy of Prostate Cancer Diagnosis

    PubMed Central

    Ishikawa, Tomokazu; Yoneyama, Tohru; Tobisawa, Yuki; Hatakeyama, Shingo; Kurosawa, Tatsuo; Nakamura, Kenji; Narita, Shintaro; Mitsuzuka, Koji; Duivenvoorden, Wilhelmina; Pinthus, Jehonathan H.; Hashimoto, Yasuhiro; Koie, Takuya; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara

    2017-01-01

    The low specificity of the prostate-specific antigen (PSA) for early detection of prostate cancer (PCa) is a major issue worldwide. The aim of this study to examine whether the serum PCa-associated α2,3-linked sialyl N-glycan-carrying PSA (S2,3PSA) ratio measured by automated micro-total immunoassay systems (μTAS system) can be applied as a diagnostic marker of PCa. The μTAS system can utilize affinity-based separation involving noncovalent interaction between the immunocomplex of S2,3PSA and Maackia amurensis lectin to simultaneously determine concentrations of free PSA and S2,3PSA. To validate quantitative performance, both recombinant S2,3PSA and benign-associated α2,6-linked sialyl N-glycan-carrying PSA (S2,6PSA) purified from culture supernatant of PSA cDNA transiently-transfected Chinese hamster ovary (CHO)-K1 cells were used as standard protein. Between 2007 and 2016, fifty patients with biopsy-proven PCa were pair-matched for age and PSA levels, with the same number of benign prostatic hyperplasia (BPH) patients used to validate the diagnostic performance of serum S2,3PSA ratio. A recombinant S2,3PSA- and S2,6PSA-spiked sample was clearly discriminated by μTAS system. Limit of detection of S2,3PSA was 0.05 ng/mL and coefficient variation was less than 3.1%. The area under the curve (AUC) for detection of PCa for the S2,3PSA ratio (%S2,3PSA) with cutoff value 43.85% (AUC; 0.8340) was much superior to total PSA (AUC; 0.5062) using validation sample set. Although the present results are preliminary, the newly developed μTAS platform for measuring %S2,3PSA can achieve the required assay performance specifications for use in the practical and clinical setting and may improve the accuracy of PCa diagnosis. Additional validation studies are warranted. PMID:28241428

  15. The epigenetics of prostate cancer diagnosis and prognosis: update on clinical applications.

    PubMed

    Blute, Michael L; Damaschke, Nathan A; Jarrard, David F

    2015-01-01

    There is a major deficit in our ability to detect and predict the clinical behavior of prostate cancer (PCa). Epigenetic changes are associated with PCa development and progression. This review will focus on recent results in the clinical application of diagnostic and prognostic epigenetic markers. The development of high throughput technology has seen an enormous increase in the discovery of new markers that encompass epigenetic changes including those in DNA methylation and histone modifications. Application of these findings to urine and other biofluids, but also cancer and noncancerous prostate tissue, has resulted in new biomarkers. There has been a recent commercial development of a DNA methylation-based assay for identifying PCa risk from normal biopsy tissue. Other biomarkers are currently in the validation phase and encompass combinations of multiple genes. Epigenetic changes improve the specificity and sensitivity of PCa diagnosis and have the potential to help determine clinical prognosis. Additional studies will not only provide new and better biomarker candidates, but also have the potential to inform new therapeutic strategies given the reversibility of these processes.

  16. Triptorelin for the relief of lower urinary tract symptoms in men with advanced prostate cancer: results of a prospective, observational, grouped-analysis study

    PubMed Central

    Gil, Thierry; Aoun, Fouad; Cabri, Patrick; Perrot, Valérie; van Velthoven, Roland

    2017-01-01

    Background: Lower urinary tract symptoms (LUTSs) may develop in men with prostate cancer (PCa) and can impact quality of life (QoL). Gonadotropin-releasing hormone (GnRH) agonists as androgen deprivation therapy are standard treatment for PCa, however, data are limited on their effects on LUTSs. A grouped analysis of national observational, non-interventional studies initiated in clinical practice was performed to assess the effectiveness of triptorelin in reducing moderate or severe LUTSs, measured using the International Prostate Symptom Score (IPSS) in men with advanced or metastatic PCa. Methods: Men with PCa and LUTSs scheduled to receive triptorelin (3-month or 1-month extended release formulation) were recruited into prospective, non-interventional studies at centres in Algeria, Australia, Belgium, China, Hungary, Romania and South Korea. The primary effectiveness endpoint was the proportion of patients with moderate or severe LUTSs, assessed by IPSS, after 48 weeks. Secondary endpoints included: total IPSS, QoL due to urinary symptoms (IPSS Question 8) and prostate-specific antigen (PSA) levels at 24 and 48 weeks. Results: A total of 2701 patients were recruited; 1851 patients with moderate or severe LUTSs at baseline (IPSS > 7), received triptorelin and had follow-up IPSS (efficacy population). The proportion of patients with moderate or severe LUTSs was reduced to 67.2% from baseline at week 48, following a reduction to 75.9% at week 24: the overall time effect was significant (p < 0.001). QoL due to urinary symptoms significantly improved from a mean score of 3.7 at baseline, to adjusted means of 2.5 and 2.1, at weeks 24 and 48, respectively (p < 0.001 versus baseline). Mean PSA levels were reduced from 158.8 ng/ml at baseline to 11.5 and 16.0 ng/ml at weeks 24 and 48, respectively. Conclusions: Within the limitations of these observational studies, improvements in LUTSs and QoL observed after 24 weeks and maintained at 48 weeks indicate that triptorelin-induced effects improve LUTSs in patients with advanced PCa. PMID:28747996

  17. 68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients.

    PubMed

    Zang, Shiming; Shao, Guoqiang; Cui, Can; Li, Tian-Nv; Huang, Yue; Yao, Xiaochen; Fan, Qiu; Chen, Zejun; Du, Jin; Jia, Ruipeng; Sun, Hongbin; Hua, Zichun; Tang, Jun; Wang, Feng

    2017-02-14

    We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis.

  18. Synergistic killing effect of chloroquine and androgen deprivation in LNCaP cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kaini, Ramesh R.; Hu, Chien-An A., E-mail: AHu@salud.unm.edu

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Chloroquine synergistically killed LNCaP cells during androgen deprivation treatment. Black-Right-Pointing-Pointer Chloroquine inhibited the function of autolysosomes and decreases the cytosolic ATP. Black-Right-Pointing-Pointer Chloroquine induced nuclear and DNA fragmentation in androgen deprived LNCaP. Black-Right-Pointing-Pointer Chloroquine may be an useful adjuvant in hormone ablation therapy in PCa patients. -- Abstract: Modulation of autophagy is a new paradigm in cancer therapeutics. Recently a novel function of chloroquine (CLQ) in inhibiting degradation of autophagic vesicles has been revealed, which raises the question whether CLQ can be used as an adjuvant in targeting autophagic pro-survival mechanism in prostate cancer (PCa). We previously showedmore » that autophagy played a protective role during hormone ablation therapy, in part, by consuming lipid droplets in PCa cells. In addition, blocking autophagy by genetic and pharmacological means in the presence of androgen deprivation caused cell death in PCa cells. To further investigate the importance of autophagy in PCa survival and dissect the role of CLQ in PCa death, we treated hormone responsive LNCaP cells with CLQ in combination with androgen deprivation. We observed that CLQ synergistically killed LNCaP cells during androgen deprivation in a dose- and time-dependent manner. We further confirmed that CLQ inhibited the maturation of autophagic vesicles and decreased the cytosolic ATP. Moreover, CLQ induced nuclear condensation and DNA fragmentation, a hallmark of apoptosis, in androgen deprived LNCaP cells. Taken together, our finding suggests that CLQ may be an useful adjuvant in hormone ablation therapy to improve the therapeutic efficacy.« less

  19. Endovascular Treatment of Posterior Cerebral Artery Aneurysms With Flow Diversion: Case Series and Systematic Review.

    PubMed

    Wallace, Adam N; Grossberg, Jonathan A; Almandoz, Josser E Delgado; Kamran, Mudassar; Roy, Anil K; Kayan, Yasha; Austin, Matthew J; Howard, Brian M; Moran, Christopher J; Cawley, C Michael; Cross, DeWitte T; Dion, Jacques E; Kansagra, Akash P; Osbun, Joshua W

    2018-03-08

    Flow diversion of posterior cerebral artery (PCA) aneurysms has not been widely reported, possibly owing to concerns regarding parent vessel size and branch vessel coverage. To examine the safety and effectiveness of PCA aneurysm flow diverter treatment. Retrospective review of PCA aneurysms treated with the Pipeline Embolization Device (PED; Medtronic Inc, Dublin, Ireland) at 3 neurovascular centers, including periprocedural complications and clinical and angiographic outcomes. Systematic review of the literature identified published reports of PCA aneurysms treated with flow diversion. Rates of aneurysm occlusion and complications were calculated, and outcomes of saccular and fusiform aneurysm treatments were compared. Ten PCA aneurysms in 9 patients were treated with the PED. There were 2 intraprocedural thromboembolic events (20%), including 1 symptomatic infarction and 1 delayed PED thrombosis. Eight of 10 patients returned to or improved from their baseline functional status. Complete aneurysm occlusion with parent vessel preservation was achieved in 75% (6/8) of cases at mean follow-up of 16.7 mo. Eleven of 12 (92%) major branch vessels covered by a PED remained patent. Including the present study, systematic review of 15 studies found a complete aneurysm occlusion rate of 88% (30/34) and complication rate of 26% (10/38), including 5 symptomatic ischemic strokes (13%; 5/38). Fusiform aneurysms more frequently completely occluded compared with saccular aneurysms (100% vs 70%; P = .03) but were associated with a higher complication rate (43% vs 9%; P = .06). The safety and effectiveness profile of flow diverter treatment of PCA aneurysms may be acceptable in select cases.

  20. Label free aggressive prostate cancer identification with ultraviolet photoacoustic spectral analysis (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Xu, Guan; Davis, Mandy A.; Siddiqui, Javed; Chao, Wan-yu; Tomlins, Scott A.; Wei, John T.; Wang, Xueding

    2017-03-01

    Prostate cancer (PCa) is the most commonly diagnosed cancer in American men for the past decades. PCa has a relatively low progression rate but the 5 year survival rate decreases dramatically once the cancer has metastasized. Differentiating aggressive from indolent PCa is critical for improving PCa patient outcomes and preventing metastasis and death. Prostate biopsy is the standard procedure for evaluating the presence and aggressiveness of PCa. The microarchitecture of the biopsied tissues visualized by histology process is evaluated by pathologists and assigned a Gleason score as a quantification of the aggressiveness. In our previous study, we have shown that photoacoustic spectral analysis (PASA) is capable of quantifying the Gleason scores of the H&E stained human prostate tissues. In this study, we attempt to assess the Gleason scores without any staining by taking advantage of the strong optical absorption of nucleic acid at ultraviolet wavelengths. PA signals were generated by wide field illumination at 266 nm and received by a hydrophone with a bandwidth of 0-20 MHz. DU145 prostate cancer cells at the concentrations of 0.8, 0.4, 0.05, 0.025 and 0.0125 million per cm3 simulating those in cancerous and normal tissues were first attempted. The measurements were repeated for 10 times at each concentration. A correlation of 0.86 was observed between the PA signal intensities and the cell concentrations. Human PCa tissues with Gleason score 6, 7 and 8 and normal tissues were assessed. With 11 samples, a correlation of 0.89 was found between the Gleason scores and PASA slopes.

  1. Lgr4 promotes prostate tumorigenesis through the Jmjd2a/AR signaling pathway.

    PubMed

    Zhang, Jianwei; Li, Qi; Zhang, Shaojin; Xu, Quanquan; Wang, Tianen

    2016-11-15

    Lgr4 (leucine-rich repeat domain containing G protein-coupled receptor 4) is implicated in the transcriptional regulation of multiple histone demethylases in the progression of diverse cancers, but there are few reports concerning the molecular mechanism by which Lgr4 regulates histone demethylase activation in prostate cancer (PCa) progression. As Jmjd2a is a histone demethylase, in the current study, we investigated the relationship between interaction Lgr4 with Jmjd 2a and Jmjd2a/androgen receptor (AR) signaling pathway in PCa progression. Firstly, Lgr4 was overexpressed by transfecting pcDNA3.1(+)/Lgr4 plasmids into PCa (LNCaP and PC-3) cell lines. Next, we found that Lgr4 overexpression promoted Jmjd2a mRNA expression, reduced cell apoptosis and arrested cell cycle in the S phase, these effects were reversed by Jmjd2a silencing. Moreover, Lgr4 overexpression markedly elevated AR levels and its interaction with Jmjd2a, which was tested by co-immunoprecipitation and luciferase reporter assays. Furthermore, interaction AR with PSA promoter (containing an AR response element) was obviously improved by Lgr4 overexpression, and PSA silencing reduced Lgr4-induced cell apoptosis and cell cycle arrest in PCa cells. Taken together, Lgr4 may be a novel tumor marker providing new mechanistic insights into PCa progression. Lgr4 activates Jmjd2a/AR signaling pathway to promote interaction AR with PSA promoter, causing reduction of PCa apoptosis and cell cycle arrest. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. 68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients

    PubMed Central

    Cui, Can; Li, Tian-Nv; Huang, Yue; Yao, Xiaochen; Fan, Qiu; Chen, Zejun; Du, Jin; Jia, Ruipeng; Sun, Hongbin; Hua, Zichun; Tang, Jun; Wang, Feng

    2017-01-01

    We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis. PMID:28103574

  3. Development of an Electrochemical Ceramic Membrane Filtration System for Efficient Contaminant Removal from Waters.

    PubMed

    Zheng, Junjian; Wang, Zhiwei; Ma, Jinxing; Xu, Shaoping; Wu, Zhichao

    2018-04-03

    Inability to remove low-molecular-weight anthropogenic contaminants is a critical issue in low-pressure membrane filtration processes for water treatment. In this work, a novel electrochemical ceramic membrane filtration (ECMF) system using TiO 2 @SnO 2 -Sb anode was developed for removing persistent p-chloroaniline (PCA). Results showed that the ECMF system achieved efficient removal of PCA from contaminated waters. At a charging voltage of 3 V, the PCA removal rate of TiO 2 @SnO 2 -Sb ECMF system under flow-through mode was 2.4 times that of flow-by mode. The energy consumption for 50% of PCA removal for TiO 2 @SnO 2 -Sb ECMF at 3 V under flow-through mode was 0.38 Wh/L, much lower than that of flow-by operation (1.5 Wh/L), which was attributed to the improved utilization of the surface adsorbed HO· and dissociated HO· driven by the enhanced mass transfer of PCA toward the anode surface. Benefiting from the increased production of reactive oxygen species such as O 2 •- , H 2 O 2 , and HO· arising from excitation of anatase TiO 2 , TiO 2 @SnO 2 -Sb ECMF exhibited a superior electrocatalytic activity to the SnO 2 -Sb ECMF system. The degradation pathways of PCA initiated by OH· attack were further proposed, with the biodegradable short-chain carboxylic acids (mainly formic, acetic, and oxalic acids) identified as the dominant oxidized products. These results highlight the potential of the ECMF system for cost-effective water purification.

  4. Innovations in diagnostic imaging of localized prostate cancer.

    PubMed

    Pummer, Karl; Rieken, Malte; Augustin, Herbert; Gutschi, Thomas; Shariat, Shahrokh F

    2014-08-01

    In recent years, various imaging modalities have been developed to improve diagnosis, staging, and localization of early-stage prostate cancer (PCa). A MEDLINE literature search of the time frame between 01/2007 and 06/2013 was performed on imaging of localized PCa. Conventional transrectal ultrasound (TRUS) is mainly used to guide prostate biopsy. Contrast-enhanced ultrasound is based on the assumption that PCa tissue is hypervascularized and might be better identified after intravenous injection of a microbubble contrast agent. However, results on its additional value for cancer detection are controversial. Computer-based analysis of the transrectal ultrasound signal (C-TRUS) appears to detect cancer in a high rate of patients with previous biopsies. Real-time elastography seems to have higher sensitivity, specificity, and positive predictive value than conventional TRUS. However, the method still awaits prospective validation. The same is true for prostate histoscanning, an ultrasound-based method for tissue characterization. Currently, multiparametric MRI provides improved tissue visualization of the prostate, which may be helpful in the diagnosis and targeting of prostate lesions. However, most published series are small and suffer from variations in indication, methodology, quality, interpretation, and reporting. Among ultrasound-based techniques, real-time elastography and C-TRUS seem the most promising techniques. Multiparametric MRI appears to have advantages over conventional T2-weighted MRI in the detection of PCa. Despite these promising results, currently, no recommendation for the routine use of these novel imaging techniques can be made. Prospective studies defining the value of various imaging modalities are urgently needed.

  5. Investigation of gastric cancers in nude mice using X-ray in-line phase contrast imaging

    PubMed Central

    2014-01-01

    Background This paper is to report the new imaging of gastric cancers without the use of imaging agents. Both gastric normal regions and gastric cancer regions can be distinguished by using the principal component analysis (PCA) based on the gray level co-occurrence matrix (GLCM). Methods Human gastric cancer BGC823 cells were implanted into the stomachs of nude mice. Then, 3, 5, 7, 9 or 11 days after cancer cells implantation, the nude mice were sacrificed and their stomachs were removed. X-ray in-line phase contrast imaging (XILPCI), an X-ray phase contrast imaging method, has greater soft tissue contrast than traditional absorption radiography and generates higher-resolution images. The gastric specimens were imaged by an XILPCIs’ charge coupled device (CCD) of 9 μm image resolution. The PCA of the projective images’ region of interests (ROIs) based on GLCM were extracted to discriminate gastric normal regions and gastric cancer regions. Different stages of gastric cancers were classified by using support vector machines (SVMs). Results The X-ray in-line phase contrast images of nude mice gastric specimens clearly show the gastric architectures and the details of the early gastric cancers. The phase contrast computed tomography (CT) images of nude mice gastric cancer specimens are better than the traditional absorption CT images without the use of imaging agents. The results of the PCA of the texture parameters based on GLCM of normal regions is (F1 + F2) > 8.5, but those of cancer regions is (F1 + F2) < 8.5. The classification accuracy is 83.3% that classifying gastric specimens into different stages using SVMs. Conclusions This is a very preliminary feasibility study. With further researches, XILPCI could become a noninvasive method for future the early detection of gastric cancers or medical researches. PMID:25060352

  6. Use of electrospray ionization ion-trap tandem mass spectrometry and principal component analysis to directly distinguish monosaccharides.

    PubMed

    Xia, Bing; Zhou, Yan; Liu, Xin; Xiao, Juan; Liu, Qing; Gu, Yucheng; Ding, Lisheng

    2012-06-15

    Carbohydrates are good source of drugs and play important roles in metabolism processes and cellular interactions in organisms. Distinguishing monosaccharide isomers in saccharide derivates is an important and elementary work in investigating saccharides. It is important to develop a fast, simple and direct method for this purpose, which is described in this study. Stock solutions of monosaccharide with a concentration of 400 μM and sodium chloride at a concentration of 10 μM were made in water/methanol (50:50, v/v). The samples were subjected to electrospray ionization ion-trap tandem mass spectrometry (ESI-MS) and the detected [2M + Na - H(2)O](+) ions were further investigated by tandem mass spectrometry (MS/MS), followed by applying principal component analysis (PCA) on the obtained MS/MS data sets. The MS/MS spectra of the [2M + Na - H(2)O](+) ions at m/z 365 for hexoses and m/z 305 for pentoses yielded unambiguous fragment patterns, while rhamnose can be directly identified by its ESI-MS [M + Na](+) ion at m/z 187. PCA showed clustering of MS/MS data of identical monosaccharide samples obtained from different experiments. By using this method, the monosaccharide in daucosterol hydrolysate was successfully identified. A new strategy was developed for differentiation of the monosaccharides using ESI-MS/MS and PCA. In MS/MS spectra, the [2M + Na - H(2)O](+) ions yielded unambiguous distinction. PCA of the archived MS/MS data sets was applied to demonstrate the spatial resolution of the studied samples. This method presented a simple and reliable way for distinguishing monosaccharides by ESI-MS/MS. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Effect of intra-fraction motion on the accumulated dose for free-breathing MR-guided stereotactic body radiation therapy of renal-cell carcinoma

    NASA Astrophysics Data System (ADS)

    Stemkens, Bjorn; Glitzner, Markus; Kontaxis, Charis; de Senneville, Baudouin Denis; Prins, Fieke M.; Crijns, Sjoerd P. M.; Kerkmeijer, Linda G. W.; Lagendijk, Jan J. W.; van den Berg, Cornelis A. T.; Tijssen, Rob H. N.

    2017-09-01

    Stereotactic body radiation therapy (SBRT) has shown great promise in increasing local control rates for renal-cell carcinoma (RCC). Characterized by steep dose gradients and high fraction doses, these hypo-fractionated treatments are, however, prone to dosimetric errors as a result of variations in intra-fraction respiratory-induced motion, such as drifts and amplitude alterations. This may lead to significant variations in the deposited dose. This study aims to develop a method for calculating the accumulated dose for MRI-guided SBRT of RCC in the presence of intra-fraction respiratory variations and determine the effect of such variations on the deposited dose. For this, RCC SBRT treatments were simulated while the underlying anatomy was moving, based on motion information from three motion models with increasing complexity: (1) STATIC, in which static anatomy was assumed, (2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, and (3) PCA, a method that generates 3D volumes with sufficient spatio-temporal resolution to capture respiration and intra-fraction variations. Five RCC patients and two volunteers were included and treatments delivery was simulated, using motion derived from subject-specific MR imaging. Motion was most accurately estimated using the PCA method with root-mean-squared errors of 2.7, 2.4, 1.0 mm for STATIC, AVG-RESP and PCA, respectively. The heterogeneous patient group demonstrated relatively large dosimetric differences between the STATIC and AVG-RESP, and the PCA reconstructed dose maps, with hotspots up to 40% of the D99 and an underdosed GTV in three out of the five patients. This shows the potential importance of including intra-fraction motion variations in dose calculations.

  8. Pilot study for supervised target detection applied to spatially registered multiparametric MRI in order to non-invasively score prostate cancer.

    PubMed

    Mayer, Rulon; Simone, Charles B; Skinner, William; Turkbey, Baris; Choykey, Peter

    2018-03-01

    Gleason Score (GS) is a validated predictor of prostate cancer (PCa) disease progression and outcomes. GS from invasive needle biopsies suffers from significant inter-observer variability and possible sampling error, leading to underestimating disease severity ("underscoring") and can result in possible complications. A robust non-invasive image-based approach is, therefore, needed. Use spatially registered multi-parametric MRI (MP-MRI), signatures, and supervised target detection algorithms (STDA) to non-invasively GS PCa at the voxel level. This study retrospectively analyzed 26 MP-MRI from The Cancer Imaging Archive. The MP-MRI (T2, Diffusion Weighted, Dynamic Contrast Enhanced) were spatially registered to each other, combined into stacks, and stitched together to form hypercubes. Multi-parametric (or multi-spectral) signatures derived from a training set of registered MP-MRI were transformed using statistics-based Whitening-Dewhitening (WD). Transformed signatures were inserted into STDA (having conical decision surfaces) applied to registered MP-MRI determined the tumor GS. The MRI-derived GS was quantitatively compared to the pathologist's assessment of the histology of sectioned whole mount prostates from patients who underwent radical prostatectomy. In addition, a meta-analysis of 17 studies of needle biopsy determined GS with confusion matrices and was compared to the MRI-determined GS. STDA and histology determined GS are highly correlated (R = 0.86, p < 0.02). STDA more accurately determined GS and reduced GS underscoring of PCa relative to needle biopsy as summarized by meta-analysis (p < 0.05). This pilot study found registered MP-MRI, STDA, and WD transforms of signatures shows promise in non-invasively GS PCa and reducing underscoring with high spatial resolution. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Detecting phase separation of freeze-dried binary amorphous systems using pair-wise distribution function and multivariate data analysis.

    PubMed

    Chieng, Norman; Trnka, Hjalte; Boetker, Johan; Pikal, Michael; Rantanen, Jukka; Grohganz, Holger

    2013-09-15

    The purpose of this study is to investigate the use of multivariate data analysis for powder X-ray diffraction-pair-wise distribution function (PXRD-PDF) data to detect phase separation in freeze-dried binary amorphous systems. Polymer-polymer and polymer-sugar binary systems at various ratios were freeze-dried. All samples were analyzed by PXRD, transformed to PDF and analyzed by principal component analysis (PCA). These results were validated by differential scanning calorimetry (DSC) through characterization of glass transition of the maximally freeze-concentrate solute (Tg'). Analysis of PXRD-PDF data using PCA provides a more clear 'miscible' or 'phase separated' interpretation through the distribution pattern of samples on a score plot presentation compared to residual plot method. In a phase separated system, samples were found to be evenly distributed around the theoretical PDF profile. For systems that were miscible, a clear deviation of samples away from the theoretical PDF profile was observed. Moreover, PCA analysis allows simultaneous analysis of replicate samples. Comparatively, the phase behavior analysis from PXRD-PDF-PCA method was in agreement with the DSC results. Overall, the combined PXRD-PDF-PCA approach improves the clarity of the PXRD-PDF results and can be used as an alternative explorative data analytical tool in detecting phase separation in freeze-dried binary amorphous systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. An improved geographically weighted regression model for PM2.5 concentration estimation in large areas

    NASA Astrophysics Data System (ADS)

    Zhai, Liang; Li, Shuang; Zou, Bin; Sang, Huiyong; Fang, Xin; Xu, Shan

    2018-05-01

    Considering the spatial non-stationary contributions of environment variables to PM2.5 variations, the geographically weighted regression (GWR) modeling method has been using to estimate PM2.5 concentrations widely. However, most of the GWR models in reported studies so far were established based on the screened predictors through pretreatment correlation analysis, and this process might cause the omissions of factors really driving PM2.5 variations. This study therefore developed a best subsets regression (BSR) enhanced principal component analysis-GWR (PCA-GWR) modeling approach to estimate PM2.5 concentration by fully considering all the potential variables' contributions simultaneously. The performance comparison experiment between PCA-GWR and regular GWR was conducted in the Beijing-Tianjin-Hebei (BTH) region over a one-year-period. Results indicated that the PCA-GWR modeling outperforms the regular GWR modeling with obvious higher model fitting- and cross-validation based adjusted R2 and lower RMSE. Meanwhile, the distribution map of PM2.5 concentration from PCA-GWR modeling also clearly depicts more spatial variation details in contrast to the one from regular GWR modeling. It can be concluded that the BSR enhanced PCA-GWR modeling could be a reliable way for effective air pollution concentration estimation in the coming future by involving all the potential predictor variables' contributions to PM2.5 variations.

  11. Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer.

    PubMed

    Barrabés, Sílvia; Llop, Esther; Ferrer-Batallé, Montserrat; Ramírez, Manel; Aleixandre, Rosa N; Perry, Antoinette S; de Llorens, Rafael; Peracaula, Rosa

    2017-07-01

    The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. An electrochemiluminescence-supramolecular approach to sarcosine detection for early diagnosis of prostate cancer.

    PubMed

    Valenti, Giovanni; Rampazzo, Enrico; Biavardi, Elisa; Villani, Elena; Fracasso, Giulio; Marcaccio, Massimo; Bertani, Federico; Ramarli, Dunia; Dalcanale, Enrico; Paolucci, Francesco; Prodi, Luca

    2015-01-01

    Monitoring Prostate Cancer (PCa) biomarkers is an efficient way to diagnosis this disease early, since it improves the therapeutic success rate and suppresses PCa patient mortality: for this reason a powerful analytical technique such as electrochemiluminescence (ECL) is already used for this application, but its widespread usability is still hampered by the high cost of commercial ECL equipment. We describe an innovative approach for the selective and sensitive detection of the PCa biomarker sarcosine, obtained by a synergistic ECL-supramolecular approach, in which the free base form of sarcosine acts as co-reagent in a Ru(bpy)3(2+)-ECL process. We used magnetic micro-beads decorated with a supramolecular tetraphosphonate cavitand (Tiiii) for the selective capture of sarcosine hydrochloride in a complex matrix like urine. Sarcosine determination was then obtained with ECL measurements thanks to the complexation properties of Tiiii, with a protocol involving simple pH changes - to drive the capture-release process of sarcosine from the receptor - and magnetic micro-bead technology. With this approach we were able to measure sarcosine in the μM to mM window, a concentration range that encompasses the diagnostic urinary value of sarcosine in healthy subjects and PCa patients, respectively. These results indicate how this ECL-supramolecular approach is extremely promising for the detection of sarcosine and for PCa diagnosis and monitoring, and for the development of portable and more affordable devices.

  13. Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia.

    PubMed

    Morote, Juan; Rigau, Marina; Garcia, Marta; Mir, Carmen; Ballesteros, Carlos; Planas, Jacques; Raventós, Carles X; Placer, José; de Torres, Inés M; Reventós, Jaume; Doll, Andreas

    2010-12-01

    An ideal marker for the early detection of prostate cancer (PCa) should also differentiate between men with isolated high grade prostatic intraepithelial neoplasia (HGPIN) and those with PCa. Prostate Cancer Gene 3 (PCA3) is a highly specific PCa gene and its score, in relation to the PSA gene in post-prostate massage urine (PMU-PCA3), seems to be useful in ruling out PCa, especially after a negative prostate biopsy. Because PCA3 is also expressed in the HGPIN lesion, the aim of this study was to determine the efficacy of PMU-PCA3 scores for ruling out PCa in men with previous HGPIN. The PMU-PCA3 score was assessed by quantitative PCR (multiplex research assay) in 244 men subjected to prostate biopsy: 64 men with an isolated HGPIN (no cancer detected after two or more repeated biopsies), 83 men with PCa and 97 men with benign pathology findings (BP: no PCa, HGPIN or ASAP). The median PMU-PCA3 score was 1.56 in men with BP, 2.01 in men with HGPIN (p = 0.128) and 9.06 in men with PCa (p = 0.008). The AUC in the ROC analysis was 0.705 in the subset of men with BP and PCa, while it decreased to 0.629 when only men with isolated HGPIN and PCa were included in the analysis. Fixing the sensitivity of the PMU-PCA3 score at 90%, its specificity was 79% in men with BP and 69% in men with isolated HGPIN. The efficacy of the PMU-PCA3 score to rule out PCa in men with HGPIN is lower than in men with BP.

  14. Risk Stratification Among Men With Prostate Imaging Reporting and Data System Version 2 Category 3 Transition Zone Lesions: Is Biopsy Always Necessary?

    PubMed Central

    Felker, Ely R.; Raman, Steven S.; Margolis, Daniel J.; Lu, David S. K.; Shaheen, Nicholas; Natarajan, Shyam; Sharma, Devi; Huang, Jiaoti; Dorey, Fred; Marks, Leonard S.

    2017-01-01

    OBJECTIVE The objective of our study was to determine the clinical and MRI characteristics of clinically significant prostate cancer (PCA) (Gleason score ≥ 3 + 4) in men with Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 3 transition zone (TZ) lesions. MATERIALS AND METHODS From 2014 to 2016, 865 men underwent prostate MRI and MRI/ultrasound (US) fusion biopsy (FB). A subset of 90 FB-naïve men with 96 PI-RADSv2 category 3 TZ lesions was identified. Patients were imaged at 3 T using a body coil. Images were assigned a PI-RADSv2 category by an experienced radiologist. Using clinical data and imaging features, we performed univariate and multivariate analyses to identify predictors of clinically significant PCA. RESULTS The mean patient age was 66 years, and the mean prostate-specific antigen density (PSAD) was 0.13 ng/mL2. PCA was detected in 34 of 96 (35%) lesions, 14 of which (15%) harbored clinically significant PCA. In univariate analysis, DWI score, prostate volume, and PSAD were significant predictors (p < 0.05) of clinically significant PCA with a suggested significance for apparent diffusion coefficient (ADC) and prostate-specific antigen value (p < 0.10). On multivariate analysis, PSAD and lesion ADC were the most important covariates. The combination of both PSAD of 0.15 ng/mL2 or greater and an ADC value of less than 1000 mm2/s yielded an AUC of 0.91 for clinically significant PCA (p < 0.001). If FB had been restricted to these criteria, only 10 of 90 men would have undergone biopsy, resulting in diagnosis of clinically significant PCA in 60% with eight men (9%) misdiagnosed (false-negative). CONCLUSION The yield of FB in men with PI-RADSv2 category 3 TZ lesions for clinically significant PCA is 15% but significantly improves to 60% (AUC > 0.9) among men with PSAD of 0.15 ng/mL2 or greater and lesion ADC value of less than 1000 mm2/s. PMID:28858541

  15. Cognitive Impacts of Estrogen Treatment in Androgen-Deprived Males: What Needs to be Resolved.

    PubMed

    Wibowo, Erik

    2017-01-01

    Many prostate cancer (PCa) patients are on androgen deprivation therapy (ADT) as part of their cancer treatments but ADT may lead to cognitive impairments. ADT depletes men of both androgen and estrogen. Whether estradiol supplementation can improve cognitive impairments in patients on ADT is understudied. To summarize data on the effects of estradiol treatment on cognitive function of androgen-deprived genetic male populations (PCa patients and male-to-female transsexuals) and castrated male animals. Publications were identified by a literature search on PubMed and Google Scholar. While some studies showed that estradiol improves cognitive function (most notably, spatial ability) for castrated rats, what remains uninvestigated are: 1) whether estradiol can improve cognition after long-term androgen deprivation, 2) how estradiol affects memory retention, and 3) how early vs. delayed estradiol treatment after castration influences cognition. For androgendeprived genetic males, estradiol treatment may improve some cognitive functions (e.g., verbal and visual memory), but the findings are not consistent due to large variability in the study design between studies. Future studies are required to determine the best estradiol treatment protocol to maximize cognitive benefits for androgen-deprived genetic males. Tests that assess comparable cognitive domains in human and rodents are needed. What particularly under-investigated is how the effects of estradiol on cognitive ability intersect with other parameters; sleep, depression and physical fatigue. Such studies have clinical implications to improve the quality of life for both PCa patients on ADT as well as for male-to-female transsexuals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Clinical significance of miRNA host gene promoter methylation in prostate cancer.

    PubMed

    Daniunaite, Kristina; Dubikaityte, Monika; Gibas, Povilas; Bakavicius, Arnas; Rimantas Lazutka, Juozas; Ulys, Albertas; Jankevicius, Feliksas; Jarmalaite, Sonata

    2017-07-01

    Only a part of prostate cancer (PCa) patients has aggressive malignancy requiring adjuvant treatment after radical prostatectomy (RP). Biomarkers capable to predict biochemical PCa recurrence (BCR) after RP would significantly improve preoperative risk stratification and treatment decisions. MicroRNA (miRNA) deregulation has recently emerged as an important phenomenon in tumor development and progression, however, the mechanisms remain largely unstudied. In the present study, based on microarray profiling of DNA methylation in 9 pairs of PCa and noncancerous prostate tissues (NPT), host genes of miR-155-5p, miR-152-3p, miR-137, miR-31-5p, and miR-642a, -b were analyzed for promoter methylation in 129 PCa, 35 NPT, and 17 benign prostatic hyperplasia samples (BPH) and compared to the expression of mature miRNAs and their selected targets (DNMT1, KDM1A, and KDM5B). The Cancer Genome Atlas dataset was utilized for validation. Methylation of mir-155, mir-152, and mir-137 host genes was PCa-specific, and downregulation of miR-155-5p significantly correlated with promoter methylation. Higher KDM5B expression was observed in samples with methylated mir-155 or mir-137 promoters, whereas upregulation of KDM1A and DNMT1 was associated with mir-155 and mir-152 methylation status, respectively. Promoter methylation of mir-155, mir-152, and mir-31 was predictive of BCR-free survival in various Cox models and increased the prognostic value of clinicopathologic factors. In conclusion, methylated mir-155, mir-152, mir-137, and mir-31 host genes are promising diagnostic and/or prognostic biomarkers of PCa. Methylation status of particular miRNA host genes as independent variables or in combinations might assist physicians in identifying poor prognosis PCa patients preoperatively. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Prospective randomized trial comparing magnetic resonance imaging (MRI)-guided in-bore biopsy to MRI-ultrasound fusion and transrectal ultrasound-guided prostate biopsy in patients with prior negative biopsies.

    PubMed

    Arsov, Christian; Rabenalt, Robert; Blondin, Dirk; Quentin, Michael; Hiester, Andreas; Godehardt, Erhard; Gabbert, Helmut E; Becker, Nikolaus; Antoch, Gerald; Albers, Peter; Schimmöller, Lars

    2015-10-01

    A significant proportion of prostate cancers (PCas) are missed by conventional transrectal ultrasound-guided biopsy (TRUS-GB). It remains unclear whether the combined approach using targeted magnetic resonance imaging (MRI)-ultrasound fusion-guided biopsy (FUS-GB) and systematic TRUS-GB is superior to targeted MRI-guided in-bore biopsy (IB-GB) for PCa detection. To compare PCa detection between IB-GB alone and FUS-GB + TRUS-GB in patients with at least one negative TRUS-GB and prostate-specific antigen ≥4 ng/ml. Patients were prospectively randomized after multiparametric prostate MRI to IB-GB (arm A) or FUS-GB + TRUS-GB (arm B) from November 2011 to July 2014. The study was powered at 80% to demonstrate an overall PCa detection rate of ≥60% in arm B compared to 40% in arm A. Secondary endpoints were the distribution of highest Gleason scores, the rate of detection of significant PCa (Gleason ≥7), the number of biopsy cores to detect one (significant) PCa, the positivity rate for biopsy cores, and tumor involvement per biopsy core. The study was halted after interim analysis because the primary endpoint was not met. The trial enrolled 267 patients, of whom 210 were analyzed (106 randomized to arm A and 104 to arm B). PCa detection was 37% in arm A and 39% in arm B (95% confidence interval for difference, -16% to 11%; p=0.7). Detection rates for significant PCa (29% vs 32%; p=0.7) and the highest percentage tumor involvement per biopsy core (48% vs 42%; p=0.4) were similar between the arms. The mean number of cores was 5.6 versus 17 (p<0.001). A limitation is the limited number of patients because of early cessation of accrual. This trial failed to identify an important improvement in detection rate for the combined biopsy approach over MRI-targeted biopsy alone. A prospective comparison between MRI-targeted biopsy alone and systematic TRUS-GB is justified. Our randomized study showed similar prostate cancer detection rates between targeted prostate biopsy guided by magnetic resonance imaging and the combination of targeted biopsy and systematic transrectal ultrasound-guided prostate biopsy. An important improvement in detection rates using the combined biopsy approach can be excluded. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  18. D Object Classification Based on Thermal and Visible Imagery in Urban Area

    NASA Astrophysics Data System (ADS)

    Hasani, H.; Samadzadegan, F.

    2015-12-01

    The spatial distribution of land cover in the urban area especially 3D objects (buildings and trees) is a fundamental dataset for urban planning, ecological research, disaster management, etc. According to recent advances in sensor technologies, several types of remotely sensed data are available from the same area. Data fusion has been widely investigated for integrating different source of data in classification of urban area. Thermal infrared imagery (TIR) contains information on emitted radiation and has unique radiometric properties. However, due to coarse spatial resolution of thermal data, its application has been restricted in urban areas. On the other hand, visible image (VIS) has high spatial resolution and information in visible spectrum. Consequently, there is a complementary relation between thermal and visible imagery in classification of urban area. This paper evaluates the potential of aerial thermal hyperspectral and visible imagery fusion in classification of urban area. In the pre-processing step, thermal imagery is resampled to the spatial resolution of visible image. Then feature level fusion is applied to construct hybrid feature space include visible bands, thermal hyperspectral bands, spatial and texture features and moreover Principle Component Analysis (PCA) transformation is applied to extract PCs. Due to high dimensionality of feature space, dimension reduction method is performed. Finally, Support Vector Machines (SVMs) classify the reduced hybrid feature space. The obtained results show using thermal imagery along with visible imagery, improved the classification accuracy up to 8% respect to visible image classification.

  19. Impact of a Structured Reporting Template on Adherence to Prostate Imaging Reporting and Data System Version 2 and on the Diagnostic Performance of Prostate MRI for Clinically Significant Prostate Cancer.

    PubMed

    Shaish, Hiram; Feltus, Whitney; Steinman, Jonathan; Hecht, Elizabeth; Wenske, Sven; Ahmed, Firas

    2018-05-01

    The aim of this study was to assess the impact of a structured reporting template on adherence to the Prostate Imaging Reporting and Data System (PI-RADS) version 2 lexicon and on the diagnostic performance of prostate MRI to detect clinically significant prostate cancer (CS-PCa). An imaging database was searched for consecutive patients who underwent prostate MRI followed by MRI-ultrasound fusion biopsy from October 2015 through October 2017. The initial MRI reporting template used included only subheadings. In July 2016, the template was changed to a standardized PI-RADS-compliant structured template incorporating dropdown menus. Lesion, patient characteristics, pathology, and adherence to the PI-RADS lexicon were extracted from MRI reports and patient charts. Diagnostic performance of prostate MRI to detect CS-PCa using combined ultrasound-MRI fusion and systematic biopsy as a reference standard was assessed. Three hundred twenty-four lesions in 202 patients (average age, 67 years; average prostate-specific antigen level, 5.9 ng/mL) were analyzed, including 217 MRI peripheral zone (PZ) lesions, 84 MRI non-PZ lesions, and 23 additional PZ lesions found on systematic biopsy but missed on MRI. Thirty-three percent (106 of 324) were CS-PCa. Adherence to the PI-RADS lexicon improved from 32.9% (50 of 152) to 88.4% (152 of 172) (P < .0001) after introduction of the structured template. The sensitivity of prostate MRI for CS-PCa in the PZ increased from 53% to 70% (P = .011). There was no significant change in specificity (60% versus 55%, P = .458). A structured template with dropdown menus incorporating the PI-RADS lexicon and classification rules improves adherence to PI-RADS and may increase the diagnostic performance of prostate MRI for CS-PCa. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  20. Why and Where do We Miss Significant Prostate Cancer with Multi-parametric Magnetic Resonance Imaging followed by Magnetic Resonance-guided and Transrectal Ultrasound-guided Biopsy in Biopsy-naïve Men?

    PubMed

    Schouten, Martijn G; van der Leest, Marloes; Pokorny, Morgan; Hoogenboom, Martijn; Barentsz, Jelle O; Thompson, Les C; Fütterer, Jurgen J

    2017-06-01

    Knowledge of significant prostate (sPCa) locations being missed with magnetic resonance (MR)- and transrectal ultrasound (TRUS)-guided biopsy (Bx) may help to improve these techniques. To identify the location of sPCa lesions being missed with MR- and TRUS-Bx. In a referral center, 223 consecutive Bx-naive men with elevated prostate specific antigen level and/or abnormal digital rectal examination were included. Histopathologically-proven cancer locations, Gleason score, and tumor length were determined. All patients underwent multi-parametric MRI and 12-core systematic TRUS-Bx. MR-Bx was performed in all patients with suspicion of PCa on multi-parametric MRI (n=142). Cancer locations were compared between MR- and TRUS-Bx. Proportions were expressed as percentages, and the corresponding 95% confidence intervals were calculated. In total, 191 lesions were found in 108 patients with sPCa. From these lesion 74% (141/191) were defined as sPCa on either MR- or TRUS-Bx. MR-Bx detected 74% (105/141) of these lesions and 61% (86/141) with TRUS-Bx. TRUS-Bx detected more lesions compared with MR-Bx (140 vs 109). However, these lesions were often low risk (39%). Significant lesions missed with MR-Bx most often had involvement of dorsolateral (58%) and apical (37%) segments and missed segments with TRUS-Bx were located anteriorly (79%), anterior midprostate (50%), and anterior apex (23%). Both techniques have difficulties in detecting apical lesions. MR-Bx most often missed cancer with involvement of the dorsolateral part (58%) and TRUS-Bx with involvement of the anterior part (79%). Both biopsy techniques miss cancer in specific locations within the prostate. Identification of these lesions may help to improve these techniques. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  1. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, J; Gong, G; Cui, Y

    Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitativemore » Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.« less

  2. Downscaling of inundation extents

    NASA Astrophysics Data System (ADS)

    Aires, Filipe; Prigent, Catherine; Papa, Fabrice

    2014-05-01

    The Global Inundation Extent from Multi-Satellite (GIEMS) provides multi-year monthly variations of the global surface water extent at about 25 kmx25 km resolution, from 1993 to 2007. It is derived from multiple satellite observations. Its spatial resolution is usually compatible with climate model outputs and with global land surface model grids but is clearly not adequate for local applications that require the characterization of small individual water bodies. There is today a strong demand for high-resolution inundation extent datasets, for a large variety of applications such as water management, regional hydrological modeling, or for the analysis of mosquitos-related diseases. This paper present three approaches to do downscale GIEMS: The first one is based on a image-processing technique using neighborhood constraints. The third approach uses a PCA representation to perform an algebraic inversion. The PCA-representation is also very convenient to perform temporal and spatial interpolation of complexe inundation fields. The third downscaling method uses topography information from Hydroshed Digital Elevation Model (DEM). Information such as the elevation, distance to river and flow accumulation are used to define a ``flood ability index'' that is used by the downscaling. Three basins will be considered for illustrative purposes: Amazon, Niger and Mekong. Aires, F., F. Papa, C. Prigent, J.-F. Cretaux and M. Berge-Nguyen, Characterization and downscaling of the inundation extent over the Inner Niger delta using a multi-wavelength retrievals and Modis data, J. of Hydrometeorology, in press, 2014. Aires, F., F. Papa and C. Prigent, A long-term, high-resolution wetland dataset over the Amazon basin, downscaled from a multi-wavelength retrieval using SAR, J. of Hydrometeorology, 14, 594-6007, 2013. Prigent, C., F. Papa, F. Aires, C. Jimenez, W.B. Rossow, and E. Matthews. Changes in land surface water dynamics since the 1990s and relation to population pressure. Geophys. Res. Lett., 39(L08403), 2012.

  3. Improved Classification of Orthosiphon stamineus by Data Fusion of Electronic Nose and Tongue Sensors

    PubMed Central

    Zakaria, Ammar; Shakaff, Ali Yeon Md.; Adom, Abdul Hamid; Ahmad, Mohd Noor; Masnan, Maz Jamilah; Aziz, Abdul Hallis Abdul; Fikri, Nazifah Ahmad; Abdullah, Abu Hassan; Kamarudin, Latifah Munirah

    2010-01-01

    An improved classification of Orthosiphon stamineus using a data fusion technique is presented. Five different commercial sources along with freshly prepared samples were discriminated using an electronic nose (e-nose) and an electronic tongue (e-tongue). Samples from the different commercial brands were evaluated by the e-tongue and then followed by the e-nose. Applying Principal Component Analysis (PCA) separately on the respective e-tongue and e-nose data, only five distinct groups were projected. However, by employing a low level data fusion technique, six distinct groupings were achieved. Hence, this technique can enhance the ability of PCA to analyze the complex samples of Orthosiphon stamineus. Linear Discriminant Analysis (LDA) was then used to further validate and classify the samples. It was found that the LDA performance was also improved when the responses from the e-nose and e-tongue were fused together. PMID:22163381

  4. Improved classification of Orthosiphon stamineus by data fusion of electronic nose and tongue sensors.

    PubMed

    Zakaria, Ammar; Shakaff, Ali Yeon Md; Adom, Abdul Hamid; Ahmad, Mohd Noor; Masnan, Maz Jamilah; Aziz, Abdul Hallis Abdul; Fikri, Nazifah Ahmad; Abdullah, Abu Hassan; Kamarudin, Latifah Munirah

    2010-01-01

    An improved classification of Orthosiphon stamineus using a data fusion technique is presented. Five different commercial sources along with freshly prepared samples were discriminated using an electronic nose (e-nose) and an electronic tongue (e-tongue). Samples from the different commercial brands were evaluated by the e-tongue and then followed by the e-nose. Applying Principal Component Analysis (PCA) separately on the respective e-tongue and e-nose data, only five distinct groups were projected. However, by employing a low level data fusion technique, six distinct groupings were achieved. Hence, this technique can enhance the ability of PCA to analyze the complex samples of Orthosiphon stamineus. Linear Discriminant Analysis (LDA) was then used to further validate and classify the samples. It was found that the LDA performance was also improved when the responses from the e-nose and e-tongue were fused together.

  5. An improved principal component analysis based region matching method for fringe direction estimation

    NASA Astrophysics Data System (ADS)

    He, A.; Quan, C.

    2018-04-01

    The principal component analysis (PCA) and region matching combined method is effective for fringe direction estimation. However, its mask construction algorithm for region matching fails in some circumstances, and the algorithm for conversion of orientation to direction in mask areas is computationally-heavy and non-optimized. We propose an improved PCA based region matching method for the fringe direction estimation, which includes an improved and robust mask construction scheme, and a fast and optimized orientation-direction conversion algorithm for the mask areas. Along with the estimated fringe direction map, filtered fringe pattern by automatic selective reconstruction modification and enhanced fast empirical mode decomposition (ASRm-EFEMD) is used for Hilbert spiral transform (HST) to demodulate the phase. Subsequently, windowed Fourier ridge (WFR) method is used for the refinement of the phase. The robustness and effectiveness of proposed method are demonstrated by both simulated and experimental fringe patterns.

  6. Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: data from the malmö preventive project

    PubMed Central

    Assel, Melissa J.; Gerdtsson, Axel; Thorek, Daniel L.J.; Carlsson, Sigrid V.; Malm, Johan; Scardino, Peter T.; Vickers, Andrew; Lilja, Hans; Ulmert, David

    2018-01-01

    Objectives To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. Results After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. Materials and Methods In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Conclusions Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multi-variable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics. PMID:29464033

  7. Evaluating motion processing algorithms for use with functional near-infrared spectroscopy data from young children.

    PubMed

    Delgado Reyes, Lourdes M; Bohache, Kevin; Wijeakumar, Sobanawartiny; Spencer, John P

    2018-04-01

    Motion artifacts are often a significant component of the measured signal in functional near-infrared spectroscopy (fNIRS) experiments. A variety of methods have been proposed to address this issue, including principal components analysis (PCA), correlation-based signal improvement (CBSI), wavelet filtering, and spline interpolation. The efficacy of these techniques has been compared using simulated data; however, our understanding of how these techniques fare when dealing with task-based cognitive data is limited. Brigadoi et al. compared motion correction techniques in a sample of adult data measured during a simple cognitive task. Wavelet filtering showed the most promise as an optimal technique for motion correction. Given that fNIRS is often used with infants and young children, it is critical to evaluate the effectiveness of motion correction techniques directly with data from these age groups. This study addresses that problem by evaluating motion correction algorithms implemented in HomER2. The efficacy of each technique was compared quantitatively using objective metrics related to the physiological properties of the hemodynamic response. Results showed that targeted PCA (tPCA), spline, and CBSI retained a higher number of trials. These techniques also performed well in direct head-to-head comparisons with the other approaches using quantitative metrics. The CBSI method corrected many of the artifacts present in our data; however, this approach produced sometimes unstable HRFs. The targeted PCA and spline methods proved to be the most robust, performing well across all comparison metrics. When compared head to head, tPCA consistently outperformed spline. We conclude, therefore, that tPCA is an effective technique for correcting motion artifacts in fNIRS data from young children.

  8. Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: data from the malmö preventive project.

    PubMed

    Assel, Melissa J; Gerdtsson, Axel; Thorek, Daniel L J; Carlsson, Sigrid V; Malm, Johan; Scardino, Peter T; Vickers, Andrew; Lilja, Hans; Ulmert, David

    2018-01-19

    To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multi-variable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics.

  9. Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis.

    PubMed

    Koie, Takuya; Mitsuzuka, Koji; Yoneyama, Takahiro; Narita, Shintaro; Kawamura, Sadafumi; Kaiho, Yasuhiro; Tsuchiya, Norihiko; Tochigi, Tatsuo; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara; Yoneyama, Tohru; Tobisawa, Yuki

    2015-10-01

    The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca. The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS. The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P < 0.0001). The 5-year OS rates were 100 and 96.1 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P = 0.110). Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP appeared to reduce the risk of biochemical recurrence. A prospective randomized study is warranted to determine the clinical implications of the neoadjuvant therapy described here.

  10. PI-RADS v2 and ADC values: is there room for improvement?

    PubMed

    Jordan, Eric J; Fiske, Charles; Zagoria, Ronald; Westphalen, Antonio C

    2018-03-17

    To determine the diagnostic accuracy of ADC values in combination with PI-RADS v2 for the diagnosis of clinically significant prostate cancer (CS-PCa) compared to PI-RADS v2 alone. This retrospective study included 155 men whom underwent 3-Tesla prostate MRI and subsequent MR/US fusion biopsies at a single non-academic center from 11/2014 to 3/2016. All scans were performed with a surface coil and included T2, diffusion-weighted, and dynamic contrast-enhanced sequences. Suspicious findings were classified using Prostate Imaging Reporting and Data System (PI-RADS) v2 and targeted using MR/US fusion biopsies. Mixed-effect logistic regression analyses were used to determine the ability of PIRADS v2 alone and combined with ADC values to predict CS-PCa. As ADC categories are more practical in clinical situations than numeric values, an additional model with ADC categories of ≤ 800 and > 800 was performed. A total of 243 suspicious lesions were included, 69 of which were CS-PCa, 34 were Gleason score 3+3 PCa, and 140 were negative. The overall PIRADS v2 score, ADC values, and ADC categories are independent statistically significant predictors of CS-PCa (p < 0.001). However, the area under the ROC of PIRADS v2 alone and PIRADS v2 with ADC categories are significantly different in both peripheral and transition zone lesions (p = 0.026 and p = 0.03, respectively) Further analysis of the ROC curves also shows that the main benefit of utilizing ADC values or categories is better discrimination of PI-RADS v2 4 lesions. ADC values and categories help to diagnose CS-PCa when lesions are assigned a PI-RADS v2 score of 4.

  11. Multivariate Analysis of Two-Dimensional 1H, 13C Methyl NMR Spectra of Monoclonal Antibody Therapeutics To Facilitate Assessment of Higher Order Structure.

    PubMed

    Arbogast, Luke W; Delaglio, Frank; Schiel, John E; Marino, John P

    2017-11-07

    Two-dimensional (2D) 1 H- 13 C methyl NMR provides a powerful tool to probe the higher order structure (HOS) of monoclonal antibodies (mAbs), since spectra can readily be acquired on intact mAbs at natural isotopic abundance, and small changes in chemical environment and structure give rise to observable changes in corresponding spectra, which can be interpreted at atomic resolution. This makes it possible to apply 2D NMR spectral fingerprinting approaches directly to drug products in order to systematically characterize structure and excipient effects. Systematic collections of NMR spectra are often analyzed in terms of the changes in specifically identified peak positions, as well as changes in peak height and line widths. A complementary approach is to apply principal component analysis (PCA) directly to the matrix of spectral data, correlating spectra according to similarities and differences in their overall shapes, rather than according to parameters of individually identified peaks. This is particularly well-suited for spectra of mAbs, where some of the individual peaks might not be well resolved. Here we demonstrate the performance of the PCA method for discriminating structural variation among systematic sets of 2D NMR fingerprint spectra using the NISTmAb and illustrate how spectral variability identified by PCA may be correlated to structure.

  12. Fusion of multi-parametric MRI and temporal ultrasound for characterization of prostate cancer: in vivo feasibility study

    NASA Astrophysics Data System (ADS)

    Imani, Farhad; Ghavidel, Sahar; Abolmaesumi, Purang; Khallaghi, Siavash; Gibson, Eli; Khojaste, Amir; Gaed, Mena; Moussa, Madeleine; Gomez, Jose A.; Romagnoli, Cesare; Cool, Derek W.; Bastian-Jordan, Matthew; Kassam, Zahra; Siemens, D. Robert; Leveridge, Michael; Chang, Silvia; Fenster, Aaron; Ward, Aaron D.; Mousavi, Parvin

    2016-03-01

    Recently, multi-parametric Magnetic Resonance Imaging (mp-MRI) has been used to improve the sensitivity of detecting high-risk prostate cancer (PCa). Prior to biopsy, primary and secondary cancer lesions are identified on mp-MRI. The lesions are then targeted using TRUS guidance. In this paper, for the first time, we present a fused mp-MRI-temporal-ultrasound framework for characterization of PCa, in vivo. Cancer classification results obtained using temporal ultrasound are fused with those achieved using consolidated mp-MRI maps determined by multiple observers. We verify the outcome of our study using histopathology following deformable registration of ultrasound and histology images. Fusion of temporal ultrasound and mp-MRI for characterization of the PCa results in an area under the receiver operating characteristic curve (AUC) of 0.86 for cancerous regions with Gleason scores (GSs)>=3+3, and AUC of 0.89 for those with GSs>=3+4.

  13. Vegetation characteristics important to common songbirds in east Texas

    USGS Publications Warehouse

    Conner, Richard N.; Dickson, James G.; Locke, Brian A.; Segelquist, Charles A.

    1983-01-01

    Multivariate studies of breeding bird communities have used principal component analysis (PCA) or several-group (three or more groups) discriminant function analysis (DFA) to ordinate bird species on vegetational continua (Cody 1968, James 1971, Whitmore 1975). In community studies, high resolution of habitat requirements for individual species is not always possible with either PCA or several-group DFA. When habitat characteristics of several species are examined with a DFA the resultant axes optimally discriminate among all species simultaneously. Hence, the characteristics assigned to a particular species reflect in part the presence of other species in the analyses. A better resolution of each species' habitat requirements may be obtained from a two-group DFA, wherein habitats selected by a species are discriminated from all other available habitats. Analyses using two-group DFAs to compare habitat used by a species with habitat unused by the same species have the potential to provide an optimal frame of reference from which to examine habitat variables (Martinka 1972, Conner and Adkisson 1976, Whitmore 1981). Mathematically (DFA) it is possible to maximally separate two groups of multivariate observations with a single axis (Harner and whitmore 1977). A line drawn in three or n-dimensional space can easily be positioned to intersect two multivariate means (centroids). If three or more centroids for species are analyzed simultaneously, a single line can no longer intersect all centroids unless a perfectly linear relationship exists for the species being examined. The probability of such an occurrence is extremely low. Thus, a high degree of resolution can be realized when a two-group DFA is used to determine habitat parameters important to individual species. We have used two-group DFA to identify vegetation variable important to 12 common species of songbirds in East Texas.

  14. Pan Sharpening Quality Investigation of Turkish In-Operation Remote Sensing Satellites: Applications with Rasat and GÖKTÜRK-2 Images

    NASA Astrophysics Data System (ADS)

    Ozendi, Mustafa; Topan, Hüseyin; Cam, Ali; Bayık, Çağlar

    2016-10-01

    Recently two optical remote sensing satellites, RASAT and GÖKTÜRK-2, launched successfully by the Republic of Turkey. RASAT has 7.5 m panchromatic, and 15 m visible bands whereas GÖKTÜRK-2 has 2.5 m panchromatic and 5 m VNIR (Visible and Near Infrared) bands. These bands with various resolutions can be fused by pan-sharpening methods which is an important application area of optical remote sensing imagery. So that, the high geometric resolution of panchromatic band and the high spectral resolution of VNIR bands can be merged. In the literature there are many pan-sharpening methods. However, there is not a standard framework for quality investigation of pan-sharpened imagery. The aim of this study is to investigate pan-sharpening performance of RASAT and GÖKTÜRK-2 images. For this purpose, pan-sharpened images are generated using most popular pan-sharpening methods IHS, Brovey and PCA at first. This procedure is followed by quantitative evaluation of pan-sharpened images using Correlation Coefficient (CC), Root Mean Square Error (RMSE), Relative Average Spectral Error (RASE), Spectral Angle Mapper (SAM) and Erreur Relative Globale Adimensionnelle de Synthése (ERGAS) metrics. For generation of pan-sharpened images and computation of metrics SharpQ tool is used which is developed with MATLAB computing language. According to metrics, PCA derived pan-sharpened image is the most similar one to multispectral image for RASAT, and Brovey derived pan-sharpened image is the most similar one to multispectral image for GÖKTÜRK-2. Finally, pan-sharpened images are evaluated qualitatively in terms of object availability and completeness for various land covers (such as urban, forest and flat areas) by a group of operators who are experienced in remote sensing imagery.

  15. Automatic age and gender classification using supervised appearance model

    NASA Astrophysics Data System (ADS)

    Bukar, Ali Maina; Ugail, Hassan; Connah, David

    2016-11-01

    Age and gender classification are two important problems that recently gained popularity in the research community, due to their wide range of applications. Research has shown that both age and gender information are encoded in the face shape and texture, hence the active appearance model (AAM), a statistical model that captures shape and texture variations, has been one of the most widely used feature extraction techniques for the aforementioned problems. However, AAM suffers from some drawbacks, especially when used for classification. This is primarily because principal component analysis (PCA), which is at the core of the model, works in an unsupervised manner, i.e., PCA dimensionality reduction does not take into account how the predictor variables relate to the response (class labels). Rather, it explores only the underlying structure of the predictor variables, thus, it is no surprise if PCA discards valuable parts of the data that represent discriminatory features. Toward this end, we propose a supervised appearance model (sAM) that improves on AAM by replacing PCA with partial least-squares regression. This feature extraction technique is then used for the problems of age and gender classification. Our experiments show that sAM has better predictive power than the conventional AAM.

  16. Utilization of an Enhanced Canonical Correlation Analysis (ECCA) to Predict Daily Precipitation and Temperature in a Semi-Arid Environment

    NASA Astrophysics Data System (ADS)

    Lopez, S. R.; Hogue, T. S.

    2011-12-01

    Global climate models (GCMs) are primarily used to generate historical and future large-scale circulation patterns at a coarse resolution (typical order of 50,000 km2) and fail to capture climate variability at the ground level due to localized surface influences (i.e topography, marine, layer, land cover, etc). Their inability to accurately resolve these processes has led to the development of numerous 'downscaling' techniques. The goal of this study is to enhance statistical downscaling of daily precipitation and temperature for regions with heterogeneous land cover and topography. Our analysis was divided into two periods, historical (1961-2000) and contemporary (1980-2000), and tested using sixteen predictand combinations from four GCMs (GFDL CM2.0, GFDL CM2.1, CNRM-CM3 and MRI-CGCM2 3.2a. The Southern California area was separated into five county regions: Santa Barbara, Ventura, Los Angeles, Orange and San Diego. Principle component analysis (PCA) was performed on ground-based observations in order to (1) reduce the number of redundant gauges and minimize dimensionality and (2) cluster gauges that behave statistically similarly for post-analysis. Post-PCA analysis included extensive testing of predictor-predictand relationships using an enhanced canonical correlation analysis (ECCA). The ECCA includes obtaining the optimal predictand sets for all models within each spatial domain (county) as governed by daily and monthly overall statistics. Results show all models maintain mean annual and monthly behavior within each county and daily statistics are improved. The level of improvement highly depends on the vegetation extent within each county and the land-to-ocean ratio within the GCM spatial grid. The utilization of the entire historical period also leads to better statistical representation of observed daily precipitation. The validated ECCA technique is being applied to future climate scenarios distributed by the IPCC in order to provide forcing data for regional hydrologic models and assess future water resources in the Southern California region.

  17. Vascular Reactivity Profile of Novel KCa3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed

    PubMed Central

    Oliván-Viguera, Aida; Valero, Marta Sofía; Pinilla, Estéfano; Amor, Sara; García-Villalón, Ángel Luis; Coleman, Nichole; Laría, Celia; Calvín-Tienza, Víctor; García-Otín, Ángel-Luis; Fernández-Fernández, José M.; Murillo, Ma Divina; Gálvez, José A.; Díaz-de-Villegas, María D.; Badorrey, Ramón; Simonsen, Ulf; Rivera, Luis; Wulff, Heike; Köhler, Ralf

    2017-01-01

    Opening of intermediate-conductance calcium-activated potassium channels (KCa3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KCa3.1-selective positive-gating modulators, SKA-111 and SKA-121, to (1) evoke porcine endothelial cell KCa3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KCa currents evoked by bradykinin (BK) were potentiated ≈7-fold by either SKA-111 or SKA-121 (both at 1 μM) and were blocked by a KCa3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinin-induced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by ≈2-fold. Potentiation of the BK response was prevented by KCa3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KCa3.1 channels improves BK-induced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KCa3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease. PMID:26821335

  18. Predicting timing of foot strike during running, independent of striking technique, using principal component analysis of joint angles.

    PubMed

    Osis, Sean T; Hettinga, Blayne A; Leitch, Jessica; Ferber, Reed

    2014-08-22

    As 3-dimensional (3D) motion-capture for clinical gait analysis continues to evolve, new methods must be developed to improve the detection of gait cycle events based on kinematic data. Recently, the application of principal component analysis (PCA) to gait data has shown promise in detecting important biomechanical features. Therefore, the purpose of this study was to define a new foot strike detection method for a continuum of striking techniques, by applying PCA to joint angle waveforms. In accordance with Newtonian mechanics, it was hypothesized that transient features in the sagittal-plane accelerations of the lower extremity would be linked with the impulsive application of force to the foot at foot strike. Kinematic and kinetic data from treadmill running were selected for 154 subjects, from a database of gait biomechanics. Ankle, knee and hip sagittal plane angular acceleration kinematic curves were chained together to form a row input to a PCA matrix. A linear polynomial was calculated based on PCA scores, and a 10-fold cross-validation was performed to evaluate prediction accuracy against gold-standard foot strike as determined by a 10 N rise in the vertical ground reaction force. Results show 89-94% of all predicted foot strikes were within 4 frames (20 ms) of the gold standard with the largest error being 28 ms. It is concluded that this new foot strike detection is an improvement on existing methods and can be applied regardless of whether the runner exhibits a rearfoot, midfoot, or forefoot strike pattern. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Towards Improved Radiative Transfer Simulations of Hyperspectral Measurements for Cloudy Atmospheres

    NASA Astrophysics Data System (ADS)

    Natraj, V.; Li, C.; Aumann, H. H.; Yung, Y. L.

    2016-12-01

    Usage of hyperspectral measurements in the infrared for weather forecasting requires radiative transfer (RT) models that can accurately compute radiances given the atmospheric state. On the other hand, it is necessary for the RT models to be fast enough to meet operational processing processing requirements. Until recently, this has proven to be a very hard challenge. In the last decade, however, significant progress has been made in this regard, due to computer speed increases, and improved and optimized RT models. This presentation will introduce a new technique, based on principal component analysis (PCA) of the inherent optical properties (such as profiles of trace gas absorption and single scattering albedo), to perform fast and accurate hyperspectral RT calculations in clear or cloudy atmospheres. PCA is a technique to compress data while capturing most of the variability in the data. By performing PCA on the optical properties, we limit the number of computationally expensive multiple scattering RT calculations to the PCA-reduced data set, and develop a series of PC-based correction factors to obtain the hyperspectral radiances. This technique has been showed to deliver accuracies of 0.1% of better with respect to brute force, line-by-line (LBL) models such as LBLRTM and DISORT, but is orders of magnitude faster than the LBL models. We will compare the performance of this method against other models on a large atmospheric state data set (7377 profiles) that includes a wide range of thermodynamic and cloud profiles, along with viewing geometry and surface emissivity information. 2016. All rights reserved.

  20. Cognitive decline in prostate cancer patients undergoing ADT: a potential role for exercise training.

    PubMed

    Mundell, Niamh L; Daly, Robin M; Macpherson, Helen; Fraser, Steve F

    2017-04-01

    Androgen deprivation therapy (ADT) is an effective and widely prescribed treatment for prostate cancer (PCa), but it is associated with multiple treatment-induced adverse effects that impact on various musculoskeletal and cardiometabolic health outcomes. Emerging research has shown that ADT is also associated with cognitive impairment, which has been linked to a loss of independence, increased falls and fracture risk and greater use of medical services. The aim of this review is to outline the evidence related to the effect of ADT use on cognitive function, and propose a role for exercise training as part of usual care to prevent and/or manage cognitive impairments for PCa survivors on ADT. The following results have been obtained from this study. ADT has been shown to adversely affect specific cognitive domains, particularly verbal memory, visuomotor function, attention and executive function. However, current clinical guidelines do not recommend routine assessment of cognitive function in these men. No studies have examined whether exercise training can preserve or improve cognitive function in these men, but in healthy adults', multimodal exercise training incorporating aerobic training, progressive resistance training (PRT) and challenging motor control exercises have the potential to attenuate cognitive decline. In conclusion, as treatment with ADT for men with PCa has been associated with a decline in cognition, it is recommended that cognitive function be routinely monitored in these men and that regular exercise training be prescribed to preserve (or improve) cognitive function. Assessment of cognition and individualised exercise training should be considered in the usual treatment plan of PCa patients receiving ADT. © 2017 Society for Endocrinology.

  1. PCA3 Silencing Sensitizes Prostate Cancer Cells to Enzalutamide-mediated Androgen Receptor Blockade.

    PubMed

    Özgür, Emre; Celik, Ayca Iribas; Darendeliler, Emin; Gezer, Ugur

    2017-07-01

    Prostate cancer (PCa) is an androgen-dependent disease. Novel anti-androgens (i.e. enzalutamide) have recently been developed for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Evidence is accumulating that prostate cancer antigen 3 (PCA3) is involved in androgen receptor (AR) signaling. Here, in combination with enzalutamide-mediated AR blockade, we investigated the effect of PCA3 targeting on the viability of PCa cells. In hormone-sensitive LNCaP cells, AR-overexpressing LNCaP-AR + cells and VCaP cells (representing CRPC), PCA3 was silenced using siRNA oligonucleotides. Gene expression and cell viability was assessed in PCA3-silenced and/or AR-blocked cells. PCA3 targeting reduced the expression of AR-related genes (i.e. prostate-specific antigen (PSA) and prostate-specific transcript 1 (non-protein coding) (PCGEM1)) and potentiated the effect of enzalutamide. Proliferation of PCa cells was suppressed upon PCA3 silencing with a greater effect in LNCaP-AR + cells. Furthermore, PCA3 silencing sensitized PCa cells to enzalutamide-induced loss of cell growth. PCA3, as a therapeutic target in PCa, might be used to potentiate AR antagonists. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer

    PubMed Central

    Qu, Sifeng; Ci, Xinpei; Xue, Hui; Dong, Xin; Hao, Jun; Lin, Dong; Clermont, Pier-Luc; Wu, Rebecca; Collins, Colin C; Gout, Peter W; Wang, Yuzhuo

    2018-01-01

    Background: Docetaxel used for first-line treatment of advanced prostate cancer (PCa) is only marginally effective. We previously showed, using the LTL-313H subrenal capsule patient-derived metastatic PCa xenograft model, that docetaxel combined with Aneustat (OMN54), a multivalent plant-derived therapeutic, led to marked synergistic tumour growth inhibition. Here, we investigated the effect of docetaxel+Aneustat on metastasis. Methods: C4-2 cells were incubated with docetaxel, Aneustat and docetaxel+Aneustat to assess effects on cell migration. The LTL-313H model, similarly treated, was analysed for effects on lung micro-metastasis and kidney invasion. The LTL-313H gene expression profile was compared with profiles of PCa patients (obtained from Oncomine) and subjected to IPA to determine involvement of cancer driver genes. Results: Docetaxel+Aneustat markedly inhibited C4-2 cell migration and LTL-313H lung micro-metastasis/kidney invasion. Oncomine analysis indicated that treatment with docetaxel+Aneustat was associated with improved patient outcome. The drug combination markedly downregulated expression of cancer driver genes such as FOXM1 (and FOXM1-target genes). FOXM1 overexpression reduced the anti-metastatic activity of docetaxel+Aneustat. Conclusions: Docetaxel+Aneustat can inhibit PCa tissue invasion and metastasis. This activity appears to be based on reduced expression of cancer driver genes such as FOXM1. Use of docetaxel+Aneustat may provide a new, more effective regimen for therapy of metastatic PCa. PMID:29381682

  3. Comparison Between the Four-kallikrein Panel and Prostate Health Index for Predicting Prostate Cancer.

    PubMed

    Nordström, Tobias; Vickers, Andrew; Assel, Melissa; Lilja, Hans; Grönberg, Henrik; Eklund, Martin

    2015-07-01

    The four-kallikrein panel and the Prostate Health Index (PHI) have been shown to improve prediction of prostate cancer (PCa) compared with prostate-specific antigen (PSA). No comparison of the four-kallikrein panel and PHI has been presented. To compare the four-kallikrein panel and PHI for predicting PCa in an independent cohort. Participants were from a population-based cohort of PSA-tested men in Stockholm County. We included 531 men with PSA levels between 3 and 15 ng/ml undergoing first-time prostate biopsy during 2010-2012. Models were fitted to case status. We computed calibration curves, the area under the receiver-operating characteristics curve (AUC), decision curves, and percentage of saved biopsies. The four-kallikrein panel showed AUCs of 69.0 when predicting any-grade PCa and 71.8 when predicting high-grade cancer (Gleason score ≥7). Similar values were found for PHI: 70.4 and 71.1, respectively. Both models had higher AUCs than a base model with PSA value and age (p<0.0001 for both); differences between models were not significant. Sensitivity analyses including men with any PSA level or a previous biopsy did not materially affect our findings. Using 10% predicted risk of high-grade PCa by the four-kallikrein panel or PHI of 39 as cut-off for biopsy saved 29% of performed biopsies at a cost of delayed diagnosis for 10% of the men with high-grade cancers. Both models showed limited net benefit in decision analysis. The main study limitation was lack of digital rectal examination data and biopsy decision being based on PSA information. The four-kallikrein panel and PHI similarly improved discrimination when predicting PCa and high-grade PCa. Both are simple blood tests that can reduce the number of unnecessary biopsies compared with screening with total PSA, representing an important new option to reduce harm. Prostate-specific antigen screening is controversial due to limitations of the test. We found that two blood tests, the Prostate Health Index and the four-kallikrein panel, performed similarly and could both aid in decision making among Swedish men undergoing a prostate biopsy. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  4. Evaluation of a PSMA-targeted BNF nanoparticle construct

    NASA Astrophysics Data System (ADS)

    Behnam Azad, Babak; Banerjee, Sangeeta R.; Pullambhatla, Mrudula; Lacerda, Silvia; Foss, Catherine A.; Wang, Yuchuan; Ivkov, Robert; Pomper, Martin G.

    2015-02-01

    Early detection enables improved prognosis for prostate cancer (PCa). A promising target for imaging and therapy of PCa is the prostate-specific membrane antigen (PSMA), which exhibits both expression within the epithelium of PCa cells, and becomes internalized upon ligand binding. Here we report the synthesis of a PSMA-targeted bionized nanoferrite (BNF) nanoparticle and its biological evaluation in an experimental model of PCa. The BNF nanoparticle formulation exhibits properties conducive to targeted imaging such as stealth, prolonged circulation time and enhanced clearance from non-target sites. Optical imaging of the targeted BNF in vivo indicates preferential accumulation in PSMA+ tumors 4 h post-injection, suggesting target specificity. On the other hand, non-targeted nanoparticles exhibit lower uptake with similar accumulation in both PSMA+ and PSMA- tumors indicating tumor access without preferential accumulation. Imaging with single photon emission computed tomography (SPECT) and biodistribution studies of a modified construct indicate highest tumor accumulation at 48 h post-injection [4.3 +/- 0.4 percentage injected dose per gram of tissue (%ID g-1)], with tumor/blood and tumor/muscle ratios of 7.5 +/- 2.4 and 11.6 +/- 1.2 %ID g-1, respectively. Ex vivo fluorescence microscopy, Prussian blue staining, immunohistochemistry and biodistribution studies confirm enhanced nanoparticle uptake in PSMA+ tumors compared to those not expressing PSMA. The BNF nano-formulation described is promising for PSMA-targeted imaging applications in vivo.Early detection enables improved prognosis for prostate cancer (PCa). A promising target for imaging and therapy of PCa is the prostate-specific membrane antigen (PSMA), which exhibits both expression within the epithelium of PCa cells, and becomes internalized upon ligand binding. Here we report the synthesis of a PSMA-targeted bionized nanoferrite (BNF) nanoparticle and its biological evaluation in an experimental model of PCa. The BNF nanoparticle formulation exhibits properties conducive to targeted imaging such as stealth, prolonged circulation time and enhanced clearance from non-target sites. Optical imaging of the targeted BNF in vivo indicates preferential accumulation in PSMA+ tumors 4 h post-injection, suggesting target specificity. On the other hand, non-targeted nanoparticles exhibit lower uptake with similar accumulation in both PSMA+ and PSMA- tumors indicating tumor access without preferential accumulation. Imaging with single photon emission computed tomography (SPECT) and biodistribution studies of a modified construct indicate highest tumor accumulation at 48 h post-injection [4.3 +/- 0.4 percentage injected dose per gram of tissue (%ID g-1)], with tumor/blood and tumor/muscle ratios of 7.5 +/- 2.4 and 11.6 +/- 1.2 %ID g-1, respectively. Ex vivo fluorescence microscopy, Prussian blue staining, immunohistochemistry and biodistribution studies confirm enhanced nanoparticle uptake in PSMA+ tumors compared to those not expressing PSMA. The BNF nano-formulation described is promising for PSMA-targeted imaging applications in vivo. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06069e

  5. A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer.

    PubMed

    Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

    2017-09-01

    We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa -high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa -low PSA and non PCa -high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa.

  6. A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer

    PubMed Central

    Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

    2017-01-01

    Objective We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). Material and methods We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. Results The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa –high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa –low PSA and non PCa –high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. Conclusion According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa. PMID:28861298

  7. Accuracy of the prostate health index versus the urinary prostate cancer antigen 3 score to predict overall and significant prostate cancer at initial biopsy.

    PubMed

    Seisen, Thomas; Rouprêt, Morgan; Brault, Didier; Léon, Priscilla; Cancel-Tassin, Géraldine; Compérat, Eva; Renard-Penna, Raphaële; Mozer, Pierre; Guechot, Jérome; Cussenot, Olivier

    2015-01-01

    It remains unclear whether the Prostate Health Index (PHI) or the urinary Prostate-Cancer Antigen 3 (PCA-3) score is more accurate at screening for prostate cancer (PCa). The aim of this study was to prospectively compare the accuracy of PHI and PCA-3 scores to predict overall and significant PCa in men undergoing an initial prostate biopsy. Double-blind assessments of PHI and PCA-3 were conducted by referent physicians in 138 patients who subsequently underwent trans-rectal ultrasound-guided prostate biopsy according to a 12-core scheme. Predictive accuracies of PHI and PCA-3 were assessed using AUC and compared according to the DeLong method. Diagnostic performances with usual cut-off values for positivity (i.e., PHI >40 and PCA-3 >35) were calculated, and odds ratios associated with predicting PCa overall and significant PCa as defined by pathological updated Epstein criteria (i.e., Gleason score ≥7, more than three positive cores, or >50% cancer involvement in any core) were estimated using logistic regression. Prevalences of overall and significant PCa were 44.9% and 28.3%, respectively. PCA-3 (AUC = 0.71) was the most accurate predictor of PCa overall, and significantly outperformed PHI (AUC = 0.65; P = 0.03). However, PHI (AUC = 0.80) remained the most accurate predictor when screening exclusively for significant PCa and significantly outperformed PCA-3 (AUC = 0.55; P = 0.03). Furthermore, PCA-3 >35 had the best accuracy, and positive or negative predictive values when screening for PCa overall whereas these diagnostic performances were greater for PHI >40 when exclusively screening for significant PCa. PHI > 40 combined with PCA-3 > 35 was more specific in both cases. In multivariate analyses, PCA-3 >35 (OR = 5.68; 95%CI = [2.21-14.59]; P < 0.001) was significantly correlated with the presence of PCa overall, but PHI >40 (OR = 9.60; 95%CI = [1.72-91.32]; P = 0.001) was the only independent predictor for detecting significant PCa. Although PCA-3 score is the best predictor for PCa overall at initial biopsy, our findings strongly indicate that PHI should be used for population-based screening to avoid over-diagnosis of indolent tumors that are unlikely to cause death. © 2014 Wiley Periodicals, Inc.

  8. Sampling methods for the study of volatile profile of PDO wine vinegars. A comparison using multivariate data analysis.

    PubMed

    Ríos-Reina, Rocío; Morales, M Lourdes; García-González, Diego L; Amigo, José M; Callejón, Raquel M

    2018-03-01

    High-quality wine vinegars have been registered in Spain under protected designation of origin (PDO): "Vinagre de Jerez", "Vinagre de Condado de Huelva" and "Vinagre de Montilla-Moriles". The raw material, production and aging processes determine their quality and their aromatic composition. Vinegar volatile profile is usually analyzed by gas chromatography-mass spectrometry (GC-MS), being necessary a previous extraction step. Thus, three different sampling methods (Headspace solid phase microextraction "HS-SPME", Headspace stir bar sorptive extraction "HSSE" and Dynamic headspace extraction "DHS") were studied for the analysis of the volatile composition of Spanish PDO wine vinegars. Multivariate curve resolution (MCR) was used to solve chromatographic problems, improving the results obtained. Principal component analysis (PCA) showed that not all the sampling methods were equally suitable for the characterization and differentiation between PDOs and categories, being HSSE the technique that made able the best vinegar characterization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Anomaly metrics to differentiate threat sources from benign sources in primary vehicle screening.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cohen, Israel Dov; Mengesha, Wondwosen

    2011-09-01

    Discrimination of benign sources from threat sources at Port of Entries (POE) is of a great importance in efficient screening of cargo and vehicles using Radiation Portal Monitors (RPM). Currently RPM's ability to distinguish these radiological sources is seriously hampered by the energy resolution of the deployed RPMs. As naturally occurring radioactive materials (NORM) are ubiquitous in commerce, false alarms are problematic as they require additional resources in secondary inspection in addition to impacts on commerce. To increase the sensitivity of such detection systems without increasing false alarm rates, alarm metrics need to incorporate the ability to distinguish benign andmore » threat sources. Principal component analysis (PCA) and clustering technique were implemented in the present study. Such techniques were investigated for their potential to lower false alarm rates and/or increase sensitivity to weaker threat sources without loss of specificity. Results of the investigation demonstrated improved sensitivity and specificity in discriminating benign sources from threat sources.« less

  10. Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial).

    PubMed

    Jambor, Ivan; Boström, Peter J; Taimen, Pekka; Syvänen, Kari; Kähkönen, Esa; Kallajoki, Markku; Perez, Ileana Montoya; Kauko, Tommi; Matomäki, Jaakko; Ettala, Otto; Merisaari, Harri; Kiviniemi, Aida; Dean, Peter B; Aronen, Hannu J

    2017-10-01

    To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T 2 -weighted imaging, and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate-specific antigen (PSA). Between March 2013 and February 2015, 175 men with a clinical suspicion of prostate cancer (PCa) were offered bpMRI (NCT01864135) based on a suspicion of PCa (two repeated PSA measurements in the range 2.5-20.0 ng/ml and/or abnormal digital rectal examination). Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance, followed by systematic biopsy (SB). Men with a low to very low suspicion had only SB. In total, 161 (161/175, 92%) prospectively enrolled men completed the trial and were included in the final analyses. The primary endpoint of the trial was the cancer detection rate (CDR) of TB and SB. Clinically significant cancer (SPCa) was defined as Gleason score ≥3 + 4. TB compared with SB had higher CDR for SPCa (45%, 72/161 vs. 39%, 63/161, respectively; P > 0.05) and a lower CDR for Gleason score 3 + 3 (8%, 15/161 vs. 16%, 30/161; P < 0.05). Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have resulted in a 24% (38/161) reduction in the number of men undergoing biopsy, while missing 4 (2%) with SPCa. All anonymized datasets, including bpMRI reports and follow up information, are freely available on the trial server. Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification. 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1089-1095. © 2017 International Society for Magnetic Resonance in Medicine.

  11. Comparison of the Booster Interface Temperature in Stainless Steel (SS) V-Channel Versus the Aluminum (Al) Y-Channel Primer Chamber Assemblies (PCAs). Volume 2; Appendices

    NASA Technical Reports Server (NTRS)

    Garcia, Roberto; Saulsberry, Regor L.

    2011-01-01

    NASA's Technical Fellow for Propulsion, requested a technical assessment of the performance improvement achieved by the introduction of the stainless steel (SS) V-channel compared to the aluminum (Al) Y-channel Primer Chamber Assembly (PCA) design. The SS V-channel PCA was developed for NASA's Mars Science Laboratory (MSL) Project. The principle focus of the assessment was to measure the transient temperature at the booster interface with both designs. This document contains the Appendices to the Volume I main report.

  12. Comparison of the Booster Interface Temperature in Stainless Steel (SS) V-Channel versus the Aluminum (Al) Y-Channel Primer Chamber Assemblies (PCAs). Volume 1; Technical Assessment Report

    NASA Technical Reports Server (NTRS)

    Garcia, Roberto; Saulsberry, Regor L.

    2011-01-01

    NASA's Technical Fellow for Propulsion, requested a technical assessment of the performance improvement achieved by the introduction of the stainless steel (SS) V-channel compared to the aluminum (Al) Y-channel Primer Chamber Assembly (PCA) design. The SS V-channel PCA was developed for NASA's Mars Science Laboratory (MSL) Project. The principle focus of the assessment was to measure the transient temperature at the booster interface with both designs. This document contains the findings of the assessment.

  13. Genetic Progression of High Grade Prostatic Intraepithelial Neoplasia to Prostate Cancer.

    PubMed

    Jung, Seung-Hyun; Shin, Sun; Kim, Min Sung; Baek, In-Pyo; Lee, Ji Youl; Lee, Sung Hak; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

    2016-05-01

    Although high grade prostatic intraepithelial neoplasia (HGPIN) is considered a neoplastic lesion that precedes prostate cancer (PCA), the genomic structures of HGPIN remain unknown. Identification of the genomic landscape of HGPIN and the genomic differences between HGPIN and PCA that may drive the progression to PCA. We analyzed 20 regions of paired HGPIN and PCA from six patients using whole-exome sequencing and array-comparative genomic hybridization. Somatic mutation and copy number alteration (CNA) profiles of paired HGPIN and PCA were measured and compared. The number of total mutations and CNAs of HGPINs were significantly fewer than those of PCAs. Mutations in FOXA1 and CNAs (1q and 8q gains) were detected in both HGPIN and PCA ('common'), suggesting their roles in early PCA development. Mutations in SPOP, KDM6A, and KMT2D were 'PCA-specific', suggesting their roles in HGPIN progression to PCA. The 8p loss was either 'common' or 'PCA-specific'. In-silico estimation of evolutionary ages predicted that HGPIN genomes were much younger than PCA genomes. Our data show that PCAs are direct descendants of HGPINs in most cases that require more genomic alterations to progress to PCA. The nature of heterogeneous HGPIN population that might attenuate genomic signals should further be studied. HGPIN genomes harbor relatively fewer mutations and CNAs than PCA but require additional hits for the progression. In this study, we suggest a systemic diagram from high grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PCA). Our results provide a clue to explain the long latency from HGPIN to PCA and provide useful information for the genetic diagnosis of HGPIN and PCA. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  14. Occipital-posterior cerebral artery bypass via the occipital interhemispheric approach

    PubMed Central

    Kazumata, Ken; Yokoyama, Yuka; Sugiyama, Taku; Asaoka, Katsuyuki

    2013-01-01

    Background: The unavailability of the superficial temporal artery (STA) and the location of lesions pose a more technically demanding challenge when compared with conventional STA-superior cerebellar or posterior cerebral artery (PCA) bypass in vascular reconstruction procedures. To describe a case series of patients with cerebrovascular lesions who were treated using an occipital artery (OA) to PCA bypass via the occipital interhemispheric approach. Methods: We retrospectively reviewed three consecutive cases of patients with cerebrovascular lesions who were treated using OA-PCA bypass. Results: OA-PCA bypass was performed via the occipital interhemispheric approach. This procedure included: (1) OA-PCA bypass (n = 1), and combined OA-posterior inferior cerebellar artery and OA-PCA saphenous vein interposition graft bypass (n = 1) in patients with vertebrobasilar ischemia; (2) OA-PCA radial artery interposition graft bypass in one patient with residual PCA aneurysm. Conclusions: OA-PCA bypass represents a useful alternative to conventional STA-SCA or PCA bypass. PMID:23956933

  15. Diagnostic and predictive value of urine PCA3 gene expression for the clinical management of patients with altered prostatic specific antigen.

    PubMed

    Rodón, N; Trías, I; Verdú, M; Román, R; Domínguez, A; Calvo, M; Banus, J M; Ballesta, A M; Maestro, M L; Puig, X

    2014-04-01

    Analyze the impact of the introduction of the study of PCA3 gene in post-prostatic massage urine in the clinical management of patients with PSA altered, evaluating its diagnostic ability and predictive value of tumor aggressiveness. Observational, prospective, multicenter study of patients with suspected prostate cancer (PC) candidates for biopsy. We present a series of 670 consecutive samples of urine collected post-prostatic massage for three years in which we determined the "PCA3 score" (s-PCA3). Biopsy was only indicated in cases with s-positive PCA3. The s-PCA3 was positive in 43.7% of samples. In the 124 biopsies performed, the incidence of PC or atypical small acinar proliferation was 54%, reaching 68,6% in s-PCA3≥100. Statistically significant relationship between the s-PCA3 and tumor grade was demonstrated. In cases with s-PCA3 between 35 and 50 only 23% of PC were high grade (Gleason≥7), compared to 76.7% in cases with s-PCA3 over 50. There was a statistically significant correlation between s-PCA3 and cylinders affected. Both relationships were confirmed by applying a log-linear model. The incorporation of PCA3 can avoid the need for biopsies in 54% of patients. s-PCA3 positivity increases the likelihood of a positive biopsy, especially in higher s-PCA3 100 (68.6%). s-PCA3 is also an indicator of tumor aggressiveness and provides essential information in making treatment decisions. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  16. Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

    PubMed

    Seibert, Tyler M; Fan, Chun Chieh; Wang, Yunpeng; Zuber, Verena; Karunamuni, Roshan; Parsons, J Kellogg; Eeles, Rosalind A; Easton, Douglas F; Kote-Jarai, ZSofia; Al Olama, Ali Amin; Garcia, Sara Benlloch; Muir, Kenneth; Grönberg, Henrik; Wiklund, Fredrik; Aly, Markus; Schleutker, Johanna; Sipeky, Csilla; Tammela, Teuvo Lj; Nordestgaard, Børge G; Nielsen, Sune F; Weischer, Maren; Bisbjerg, Rasmus; Røder, M Andreas; Iversen, Peter; Key, Tim J; Travis, Ruth C; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S; Cybulski, Cezary; Wokolorczyk, Dominika; Kluzniak, Wojciech; Cannon-Albright, Lisa; Brenner, Hermann; Cuk, Katarina; Saum, Kai-Uwe; Park, Jong Y; Sellers, Thomas A; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Clements, Judith A; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Karow, David S; Mills, Ian G; Andreassen, Ole A; Dale, Anders M

    2018-01-10

    To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. Multiple institutions that were members of international PRACTICAL consortium. All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men. Prediction with hazard score of age of onset of aggressive cancer in validation set. In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10 -16 ). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa. 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.

  17. A novel urinary long non-coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy.

    PubMed

    Zhang, Wei; Ren, Shan-Cheng; Shi, Xiao-Lei; Liu, Ya-Wei; Zhu, Ya-Sheng; Jing, Tai-Le; Wang, Fu-Bo; Chen, Rui; Xu, Chuan-Liang; Wang, Hui-Qing; Wang, Hai-Feng; Wang, Yan; Liu, Bing; Li, Yao-Ming; Fang, Zi-Yu; Guo, Fei; Lu, Xin; Shen, Dan; Gao, Xu; Hou, Jian-Guo; Sun, Ying-Hao

    2015-05-01

    Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis. © 2015 Wiley Periodicals, Inc.

  18. The Application of Infrared Thermographic Inspection Techniques to the Space Shuttle Thermal Protection System

    NASA Technical Reports Server (NTRS)

    Cramer, K. E.; Winfree, W. P.

    2005-01-01

    The Nondestructive Evaluation Sciences Branch at NASA s Langley Research Center has been actively involved in the development of thermographic inspection techniques for more than 15 years. Since the Space Shuttle Columbia accident, NASA has focused on the improvement of advanced NDE techniques for the Reinforced Carbon-Carbon (RCC) panels that comprise the orbiter s wing leading edge. Various nondestructive inspection techniques have been used in the examination of the RCC, but thermography has emerged as an effective inspection alternative to more traditional methods. Thermography is a non-contact inspection method as compared to ultrasonic techniques which typically require the use of a coupling medium between the transducer and material. Like radiographic techniques, thermography can be used to inspect large areas, but has the advantage of minimal safety concerns and the ability for single-sided measurements. Principal Component Analysis (PCA) has been shown effective for reducing thermographic NDE data. A typical implementation of PCA is when the eigenvectors are generated from the data set being analyzed. Although it is a powerful tool for enhancing the visibility of defects in thermal data, PCA can be computationally intense and time consuming when applied to the large data sets typical in thermography. Additionally, PCA can experience problems when very large defects are present (defects that dominate the field-of-view), since the calculation of the eigenvectors is now governed by the presence of the defect, not the "good" material. To increase the processing speed and to minimize the negative effects of large defects, an alternative method of PCA is being pursued where a fixed set of eigenvectors, generated from an analytic model of the thermal response of the material under examination, is used to process the thermal data from the RCC materials. Details of a one-dimensional analytic model and a two-dimensional finite-element model will be presented. An overview of the PCA process as well as a quantitative signal-to-noise comparison of the results of performing both embodiments of PCA on thermographic data from various RCC specimens will be shown. Finally, a number of different applications of this technology to various RCC components will be presented.

  19. [Vis-NIR spectroscopic pattern recognition combined with SG smoothing applied to breed screening of transgenic sugarcane].

    PubMed

    Liu, Gui-Song; Guo, Hao-Song; Pan, Tao; Wang, Ji-Hua; Cao, Gan

    2014-10-01

    Based on Savitzky-Golay (SG) smoothing screening, principal component analysis (PCA) combined with separately supervised linear discriminant analysis (LDA) and unsupervised hierarchical clustering analysis (HCA) were used for non-destructive visible and near-infrared (Vis-NIR) detection for breed screening of transgenic sugarcane. A random and stability-dependent framework of calibration, prediction, and validation was proposed. A total of 456 samples of sugarcane leaves planting in the elongating stage were collected from the field, which was composed of 306 transgenic (positive) samples containing Bt and Bar gene and 150 non-transgenic (negative) samples. A total of 156 samples (negative 50 and positive 106) were randomly selected as the validation set; the remaining samples (negative 100 and positive 200, a total of 300 samples) were used as the modeling set, and then the modeling set was subdivided into calibration (negative 50 and positive 100, a total of 150 samples) and prediction sets (negative 50 and positive 100, a total of 150 samples) for 50 times. The number of SG smoothing points was ex- panded, while some modes of higher derivative were removed because of small absolute value, and a total of 264 smoothing modes were used for screening. The pairwise combinations of first three principal components were used, and then the optimal combination of principal components was selected according to the model effect. Based on all divisions of calibration and prediction sets and all SG smoothing modes, the SG-PCA-LDA and SG-PCA-HCA models were established, the model parameters were optimized based on the average prediction effect for all divisions to produce modeling stability. Finally, the model validation was performed by validation set. With SG smoothing, the modeling accuracy and stability of PCA-LDA, PCA-HCA were signif- icantly improved. For the optimal SG-PCA-LDA model, the recognition rate of positive and negative validation samples were 94.3%, 96.0%; and were 92.5%, 98.0% for the optimal SG-PCA-LDA model, respectively. Vis-NIR spectro- scopic pattern recognition combined with SG smoothing could be used for accurate recognition of transgenic sugarcane leaves, and provided a convenient screening method for transgenic sugarcane breeding.

  20. Development and external multicenter validation of Chinese Prostate Cancer Consortium prostate cancer risk calculator for initial prostate biopsy.

    PubMed

    Chen, Rui; Xie, Liping; Xue, Wei; Ye, Zhangqun; Ma, Lulin; Gao, Xu; Ren, Shancheng; Wang, Fubo; Zhao, Lin; Xu, Chuanliang; Sun, Yinghao

    2016-09-01

    Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men. Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals. Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa. CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared with Western risk calculators. CPCC-RC may aid in decision-making of prostate biopsy in Chinese or in other Asian populations with similar genetic and environmental backgrounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Score-moment combined linear discrimination analysis (SMC-LDA) as an improved discrimination method.

    PubMed

    Han, Jintae; Chung, Hoeil; Han, Sung-Hwan; Yoon, Moon-Young

    2007-01-01

    A new discrimination method called the score-moment combined linear discrimination analysis (SMC-LDA) has been developed and its performance has been evaluated using three practical spectroscopic datasets. The key concept of SMC-LDA was to use not only the score from principal component analysis (PCA), but also the moment of the spectrum, as inputs for LDA to improve discrimination. Along with conventional score, moment is used in spectroscopic fields as an effective alternative for spectral feature representation. Three different approaches were considered. Initially, the score generated from PCA was projected onto a two-dimensional feature space by maximizing Fisher's criterion function (conventional PCA-LDA). Next, the same procedure was performed using only moment. Finally, both score and moment were utilized simultaneously for LDA. To evaluate discrimination performances, three different spectroscopic datasets were employed: (1) infrared (IR) spectra of normal and malignant stomach tissue, (2) near-infrared (NIR) spectra of diesel and light gas oil (LGO) and (3) Raman spectra of Chinese and Korean ginseng. For each case, the best discrimination results were achieved when both score and moment were used for LDA (SMC-LDA). Since the spectral representation character of moment was different from that of score, inclusion of both score and moment for LDA provided more diversified and descriptive information.

  2. Spectral data compression using weighted principal component analysis with consideration of human visual system and light sources

    NASA Astrophysics Data System (ADS)

    Cao, Qian; Wan, Xiaoxia; Li, Junfeng; Liu, Qiang; Liang, Jingxing; Li, Chan

    2016-10-01

    This paper proposed two weight functions based on principal component analysis (PCA) to reserve more colorimetric information in spectral data compression process. One weight function consisted of the CIE XYZ color-matching functions representing the characteristic of the human visual system, while another was made up of the CIE XYZ color-matching functions of human visual system and relative spectral power distribution of the CIE standard illuminant D65. The improvement obtained from the proposed two methods were tested to compress and reconstruct the reflectance spectra of 1600 glossy Munsell color chips and 1950 Natural Color System color chips as well as six multispectral images. The performance was evaluated by the mean values of color difference under the CIE 1931 standard colorimetric observer and the CIE standard illuminant D65 and A. The mean values of root mean square errors between the original and reconstructed spectra were also calculated. The experimental results show that the proposed two methods significantly outperform the standard PCA and another two weighted PCA in the aspects of colorimetric reconstruction accuracy with very slight degradation in spectral reconstruction accuracy. In addition, weight functions with the CIE standard illuminant D65 can improve the colorimetric reconstruction accuracy compared to weight functions without the CIE standard illuminant D65.

  3. Prostate cancer molecular profiling: the Achilles heel for the implementation of precision medicine.

    PubMed

    Oliveira-Barros, Eliane Gouvêa; Nicolau-Neto, Pedro; Da Costa, Nathalia Meireles; Pinto, Luís Felipe Ribeiro; Palumbo, Antonio; Nasciutti, Luiz Eurico

    2017-11-01

    Cancer has been mainly treated by traditional therapeutic approaches which do not consider the human genetic diversity and present limitations, probably as a consequence of a poor knowledge of both patient's genetic background and tumor biology. Due to genome project conclusion and large-scale gene analyses emergence, the therapeutic management of several prevalent and aggressive tumors has dramatically improved and represents the closest examples of a precision medicine intervention in this field. Nonetheless, prostate cancer (PCa) remains as a challenge to personalized medicine implementation, probably due to its notorious heterogeneous molecular profile. Cancer treatment personalized approaches rely on the premise that a well-defined panorama of tumor molecular alterations can help selecting new and specific therapeutic targets for its treatment and potentially discriminate tumors which behave differentially. Lately, molecular and genetic studies have been investigating PCa basis, revealing multiple recurrent genomic alterations that include mutations, DNA copy-number variations, rearrangements, and gene fusions, among others. In addition to the increment on PCa molecular biology knowledge, mapping the molecular alterations pattern of this neoplasia, especially the differences existent between tumors displaying distinct behaviors, could represent a great improvement concerning the identification of new targets, personalized medicine, and patients' management and prognosis. © 2017 International Federation for Cell Biology.

  4. Plant microRNA-Target Interaction Identification Model Based on the Integration of Prediction Tools and Support Vector Machine

    PubMed Central

    Meng, Jun; Shi, Lin; Luan, Yushi

    2014-01-01

    Background Confident identification of microRNA-target interactions is significant for studying the function of microRNA (miRNA). Although some computational miRNA target prediction methods have been proposed for plants, results of various methods tend to be inconsistent and usually lead to more false positive. To address these issues, we developed an integrated model for identifying plant miRNA–target interactions. Results Three online miRNA target prediction toolkits and machine learning algorithms were integrated to identify and analyze Arabidopsis thaliana miRNA-target interactions. Principle component analysis (PCA) feature extraction and self-training technology were introduced to improve the performance. Results showed that the proposed model outperformed the previously existing methods. The results were validated by using degradome sequencing supported Arabidopsis thaliana miRNA-target interactions. The proposed model constructed on Arabidopsis thaliana was run over Oryza sativa and Vitis vinifera to demonstrate that our model is effective for other plant species. Conclusions The integrated model of online predictors and local PCA-SVM classifier gained credible and high quality miRNA-target interactions. The supervised learning algorithm of PCA-SVM classifier was employed in plant miRNA target identification for the first time. Its performance can be substantially improved if more experimentally proved training samples are provided. PMID:25051153

  5. An artificial intelligence based improved classification of two-phase flow patterns with feature extracted from acquired images.

    PubMed

    Shanthi, C; Pappa, N

    2017-05-01

    Flow pattern recognition is necessary to select design equations for finding operating details of the process and to perform computational simulations. Visual image processing can be used to automate the interpretation of patterns in two-phase flow. In this paper, an attempt has been made to improve the classification accuracy of the flow pattern of gas/ liquid two- phase flow using fuzzy logic and Support Vector Machine (SVM) with Principal Component Analysis (PCA). The videos of six different types of flow patterns namely, annular flow, bubble flow, churn flow, plug flow, slug flow and stratified flow are recorded for a period and converted to 2D images for processing. The textural and shape features extracted using image processing are applied as inputs to various classification schemes namely fuzzy logic, SVM and SVM with PCA in order to identify the type of flow pattern. The results obtained are compared and it is observed that SVM with features reduced using PCA gives the better classification accuracy and computationally less intensive than other two existing schemes. This study results cover industrial application needs including oil and gas and any other gas-liquid two-phase flows. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  6. The Relevance of the Procedures Related to the Physiotherapy in the Interventions in Patients with Prostate Cancer: Short Review with Practice Approach

    PubMed Central

    Bernardo-Filho, Mario; Barbosa Júnior, Mauro Luis; da Cunha Sá-Caputo, Danúbia; de Aguiar, Eliane de Oliveira Guedes; de Lima, Rafaelle Pacheco Carvalho; Santos-Filho, Sebastião David; de Paoli, Severo; Presta, Giuseppe Antonio; de Oliveira Bravo Monteiro, Milena; Tavares, Ângela

    2014-01-01

    Advances in medical science procedures and their utilization in the field of oncology improved the survival of patients. In consequence, these advances have influenced the practice of physiotherapy. Physiotherapists utilize physical agents with the objective to enhance the health, welfare and quality of life and thus they can play important role in the management and rehabilitation of patients with prostate cancer (PCa). Urinary incontinence (UI) and erectile dysfunction (ED) are effects normally associated with the radical prostatectomy and radiotherapy due to the damage of the muscles of the pelvic floor (MPV). The aim of this work is to present findings related to the PCa and how the physiotherapist can guide the patient in relation to the knowledge and understanding of the anatomic structures related directly with the pelvic floor, the correct breathing and the perception of the MPV, as other muscles of the pelvis. Interventions of the physiotherapy will re-train the muscles of the pelvis by improving the active retention strength of the MPV in order to overcome the insufficiency (mainly the UI and ED) of the injured muscles. In conclusion, it is suggested to consider and to offer to the PCa patients the techniques related to the physiotherapy before and after the treatment. PMID:25018676

  7. Vascular Reactivity Profile of Novel KCa 3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed.

    PubMed

    Oliván-Viguera, Aida; Valero, Marta Sofía; Pinilla, Estéfano; Amor, Sara; García-Villalón, Ángel Luis; Coleman, Nichole; Laría, Celia; Calvín-Tienza, Víctor; García-Otín, Ángel-Luis; Fernández-Fernández, José M; Murillo, M Divina; Gálvez, José A; Díaz-de-Villegas, María D; Badorrey, Ramón; Simonsen, Ulf; Rivera, Luis; Wulff, Heike; Köhler, Ralf

    2016-08-01

    Opening of intermediate-conductance calcium-activated potassium channels (KC a 3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KC a 3.1-selective positive-gating modulators, SKA-111 and SKA-121, to (1) evoke porcine endothelial cell KC a 3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KC a currents evoked by bradykinin (BK) were potentiated ≈7-fold by either SKA-111 or SKA-121 (both at 1 μM) and were blocked by a KC a 3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinin-induced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by ≈2-fold. Potentiation of the BK response was prevented by KC a 3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KC a 3.1 channels improves BK-induced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KC a 3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  8. Simply enhancing throughput of free-flow electrophoresis via organic-aqueous environment for purification of weak polarity solute of phenazine-1-carboxylic acid in fermentation of Pseudomonas sp. M18.

    PubMed

    Yang, Jing-Hua; Shao, Jing; Wang, Hou-Yu; Dong, Jing-Yu; Fan, Liu-Yin; Cao, Cheng-Xi; Xu, Yu-Quan

    2012-09-01

    Herein, a simple novel free-flow electrophoresis (FFE) method was developed via introduction of organic solvent into the electrolyte system, increasing the solute solubility and throughput of the sample. As a proof of concept, phenazine-1-carboxylic acid (PCA) from Pseudomonas sp. M18 was selected as a model solute for the demonstration on feasibility of novel FFE method on account of its faint solubility in aqueous circumstance. In the developed method, the organic solvent was added into not only the sample buffer to improve the solubility of the solute, but also the background buffer to construct a uniform aqueous-organic circumstance. These factors of organic solvent percentage and types as well as pH value of background buffer were investigated for the purification of PCA in the FFE device via CE. The experiments revealed that the percentage and the types of organic solvent exerted major influence on the purification of PCA. Under the optimized conditions (30 mM phosphate buffer in 60:40 (v/v) water-methanol at an apparent pH 7.0, 3.26 mL/min background flux, 10-min residence time of injected sample, and 400 V), PCA could be continuously purified from its impurities. The flux of sample injection was 10.05 μL/min, and the recovery was up to 93.7%. An 11.9-fold improvement of throughput was found with a carrier buffer containing 40% (v/v) methanol, compared with the pure aqueous phase. The developed procedure is of evident significance for the purification of weak polarity solute via FFE. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Under-representation of racial minorities in prostate cancer studies submitted to the US Food and Drug Administration to support potential marketing approval, 1993-2013.

    PubMed

    Wissing, Michel D; Kluetz, Paul G; Ning, Yang-Min; Bull, Jonca; Merenda, Christine; Murgo, Anthony J; Pazdur, Richard

    2014-10-01

    US Food and Drug Administration (FDA) approval of new drugs depends on results from clinical trials that must be generalized to the US population. However, racial minorities are frequently under-represented in clinical studies. The enrollment of racial minorities was compared in key clinical studies submitted to the FDA in the last 10 years in support of potential marketing approval for prostate cancer (PCa) prevention or treatment. Patient demographic data were obtained from archival data sets of large registration trials submitted to the FDA to support proposed PCa indications. Six countries/regions were analyzed: the United States, Canada, Australia, Europe, the United Kingdom, and Eastern Europe. Background racial demographics were collected from national census data. Seventeen key PCa clinical trials were analyzed. These trials were conducted in the past 20 years, comprising 39,574 patients with known racial information. Most patients were enrolled in the United States, but there appeared to be a trend toward increased non-US enrollment over time. In all countries, racial minorities were generally under-represented. There was no significant improvement in racial minority enrollment over time. The United States enrolled the largest nonwhite population (7.1%). Over the past 20 years, racial minorities were consistently under-represented in key PCa trials. There is a need for effective measures that will improve enrollment of racial minorities. With increased global enrollment, drug developers should aim to recruit a patient population that resembles the racial demographics of the patient population to which drug use will be generalized upon approval. © 2014 American Cancer Society.

  10. PCA-LBG-based algorithms for VQ codebook generation

    NASA Astrophysics Data System (ADS)

    Tsai, Jinn-Tsong; Yang, Po-Yuan

    2015-04-01

    Vector quantisation (VQ) codebooks are generated by combining principal component analysis (PCA) algorithms with Linde-Buzo-Gray (LBG) algorithms. All training vectors are grouped according to the projected values of the principal components. The PCA-LBG-based algorithms include (1) PCA-LBG-Median, which selects the median vector of each group, (2) PCA-LBG-Centroid, which adopts the centroid vector of each group, and (3) PCA-LBG-Random, which randomly selects a vector of each group. The LBG algorithm finds a codebook based on the better vectors sent to an initial codebook by the PCA. The PCA performs an orthogonal transformation to convert a set of potentially correlated variables into a set of variables that are not linearly correlated. Because the orthogonal transformation efficiently distinguishes test image vectors, the proposed PCA-LBG-based algorithm is expected to outperform conventional algorithms in designing VQ codebooks. The experimental results confirm that the proposed PCA-LBG-based algorithms indeed obtain better results compared to existing methods reported in the literature.

  11. Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis

    PubMed Central

    Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Li, Qinlong; Hu, Peizhen; Shi, Changhong; Li, Yang; Chen, Yi-Ting; Yin, Fei; Liao, Chun-Peng; Stiles, Bangyan L.; Zhau, Haiyen E.; Shih, Jean C.; Chung, Leland W.K.

    2014-01-01

    Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines. Despite the association between MAOA and aggressive PCa, it is unclear how MAOA promotes PCa progression. Here, we found that MAOA functions to induce epithelial-to-mesenchymal transition (EMT) and stabilize the transcription factor HIF1α, which mediates hypoxia through an elevation of ROS, thus enhancing growth, invasiveness, and metastasis of PCa cells. Knockdown and overexpression of MAOA in human PCa cell lines indicated that MAOA induces EMT through activation of VEGF and its coreceptor neuropilin-1. MAOA-dependent activation of neuropilin-1 promoted AKT/FOXO1/TWIST1 signaling, allowing FOXO1 binding at the TWIST1 promoter. Importantly, the MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway was activated in high-grade PCa specimens, and knockdown of MAOA reduced or even eliminated prostate tumor growth and metastasis in PCa xenograft mouse models. Pharmacological inhibition of MAOA activity also reduced PCa xenograft growth in mice. Moreover, high MAOA expression in PCa tissues correlated with worse clinical outcomes in PCa patients. These findings collectively characterize the contribution of MAOA in PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in PCa. PMID:24865426

  12. Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis.

    PubMed

    Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Li, Qinlong; Hu, Peizhen; Shi, Changhong; Li, Yang; Chen, Yi-Ting; Yin, Fei; Liao, Chun-Peng; Stiles, Bangyan L; Zhau, Haiyen E; Shih, Jean C; Chung, Leland W K

    2014-07-01

    Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines. Despite the association between MAOA and aggressive PCa, it is unclear how MAOA promotes PCa progression. Here, we found that MAOA functions to induce epithelial-to-mesenchymal transition (EMT) and stabilize the transcription factor HIF1α, which mediates hypoxia through an elevation of ROS, thus enhancing growth, invasiveness, and metastasis of PCa cells. Knockdown and overexpression of MAOA in human PCa cell lines indicated that MAOA induces EMT through activation of VEGF and its coreceptor neuropilin-1. MAOA-dependent activation of neuropilin-1 promoted AKT/FOXO1/TWIST1 signaling, allowing FOXO1 binding at the TWIST1 promoter. Importantly, the MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway was activated in high-grade PCa specimens, and knockdown of MAOA reduced or even eliminated prostate tumor growth and metastasis in PCa xenograft mouse models. Pharmacological inhibition of MAOA activity also reduced PCa xenograft growth in mice. Moreover, high MAOA expression in PCa tissues correlated with worse clinical outcomes in PCa patients. These findings collectively characterize the contribution of MAOA in PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in PCa.

  13. MD-11 PCA - Research flight team photo

    NASA Technical Reports Server (NTRS)

    1995-01-01

    On Aug. 30, 1995, a the McDonnell Douglas MD-11 transport aircraft landed equipped with a computer-assisted engine control system that has the potential to increase flight safety. In landings at NASA Dryden Flight Research Center, Edwards, California, on August 29 and 30, the aircraft demonstrated software used in the aircraft's flight control computer that essentially landed the MD-11 without a need for the pilot to manipulate the flight controls significantly. In partnership with McDonnell Douglas Aerospace (MDA), with Pratt & Whitney and Honeywell helping to design the software, NASA developed this propulsion-controlled aircraft (PCA) system following a series of incidents in which hydraulic failures resulted in the loss of flight controls. This new system enables a pilot to operate and land the aircraft safely when its normal, hydraulically-activated control surfaces are disabled. This August 29, 1995, photo shows the MD-11 team. Back row, left to right: Tim Dingen, MDA pilot; John Miller, MD-11 Chief pilot (MDA); Wayne Anselmo, MD-11 Flight Test Engineer (MDA); Gordon Fullerton, PCA Project pilot; Bill Burcham, PCA Chief Engineer; Rudey Duran, PCA Controls Engineer (MDA); John Feather, PCA Controls Engineer (MDA); Daryl Townsend, Crew Chief; Henry Hernandez, aircraft mechanic; Bob Baron, PCA Project Manager; Don Hermann, aircraft mechanic; Jerry Cousins, aircraft mechanic; Eric Petersen, PCA Manager (Honeywell); Trindel Maine, PCA Data Engineer; Jeff Kahler, PCA Software Engineer (Honeywell); Steve Goldthorpe, PCA Controls Engineer (MDA). Front row, left to right: Teresa Hass, Senior Project Management Analyst; Hollie Allingham (Aguilera), Senior Project Management Analyst; Taher Zeglum, PCA Data Engineer (MDA); Drew Pappas, PCA Project Manager (MDA); John Burken, PCA Control Engineer.

  14. The utilization of Depth Invariant Index and Principle Component Analysis for mapping seagrass ecosystem of Kotok Island and Karang Bongkok, Indonesia

    NASA Astrophysics Data System (ADS)

    Manuputty, Agnestesya; Lumban Gaol, Jonson; Bahri Agus, Syamsul; Wayan Nurjaya, I.

    2017-01-01

    Seagrass perform a variety of functions within ecosystems, and have both economic and ecological values, therefore it has to be kept sustainable. One of the stages to preserve seagrass ecosystems is monitoring by utilizing thespatial data accurately. The purpose of the study was to assess and compare the accuracy of DII and PCA transformationsfor mapping of seagrass ecosystems. Fieldstudy was carried out in Karang Bongkok and Kotok Island waters, in Agustus 2014 and in March 2015. A WorldView-2 image acquisition date of 5 October 2013 was used in the study. The transformations for image processing data were Depth Invariant Index (DII) and Principle Component Analysis (PCA) using Support Vector Machine (SVM) classification. The result shows that benthic habitat mapping of Karang Bongkok using DII and PCA transformations were 72%and 81% overall’s accuracy respectively, whereas of Kotok Island were 83% and 84% overall’s accuracy respectively. There were seven benthic habitat types found in karang Bongkok waters and in Kotok Island namely seagrass, sand, rubble, coral, logoon, sand mix seagrass, and sand mix rubble. PCA transformation was effectively to improve mapping accuracy of sea grass mapping in Kotok Island and Karang Bongkok.

  15. Biomarkers in prostate cancer: what’s new?

    PubMed Central

    Sartori, David A.; Chan, Daniel W.

    2014-01-01

    Purpose of review This review is intended to provide an overview of the current state of biomarkers for prostate cancer (PCa), with a focus on biomarkers approved by the US Food and Drug Administration (FDA) as well as biomarkers available from Clinical Laboratory Improvement Amendment (CLIA)-certified clinical laboratories within the last 1–2 years. Recent findings During the past 2 years, two biomarkers have been approved by the US FDA. These include proPSA as part of the Prostate Health Index (phi) by Beckman Coulter, Inc and PCA3 as Progensa by Gen Probe, Inc. With the advances in genomic and proteomic technologies, several new CLIA-based laboratory-developed tests have become available. Examples are Oncotype DX from Genomics Health, Inc, and Prolaris from Myriad Genetics, Inc. In most cases, these new tests are based on a combination of multiple genomic or proteomic biomarkers. Summary Several new tests, as discussed in this review, have become available during the last 2 years. Although the intended use of most of these tests is to distinguish PCa from benign prostatic conditions with better sensitivity and specificity than prostate-specific antigen, studies have shown that some of them may also be useful in the differentiation of aggressive from nonaggressive forms of PCa. PMID:24626128

  16. Identification of parallel and divergent optimization solutions for homologous metabolic enzymes

    DOE PAGES

    Standaert, Robert F.; Giannone, Richard J.; Michener, Joshua K.

    2018-04-18

    Here, metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB), a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI, from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA), the oxidation product of 4-HB. Neithermore » enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA, duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI, growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity.« less

  17. Principal Component Analysis in the Spectral Analysis of the Dynamic Laser Speckle Patterns

    NASA Astrophysics Data System (ADS)

    Ribeiro, K. M.; Braga, R. A., Jr.; Horgan, G. W.; Ferreira, D. D.; Safadi, T.

    2014-02-01

    Dynamic laser speckle is a phenomenon that interprets an optical patterns formed by illuminating a surface under changes with coherent light. Therefore, the dynamic change of the speckle patterns caused by biological material is known as biospeckle. Usually, these patterns of optical interference evolving in time are analyzed by graphical or numerical methods, and the analysis in frequency domain has also been an option, however involving large computational requirements which demands new approaches to filter the images in time. Principal component analysis (PCA) works with the statistical decorrelation of data and it can be used as a data filtering. In this context, the present work evaluated the PCA technique to filter in time the data from the biospeckle images aiming the reduction of time computer consuming and improving the robustness of the filtering. It was used 64 images of biospeckle in time observed in a maize seed. The images were arranged in a data matrix and statistically uncorrelated by PCA technique, and the reconstructed signals were analyzed using the routine graphical and numerical methods to analyze the biospeckle. Results showed the potential of the PCA tool in filtering the dynamic laser speckle data, with the definition of markers of principal components related to the biological phenomena and with the advantage of fast computational processing.

  18. Metformin association with lower prostate cancer recurrence in type 2 diabetes: a systematic review and meta-analysis.

    PubMed

    Hwang, In Cheol; Park, Sang Min; Shin, Doosup; Ahn, Hong Yup; Rieken, Malte; Shariat, Shahrokh F

    2015-01-01

    Accumulating evidence suggests that metformin possesses anticarcinogenic properties, and its use is associated with favorable outcomes in several cancers. However, it remains unclear whether metformin influences prognosis in prostate cancer (PCa) with concurrent type 2 diabetes (T2D). We searched PubMed, EMBASE, and the Cochrane Library from database inception to April 16, 2014 without language restrictions to identify studies investigating the effect of metformin treatment on outcomes of PCa with concurrent T2D. We conducted a meta-analysis to quantify the risk of recurrence, progression, cancer-specific mortality, and all-cause mortality. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Publication bias was assessed by Begg's rank correlation test. A total of eight studies fulfilled the eligibility criteria. We found that diabetic PCa patients who did not use metformin were at increased risk of cancer recurrence (RR, 1.20; 95%CI, 1.00-1.44), compared with those who used metformin. A similar trend was observed for other outcomes, but their relationships did not reach statistical significance. Funnel plot asymmetry was not observed among studies reporting recurrence (p=0.086). Our results suggest that metformin may improve outcomes in PCa patients with concurrent T2D. Well-designed large studies and collaborative basic research are warranted.

  19. Enlightening discriminative network functional modules behind Principal Component Analysis separation in differential-omic science studies

    PubMed Central

    Ciucci, Sara; Ge, Yan; Durán, Claudio; Palladini, Alessandra; Jiménez-Jiménez, Víctor; Martínez-Sánchez, Luisa María; Wang, Yuting; Sales, Susanne; Shevchenko, Andrej; Poser, Steven W.; Herbig, Maik; Otto, Oliver; Androutsellis-Theotokis, Andreas; Guck, Jochen; Gerl, Mathias J.; Cannistraci, Carlo Vittorio

    2017-01-01

    Omic science is rapidly growing and one of the most employed techniques to explore differential patterns in omic datasets is principal component analysis (PCA). However, a method to enlighten the network of omic features that mostly contribute to the sample separation obtained by PCA is missing. An alternative is to build correlation networks between univariately-selected significant omic features, but this neglects the multivariate unsupervised feature compression responsible for the PCA sample segregation. Biologists and medical researchers often prefer effective methods that offer an immediate interpretation to complicated algorithms that in principle promise an improvement but in practice are difficult to be applied and interpreted. Here we present PC-corr: a simple algorithm that associates to any PCA segregation a discriminative network of features. Such network can be inspected in search of functional modules useful in the definition of combinatorial and multiscale biomarkers from multifaceted omic data in systems and precision biomedicine. We offer proofs of PC-corr efficacy on lipidomic, metagenomic, developmental genomic, population genetic, cancer promoteromic and cancer stem-cell mechanomic data. Finally, PC-corr is a general functional network inference approach that can be easily adopted for big data exploration in computer science and analysis of complex systems in physics. PMID:28287094

  20. Identification of parallel and divergent optimization solutions for homologous metabolic enzymes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Standaert, Robert F.; Giannone, Richard J.; Michener, Joshua K.

    Here, metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB), a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI, from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA), the oxidation product of 4-HB. Neithermore » enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA, duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI, growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity.« less

  1. Fabrication of Oxide Dispersion Strengthened Bond Coats with Low Al2O3 Content

    NASA Astrophysics Data System (ADS)

    Bergholz, Jan; Pint, Bruce A.; Unocic, Kinga A.; Vaßen, Robert

    2017-06-01

    Nanoscale oxide dispersions have long been used to increase the oxidation and wear resistance of alloys used as bond coatings in thermal barrier coatings. Their manufacturing via mechanical alloying is often accompanied by difficulties regarding their particle size, homogeneous distribution of the oxide dispersions inside the powder, involving considerable costs, due to cold welding of the powder during milling. A significant improvement in this process can be achieved by the use of process control agent (PCA) to achieve the critical balance between cold welding and fracturing, thereby enhancing the process efficiency. In this investigation, the influence of the organic additive stearic acid on the manufacturing process of Al2O3-doped CoNiCrAlY powder was investigated. Powders were fabricated via mechanical alloying at different milling times and PCA concentrations. The results showed a decrease in particle size, without hindering the homogeneous incorporation of the oxide dispersions. Two powders manufactured with 0.5 and 1.0 wt.% PCA were deposited by high velocity oxygen fuel (HVOF) spraying. Results showed that a higher content of elongated particles in the powder with the higher PCA content led to increased surface roughness, porosity and decreased coating thickness, with areas without embedded oxide particles.

  2. Identification of parallel and divergent optimization solutions for homologous metabolic enzymes.

    PubMed

    Standaert, Robert F; Giannone, Richard J; Michener, Joshua K

    2018-06-01

    Metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB), a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI , from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA), the oxidation product of 4-HB. Neither enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA , duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI , growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity.

  3. Comparative analysis of prostate-specific antigen by two-dimensional gel electrophoresis and capillary electrophoresis.

    PubMed

    Barrabés, Sílvia; Farina-Gomez, Noemi; Llop, Esther; Puerta, Angel; Diez-Masa, Jose Carlos; Perry, Antoinette; de Llorens, Rafael; de Frutos, Mercedes; Peracaula, Rosa

    2017-02-01

    Serum levels of Prostate-Specific Antigen (PSA) are not fully specific for prostate cancer (PCa) diagnosis and several efforts are focused on searching to improve PCa markers through the study of PSA subforms that could be cancer associated. We have previously reported by 2DE a decrease in the sialic acid content of PSA from PCa compared to benign prostatic hyperplasia patients based on the different proportion of the PSA spots. However, faster and more quantitative techniques, easier to automate than 2DE, are desirable. In this study, we examined the potential of CE for resolving PSA subforms in different samples and compared the results with those obtained by 2DE. We first fractionated by OFFGEL the subforms of PSA from seminal plasma according to their pIs and analyzed each separated fraction by 2DE and CE. We also analyzed PSA and high pI PSA, both from seminal plasma, and PSA from urine of a PCa patient. These samples with different PSA spots proportions by 2DE, due to different posttranslational modifications, also presented different CE profiles. This study shows that CE is a useful and complementary technique to 2DE for analyzing samples with different PSA subforms, which is of high clinical interest. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Principal component analysis for the comparison of metabolic profiles from human rectal cancer biopsies and colorectal xenografts using high-resolution magic angle spinning 1H magnetic resonance spectroscopy

    PubMed Central

    Seierstad, Therese; Røe, Kathrine; Sitter, Beathe; Halgunset, Jostein; Flatmark, Kjersti; Ree, Anne H; Olsen, Dag Rune; Gribbestad, Ingrid S; Bathen, Tone F

    2008-01-01

    Background This study was conducted in order to elucidate metabolic differences between human rectal cancer biopsies and colorectal HT29, HCT116 and SW620 xenografts by using high-resolution magnetic angle spinning (MAS) magnetic resonance spectroscopy (MRS) and for determination of the most appropriate human rectal xenograft model for preclinical MR spectroscopy studies. A further aim was to investigate metabolic changes following irradiation of HT29 xenografts. Methods HR MAS MRS of tissue samples from xenografts and rectal biopsies were obtained with a Bruker Avance DRX600 spectrometer and analyzed using principal component analysis (PCA) and partial least square (PLS) regression analysis. Results and conclusion HR MAS MRS enabled assignment of 27 metabolites. Score plots from PCA of spin-echo and single-pulse spectra revealed separate clusters of the different xenografts and rectal biopsies, reflecting underlying differences in metabolite composition. The loading profile indicated that clustering was mainly based on differences in relative amounts of lipids, lactate and choline-containing compounds, with HT29 exhibiting the metabolic profile most similar to human rectal cancers tissue. Due to high necrotic fractions in the HT29 xenografts, radiation-induced changes were not detected when comparing spectra from untreated and irradiated HT29 xenografts. However, PLS calibration relating spectral data to the necrotic fraction revealed a significant correlation, indicating that necrotic fraction can be assessed from the MR spectra. PMID:18439252

  5. Evaluation of Vitronectin Expression in Prostate Cancer and the Clinical Significance of the Association of Vitronectin Expression with Prostate Specific Antigen in Detecting Prostate Cancer.

    PubMed

    Niu, Yue; Zhang, Ling; Bi, Xing; Yuan, Shuai; Chen, Peng

    2016-03-05

    To detect the expression of vitronectin (VTN) in the tissues and blood serum of prostate cancer (PCa) patients, and evaluate its clinical significance and to evaluate the significance of the combined assay of VTN and prostate specific antigens (PSA) in PCa diagnosis. To detect the expression of VTN as a potential marker for PCa diagnosis and prognosis, immunohistochemistry was performed on the tissues of 32 patients with metastatic PCa (PCaM), 34 patients with PCa without metastasis (PCa), and 41 patients with benign prostatic hyperplasia (BPH). The sera were then subjected to Western blot analysis. All cases were subsequently examined to determine the concentrations of PSA and VTN in the sera. The collected data were collated and analyzed. The positive expression rates of VTN in the tissues of the BPH and PCa groups (including PCa and PCaM groups) were 75.61% and 45.45%, respectively (P = .005). VTN was more highly expressed in the sera of the BPH patients (0.83 ± 0.07) than in the sera of the PCa patients (0.65 ± 0.06) (P < .05). It was also more highly expressed in the sera of the PCa patients than in the sera of the PCaM patients (0.35 ± 0.08) (P < .05). In the diagnosis of BPH and PCa, the Youden indexes of PSA detection, VTN detection, and combined detection were 0.2620, 0.3468, and 0.5635; the kappa values were 0.338, 0.304, and 0.448, respectively, and the areas under the receiver operating characteristic curve were 0.625, 0.673, and 0.703 (P < .05), respectively. VTN levels in sera may be used as a potential marker of PCa for the diagnosis and assessment of disease progression and metastasis. The combined detection of VTN and PSA in sera can be clinically applied in PCa diagnosis. .

  6. The impact of metformin use on survival in prostate cancer: a systematic review and meta-analysis

    PubMed Central

    Xiao, Yao; Zheng, Lei; Mei, Zubing; Xu, Changbao; Liu, Changwei; Chu, Xiaohan; Hao, Bin

    2017-01-01

    Background Metformin has been implicated to reduce the risk of prostate cancer (PCa) beyond its glucose-lowering effect. However, the influence of metformin on prognosis of PCa is often controversial. Results A total of 13 cohort studies encompassing 177,490 individuals were included in the meta-analysis. Data on overall survival (OS) and cancer-specific survival (CSS) was extracted from 8 and six studies, respectively. Comparing metformin users with non-metformin users, the pooled hazard ratios (HRs) for OS and CSS were 0.79 (95% confidence interval [CI] 0.63–0.98) and 0.76 (95% CI 0.57–1.02), respectively. Subgroup analyses stratified by baseline charcteristics indicated significant CSS benefits were noted in studies conducted in USA/Canada with prospective, large sample size, multiple-centered study design. Five studies reported the PCa prognosis for recurrence-free survival (RFS) and metformin use was significantly associated with patient RFS (HR 0.74, 95% CI, 0.58–0.95). Methods Relevant studies were searched and identified using PubMed, Embase and Cochrane databases from inception through January 2017, which investigated associations between the use of metformin and PCa prognosis. Combined HRs with 95% CI were pooled using a random-effects model. The primary outcomes of interest were OS and CSS. Conclusions Our findings provide indication that metformin therapy has a trend to improve survival for patients with PCa. Further prospective, multi-centered, large sample size cohort studies are warranted to determine the true relationship. PMID:29245991

  7. Nanocrystalline Nb-Al-Ge mixtures fabricated using wet mechanical milling

    NASA Astrophysics Data System (ADS)

    Pusceddu, E.; Charlton, S.; Hampshire, D. P.

    2008-02-01

    An investigation into Nb-Al-Ge mixtures is presented with special attention to the superconducting compounds Nb3(Al1-xGex) with x = 0, 0.3 and 1, which are reported to provide the highest upper critical field values for Nb-based compounds. Wet mechanical milling using copper milling media and distilled water as a process control agent (PCA) was used with the intention of improving the yield, properties and the performance of these materials. Very high yields of nanocrystalline material were achieved but significant copper contamination occurred - confirmed using inductively-coupled-plasma atomic-emission-spectroscopy. Simultaneous thermogravimetric measurements and differential scanning calorimetry were performed on powders milled for up to 20 h with different PCA content, to quantify the work done on the powders. A typical grain size of a few nm was obtained for the Nb-Al-Ge mixtures after several hours milling. Powder ground for 20 h with 5% PCA was processed using a hot isostatic press (HIP) operating at 2000 atm and temperatures up to 750 °C. The room temperature resistivity decreased as the temperature of the HIPing increased. Unfortunately, despite the nanocrystalline microstructure of the powders and the high HIP temperatures, if superconducting material was formed it was below the detection level of resistivity, Ac. susceptibility and SQUID measurements. We conclude that during milling there was widespread contamination of the powders by the PCA so that milling with distilled water as a PCA is not to be recommended for fabricating nanocrystalline Nb3(Al1-xGex) A15 superconducting compounds.

  8. Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease.

    PubMed

    Xu, San-Qing; Li, Xu-Fang; Zhu, Hui-Yun; Liu, Yan; Fang, Feng; Chen, Ling

    2013-10-01

    The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.

  9. Overexpression of a BAHD Acyltransferase, OsAt10, Alters Rice Cell Wall Hydroxycinnamic Acid Content and Saccharification1[C][W][OA

    PubMed Central

    Bartley, Laura E.; Peck, Matthew L.; Kim, Sung-Ryul; Ebert, Berit; Manisseri, Chithra; Chiniquy, Dawn M.; Sykes, Robert; Gao, Lingfang; Rautengarten, Carsten; Vega-Sánchez, Miguel E.; Benke, Peter I.; Canlas, Patrick E.; Cao, Peijian; Brewer, Susan; Lin, Fan; Smith, Whitney L.; Zhang, Xiaohan; Keasling, Jay D.; Jentoff, Rolf E.; Foster, Steven B.; Zhou, Jizhong; Ziebell, Angela; An, Gynheung; Scheller, Henrik V.; Ronald, Pamela C.

    2013-01-01

    Grass cell wall properties influence food, feed, and biofuel feedstock usage efficiency. The glucuronoarabinoxylan of grass cell walls is esterified with the phenylpropanoid-derived hydroxycinnamic acids ferulic acid (FA) and para-coumaric acid (p-CA). Feruloyl esters undergo oxidative coupling with neighboring phenylpropanoids on glucuronoarabinoxylan and lignin. Examination of rice (Oryza sativa) mutants in a grass-expanded and -diverged clade of BAHD acyl-coenzyme A-utilizing transferases identified four mutants with altered cell wall FA or p-CA contents. Here, we report on the effects of overexpressing one of these genes, OsAt10 (LOC_Os06g39390), in rice. An activation-tagged line, OsAT10-D1, shows a 60% reduction in matrix polysaccharide-bound FA and an approximately 300% increase in p-CA in young leaf tissue but no discernible phenotypic alterations in vegetative development, lignin content, or lignin composition. Two additional independent OsAt10 overexpression lines show similar changes in FA and p-CA content. Cell wall fractionation and liquid chromatography-mass spectrometry experiments isolate the cell wall alterations in the mutant to ester conjugates of a five-carbon sugar with p-CA and FA. These results suggest that OsAT10 is a p-coumaroyl coenzyme A transferase involved in glucuronoarabinoxylan modification. Biomass from OsAT10-D1 exhibits a 20% to 40% increase in saccharification yield depending on the assay. Thus, OsAt10 is an attractive target for improving grass cell wall quality for fuel and animal feed. PMID:23391577

  10. Researches of fruit quality prediction model based on near infrared spectrum

    NASA Astrophysics Data System (ADS)

    Shen, Yulin; Li, Lian

    2018-04-01

    With the improvement in standards for food quality and safety, people pay more attention to the internal quality of fruits, therefore the measurement of fruit internal quality is increasingly imperative. In general, nondestructive soluble solid content (SSC) and total acid content (TAC) analysis of fruits is vital and effective for quality measurement in global fresh produce markets, so in this paper, we aim at establishing a novel fruit internal quality prediction model based on SSC and TAC for Near Infrared Spectrum. Firstly, the model of fruit quality prediction based on PCA + BP neural network, PCA + GRNN network, PCA + BP adaboost strong classifier, PCA + ELM and PCA + LS_SVM classifier are designed and implemented respectively; then, in the NSCT domain, the median filter and the SavitzkyGolay filter are used to preprocess the spectral signal, Kennard-Stone algorithm is used to automatically select the training samples and test samples; thirdly, we achieve the optimal models by comparing 15 kinds of prediction model based on the theory of multi-classifier competition mechanism, specifically, the non-parametric estimation is introduced to measure the effectiveness of proposed model, the reliability and variance of nonparametric estimation evaluation of each prediction model to evaluate the prediction result, while the estimated value and confidence interval regard as a reference, the experimental results demonstrate that this model can better achieve the optimal evaluation of the internal quality of fruit; finally, we employ cat swarm optimization to optimize two optimal models above obtained from nonparametric estimation, empirical testing indicates that the proposed method can provide more accurate and effective results than other forecasting methods.

  11. Resolution of coi-dominant phytoplankton species in a eutrophiclake using synchrotron-based Fourier transform infraredspectroscopy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dean, A.P.; Martin, Michael C.; Sigee, D.C.

    2006-10-09

    Synchrotron-based Fourier-transform infrared (FTIR)microspectroscopy was used to distinguish micropopulations of thecodominant algae Microcystis aeruginosa (Cyanophyceae) and Ceratiumhirundinella (Dinophyceae) in mixed phytoplankton samples taken from thewater column of a stratified eutrophic lake (Rostherne Mere, UK). FTIRspectra of the two algae showed a closely similar sequence of 10 bandsover the wave-number range 4000-900 cm-1. These were assigned to a rangeof vibrationally active chemical groups using published band assignmentsand on the basis of correlation and factor analysis. In both algae,intracellular concentrations of macromolecular components (determined asband intensity) varied considerably within the same population,indicating substantial intraspecific heterogeneity. Interspecificdifferences were separately analysed in relation tomore » discrete bands and bymultivariate analysis of the entire spectral region 1750-900 cm-1. Interms of discrete bands, comparison of individual intensities (normalisedto amide 1) demonstrated significant (99 percent probability level)differences in relation to six bands between the two algal species. Keyinterspecific differences were also noted in relation to the positions ofbands 2, 10 (carbohydrate) and 7 (protein) and in the 3-D plots derivedby principal component analysis (PCA) of the sequence of bandintensities. PCA of entire spectral regions showed clear resolutionofspecies in the PCA plot, with indication of separation on the basis ofprotein (region 1700-1500 cm1) and carbohydrate (region 1150-900 cm1)composition in the loading plot. Hierarchical cluster analysis (Wardalgorithm) of entire spectral regions also showed clear discrimination ofthe two species within the resulting dendrogram.« less

  12. From the ocean to a salt marsh: towards understanding iron reduction processes with FORC-PCA.

    NASA Astrophysics Data System (ADS)

    Muraszko, J. R.; Lascu, I.; Collins, S. M.; Harrison, R. J.

    2017-12-01

    Biogenic magnetic minerals are a high fidelity recorder of climate change. Their sensitivity to sedimentary redox conditions and bottom water ventilation have the potential to provide useful insights into past diagenetic conditions. However, the mechanisms controlling preservation and dissolution of magnetosomes are not fully understood, thus undermining the reliability of the paleomagnetic records in marine environments. Recovering information about the diagenetic past of the sediment is a crucial challenge; specifically, the biogenic components need to be identified and unmixed from the bulk magnetic signal. We address the issue in this study by applying Principal Component Analysis on First Order Reversal Curve diagrams (FORC-PCA) in case studies of cores obtained from the Iberian Margin and the sedimentologically active coastal salt marshes of Norfolk. We demonstrate the applicability of FORC-PCA as a new environmental proxy, yielding a high resolution temporal marine record of environmental changes reflected in magnetic composition over the last 194 kyr. The strongest variations are observed in the microbially derived components, the bulk properties of the sediment being controlled by a low coercivity SP-SD component which is generally anticorrelated with the magnetosome signal. Supported by TEM studies, we suggest the prevalence of clusters of nano-particles of magnetite associated with iron reduction. To further investigate the mechanisms controlling these processes, the active sedimentary environment of Norfolk was chosen as a case study of early diagenesis controlled by strong vertical geochemical gradients.

  13. Radar target classification method with high accuracy and decision speed performance using MUSIC spectrum vectors and PCA projection

    NASA Astrophysics Data System (ADS)

    Secmen, Mustafa

    2011-10-01

    This paper introduces the performance of an electromagnetic target recognition method in resonance scattering region, which includes pseudo spectrum Multiple Signal Classification (MUSIC) algorithm and principal component analysis (PCA) technique. The aim of this method is to classify an "unknown" target as one of the "known" targets in an aspect-independent manner. The suggested method initially collects the late-time portion of noise-free time-scattered signals obtained from different reference aspect angles of known targets. Afterward, these signals are used to obtain MUSIC spectrums in real frequency domain having super-resolution ability and noise resistant feature. In the final step, PCA technique is applied to these spectrums in order to reduce dimensionality and obtain only one feature vector per known target. In the decision stage, noise-free or noisy scattered signal of an unknown (test) target from an unknown aspect angle is initially obtained. Subsequently, MUSIC algorithm is processed for this test signal and resulting test vector is compared with feature vectors of known targets one by one. Finally, the highest correlation gives the type of test target. The method is applied to wire models of airplane targets, and it is shown that it can tolerate considerable noise levels although it has a few different reference aspect angles. Besides, the runtime of the method for a test target is sufficiently low, which makes the method suitable for real-time applications.

  14. Design of experiments and principal component analysis as approaches for enhancing performance of gas-diffusional air-breathing bilirubin oxidase cathode

    NASA Astrophysics Data System (ADS)

    Babanova, Sofia; Artyushkova, Kateryna; Ulyanova, Yevgenia; Singhal, Sameer; Atanassov, Plamen

    2014-01-01

    Two statistical methods, design of experiments (DOE) and principal component analysis (PCA) are employed to investigate and improve performance of air-breathing gas-diffusional enzymatic electrodes. DOE is utilized as a tool for systematic organization and evaluation of various factors affecting the performance of the composite system. Based on the results from the DOE, an improved cathode is constructed. The current density generated utilizing the improved cathode (755 ± 39 μA cm-2 at 0.3 V vs. Ag/AgCl) is 2-5 times higher than the highest current density previously achieved. Three major factors contributing to the cathode performance are identified: the amount of enzyme, the volume of phosphate buffer used to immobilize the enzyme, and the thickness of the gas-diffusion layer (GDL). PCA is applied as an independent confirmation tool to support conclusions made by DOE and to visualize the contribution of factors in individual cathode configurations.

  15. Rolling Bearing Fault Diagnosis Based on an Improved HTT Transform

    PubMed Central

    Tang, Guiji; Tian, Tian; Zhou, Chong

    2018-01-01

    When rolling bearing failure occurs, vibration signals generally contain different signal components, such as impulsive fault feature signals, background noise and harmonic interference signals. One of the most challenging aspects of rolling bearing fault diagnosis is how to inhibit noise and harmonic interference signals, while enhancing impulsive fault feature signals. This paper presents a novel bearing fault diagnosis method, namely an improved Hilbert time–time (IHTT) transform, by combining a Hilbert time–time (HTT) transform with principal component analysis (PCA). Firstly, the HTT transform was performed on vibration signals to derive a HTT transform matrix. Then, PCA was employed to de-noise the HTT transform matrix in order to improve the robustness of the HTT transform. Finally, the diagonal time series of the de-noised HTT transform matrix was extracted as the enhanced impulsive fault feature signal and the contained fault characteristic information was identified through further analyses of amplitude and envelope spectrums. Both simulated and experimental analyses validated the superiority of the presented method for detecting bearing failures. PMID:29662013

  16. Phenazine-1-carboxylic acid and soil moisture influence biofilm development and turnover of rhizobacterial biomass on wheat root surfaces.

    PubMed

    LeTourneau, Melissa K; Marshall, Matthew J; Cliff, John B; Bonsall, Robert F; Dohnalkova, Alice C; Mavrodi, Dmitri V; Devi, S Indira; Mavrodi, Olga V; Harsh, James B; Weller, David M; Thomashow, Linda S

    2018-04-24

    Phenazine-1-carboxylic acid (PCA) is produced by rhizobacteria in dryland but not in irrigated wheat fields of the Pacific Northwest, USA. PCA promotes biofilm development in bacterial cultures and bacterial colonization of wheat rhizospheres. However, its impact upon biofilm development has not been demonstrated in the rhizosphere, where biofilms influence terrestrial carbon and nitrogen cycles with ramifications for crop and soil health. Furthermore, the relationships between soil moisture and the rates of PCA biosynthesis and degradation have not been established. In this study, expression of PCA biosynthesis genes was up-regulated relative to background transcription, and persistence of PCA was slightly decreased in dryland relative to irrigated wheat rhizospheres. Biofilms in dryland rhizospheres inoculated with the PCA-producing (PCA + ) strain Pseudomonas synxantha 2-79RN 10 were more robust than those in rhizospheres inoculated with an isogenic PCA-deficient (PCA - ) mutant strain. This trend was reversed in irrigated rhizospheres. In dryland PCA + rhizospheres, the turnover of 15 N-labelled rhizobacterial biomass was slower than in the PCA - and irrigated PCA + treatments, and incorporation of bacterial 15 N into root cell walls was observed in multiple treatments. These results indicate that PCA promotes biofilm development in dryland rhizospheres, and likely influences crop nutrition and soil health in dryland wheat fields. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

  17. Incidental prostate cancer in radical cystoprostatectomy specimens.

    PubMed

    Jin, Xiao-Dong; Chen, Zhao-Dian; Wang, Bo; Cai, Song-Liang; Yao, Xiao-Lin; Jin, Bai-Ye

    2008-09-01

    To investigate the rates of prostate cancer (PCa) in radical cystoprostatectomy (RCP) specimens for bladder cancer in mainland China. To determine the follow-up outcome of patients with two concurrent cancers and identify whether prostate-specific antigen (PSA) is a useful tool for the detection of PCa prior to surgery. From January 2002 to January 2007, 264 male patients with bladder cancer underwent RCP at our center. All patients underwent digital rectal examination (DRE) and B ultrasound. Serum PSA levels were tested in 168 patients. None of the patients had any evidence of PCa before RCP. Entire prostates were embedded and sectioned at 5 mm intervals. Incidental PCa was observed in 37 of 264 (14.0%) RCP specimens. Of these, 12 (32.4%) were clinically significant according to an accepted definition. The PSA levels were not significantly different between patients with PCa and those without PCa, nor between patients with significant PCa and those with insignificant PCa. Thirty-four patients with incidental PCa were followed up. During a mean follow-up period of 26 months, two patients with PSA > 4 ng/mL underwent castration. None of the patients died of PCa. The incidence of PCa in RCP specimens in mainland China is lower than that in most developed countries. PSA cannot identify asymptomatic PCa prior to RCP. In line with published reports, incidental PCa does not impact the prognosis of bladder cancer patients undergoing RCP. (c) 2008, Asian Journal of Andrology, SIMM and SJTU. All rights reserved.

  18. Impact of phenazine-1-carboxylic acid upon iron speciation and microbial biomass in the rhizosphere of wheat

    NASA Astrophysics Data System (ADS)

    LeTourneau, M.; Marshall, M.; Grant, M.; Freeze, P.; Cliff, J. B.; Lai, B.; Strawn, D. G.; Thomashow, L. S.; Weller, D. M.; Harsh, J. B.

    2015-12-01

    Phenazine-1-carboxylic acid (PCA) is a redox-active antibiotic produced by diverse bacterial taxa, and has been shown to facilitate interactions between biofilms and iron (hydr)oxides in culture systems (Wang et al. 2011, J Bacteriol 192: 365). Because rhizobacterial biofilms are a major sink for plant-derived carbon and source for soil organic matter (SOM), and Fe (hydr)oxides have reactive surfaces that influence the stability of microbial biomass and SOM, PCA-producing rhizobacteria could influence soil carbon fluxes. Large populations of Pseudomonas fluorescens strains producing PCA in concentrations up to 1 μg/g root have been observed in the rhizosphere of non-irrigated wheat fields covering 1.56 million hectares of central Washington state. This is one of the highest concentrations ever reported for a natural antibiotic in a terrestrial ecosystem (Mavrodi et al. 2012, Appl Environ Microb 78: 804). Microscopic comparisons of PCA-producing (PCA+) and non-PCA-producing (PCA-) rhizobacterial colony morphologies, and comparisons of Fe extractions from rhizosphere soil inoculated with PCA+ and PCA- strains suggest that PCA promotes biofilm development as well as dramatic Fe transformations throughout the rhizosphere (unpublished data). In order to illustrate PCA-mediated interactions between biofilms and Fe (hydr)oxides in the rhizosphere, identify the specific Fe phases favored by PCA, and establish the ramifications for stability and distribution of microbial biomass and SOM, we have collected electron micrographs, X-ray fluorescence images, X-ray absorption near-edge spectra, and secondary-ion mass spectrometry images of wheat root sections inoculated with 15N-labelled PCA+ or PCA- rhizobacteria. These images and spectra allow us to assess the accumulation, turnover, and distribution of microbial biomass, the associations between Fe and other nutrients such as phosphorus, and the redox status and speciation of iron in the presence and absence of PCA. This information provides a starting point to model the impact of PCA upon carbon fluxes in Columbia Basin agro-ecosystems and other environments where PCA-producing bacteria are prevalent.

  19. Blunted neural responses to reward in remitted major depression: A high-density event-related potential study

    PubMed Central

    Whitton, Alexis E.; Kakani, Pragya; Foti, Dan; Van’t Veer, Ashlee; Haile, Anja; Crowley, David J.; Pizzagalli, Diego A.

    2015-01-01

    Background Major depressive disorder (MDD) is a highly recurrent condition, and improving our understanding of the abnormalities that persist in remitted MDD (rMDD) may provide insight into mechanisms that contribute to relapse. MDD has been characterized by reward learning deficits linked to dysfunction in frontostriatal regions. Although initial behavioral evidence of reward learning deficits in rMDD has recently emerged, it is unclear whether these reflect impairments in neural reward processing that persist into remission. Methods We examined behavioral reward learning and 128-channel event-related potentials (ERP) during a well-validated probabilistic reward task in 26 rMDD individuals and 34 never-depressed controls. Temporo-spatial principal components analysis (PCA) was used to separate overlapping ERP components, and group differences in neural activity in a priori regions were examined using low-resolution electromagnetic tomography (LORETA). Results Individuals with rMDD displayed reduced behavioral reward learning, as well as blunted ERP amplitude to reward feedback. Importantly, the reduction in ERP amplitude occurred at a PCA factor that peaked during the time at which phasic reward feedback-related signaling – hypothesized to originate in the striatum and project to the anterior cingulate cortex (ACC) – are thought to modulate scalp-recorded activity. Consistent with this, LORETA analyses revealed reduced activity in the ACC in the rMDD group, and this blunting correlated with poorer reward learning. Conclusion These findings suggest that the reward learning impairment observed in acute MDD persists into full remission and that these impairments may be attributable to abnormalities in the neural processes that support reward feedback monitoring, particularly within the ACC. PMID:26858994

  20. Optical coherence elastography (OCE) as a method for identifying benign and malignant prostate biopsies

    NASA Astrophysics Data System (ADS)

    Li, Chunhui; Guan, Guangying; Ling, Yuting; Lang, Stephen; Wang, Ruikang K.; Huang, Zhihong; Nabi, Ghulam

    2015-03-01

    Objectives. Prostate cancer is the most frequently diagnosed malignancy in men. Digital rectal examination (DRE) - a known clinical tool based on alteration in the mechanical properties of tissues due to cancer has traditionally been used for screening prostate cancer. Essentially, DRE estimates relative stiffness of cancerous and normal prostate tissue. Optical coherence elastography (OCE) are new optical imaging techniques capable of providing cross-sectional imaging of tissue microstructure as well as elastogram in vivo and in real time. In this preliminary study, OCE was used in the setting of the human prostate biopsies ex vivo, and the images acquired were compared with those obtained using standard histopathologic methods. Methods. 120 prostate biopsies were obtained by TRUS guided needle biopsy procedures from 9 patients with clinically suspected cancer of the prostate. The biopsies were approximately 0.8mm in diameter and 12mm in length, and prepared in Formalin solution. Quantitative assessment of biopsy samples using OCE was obtained in kilopascals (kPa) before histopathologic evaluation. The results obtained from OCE and standard histopathologic evaluation were compared provided the cross-validation. Sensitivity, specificity, and positive and negative predictive values were calculated for OCE (histopathology was a reference standard). Results. OCE could provide quantitative elasticity properties of prostate biopsies within benign prostate tissue, prostatic intraepithelial neoplasia, atypical hyperplasia and malignant prostate cancer. Data analysed showed that the sensitivity and specificity of OCE for PCa detection were 1 and 0.91, respectively. PCa had significantly higher stiffness values compared to benign tissues, with a trend of increasing in stiffness with increasing of malignancy. Conclusions. Using OCE, microscopic resolution elastogram is promising in diagnosis of human prostatic diseases. Further studies using this technique to improve the detection and staging of malignant cancer of the prostate are ongoing.

  1. Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

    PubMed

    Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

    2016-11-01

    To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

  2. Spectral images browsing using principal component analysis and set partitioning in hierarchical tree

    NASA Astrophysics Data System (ADS)

    Ma, Long; Zhao, Deping

    2011-12-01

    Spectral imaging technology have been used mostly in remote sensing, but have recently been extended to new area requiring high fidelity color reproductions like telemedicine, e-commerce, etc. These spectral imaging systems are important because they offer improved color reproduction quality not only for a standard observer under a particular illuminantion, but for any other individual exhibiting normal color vision capability under another illuminantion. A possibility for browsing of the archives is needed. In this paper, the authors present a new spectral image browsing architecture. The architecture for browsing is expressed as follow: (1) The spectral domain of the spectral image is reduced with the PCA transform. As a result of the PCA transform the eigenvectors and the eigenimages are obtained. (2) We quantize the eigenimages with the original bit depth of spectral image (e.g. if spectral image is originally 8bit, then quantize eigenimage to 8bit), and use 32bit floating numbers for the eigenvectors. (3) The first eigenimage is lossless compressed by JPEG-LS, the other eigenimages were lossy compressed by wavelet based SPIHT algorithm. For experimental evalution, the following measures were used. We used PSNR as the measurement for spectral accuracy. And for the evaluation of color reproducibility, ΔE was used.here standard D65 was used as a light source. To test the proposed method, we used FOREST and CORAL spectral image databases contrain 12 and 10 spectral images, respectively. The images were acquired in the range of 403-696nm. The size of the images were 128*128, the number of bands was 40 and the resolution was 8 bits per sample. Our experiments show the proposed compression method is suitable for browsing, i.e., for visual purpose.

  3. Ketamine PCA for treatment of end-of-life neuropathic pain in pediatrics.

    PubMed

    Taylor, Matthew; Jakacki, Regina; May, Carol; Howrie, Denise; Maurer, Scott

    2015-12-01

    Control of neuropathic pain (NP) for children at end of life is challenging. Ketamine improves control of NP, but its use in children is not well described. We describe a retrospective case review of 14 children with terminal prognoses treated with ketamine patient-controlled analgesia (PCA) for management of opioid-refractory NP at the end of life. Median ketamine dose was 0.06 mg/kg/h (range 0.014-0.308 mg/kg/h) with a 0.05 mg/kg (range 0.03-0.5mg/kg) demand dose available every 15 minutes (range 10-60 minutes). All patients noted subjective pain relief with ketamine, and 79% had no adverse effects. Benzodiazepines limited neuropsychiatric side effects. Ketamine treatment arrested dose escalation of opioids in 64% of patients, and 79% were discharged to home hospice. Ketamine PCA is an effective, well-tolerated therapy for opioid-refractory NP in pediatric end-of-life care. © The Author(s) 2014.

  4. Combination of multivariate curve resolution and multivariate classification techniques for comprehensive high-performance liquid chromatography-diode array absorbance detection fingerprints analysis of Salvia reuterana extracts.

    PubMed

    Hakimzadeh, Neda; Parastar, Hadi; Fattahi, Mohammad

    2014-01-24

    In this study, multivariate curve resolution (MCR) and multivariate classification methods are proposed to develop a new chemometric strategy for comprehensive analysis of high-performance liquid chromatography-diode array absorbance detection (HPLC-DAD) fingerprints of sixty Salvia reuterana samples from five different geographical regions. Different chromatographic problems occurred during HPLC-DAD analysis of S. reuterana samples, such as baseline/background contribution and noise, low signal-to-noise ratio (S/N), asymmetric peaks, elution time shifts, and peak overlap are handled using the proposed strategy. In this way, chromatographic fingerprints of sixty samples are properly segmented to ten common chromatographic regions using local rank analysis and then, the corresponding segments are column-wise augmented for subsequent MCR analysis. Extended multivariate curve resolution-alternating least squares (MCR-ALS) is used to obtain pure component profiles in each segment. In general, thirty-one chemical components were resolved using MCR-ALS in sixty S. reuterana samples and the lack of fit (LOF) values of MCR-ALS models were below 10.0% in all cases. Pure spectral profiles are considered for identification of chemical components by comparing their resolved spectra with the standard ones and twenty-four components out of thirty-one components were identified. Additionally, pure elution profiles are used to obtain relative concentrations of chemical components in different samples for multivariate classification analysis by principal component analysis (PCA) and k-nearest neighbors (kNN). Inspection of the PCA score plot (explaining 76.1% of variance accounted for three PCs) showed that S. reuterana samples belong to four clusters. The degree of class separation (DCS) which quantifies the distance separating clusters in relation to the scatter within each cluster is calculated for four clusters and it was in the range of 1.6-5.8. These results are then confirmed by kNN. In addition, according to the PCA loading plot and kNN dendrogram of thirty-one variables, five chemical constituents of luteolin-7-o-glucoside, salvianolic acid D, rosmarinic acid, lithospermic acid and trijuganone A are identified as the most important variables (i.e., chemical markers) for clusters discrimination. Finally, the effect of different chemical markers on samples differentiation is investigated using counter-propagation artificial neural network (CP-ANN) method. It is concluded that the proposed strategy can be successfully applied for comprehensive analysis of chromatographic fingerprints of complex natural samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Chemometrics resolution and quantification power evaluation: Application on pharmaceutical quaternary mixture of Paracetamol, Guaifenesin, Phenylephrine and p-aminophenol

    NASA Astrophysics Data System (ADS)

    Yehia, Ali M.; Mohamed, Heba M.

    2016-01-01

    Three advanced chemmometric-assisted spectrophotometric methods namely; Concentration Residuals Augmented Classical Least Squares (CRACLS), Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and Principal Component Analysis-Artificial Neural Networks (PCA-ANN) were developed, validated and benchmarked to PLS calibration; to resolve the severely overlapped spectra and simultaneously determine; Paracetamol (PAR), Guaifenesin (GUA) and Phenylephrine (PHE) in their ternary mixture and in presence of p-aminophenol (AP) the main degradation product and synthesis impurity of Paracetamol. The analytical performance of the proposed methods was described by percentage recoveries, root mean square error of calibration and standard error of prediction. The four multivariate calibration methods could be directly used without any preliminary separation step and successfully applied for pharmaceutical formulation analysis, showing no excipients' interference.

  6. Apo adenylate kinase encodes its holo form: a principal component and varimax analysis.

    PubMed

    Cukier, Robert I

    2009-02-12

    Adenylate kinase undergoes large-scale motions of its LID and AMP-binding (AMPbd) domains when its apo, open form closes over its substrates, AMP and Mg2+-ATP. It may be an example of an enzyme that provides an ensemble of conformations in its apo state from which its substrates can select and bind to produce catalytically competent conformations. In this work, the fluctuations of the enzyme apo Escherichia coli adenylate kinase (AKE) are obtained with molecular dynamics. The resulting trajectory is analyzed with principal component analysis (PCA) that decomposes the atom motions into orthogonal modes ordered by their decreasing contributions to the total protein fluctuation. In apo AKE, a small set of the PCA modes describes the bulk of the fluctuations. Identification of the atom motions that are important contributors to these modes is improved with the use of a varimax rotation method that rotates the PCA modes to a new mode set that concentrates the atom contributions to a smaller set of atoms in these new modes. In this way, the nature of the important motions of the LID and AMPbd domains are clarified. The dominant PCA modes are used to investigate if apo AKE can fluctuate to conformations that are holo-like, even though the apo trajectory is mainly confined to a region around the initial apo structure. This is accomplished by expressing the difference between the protein coordinates, obtained from the holo and apo crystal structures, using as a basis the PCA modes from the apo AKE trajectory. The coherent motion described by a small set of the apo PCA modes is shown to be able to produce protein conformations that are quite similar to the holo conformation of the protein. In this sense, apo AKE does encode in its fluctuations information about holo-like conformations.

  7. Plasma levels of nitrate and risk of prostate cancer: a prospective study

    PubMed Central

    Wu, Tianying; Wang, Yushan; Ho, Shuk-Mei; Giovannucci, Edward

    2013-01-01

    Background Nitrate and nitrite supplements have recently been shown to improve cardiovascular health, but there is concern that these supplements could contribute to the development of cancer.Previous small, cross-sectional studies reported positive associations between circulating nitrate/nitrite levels and cancer. Prospective studies examining the association between plasma nitrate and cancer, especially prostate cancer (PCa), are lacking. Methods We conducted a nested case-control study within the Health Professionals Follow-up Study. Baseline blood samples were collected in 1994, and incident cases of PCa were identified from 1997–2005. Baseline plasma levels of nitrate were measured in the 630 cases and 630 matched controls. Results We have found that baseline levels of plasma nitrate were not associated with risk of PCa. Compared to quintile 1, the relative risk from quintiles 2–5 were 1.13 (95% CI, 0.78–1.63), 0.93 (95% CI, 0.63–1.38), 0.95 (95% CI, 0.65–1.39), and 0.99 (95% CI, 0.68–1.48); p for trend was 0.9 after adjustment of multivariate risk factors. When analyses were restricted to men fasting more than 6 hrs, the trend was similar. Further, plasma nitrate appeared to be inversely associated with advanced-stage PCa. The relative risk across extreme quartiles was 0.44 (95% CI, 0.17–1.12; p for trend = 0.07) for the whole data set and 0.30 (95% CI, 0.09–0.99; p for trend = 0.05) for the fasting data set. Conclusions In summary, we did not find an increased risk of PCa associated with higher plasma nitrate levels. A potential protective association between nitrate and aggressive forms of PCa requires confirmation. Impact Nitrate-nitrite-nitric oxide pathway has emerged as a new therapeutic pathway for chronic diseases. The results of this study certainly merit replications in other prospective studies. PMID:23677578

  8. (Con)text-specific effects of visual dysfunction on reading in posterior cortical atrophy.

    PubMed

    Yong, Keir X X; Shakespeare, Timothy J; Cash, Dave; Henley, Susie M D; Warren, Jason D; Crutch, Sebastian J

    2014-08-01

    Reading deficits are a common early feature of the degenerative syndrome posterior cortical atrophy (PCA) but are poorly understood even at the single word level. The current study evaluated the reading accuracy and speed of 26 PCA patients, 17 typical Alzheimer's disease (tAD) patients and 14 healthy controls on a corpus of 192 single words in which the following perceptual properties were manipulated systematically: inter-letter spacing, font size, length, font type, case and confusability. PCA reading was significantly less accurate and slower than tAD patients and controls, with performance significantly adversely affected by increased letter spacing, size, length and font (cursive < non-cursive), and characterised by visual errors (69% of all error responses). By contrast, tAD and control accuracy rates were at or near ceiling, letter spacing was the only perceptual factor to influence reading speed in the same direction as controls, and, in contrast to PCA patients, control reading was faster for larger font sizes. The inverse size effect in PCA (less accurate reading of large than small font size print) was associated with lower grey matter volume in the right superior parietal lobule. Reading accuracy was associated with impairments of early visual (especially crowding), visuoperceptual and visuospatial processes. However, these deficits were not causally related to a universal impairment of reading as some patients showed preserved reading for small, unspaced words despite grave visual deficits. Rather, the impact of specific types of visual dysfunction on reading was found to be (con)text specific, being particularly evident for large, spaced, lengthy words. These findings improve the characterisation of dyslexia in PCA, shed light on the causative and associative factors, and provide clear direction for the development of reading aids and strategies to maximise and sustain reading ability in the early stages of disease. Copyright © 2014. Published by Elsevier Ltd.

  9. (Con)text-specific effects of visual dysfunction on reading in posterior cortical atrophy

    PubMed Central

    Yong, Keir X.X.; Shakespeare, Timothy J.; Cash, Dave; Henley, Susie M.D.; Warren, Jason D.; Crutch, Sebastian J.

    2014-01-01

    Reading deficits are a common early feature of the degenerative syndrome posterior cortical atrophy (PCA) but are poorly understood even at the single word level. The current study evaluated the reading accuracy and speed of 26 PCA patients, 17 typical Alzheimer's disease (tAD) patients and 14 healthy controls on a corpus of 192 single words in which the following perceptual properties were manipulated systematically: inter-letter spacing, font size, length, font type, case and confusability. PCA reading was significantly less accurate and slower than tAD patients and controls, with performance significantly adversely affected by increased letter spacing, size, length and font (cursive < non-cursive), and characterised by visual errors (69% of all error responses). By contrast, tAD and control accuracy rates were at or near ceiling, letter spacing was the only perceptual factor to influence reading speed in the same direction as controls, and, in contrast to PCA patients, control reading was faster for larger font sizes. The inverse size effect in PCA (less accurate reading of large than small font size print) was associated with lower grey matter volume in the right superior parietal lobule. Reading accuracy was associated with impairments of early visual (especially crowding), visuoperceptual and visuospatial processes. However, these deficits were not causally related to a universal impairment of reading as some patients showed preserved reading for small, unspaced words despite grave visual deficits. Rather, the impact of specific types of visual dysfunction on reading was found to be (con)text specific, being particularly evident for large, spaced, lengthy words. These findings improve the characterisation of dyslexia in PCA, shed light on the causative and associative factors, and provide clear direction for the development of reading aids and strategies to maximise and sustain reading ability in the early stages of disease. PMID:24841985

  10. A comprehensive evaluation of CHEK2 germline mutations in men with prostate cancer.

    PubMed

    Wu, Yishuo; Yu, Hongjie; Zheng, S Lilly; Na, Rong; Mamawala, Mufaddal; Landis, Tricia; Wiley, Kathleen; Petkewicz, Jacqueline; Shah, Sameep; Shi, Zhuqing; Novakovic, Kristian; McGuire, Michael; Brendler, Charles B; Ding, Qiang; Helfand, Brian T; Carter, H Ballentine; Cooney, Kathleen A; Isaacs, William B; Xu, Jianfeng

    2018-06-01

    Germline mutations in CHEK2 have been associated with prostate cancer (PCa) risk. Our objective is to examine whether germline pathogenic CHEK2 mutations can differentiate risk of lethal from indolent PCa. A case-case study of 703 lethal PCa patients and 1455 patients with low-risk localized PCa of European, African, and Chinese origin was performed. Germline DNA samples from these patients were sequenced for CHEK2. Mutation carrier rates and their association with lethal PCa were analyzed using the Fisher exact test and Kaplan-Meier survival analysis. In the entire study population, 40 (1.85%) patients were identified as carrying one of 15 different germline CHEK2 pathogenic or likely pathogenic mutations. CHEK2 mutations were detected in 16 (2.28%) of 703 lethal PCa patients compared with 24 (1.65%) of 1455 low-risk PCa patients (P = 0.31). No association was found between CHEK2 mutation status and early-diagnosis or PCa-specific survival time. However, the most common mutation in CHEK2, c.1100delC (p.T367 fs), had a significantly higher carrier rate (1.28%) in lethal PCa patients than low-risk PCa patients of European American origin (0.16%), P = 0.0038. The estimated Odds Ratio of this mutation for lethal PCa was 7.86. The carrier rate in lethal PCa was also significantly higher than that (0.46%) in 32 461 non-Finnish European subjects from the Exome Aggregation Consortium (ExAC) (P = 0.01). While overall CHEK2 mutations were not significantly more common in men with lethal compared to low-risk PCa, the specific CHEK2 mutation, c.1100delC, appears to contribute to an increased risk of lethal PCa in European American men. © 2018 Wiley Periodicals, Inc.

  11. Intra-individual comparison of (68)Ga-PSMA-11-PET/CT and multi-parametric MR for imaging of primary prostate cancer.

    PubMed

    Giesel, F L; Sterzing, F; Schlemmer, H P; Holland-Letz, T; Mier, W; Rius, M; Afshar-Oromieh, A; Kopka, K; Debus, J; Haberkorn, U; Kratochwil, C

    2016-07-01

    Multi-parametric magnetic resonance imaging (MP-MRI) is currently the most comprehensive work up for non-invasive primary tumor staging of prostate cancer (PCa). Prostate-specific membrane antigen (PSMA)-Positron emission tomography-computed tomography (PET/CT) is presented to be a highly promising new technique for N- and M-staging in recurrent PCa-patients. The actual investigation analyses the potential of (68)Ga-PSMA11-PET/CT to assess the extent of primary prostate cancer by intra-individual comparison to MP-MRI. In a retrospective study, ten patients with primary PCa underwent MP-MRI and PSMA-PET/CT for initial staging. All tumors were proven histopathological by biopsy. Image analysis was done in a quantitative (SUVmax) and qualitative (blinded read) fashion based on PI-RADS. The PI-RADS schema was then translated into a 3D-matrix and the euclidian distance of this coordinate system was used to quantify the extend of agreement. Both MP-MRI and PSMA-PET/CT presented a good allocation of the PCa, which was also in concordance to the tumor location validated in eight-segment resolution by biopsy. An Isocontour of 50 % SUVmax in PSMA-PET resulted in visually concordant tumor extension in comparison to MP-MRI (T2w and DWI). For 89.4 % of sections containing a tumor according to MP-MRI, the tumor was also identified in total or near-total agreement (euclidian distance ≤1) by PSMA-PET. Vice versa for 96.8 % of the sections identified as tumor bearing by PSMA-PET the tumor was also found in total or near-total agreement by MP-MRI. PSMA-PET/CT and MP-MRI correlated well with regard to tumor allocation in patients with a high pre-test probability for large tumors. Further research will be needed to evaluate its value in challenging situation such as prostatitis or after repeated negative biopsies.

  12. An optimized chronology for a stalagmite using seasonal trace element cycles from Shihua Cave, Beijing, North China

    NASA Astrophysics Data System (ADS)

    Ban, F.; Baker, A.; Marjo, C.; Duan, W.; Li, X.; Coleborn, K.; Akter, R.; Nagra, G.

    2017-12-01

    Stalagmites play an increasingly important role in the paleoclimatic reconstruction from seasonal to orbital timescales. One of the important reasons is that 230Th-dating can provide an absolute age enabling more accurate knowledge of the stalagmite growth. Additionally, annual trace element and optical layers can provide complementary method for determining a precise age and seasonal resolution. The trace elements of a stalagmite (XMG) in Beijing Shihua Cave, which is located in the East Asian monsoon region, were analyzed by laser ablation ICP-MS and compared with stalagmite laminae. The results show that: (1) the polished section of the topmost 4 mm of stalagmite XMG has obvious bi-optical layers (fluorescence and visible light) under a conventional transmission microscope. In the rest of the sample laminae are not observed using this method. (2) The variations of P/Ca, Sr/Ca, Ba/Ca, U/Ca and Mg/Ca show seasonal cycles throughout the sample. Sr/Ca is inversely correlated to P/Ca, and its peaks correspond with the (non-fluorescing) white layers, which deposit in late winter and spring when the climate is dry. The peaks of P/Ca match closely with the (fluorescing) opaque layers, because P is a soil-derived element which increases in the high rainfall monsoon period. (3) The PCA of the five trace elements showed that the cycles of PC1 could represent the annual cycle. This stalagmite was deposited over 148 ± 4 years through peak counting and the cycles of PC1 correspond well with the annual layers. Trace element cyclicity as shown by PC1 can increase the accuracy of stalagmite dating, especially in the absence of obvious laminae. The trace elements can be used as the marker of seasonal changes in a strongly contrasting wet-dry monsoon climate regime. Keywords: high-precision dating; LA-ICP-MS; stalagmite; trace elements; seasonal cycles; Shihua Cave

  13. An unsupervised MVA method to compare specific regions in human breast tumor tissue samples using ToF-SIMS.

    PubMed

    Bluestein, Blake M; Morrish, Fionnuala; Graham, Daniel J; Guenthoer, Jamie; Hockenbery, David; Porter, Peggy L; Gamble, Lara J

    2016-03-21

    Imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS) and principal component analysis (PCA) were used to investigate two sets of pre- and post-chemotherapy human breast tumor tissue sections to characterize lipids associated with tumor metabolic flexibility and response to treatment. The micron spatial resolution imaging capability of ToF-SIMS provides a powerful approach to attain spatially-resolved molecular and cellular data from cancerous tissues not available with conventional imaging techniques. Three ca. 1 mm(2) areas per tissue section were analyzed by stitching together 200 μm × 200 μm raster area scans. A method to isolate and analyze specific tissue regions of interest by utilizing PCA of ToF-SIMS images is presented, which allowed separation of cellularized areas from stromal areas. These PCA-generated regions of interest were then used as masks to reconstruct representative spectra from specifically stromal or cellular regions. The advantage of this unsupervised selection method is a reduction in scatter in the spectral PCA results when compared to analyzing all tissue areas or analyzing areas highlighted by a pathologist. Utilizing this method, stromal and cellular regions of breast tissue biopsies taken pre- versus post-chemotherapy demonstrate chemical separation using negatively-charged ion species. In this sample set, the cellular regions were predominantly all cancer cells. Fatty acids (i.e. palmitic, oleic, and stearic), monoacylglycerols, diacylglycerols and vitamin E profiles were distinctively different between the pre- and post-therapy tissues. These results validate a new unsupervised method to isolate and interpret biochemically distinct regions in cancer tissues using imaging ToF-SIMS data. In addition, the method developed here can provide a framework to compare a variety of tissue samples using imaging ToF-SIMS, especially where there is section-to-section variability that makes it difficult to use a serial hematoxylin and eosin (H&E) stained section to direct the SIMS analysis.

  14. 64Cu-PSMA-617 PET/CT Imaging of Prostate Adenocarcinoma: First In-Human Studies.

    PubMed

    Grubmüller, Bernhard; Baum, Richard P; Capasso, Enza; Singh, Aviral; Ahmadi, Yasaman; Knoll, Peter; Floth, Andreas; Righi, Sergio; Zandieh, Shahin; Meleddu, Carlo; Shariat, Shahrokh F; Klingler, Hans Christoph; Mirzaei, Siroos

    2016-10-07

    The prostate-specific membrane antigen (PSMA) is a cell surface protein, which is overexpressed in nearly all cases of prostate cancer (PCa). PET imaging with 68 Ga-PSMA-HBED-CC has recently found widespread application in the diagnosis of recurrent PCa. In this study, the diagnostic potential of 64 Cu-labeled PSMA ligand (PSMA-617) PET in patients with PCa has been investigated. The study was conducted simultaneously at two nuclear medicine centers, Austria (Vienna, Center 1) and Germany (Bad Berka, Center 2). The patients (n = 29) included in this study were referred for PET (Center 1, 21 patients) or PET/CT (Center 2, 8 patients) imaging with either a high suspicion of recurrent disease or for possible surgical or PSMA radioligand therapy planning. PET images of the whole body were performed at 1 hour p.i. and additional images of the pelvis at 2 hours p.i. In 23 of 29 patients, at least one focus of pathological tracer uptake suspicious for primary disease in the prostate lobe or recurrent disease was detected. Among healthy organs, the salivary glands, kidneys, and liver showed the highest radiotracer uptake. Lesions suspicious for PCa were detected with excellent contrast as early as 1 hour p.i. with high detection rates even at low prostate-specific antigen (PSA) levels. The preliminary results of this study demonstrate the high potential of 64 Cu-PSMA ligand PET/CT imaging in patients with recurrent disease and in the primary staging of selected patients with progressive local disease. The acquired PET images showed an excellent resolution of the detected lesions with very high lesion-to- background contrast. Furthermore, the long half-life of 64 Cu allows distribution of the tracer to clinical PET centers that lack radiochemistry facilities for the preparation of 68 Ga-PSMA ligand (satellite concept).

  15. Bone-induced c-kit expression in prostate cancer: a driver of intraosseous tumor growth

    PubMed Central

    Mainetti, Leandro E.; Zhe, Xiaoning; Diedrich, Jonathan; Saliganan, Allen D.; Cho, Won Jin; Cher, Michael L.; Heath, Elisabeth; Fridman, Rafael; Kim, Hyeong-Reh Choi; Bonfil, R. Daniel

    2014-01-01

    Loss of BRCA2 function stimulates prostate cancer (PCa) cell invasion and is associated with more aggressive and metastatic tumors in PCa patients. Concurrently, the receptor tyrosine kinase c-kit is highly expressed in skeletal metastases of PCa patients and induced in PCa cells placed into the bone microenvironment in experimental models. However, the precise requirement of c-kit for intraosseous growth of PCa and its relation to BRCA2 expression remain unexplored. Here, we show that c-kit expression promotes migration and invasion of PCa cells. Alongside, we found that c-kit expression in PCa cells parallels BRCA2 downregulation. Gene rescue experiments with human BRCA2 transgene in c-kit-transfected PCa cells resulted in reduction of c-kit protein expression and migration and invasion, suggesting a functional significance of BRCA2 downregulation by c-kit. The inverse association between c-kit and BRCA2 gene expressions in PCa cells was confirmed using laser capture microdissection in experimental intraosseous tumors and bone metastases of PCa patients. Inhibition of bone-induced c-kit expression in PCa cells transduced with lentiviral short hairpin RNA reduced intraosseous tumor incidence and growth. Overall, our results provide evidence of a novel pathway that links bone-induced c-kit expression in PCa cells to BRCA2 downregulation and supports bone metastasis. PMID:24798488

  16. The impact of sexual orientation on body image, self-esteem, urinary and sexual functions in the experience of prostate cancer.

    PubMed

    Thomas, C; Wootten, A C; Robinson, P; Law, P C F; McKenzie, D P

    2018-03-01

    Prostate cancer (PCa) poses a large health burden globally. Research indicates that men experience a range of psychological challenges associated with PCa including changes to identity, self-esteem and body image. The ways in which sexual orientation plays a role in the experience of PCa, and the subsequent impact on quality of life (QoL), body image and self-esteem have only recently been addressed. By addressing treatment modality, where participant numbers were sufficient, we also sought to explore whether gay (homosexual) men diagnosed with PCa (PCaDx) and with a primary treatment modality of surgery would report differences in body image and self-esteem compared with straight (heterosexual) men with PCaDx with a primary treatment modality of surgery, compared with gay and straight men without PCaDx. The results of our study identified overall differences with respect to PCaDx (related to urinary function, sexual function and health evaluation), and sexual orientation (related to self-esteem), rather than interactions between sexual orientation and PCaDx. Gay men with PCaDx exhibited higher levels of urinary functioning than straight men with PCaDx, the difference being reversed for gay and straight men without PCaDx; but this result narrowly failed to achieve statistical significance, suggesting a need for further research, with larger samples. © 2018 John Wiley & Sons Ltd.

  17. The pre-image problem in kernel methods.

    PubMed

    Kwok, James Tin-yau; Tsang, Ivor Wai-hung

    2004-11-01

    In this paper, we address the problem of finding the pre-image of a feature vector in the feature space induced by a kernel. This is of central importance in some kernel applications, such as on using kernel principal component analysis (PCA) for image denoising. Unlike the traditional method which relies on nonlinear optimization, our proposed method directly finds the location of the pre-image based on distance constraints in the feature space. It is noniterative, involves only linear algebra and does not suffer from numerical instability or local minimum problems. Evaluations on performing kernel PCA and kernel clustering on the USPS data set show much improved performance.

  18. Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy.

    PubMed

    De Luca, Stefano; Passera, Roberto; Bollito, Enrico; Manfredi, Matteo; Scarpa, Roberto Mario; Sottile, Antonino; Randone, Donato Franco; Porpiglia, Francesco

    2014-12-01

    To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE). in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals). The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97). The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Distal radius: anatomical morphometric gender characteristics. Do anatomical pre-shaped plates pay attention on it?

    PubMed

    Oppermann, Johannes; Bredow, Jan; Beyer, Frank; Neiss, Wolfram Friedrich; Spies, Christian K; Eysel, Peer; Dargel, Jens; Wacker, Max

    2015-01-01

    The purpose of the study was to investigate differences in the osseous structure anatomy of male and female distal radii. Morphometric data were obtained of 49 distal human cadaveric radii. An imprint of the distal edge was attained using silicone mass and the palmar cortical angle (PCA) of the lateral and intermediate column, here declared as medial, according to the concept of Rikli and Rigazzoni. The lateral and medial length and five widths were digitally measured by three observers. In order to compare the measurements an unpaired t test was used. To prove the reliability of the measurements an intraclass correlation analyses was done. Overall mean medial PCA was 148.25° (SD ± 6.83) and mean lateral PCA 156.07° (SD ± 7.00). In male specimens, the mean medial PCA was 147.38° (SD ± 6.01) and mean lateral PCA was 153.6° (SD ± 6.20) whereas in female specimens, the mean medial PCA was 149.41° (SD ± 7.79) and the mean lateral PCA 159.37° (SD ± 6.78), with statistical significance for the female lateral PCA. No gender significant difference for the medial PCA and no significant side difference for the PCA's could be found. The ICC of the observers was r = 0.936 and 0.976 for the medial and for lateral PCA 0.957-0.984. The palmar cortical length of the distal radius was significantly longer in male specimens. For all widths, larger values for male radii were measured, being statistically significant in all cases. Male dimensions concerning the wide were significantly larger when compared with females. Regarding the PCA at the medial and lateral column, we found significant difference for lateral PCA concerning the gender. Overall, study results demonstrated an angle of 148.25° ± 6.83 for the medial PCA and 156.07° ± 7.00 for the lateral PCA.

  20. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jeong, Jin Boo; Lee, Seong-Ho, E-mail: slee2000@umd.edu

    Highlights: Black-Right-Pointing-Pointer Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. Black-Right-Pointing-Pointer PCA enhanced transcriptional downregulation of cyclin D1 gene. Black-Right-Pointing-Pointer PCA suppressed HDAC2 expression and activity. Black-Right-Pointing-Pointer These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment ofmore » PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.« less

  1. Automated diagnosis of prostate cancer in multi-parametric MRI based on multimodal convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Le, Minh Hung; Chen, Jingyu; Wang, Liang; Wang, Zhiwei; Liu, Wenyu; (Tim Cheng, Kwang-Ting; Yang, Xin

    2017-08-01

    Automated methods for prostate cancer (PCa) diagnosis in multi-parametric magnetic resonance imaging (MP-MRIs) are critical for alleviating requirements for interpretation of radiographs while helping to improve diagnostic accuracy (Artan et al 2010 IEEE Trans. Image Process. 19 2444-55, Litjens et al 2014 IEEE Trans. Med. Imaging 33 1083-92, Liu et al 2013 SPIE Medical Imaging (International Society for Optics and Photonics) p 86701G, Moradi et al 2012 J. Magn. Reson. Imaging 35 1403-13, Niaf et al 2014 IEEE Trans. Image Process. 23 979-91, Niaf et al 2012 Phys. Med. Biol. 57 3833, Peng et al 2013a SPIE Medical Imaging (International Society for Optics and Photonics) p 86701H, Peng et al 2013b Radiology 267 787-96, Wang et al 2014 BioMed. Res. Int. 2014). This paper presents an automated method based on multimodal convolutional neural networks (CNNs) for two PCa diagnostic tasks: (1) distinguishing between cancerous and noncancerous tissues and (2) distinguishing between clinically significant (CS) and indolent PCa. Specifically, our multimodal CNNs effectively fuse apparent diffusion coefficients (ADCs) and T2-weighted MP-MRI images (T2WIs). To effectively fuse ADCs and T2WIs we design a new similarity loss function to enforce consistent features being extracted from both ADCs and T2WIs. The similarity loss is combined with the conventional classification loss functions and integrated into the back-propagation procedure of CNN training. The similarity loss enables better fusion results than existing methods as the feature learning processes of both modalities are mutually guided, jointly facilitating CNN to ‘see’ the true visual patterns of PCa. The classification results of multimodal CNNs are further combined with the results based on handcrafted features using a support vector machine classifier. To achieve a satisfactory accuracy for clinical use, we comprehensively investigate three critical factors which could greatly affect the performance of our multimodal CNNs but have not been carefully studied previously. (1) Given limited training data, how can these be augmented in sufficient numbers and variety for fine-tuning deep CNN networks for PCa diagnosis? (2) How can multimodal MP-MRI information be effectively combined in CNNs? (3) What is the impact of different CNN architectures on the accuracy of PCa diagnosis? Experimental results on extensive clinical data from 364 patients with a total of 463 PCa lesions and 450 identified noncancerous image patches demonstrate that our system can achieve a sensitivity of 89.85% and a specificity of 95.83% for distinguishing cancer from noncancerous tissues and a sensitivity of 100% and a specificity of 76.92% for distinguishing indolent PCa from CS PCa. This result is significantly superior to the state-of-the-art method relying on handcrafted features.

  2. Prostate cancer antigen 3 gene expression in peripheral blood and urine sediments from prostate cancer and benign prostatic hyperplasia patients versus healthy individuals.

    PubMed

    Moradi Sardareh, Hemen; Goodarzi, Mohammad Taghi; Yadegar-Azari, Reza; Poorolajal, Jalal; Mousavi-Bahar, Seyed Habibollah; Saidijam, Massoud

    2014-11-30

    To determine the expression of prostate cancer antigen 3 (PCA3) gene in peripheral blood and urine sediments from patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and normal subjects. A total number of 48 patients [24 with biopsy proven prostate cancer (PCa) and 24 with benign prostate hyperplasia (BPH)] were studied. Twenty-four healthy individuals were also recruited as control group. After blood and urine sampling, total RNA was extracted and cDNA was synthesized. Expression of PCA3 gene was assessed by quantitative reverse transcription polymerase chain reaction. Comparison of PCA3 gene expression between control and BPH groups indicated no statistically significant differences in both urine and blood samples. Patients with PCa demonstrated an increased PCA3 gene expression rate compared to control and BPH groups (10.64 and 7.17 folds, respectively). The rate of fold increased PCA3 gene expression in urine was 20.90, 20.90, and 20.35 in patients with PCa, BPH and normal subjects, respectively. Evaluation of PCA3 gene expression can be considered as a reliable marker for detection of PCa. Increased level of this marker in urine sediments is more sensitive than blood for distinguishing between cancerous and non-cancerous groups. 

  3. Identification of an IL-1-induced gene expression pattern in AR+ PCa cells that mimics the molecular phenotype of AR- PCa cells.

    PubMed

    Thomas-Jardin, Shayna E; Kanchwala, Mohammed S; Jacob, Joan; Merchant, Sana; Meade, Rachel K; Gahnim, Nagham M; Nawas, Afshan F; Xing, Chao; Delk, Nikki A

    2018-06-01

    In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance. Furthermore, IL-1 and AR protein levels negatively correlate in PCa tumor cells. Taken together, we hypothesize that IL-1 reprograms AR positive (AR + ) PCa cells into AR negative (AR - ) PCa cells that co-opt IL-1 signaling to ensure AR-independent survival and tumor progression in the inflammatory tumor microenvironment. LNCaP and PC3 PCa cells were treated with IL-1β or HS-5 bone marrow stromal cell (BMSC) conditioned medium and analyzed by RNA sequencing and RT-QPCR. To verify genes identified by RNA sequencing, LNCaP, MDA-PCa-2b, PC3, and DU145 PCa cell lines were treated with the IL-1 family members, IL-1α or IL-1β, or exposed to HS-5 BMSC in the presence or absence of Interleukin-1 Receptor Antagonist (IL-1RA). Treated cells were analyzed by western blot and/or RT-QPCR. Comparative analysis of sequencing data from the AR + LNCaP PCa cell line versus the AR - PC3 PCa cell line reveals an IL-1-conferred gene suite in LNCaP cells that is constitutive in PC3 cells. Bioinformatics analysis of the IL-1 regulated gene suite revealed that inflammatory and immune response pathways are primarily elicited; likely facilitating PCa cell survival and tumorigenicity in an inflammatory tumor microenvironment. Our data supports that IL-1 reprograms AR + PCa cells to mimic AR - PCa gene expression patterns that favor AR-targeted treatment resistance and cell survival. © 2018 Wiley Periodicals, Inc.

  4. Multilevel principal component analysis (mPCA) in shape analysis: A feasibility study in medical and dental imaging.

    PubMed

    Farnell, D J J; Popat, H; Richmond, S

    2016-06-01

    Methods used in image processing should reflect any multilevel structures inherent in the image dataset or they run the risk of functioning inadequately. We wish to test the feasibility of multilevel principal components analysis (PCA) to build active shape models (ASMs) for cases relevant to medical and dental imaging. Multilevel PCA was used to carry out model fitting to sets of landmark points and it was compared to the results of "standard" (single-level) PCA. Proof of principle was tested by applying mPCA to model basic peri-oral expressions (happy, neutral, sad) approximated to the junction between the mouth/lips. Monte Carlo simulations were used to create this data which allowed exploration of practical implementation issues such as the number of landmark points, number of images, and number of groups (i.e., "expressions" for this example). To further test the robustness of the method, mPCA was subsequently applied to a dental imaging dataset utilising landmark points (placed by different clinicians) along the boundary of mandibular cortical bone in panoramic radiographs of the face. Changes of expression that varied between groups were modelled correctly at one level of the model and changes in lip width that varied within groups at another for the Monte Carlo dataset. Extreme cases in the test dataset were modelled adequately by mPCA but not by standard PCA. Similarly, variations in the shape of the cortical bone were modelled by one level of mPCA and variations between the experts at another for the panoramic radiographs dataset. Results for mPCA were found to be comparable to those of standard PCA for point-to-point errors via miss-one-out testing for this dataset. These errors reduce with increasing number of eigenvectors/values retained, as expected. We have shown that mPCA can be used in shape models for dental and medical image processing. mPCA was found to provide more control and flexibility when compared to standard "single-level" PCA. Specifically, mPCA is preferable to "standard" PCA when multiple levels occur naturally in the dataset. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling

    PubMed Central

    2012-01-01

    Background PCA3 is a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, but its functional role is unknown. To investigate its putative function in PCa biology, we used gene expression knockdown by small interference RNA, and also analyzed its involvement in androgen receptor (AR) signaling. Methods LNCaP and PC3 cells were used as in vitro models for these functional assays, and three different siRNA sequences were specifically designed to target PCA3 exon 4. Transfected cells were analyzed by real-time qRT-PCR and cell growth, viability, and apoptosis assays. Associations between PCA3 and the androgen-receptor (AR) signaling pathway were investigated by treating LNCaP cells with 100 nM dihydrotestosterone (DHT) and with its antagonist (flutamide), and analyzing the expression of some AR-modulated genes (TMPRSS2, NDRG1, GREB1, PSA, AR, FGF8, CdK1, CdK2 and PMEPA1). PCA3 expression levels were investigated in different cell compartments by using differential centrifugation and qRT-PCR. Results LNCaP siPCA3-transfected cells significantly inhibited cell growth and viability, and increased the proportion of cells in the sub G0/G1 phase of the cell cycle and the percentage of pyknotic nuclei, compared to those transfected with scramble siRNA (siSCr)-transfected cells. DHT-treated LNCaP cells induced a significant upregulation of PCA3 expression, which was reversed by flutamide. In siPCA3/LNCaP-transfected cells, the expression of AR target genes was downregulated compared to siSCr-transfected cells. The siPCA3 transfection also counteracted DHT stimulatory effects on the AR signaling cascade, significantly downregulating expression of the AR target gene. Analysis of PCA3 expression in different cell compartments provided evidence that the main functional roles of PCA3 occur in the nuclei and microsomal cell fractions. Conclusions Our findings suggest that the ncRNA PCA3 is involved in the control of PCa cell survival, in part through modulating AR signaling, which may raise new possibilities of using PCA3 knockdown as an additional therapeutic strategy for PCa control. PMID:23130941

  6. Curcumin Suppresses In Vitro Proliferation and Invasion of Human Prostate Cancer Stem Cells by Modulating DLK1-DIO3 Imprinted Gene Cluster MicroRNAs.

    PubMed

    Zhang, Hu; Zheng, Jiajia; Shen, Hongliang; Huang, Yongyi; Liu, Te; Xi, Hao; Chen, Chuan

    2018-01-01

    Curcumin can suppress human prostate cancer (HuPCa) cell proliferation and invasion. However, it is not known whether curcumin can inhibit HuPCa stem cell (HuPCaSC) proliferation and invasion. We used methyl thiazolyl tetrazolium and Transwell assays to examine the proliferation and invasion of the HuPCaSC lines DU145 and 22Rv1 following curcumin or dimethyl sulfoxide (control) treatment. The microRNA (miRNA) expression levels in the DLK1-DIO3 imprinted genomic region in the cells and in tumor tissues from patients with PCa were examined using microarray and quantitative PCR. The median inhibitory concentration of curcumin for HuPCa cells significantly inhibited HuPCaSC proliferation and invasion in vitro. The miR-770-5p and miR-1247 expression levels in the DLK1-DIO3 imprinted gene cluster were significantly different between the curcumin-treated and control HuPCaSCs. Overexpression of these positive miRNAs significantly increased the inhibition rates of miR-770-5p- and miR-1247-transfected HuPCaSCs compared to the control miR-Mut-transfected HuPCaSCs. Lastly, low-tumor grade PCa tissues had higher miR-770-5p and miR-1247 expression levels than high-grade tumor tissues. Curcumin can suppress HuPCaSC proliferation and invasion in vitro by modulating specific miRNAs in the DLK1-DIO3 imprinted gene cluster.

  7. The interaction of the outflow with the molecular disk in the Active Galactic Nucleus of NGC 6951

    NASA Astrophysics Data System (ADS)

    May, D.; Steiner, J. E.; Ricci, T. V.; Menezes, R. B.; Andrade, I. S.

    2015-02-01

    Context: we present a study of the central 200 pc of NGC 6951, in the optical and NIR, taken with the Gemini North Telescope integral field spectrographs, with resolution of ~ 0''.1 Methods: we used a set of image processing techniques, as the filtering of high spatial and spectral frequencies, Richardson-Lucy deconvolution and PCA Tomography (Steiner et al. 2009) to map the distribution and kinematics of the emission lines. Results: we found a thick molecular disk, with the ionization cone highly misaligned.

  8. Detection of urban expansion in an urban-rural landscape with multitemporal QuickBird images

    PubMed Central

    Lu, Dengsheng; Hetrick, Scott; Moran, Emilio; Li, Guiying

    2011-01-01

    Accurately detecting urban expansion with remote sensing techniques is a challenge due to the complexity of urban landscapes. This paper explored methods for detecting urban expansion with multitemporal QuickBird images in Lucas do Rio Verde, Mato Grosso, Brazil. Different techniques, including image differencing, principal component analysis (PCA), and comparison of classified impervious surface images with the matched filtering method, were used to examine urbanization detection. An impervious surface image classified with the hybrid method was used to modify the urbanization detection results. As a comparison, the original multispectral image and segmentation-based mean-spectral images were used during the detection of urbanization. This research indicates that the comparison of classified impervious surface images with matched filtering method provides the best change detection performance, followed by the image differencing method based on segmentation-based mean spectral images. The PCA is not a good method for urban change detection in this study. Shadows and high spectral variation within the impervious surfaces represent major challenges to the detection of urban expansion when high spatial resolution images are used. PMID:21799706

  9. Beyond textbook neuroanatomy: The syndrome of malignant PCA infarction.

    PubMed

    Gogela, Steven L; Gozal, Yair M; Rahme, Ralph; Zuccarello, Mario; Ringer, Andrew J

    2015-01-01

    Given its limited vascular territory, occlusion of the posterior cerebral artery (PCA) usually does not result in malignant infarction. Challenging this concept, we present 3 cases of unilateral PCA infarction with secondary malignant progression, resulting from extension into what would classically be considered the posterior middle cerebral artery (MCA) territory. Interestingly, these were true PCA infarctions, not "MCA plus" strokes, since the underlying occlusive lesion was in the PCA. We hypothesize that congenital and/or acquired variability in the distribution and extent of territory supplied by the PCA may underlie this rare clinical entity. Patients with a PCA infarction should thus be followed closely and offered early surgical decompression in the event of malignant progression.

  10. Matrix Effects and Interferences of Different Citrus Fruit Coextractives in Pesticide Residue Analysis Using Ultrahigh-Performance Liquid Chromatography-High-Resolution Mass Spectrometry.

    PubMed

    Besil, Natalia; Cesio, Verónica; Heinzen, Horacio; Fernandez-Alba, Amadeo R

    2017-06-14

    The matrix effects of ethyl acetate extracts from seven different citrus fruits on the determination of 80 pesticide residues using liquid chromatography coupled to high-resolution time-of-flight mass spectrometry (UHPLC-(ESI)-HR-TOF) at 4 GHz resolution mode were studied. Only 20% of the evaluated pesticides showed noticeable matrix effects (ME) due to coelution with natural products between t R = 3 and 11 min. Principal component analysis (PCA) of the detected coextractives grouped the mandarins and the orange varieties, but separated lemon, oranges, and mandarins from each other. Matrix effects were different among species but similar between varieties, forcing the determination of pesticide residues through matrix-matched calibration curves with the same fruit. Twenty-three natural products (synephrine, naringin, poncirin, glycosides of hesperitin, limonin, nomilin, and a few fatty acids, among others) were identified in the analyzed extracts. Twelve of the identified compounds coeluted with 28 of the pesticides under study, causing different matrix effects.

  11. Androgen Receptor Expression in Epithelial and Stromal Cells of Prostatic Carcinoma and Benign Prostatic Hyperplasia.

    PubMed

    Filipovski, Vanja; Kubelka-Sabit, Katerina; Jasar, Dzengis; Janevska, Vesna

    2017-08-15

    Prostatic carcinoma (PCa) derives from prostatic epithelial cells. However stromal microenvironment, associated with malignant epithelium, also plays a role in prostatic carcinogenesis. Alterations in prostatic stromal cells contribute to the loss of growth control in epithelial cells that lead to progression of PCa. To analyse the differences between Androgen Receptor (AR) expression in both epithelial and stromal cells in PCa and the surrounding benign prostatic hyperplasia (BPH) and to compare the results with tumour grade. Samples from 70 cases of radical prostatectomy specimens were used. The expression and intensity of the signal for AR was analysed in the epithelial and stromal cells of PCa and BPH, and the data was quantified using histological score (H-score). AR showed significantly lower expression in both epithelial and stromal cells of PCa compared to BPH. In PCa a significant positive correlation of AR expression was found between stromal and epithelial cells of PCa. AR expression showed a correlation between the stromal cells of PCa and tumour grade. AR expression is reduced in epithelial and stromal cells of PCa. Expression of AR in stromal cells of PCa significantly correlates with tumour grade.

  12. Research of seafloor topographic analyses for a staged mineral exploration

    NASA Astrophysics Data System (ADS)

    Ikeda, M.; Kadoshima, K.; Koizumi, Y.; Yamakawa, T.; Asakawa, E.; Sumi, T.; Kose, M.

    2016-12-01

    J-MARES (Research and Development Partnership for Next Generation Technology of Marine Resources Survey, JAPAN) has been designing a low-cost and high-efficiency exploration system for seafloor hydrothermal massive sulfide (SMS) deposits in "Cross-ministerial Strategic Innovation Promotion Program (SIP)" granted by the Cabinet Office, Government of Japan since 2014. We proposed the multi-stage approach, which is designed from the regional scaled to the detail scaled survey stages through semi-detail scaled, focusing a prospective area by seafloor topographic analyses. We applied this method to the area of more than 100km x 100km around Okinawa Trough, including some well-known mineralized deposits. In the regional scale survey, we assume survey areas are more than 100 km x 100km. Then the spatial resolution of topography data should be bigger than 100m. The 500 m resolution data which is interpolated into 250 m resolution was used for extracting depression and performing principal component analysis (PCA) by the wavelength obtained from frequency analysis. As the result, we have successfully extracted the areas having the topographic features quite similar to well-known mineralized deposits. In the semi-local survey stage, we use the topography data obtained by bathymetric survey using multi-narrow beam echo-sounder. The 30m-resolution data was used for extracting depression, relative-large mounds, hills, lineaments as fault, and also for performing frequency analysis. As the result, wavelength as principal component constituting in the target area was extracted by PCA of wavelength obtained from frequency analysis. Therefore, color image was composited by using the second principal component (PC2) to the forth principal component (PC4) in which the continuity of specific wavelength was observed, and consistent with extracted lineaments. In addition, well-known mineralized deposits were discriminated in the same clusters by using clustering from PC2 to PC4.We applied the results described above to a new area, and successfully extract the quite similar area in vicinity to one of the well-known mineralized deposits. So we are going to verify the extracted areas by using geophysical methods, such as vertical cable seismic and time-domain EM survey, developed in this SIP project.

  13. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Das, Dibash K.; The Graduate Center Departments of Biology and Biochemistry, The City University of New York, New York, NY 10016; Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065

    Prostate cancer (PCa) is frequently diagnosed in men, and dysregulation of microRNAs is characteristic of many cancers. MicroRNA-1207-3p is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of microRNA-1207-3p in PCa is unclear. We discovered that microRNA-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells. Increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of FNDC1, a protein which contains a conserved protein domain of fibronectin (FN1). FNDC1, FN1, and themore » androgen receptor (AR) are significantly overexpressed in PCa cell lines and human PCa, and positively correlate with aggressive PCa. Prostate tumor FN1 expression in patients that experienced PCa-specific death is significantly higher than in patients that remained alive. Furthermore, FNDC1, FN1 and AR are concomitantly overexpressed in metastatic PCa. Consequently, these studies have revealed a novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in PCa. - Graphical abstract: miR-1207-3p/FNDC1/FN1/AR is a novel regulatory pathway in prostate cancer. - Highlights: • Expression of microRNA-1207-3p is significantly lost in prostate cancer (PCa) cells. • MicroRNA-1207-3p regulates proliferation, apoptosis, and migration via direct molecular targeting of the 3′UTR of FNDC1. • MicroRNA-1207-3p regulates proliferation, apoptosis, and migration via direct molecular targeting of the 3′UTR of FNDC1. • FNDC1, FN1, and AR are concurrently overexpressed in metastatic PCa.« less

  14. Circular RNA Myosin Light Chain Kinase (MYLK) Promotes Prostate Cancer Progression through Modulating Mir-29a Expression.

    PubMed

    Dai, Yuanqing; Li, Dongjie; Chen, Xiong; Tan, Xinji; Gu, Jie; Chen, Mingquan; Zhang, Xiaobo

    2018-05-25

    BACKGROUND In developed countries, prostate cancer (PCa) is a frequently diagnosed cancer with the second highest fatality rate. Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) stably expressed in cells and involved in a series of carcinomas. However, few research studies have reported on the role of circRNAs in PCa. MATERIAL AND METHODS We used qRT-PCR to detect the expression of circMYLK (circRNA ID: hsa_circ_0141940) and miR-29a in PCa tissues and cell lines. MTT, colony formation, and TUNEL assays were performed to analysis the cell viability of PCa cells. Transwell and wound scratch assays were performed to investigate the cell invasion and migration of PCa cells. RESULTS In the present study, we confirmed that circMYLK expression level was significantly higher in PCa samples and PCa cells than in normal tissues and normal prostatic cells. The upregulated circRNA-MYLK promoted PCa cells proliferation, invasion, and migration; however, si-circRNA-MYLK significantly accelerated the PCa cell apoptosis. We also observed that the aforementioned function of circRNA-MYLK on PCa cells was affected through targeting miR-29a. CONCLUSIONS We confirmed circRNA-MYLK was an oncogene in PCa and revealed a novel mechanism underlying circRNA-MYLK in PC progression.

  15. The theoretical and experimental study on dicalcium phosphate dehydrate loading with protocatechuic aldehyde.

    PubMed

    Guo, Yuehua; Qu, Shuxin; Lu, Xiong; Xie, Haodong; Zhang, Hongping; Weng, Jie

    2010-07-01

    The aim of this study is to investigate the interaction between dicalcium phosphate dihydrate (CaHPO(4) x 2H(2)O, DCPD) and Protocatechuic aldehyde (C(7)H(6)O(3), Pca), which is the water-soluble constituents of Chinese Medicine, Salvia Miltiorrhiza Bunge (SMB), by calculating the absorption energy through molecular dynamics simulation. Furthermore, the effects of functional groups of Pca and temperature on Pca adsorbed by DCPD are calculated respectively. DCPD/Pca and DCPD were analyzed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TG). The simulation results showed that Pca mostly absorbed on the (0 2 0) surface of DCPD. The aldehyde group of Pca played a moren important role on the adsorption of Pca on DCPD than hydroxyl did, while temperature had no distinct effects on the adsorption. XRD results indicated that Pca induced the preferential growth of (0 2 0) crystal surface in DCPC/Pca whereas it had no influence on the crystal structure, the crystallinity and grain size of DCPD. FTIR and TG results showed that the characteristic peak of Pca was at 1295 cm(-1) and the content of Pca in DCPD was 16%, respectively. The present results show that molecular dynamics simulation is a very effective and complementary method to study the interaction between materials and medicine.

  16. Applying robust variant of Principal Component Analysis as a damage detector in the presence of outliers

    NASA Astrophysics Data System (ADS)

    Gharibnezhad, Fahit; Mujica, Luis E.; Rodellar, José

    2015-01-01

    Using Principal Component Analysis (PCA) for Structural Health Monitoring (SHM) has received considerable attention over the past few years. PCA has been used not only as a direct method to identify, classify and localize damages but also as a significant primary step for other methods. Despite several positive specifications that PCA conveys, it is very sensitive to outliers. Outliers are anomalous observations that can affect the variance and the covariance as vital parts of PCA method. Therefore, the results based on PCA in the presence of outliers are not fully satisfactory. As a main contribution, this work suggests the use of robust variant of PCA not sensitive to outliers, as an effective way to deal with this problem in SHM field. In addition, the robust PCA is compared with the classical PCA in the sense of detecting probable damages. The comparison between the results shows that robust PCA can distinguish the damages much better than using classical one, and even in many cases allows the detection where classic PCA is not able to discern between damaged and non-damaged structures. Moreover, different types of robust PCA are compared with each other as well as with classical counterpart in the term of damage detection. All the results are obtained through experiments with an aircraft turbine blade using piezoelectric transducers as sensors and actuators and adding simulated damages.

  17. An Improved Pathological Brain Detection System Based on Two-Dimensional PCA and Evolutionary Extreme Learning Machine.

    PubMed

    Nayak, Deepak Ranjan; Dash, Ratnakar; Majhi, Banshidhar

    2017-12-07

    Pathological brain detection has made notable stride in the past years, as a consequence many pathological brain detection systems (PBDSs) have been proposed. But, the accuracy of these systems still needs significant improvement in order to meet the necessity of real world diagnostic situations. In this paper, an efficient PBDS based on MR images is proposed that markedly improves the recent results. The proposed system makes use of contrast limited adaptive histogram equalization (CLAHE) to enhance the quality of the input MR images. Thereafter, two-dimensional PCA (2DPCA) strategy is employed to extract the features and subsequently, a PCA+LDA approach is used to generate a compact and discriminative feature set. Finally, a new learning algorithm called MDE-ELM is suggested that combines modified differential evolution (MDE) and extreme learning machine (ELM) for segregation of MR images as pathological or healthy. The MDE is utilized to optimize the input weights and hidden biases of single-hidden-layer feed-forward neural networks (SLFN), whereas an analytical method is used for determining the output weights. The proposed algorithm performs optimization based on both the root mean squared error (RMSE) and norm of the output weights of SLFNs. The suggested scheme is benchmarked on three standard datasets and the results are compared against other competent schemes. The experimental outcomes show that the proposed scheme offers superior results compared to its counterparts. Further, it has been noticed that the proposed MDE-ELM classifier obtains better accuracy with compact network architecture than conventional algorithms.

  18. Principal component and normal mode analysis of proteins; a quantitative comparison using the GroEL subunit.

    PubMed

    Skjaerven, Lars; Martinez, Aurora; Reuter, Nathalie

    2011-01-01

    Principal component analysis (PCA) and normal mode analysis (NMA) have emerged as two invaluable tools for studying conformational changes in proteins. To compare these approaches for studying protein dynamics, we have used a subunit of the GroEL chaperone, whose dynamics is well characterized. We first show that both PCA on trajectories from molecular dynamics (MD) simulations and NMA reveal a general dynamical behavior in agreement with what has previously been described for GroEL. We thus compare the reproducibility of PCA on independent MD runs and subsequently investigate the influence of the length of the MD simulations. We show that there is a relatively poor one-to-one correspondence between eigenvectors obtained from two independent runs and conclude that caution should be taken when analyzing principal components individually. We also observe that increasing the simulation length does not improve the agreement with the experimental structural difference. In fact, relatively short MD simulations are sufficient for this purpose. We observe a rapid convergence of the eigenvectors (after ca. 6 ns). Although there is not always a clear one-to-one correspondence, there is a qualitatively good agreement between the movements described by the first five modes obtained with the three different approaches; PCA, all-atoms NMA, and coarse-grained NMA. It is particularly interesting to relate this to the computational cost of the three methods. The results we obtain on the GroEL subunit contribute to the generalization of robust and reproducible strategies for the study of protein dynamics, using either NMA or PCA of trajectories from MD simulations. © 2010 Wiley-Liss, Inc.

  19. Prediction of protein-protein interactions from amino acid sequences with ensemble extreme learning machines and principal component analysis.

    PubMed

    You, Zhu-Hong; Lei, Ying-Ke; Zhu, Lin; Xia, Junfeng; Wang, Bing

    2013-01-01

    Protein-protein interactions (PPIs) play crucial roles in the execution of various cellular processes and form the basis of biological mechanisms. Although large amount of PPIs data for different species has been generated by high-throughput experimental techniques, current PPI pairs obtained with experimental methods cover only a fraction of the complete PPI networks, and further, the experimental methods for identifying PPIs are both time-consuming and expensive. Hence, it is urgent and challenging to develop automated computational methods to efficiently and accurately predict PPIs. We present here a novel hierarchical PCA-EELM (principal component analysis-ensemble extreme learning machine) model to predict protein-protein interactions only using the information of protein sequences. In the proposed method, 11188 protein pairs retrieved from the DIP database were encoded into feature vectors by using four kinds of protein sequences information. Focusing on dimension reduction, an effective feature extraction method PCA was then employed to construct the most discriminative new feature set. Finally, multiple extreme learning machines were trained and then aggregated into a consensus classifier by majority voting. The ensembling of extreme learning machine removes the dependence of results on initial random weights and improves the prediction performance. When performed on the PPI data of Saccharomyces cerevisiae, the proposed method achieved 87.00% prediction accuracy with 86.15% sensitivity at the precision of 87.59%. Extensive experiments are performed to compare our method with state-of-the-art techniques Support Vector Machine (SVM). Experimental results demonstrate that proposed PCA-EELM outperforms the SVM method by 5-fold cross-validation. Besides, PCA-EELM performs faster than PCA-SVM based method. Consequently, the proposed approach can be considered as a new promising and powerful tools for predicting PPI with excellent performance and less time.

  20. β-catenin nuclear translocation induced by HIF-1α overexpression leads to the radioresistance of prostate cancer

    PubMed Central

    Luo, Yong; Li, Mingchuan; Zuo, Xuemei; Basourakos, Spyridon P.; Zhang, Jiao; Zhao, Jiahui; Han, Yili; Lin, Yunhua; Wang, Yongxing; Jiang, Yongguang; Lan, Ling

    2018-01-01

    Hypoxia-inducible factor-1α (HIF-1α) is known to play crucial roles in tumor radioresistance; however, the molecular mechanisms responsible for the promotion of tumor radioresistance by HIF-1α remain unclear. β-catenin is known to be involved in the metastatic potential of prostate cancer (PCa). In this study, to investigate the role of HIF-1α and β-catenin in the radioresistance of PCa, two PCa cell lines, LNCaP and C4-2B, were grouped as follows: Negative control (no treatment), HIF-1α overexpression group (transfected with HIF-1α overexpression plasmid) and β-catenin silenced group (transfected with HIF-1α plasmids and β-catenin-shRNA). Cell proliferation, cell cycle, cell invasion and radiosensitivity were examined under normal or hypoxic conditions. In addition, radiosensitivity was examined in two mouse PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model). Our results revealed that in both the LNCaP and C4-2B cells, transfection with HIF-1α overexpression plasmid led to an enhanced β-catenin nuclear translocation, while β-catenin silencing inhibited β-catenin nuclear translocation. The enhanced β-catenin nuclear translocation induced by HIF-1α overexpression resulted in an enhanced cell proliferation and cell invasion, an altered cell cycle distribution, decreased apoptosis, and improved non-homologous end joining (NHEJ) repair under normal and irradiation conditions. Similar results were observed in the animal models. HIF-1α overexpression enhanced β-catenin nuclear translocation, which led to the activation of the β-catenin/NHEJ signaling pathway and increased cell proliferation, cell invasion and DNA repair. These results thus suggest that HIF-1α overexpression promotes the radioresistance of PCa cells. PMID:29658569

  1. Development of Indicators to Assess Quality of Care for Prostate Cancer.

    PubMed

    Nag, Nupur; Millar, Jeremy; Davis, Ian D; Costello, Shaun; Duthie, James B; Mark, Stephen; Delprado, Warick; Smith, David; Pryor, David; Galvin, David; Sullivan, Frank; Murphy, Áine C; Roder, David; Elsaleh, Hany; Currow, David; White, Craig; Skala, Marketa; Moretti, Kim L; Walker, Tony; De Ieso, Paolo; Brooks, Andrew; Heathcote, Peter; Frydenberg, Mark; Thavaseelan, Jeffery; Evans, Sue M

    2016-02-20

    The development, monitoring, and reporting of indicator measures that describe standard of care provide the gold standard for assessing quality of care and patient outcomes. Although indicator measures have been reported, little evidence of their use in measuring and benchmarking performance is available. A standard set, defining numerator, denominator, and risk adjustments, will enable global benchmarking of quality of care. To develop a set of indicators to enable assessment and reporting of quality of care for men with localised prostate cancer (PCa). Candidate indicators were identified from the literature. An international panel was invited to participate in a modified Delphi process. Teleconferences were held before and after each voting round to provide instruction and to review results. Panellists were asked to rate each proposed indicator on a Likert scale of 1-9 in a two-round iterative process. Calculations required to report on the endorsed indicators were evaluated and modified to reflect the data capture of the Prostate Cancer Outcomes Registry-Australia and New Zealand (PCOR-ANZ). A total of 97 candidate indicators were identified, of which 12 were endorsed. The set includes indicators covering pre-, intra-, and post-treatment of PCa care, within the limits of the data captured by PCOR-ANZ. The 12 endorsed quality measures enable international benchmarking on the quality of care of men with localised PCa. Reporting on these indicators enhances safety and efficacy of treatment, reduces variation in care, and can improve patient outcomes. PCa has the highest incidence of all cancers in men. Early diagnosis and relatively high survival rates mean issues of quality of care and best possible health outcomes for patients are important. This paper identifies 12 important measurable quality indicators in PCa care. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  2. Features of Vocal Fold Adductor Paralysis and the Management of Posterior Muscle in Thyroplasty.

    PubMed

    Konomi, Ujimoto; Tokashiki, Ryoji; Hiramatsu, Hiroyuki; Motohashi, Ray; Sakurai, Eriko; Toyomura, Fumimasa; Nomoto, Masaki; Kawada, Yuri; Suzuki, Mamoru

    2016-03-01

    To present the pathologic characteristics of unilateral recurrent nerve adductor branch paralysis (AdBP), and to investigate the management of posterior cricoarytenoid (PCA) muscle on the basis of our experience of surgical treatment for AdBP. This is a retrospective review of clinical records Four cases of AdBP, in which surgical treatment was performed, are presented. AdBP shows disorders of vocal fold adduction because of paralysis of the thyroarytenoid and lateral cricoarytenoid muscles. The PCA muscle, dominated by the recurrent nerve PCA muscle branch, does not show paralysis. Thus, this type of partial recurrent nerve paresis retains the abductive function and is difficult to distinguish from arytenoid cartilage dislocation because of their similar endoscopic findings. The features include acute onset, and all cases were idiopathic etiology. Thyroarytenoid muscle paralysis was determined by electromyography and stroboscopic findings. The adduction and abduction of paralytic arytenoids were evaluated from 3 dimensional computed tomography (3DCT). In all cases, surgical treatments were arytenoid adduction combined with thyroplasty. When we adducted the arytenoid cartilage during inspiration, strong resistance was observed. In the two cases where we could cut the PCA muscle sufficiently, the maximum phonation time was improved to ≥30 seconds after surgery, from 2 to 3 seconds preoperatively, providing good postoperative voices. In contrast, in the two cases of insufficient resection, the surgical outcomes were poorer. Because the preoperative voice in AdBP patients is typically very coarse, surgical treatment is needed, as well as ordinary recurrent nerve paralysis. In our experience, adequate PCA muscle resection might be helpful in surgical treatment of AdBP. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  3. The Patient-Reported Information Multidimensional Exploration (PRIME) Framework for Investigating Emotions and Other Factors of Prostate Cancer Patients with Low Intermediate Risk Based on Online Cancer Support Group Discussions.

    PubMed

    Bandaragoda, Tharindu; Ranasinghe, Weranja; Adikari, Achini; de Silva, Daswin; Lawrentschuk, Nathan; Alahakoon, Damminda; Persad, Raj; Bolton, Damien

    2018-06-01

    This study aimed to use the Patient Reported Information Multidimensional Exploration (PRIME) framework, a novel ensemble of machine-learning and deep-learning algorithms, to extract, analyze, and correlate self-reported information from Online Cancer Support Groups (OCSG) by patients (and partners of patients) with low intermediate-risk prostate cancer (PCa) undergoing radical prostatectomy (RP), external beam radiotherapy (EBRT), and active surveillance (AS), and to investigate its efficacy in quality-of-life (QoL) and emotion measures. From patient-reported information on 10 OCSG, the PRIME framework automatically filtered and extracted conversations on low intermediate-risk PCa with active user participation. Side effects as well as emotional and QoL outcomes for 6084 patients were analyzed. Side-effect profiles differed between the methods analyzed, with men after RP having more urinary and sexual side effects and men after EBRT having more bowel symptoms. Key findings from the analysis of emotional expressions showed that PCa patients younger than 40 years expressed significantly high positive and negative emotions compared with other age groups, that partners of patients expressed more negative emotions than the patients, and that selected cohorts (< 40 years, > 70 years, partners of patients) have frequently used the same terms to express their emotions, which is indicative of QoL issues specific to those cohorts. Despite recent advances in patient-centerd care, patient emotions are largely overlooked, especially in younger men with a diagnosis of PCa and their partners. The authors present a novel approach, the PRIME framework, to extract, analyze, and correlate key patient factors. This framework improves understanding of QoL and identifies low intermediate-risk PCa patients who require additional support.

  4. MRI in early prostate cancer detection: how to manage indeterminate or equivocal PI-RADS 3 lesions?

    PubMed

    Schoots, Ivo G

    2018-02-01

    This review focuses on indeterminate lesions on prostate magnetic resonance imaging (MRI), assigned as PI-RADS category 3. The prevalence of PI-RADS 3 index lesion in the diagnostic work-up is significant, varying between one in three (32%) to one in five (22%) men, depending on patient cohort of first biopsies, previously negative biopsies, and active surveillance biopsies. A management strategy must be developed for this group of men with an indeterminate suspicion of having clinically significant prostate cancer (csPCa). Currently available data show that the actual prevalence of csPCa after targeted biopsy in PI-RADS 3 lesions vary between patients groups from one in five (21%) to one in six (16%), depending on previous biopsy status. Although this prevalence is lower in comparison to PI-RADS 4 and PI-RADS 5 lesions, still a considerable proportion of men harbor significant disease. Men with such a PI-RADS 3 lesion should therefore be adequately managed. In general, the clinical approach of using a threshold of PI-RADS ≥4 instead of PI-RADS ≥3 to select MRI for targeted biopsies is not supported by data from our explorative literature search using current definitions of csPCa. A possible adaptation to the threshold of PI-RADS ≥4 in combination with other clinical markers could be considered within an active surveillance protocol, where the balance between the individual risk of missing csPCa and the constant process of repeating prostate biopsies is crucial. In the future, improvements in MR imaging and interpretation, combined with molecular biomarkers and multivariate risk models will all be employed in prostate cancer detection and monitoring. These combinations will aid decision-making in challenging circumstances, such as unclear and diagnostic equivocal results for csPCa at early detection.

  5. The Prostate Health Index in predicting initial prostate biopsy outcomes in Asian men with prostate-specific antigen levels of 4-10 ng/mL.

    PubMed

    Ng, C F; Chiu, Peter K F; Lam, N Y; Lam, H C; Lee, Kim W M; Hou, Simon S M

    2014-04-01

    To investigate the role of the Prostate Health Index (phi) in prostate cancer (PCa) detection in patients with a prostate-specific antigen (PSA) level of 4-10 ng/mL receiving their first prostatic biopsy in an Asian population. This was a retrospective study of archived serum samples from patients enlisted in our tissue bank. Patients over 50 years old, with PSA level of 4-10 ng/mL, a negative digital rectal examination, and received their first prostatic biopsy between April 2008 and April 2013, were recruited. The serum sample collected before biopsy was retrieved for the measurement of various PSA derivatives and the phi value was calculated for each patient. The performance of these parameters in predicting the prostatic biopsy results was assessed. Two hundred and thirty consecutive patients, with 21 (9.13 %) diagnosed with PCa, were recruited for this study. Statistically significant differences between PCa patients and non-PCa patients were found for total PSA, PSA density, [-2]proPSA (p2PSA), free-to-total PSA ratio (%fPSA), p2PSA-to-free PSA ratio (%p2PSA), and phi. The areas under the curve of the receiver operating characteristic curve for total PSA, PSA density, %fPSA, %p2PSA, and phi were 0.547, 0.634, 0.654, 0.768, and 0.781, respectively. The phi was the best predictor of the prostatic biopsies results. At a sensitivity of 90 %, the use of the phi could have avoided unnecessary biopsies in 104 (45.2 %) patients. Use of the phi could improve the accuracy of PCa detection in patients with an elevated PSA level and thus avoid unnecessary prostatic biopsies.

  6. The impact of prostate cancer diagnosis and treatment decision-making on health-related quality of life before treatment onset.

    PubMed

    Cuypers, Maarten; Lamers, Romy E D; Cornel, Erik B; van de Poll-Franse, Lonneke V; de Vries, Marieke; Kil, Paul J M

    2018-04-01

    The objective of this study is to test if patients' health-related quality of life (HRQoL) declines after prostate biopsy to detect Pca, and after subsequent treatment decision-making in case Pca is confirmed, and to test whether personality state and traits are associated with these potential changes in HRQoL. Patients who were scheduled for prostate biopsy to detect Pca (N = 377) filled out a baseline questionnaire about HRQoL (EORTC QLQ-C30 and PR25), "big five" personality traits (BFI-10), optimism (LOT-r), and self-efficacy (Decision Self-efficacy Scale) (t0). Patients with confirmed Pca (N = 126) filled out a follow-up questionnaire on HRQoL within 2 weeks after treatment was chosen but had not yet started (t1). HRQoL declined between t0 and t1, reflected in impaired role and cognitive functioning, and elevated fatigue, constipation, and prostate-specific symptoms. Sexual activity and functioning improved. Baseline HRQoL scores were unrelated to the selection of a particular treatment, but for patients who chose a curative treatment, post-decision HRQoL showed a greater decline compared to patients who chose active surveillance. Optimism was associated with HRQoL at baseline; decisional self-efficacy was positively associated with HRQoL at follow-up. No associations between HRQoL and the "big five" personality traits were found. Patients who have undergone prostate biopsy and treatment decision-making for Pca experience a decline in HRQoL. Choosing treatment with a curative intent was associated with greater decline in HRQoL. Interventions aimed at optimism and decision self-efficacy could be helpful to reduce HRQoL impairment around the time of prostate biopsy and treatment decision-making.

  7. The Epidemiology of Prostate Cancer in Western Jamaica: Risk Factors, Knowledge, Attitudes and Practices.

    PubMed

    Dotson, S J; Howard, M D; Aung, M; Keenan, J A; Jolly, P E

    2015-05-08

    To investigate the epidemiology of prostate cancer (PCa) in western Jamaica and describe the health-seeking behaviour of at-risk men. This study contained both quantitative and qualitative components. The quantitative portion consisted of a retrospective, matched case-control study of two hundred and four men attending outpatient clinics who completed an interviewer-administered questionnaire. The qualitative component consisted of two focus group discussions designed to further investigate health-seeking behaviour and preferred educational channels regarding PCa. Four risk factors were identified: family history of PCa (OR 3.39, 95% CI 1.73, 6.66), age (OR 1.97, 95% CI 1.41, 2.74), any sexually transmitted disease (STD) history (OR 2.02, 95% CI 1.07, 3.83) and alcohol consumption (OR 1.86, 95% CI 1.00, 3.47). Knowledge of primary risk factors was low, especially for race (37%). Although 81% of controls knew tests were available, a stigma was associated with testing. The screening rate was higher than previously reported but still low (56% of controls), and PCa in the western region is discovered by symptoms 61% of the time. Focus group participants blamed a "male mentality" that is antagonistic to routine medical care and preventive testing. Family history, age, STDs and alcohol consumption were identified as risk factors for PCa in western Jamaica. Sexually transmitted disease history and alcohol consumption are interesting results that merit further investigation. Prostate cancer continues to be diagnosed primarily by symptoms, indicating that routine testing is not widespread enough to catch the disease in its early stages when treatment is most effective. A negative image of prostate screenings persists, and targeted educational interventions are needed to improve outcomes.

  8. The best prostate biopsy scheme is dictated by the gland volume: a monocentric study.

    PubMed

    Dell'Atti, L

    2015-08-01

    Accuracy of biopsy scheme depends on different parameters. Prostate-specific antigen (PSA) level and digital rectal examination (DRE) influenced the detection rate and suggested the biopsy scheme to approach each patient. Another parameter is the prostate volume. Sampling accuracy tends to decrease progressively with an increasing prostate volume. We prospectively observed detection cancer rate in suspicious prostate cancer (PCa) and improved by applying a protocol biopsy according to prostate volume (PV). Clinical data and pathological features of these 1356 patients were analysed and included in this study. This protocol is a combined scheme that includes transrectal (TR) 12-core PBx (TR12PBx) for PV ≤ 30 cc, TR 14-core PBx (TR14PBx) for PV > 30 cc but < 60 cc, TR 18-core PBx (TR18PBx) for PV ≥ 60 cc. Out of a total of 1356 patients, in 111 (8.2%) PCa was identified through TR12PBx scheme, in 198 (14.6%) through TR14PBx scheme and in 253 (18.6%) through TR18PBx scheme. The PCa detection rate was increased by 44% by adding two TZ cores (TR14PBx scheme). The TR18PBx scheme increased this rate by 21.7% vs. TR14PBx scheme. The diagnostic yield offered by TR18PBx was statistically significant compared to the detection rate offered by the TR14PBx scheme (p < 0.003). The biopsy Gleason score and the percentage of core involvement were comparable between PCa detected by the TR14PBx scheme diagnostic yield and those detected by the TR18PBx scheme (p = 0.362). The only PV parameter, in our opinion, can be significant in choosing the best biopsy scheme to approach in a first setting of biopsies increasing PCa detection rate.

  9. Modeling patterns of anatomical deformations in prostate patients undergoing radiation therapy with an endorectal balloon

    NASA Astrophysics Data System (ADS)

    Brion, Eliott; Richter, Christian; Macq, Benoit; Stützer, Kristin; Exner, Florian; Troost, Esther; Hölscher, Tobias; Bondar, Luiza

    2017-03-01

    External beam radiation therapy (EBRT) treats cancer by delivering daily fractions of radiation to a target volume. For prostate cancer, the target undergoes day-to-day variations in position, volume, and shape. For stereotactic photon and for proton EBRT, endorectal balloons (ERBs) can be used to limit variations. To date, patterns of non-rigid variations for patients with ERB have not been modeled. We extracted and modeled the patient-specific patterns of variations, using regularly acquired CT-images, non-rigid point cloud registration, and principal component analysis (PCA). For each patient, a non-rigid point-set registration method, called Coherent Point Drift, (CPD) was used to automatically generate landmark correspondences between all target shapes. To ensure accurate registrations, we tested and validated CPD by identifying parameter values leading to the smallest registration errors (surface matching error 0.13+/-0.09 mm). PCA demonstrated that 88+/-3.2% of the target motion could be explained using only 4 principal modes. The most dominant component of target motion is a squeezing and stretching in the anterior-posterior and superior-inferior directions. A PCA model of daily landmark displacements, generated using 6 to 10 CT-scans, could explain well the target motion for the CT-scans not included in the model (modeling error decreased from 1.83+/-0.8 mm for 6 CT-scans to 1.6+/-0.7 mm for 10 CT-scans). PCA modeling error was smaller than the naive approximation by the mean shape (approximation error 2.66+/-0.59 mm). Future work will investigate the use of the PCA-model to improve the accuracy of EBRT techniques that are highly susceptible to anatomical variations such as, proton therapy

  10. Multi-angle backscatter classification and sub-bottom profiling for improved seafloor characterization

    NASA Astrophysics Data System (ADS)

    Alevizos, Evangelos; Snellen, Mirjam; Simons, Dick; Siemes, Kerstin; Greinert, Jens

    2018-06-01

    This study applies three classification methods exploiting the angular dependence of acoustic seafloor backscatter along with high resolution sub-bottom profiling for seafloor sediment characterization in the Eckernförde Bay, Baltic Sea Germany. This area is well suited for acoustic backscatter studies due to its shallowness, its smooth bathymetry and the presence of a wide range of sediment types. Backscatter data were acquired using a Seabeam1180 (180 kHz) multibeam echosounder and sub-bottom profiler data were recorded using a SES-2000 parametric sonar transmitting 6 and 12 kHz. The high density of seafloor soundings allowed extracting backscatter layers for five beam angles over a large part of the surveyed area. A Bayesian probability method was employed for sediment classification based on the backscatter variability at a single incidence angle, whereas Maximum Likelihood Classification (MLC) and Principal Components Analysis (PCA) were applied to the multi-angle layers. The Bayesian approach was used for identifying the optimum number of acoustic classes because cluster validation is carried out prior to class assignment and class outputs are ordinal categorical values. The method is based on the principle that backscatter values from a single incidence angle express a normal distribution for a particular sediment type. The resulting Bayesian classes were well correlated to median grain sizes and the percentage of coarse material. The MLC method uses angular response information from five layers of training areas extracted from the Bayesian classification map. The subsequent PCA analysis is based on the transformation of these five layers into two principal components that comprise most of the data variability. These principal components were clustered in five classes after running an external cluster validation test. In general both methods MLC and PCA, separated the various sediment types effectively, showing good agreement (kappa >0.7) with the Bayesian approach which also correlates well with ground truth data (r2 > 0.7). In addition, sub-bottom data were used in conjunction with the Bayesian classification results to characterize acoustic classes with respect to their geological and stratigraphic interpretation. The joined interpretation of seafloor and sub-seafloor data sets proved to be an efficient approach for a better understanding of seafloor backscatter patchiness and to discriminate acoustically similar classes in different geological/bathymetric settings.

  11. Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy.

    PubMed

    Rubio-Briones, Jose; Borque, Angel; Esteban, Luis M; Casanova, Juan; Fernandez-Serra, Antonio; Rubio, Luis; Casanova-Salas, Irene; Sanz, Gerardo; Domínguez-Escrig, Jose; Collado, Argimiro; Gómez-Ferrer, Alvaro; Iborra, Inmaculada; Ramírez-Backhaus, Miguel; Martínez, Francisco; Calatrava, Ana; Lopez-Guerrero, Jose A

    2015-09-11

    PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%. PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.

  12. Pain Levels Within 24 Hours After UFE: A Comparison of Morphine and Fentanyl Patient-Controlled Analgesia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Hyun S., E-mail: sikhkim@jhmi.edu; Czuczman, Gregory J.; Nicholson, Wanda K.

    The purpose of this study was to assess the presence and severity of pain levels during 24 h after uterine fibroid embolization (UFE) for symptomatic leiomyomata and compare the effectiveness and adverse effects of morphine patient-controlled analgesia (PCA) versus fentanyl PCA. We carried out a prospective, nonrandomized study of 200 consecutive women who received UFE and morphine or fentanyl PCA after UFE. Pain perception levels were obtained on a 0-10 scale for the 24-h period after UFE. Linear regression methods were used to determine pain trends and differences in pain trends between two groups and the association between pain scoresmore » and patient covariates. One hundred eighty-five patients (92.5%) reported greater-than-baseline pain after UFE, and 198 patients (99%) required IV opioid PCA. One hundred thirty-six patients (68.0%) developed nausea during the 24-h period. Seventy-two patients (36%) received morphine PCA and 128 (64%) received fentanyl PCA, without demographic differences. The mean dose of morphine used was 33.8 {+-} 26.7 mg, while the mean dose of fentanyl was 698.7 {+-} 537.4 {mu}g. Using this regimen, patients who received morphine PCA had significantly lower pain levels than those who received fentanyl PCA (p < 0.0001). We conclude that patients develop pain requiring IV opioid PCA within 24 h after UFE. Morphine PCA is more effective in reducing post-uterine artery embolization pain than fentanyl PCA. Nausea is a significant adverse effect from opioid PCA.« less

  13. Flight test of a propulsion controlled aircraft system on the NASA F-15 airplane

    NASA Technical Reports Server (NTRS)

    Burcham, Frank W., Jr.; Maine, Trindel A.

    1995-01-01

    Flight tests of the propulsion controlled aircraft (PCA) system on the NASA F-15 airplane evolved as a result of a long series of simulation and flight tests. Initially, the simulation results were very optimistic. Early flight tests showed that manual throttles-only control was much more difficult than the simulation, and a flight investigation was flown to acquire data to resolve this discrepancy. The PCA system designed and developed by MDA evolved as these discrepancies were found and resolved, requiring redesign of the PCA software and modification of the flight test plan. Small throttle step inputs were flown to provide data for analysis, simulation update, and control logic modification. The PCA flight tests quickly revealed less than desired performance, but the extensive flexibility built into the flight PCA software allowed rapid evaluation of alternate gains, filters, and control logic, and within 2 weeks, the PCA system was functioning well. The initial objective of achieving adequate control for up-and-away flying and approaches was satisfied, and the option to continue to actual landings was achieved. After the PCA landings were accomplished, other PCA features were added, and additional maneuvers beyond those originally planned were flown. The PCA system was used to recover from extreme upset conditions, descend, and make approaches to landing. A heading mode was added, and a single engine plus rudder PCA mode was also added and flown. The PCA flight envelope was expanded far beyond that originally designed for. Guest pilots from the USAF, USN, NASA, and the contractor also flew the PCA system and were favorably impressed.

  14. An In Vitro Spectroscopic Analysis to Determine Whether para-Chloroaniline is Produced from Mixing Sodium Hypochlorite and Chlorhexidine

    PubMed Central

    Thomas, John E.; Sem, Daniel S.

    2009-01-01

    Introduction The purpose of this in vitro study was to determine whether para-chloroaniline (PCA) is formed through the reaction of mixing sodium hypochlorite (NaOCl) and chlorhexidine (CHX). Methods Initially commercially available samples of chlorhexidine acetate (CHXa) and PCA were analyzed with 1H NMR spectroscopy. Two solutions, NaOCl and CHXa, were warmed to 37°C and when mixed they produced a brown precipitate. This precipitate was separated in half and pure PCA was added to one of the samples for comparison before they were each analyzed with 1H NMR spectroscopy. Results The peaks in the 1H NMR spectra of CHXa and PCA were assigned to specific protons of the molecules, and the location of the aromatic peaks in the PCA spectrum defined the PCA doublet region. While the spectrum of the precipitate alone resulted in a complex combination of peaks, upon magnification there were no peaks in the PCA doublet region which were intense enough to be quantified. In the spectrum of the precipitate, to which PCA was added, two peaks do appear in the PCA doublet region. Comparing this spectrum to that of precipitate alone, the peaks in the PCA doublet region are not visible prior to the addition of PCA. Conclusions Based on this in vitro study, the reaction mixture of NaOCl and CHXa does not produce PCA at any measurable quantity and further investigation is needed to determine the chemical composition of the brown precipitate. PMID:20113799

  15. External validation of a PCA-3-based nomogram for predicting prostate cancer and high-grade cancer on initial prostate biopsy.

    PubMed

    Greene, Daniel J; Elshafei, Ahmed; Nyame, Yaw A; Kara, Onder; Malkoc, Ercan; Gao, Tianming; Jones, J Stephen

    2016-08-01

    The aim of this study was to externally validate a previously developed PCA3-based nomogram for the prediction of prostate cancer (PCa) and high-grade (intermediate and/or high-grade) prostate cancer (HGPCa) at the time of initial prostate biopsy. A retrospective review was performed on a cohort of 336 men from a large urban academic medical center. All men had serum PSA <20 ng/ml and underwent initial transrectal ultrasound-guided prostate biopsy with at least 10 cores sampling for suspicious exam and/or elevated PSA. Covariates were collected for the nomogram and included age, ethnicity, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and abnormal finding on digital rectal exam (DRE). These variables were used to test the accuracy (concordance index) and calibration of a previously published PCA3 nomogram. Biopsy confirms PCa and HGPCa in 51.0% and 30.4% of validation patients, respectively. This differed from the original cohort in that it had significantly more PCa and HGPCA (51% vs. 44%, P = 0.019; and 30.4% vs. 19.1%, P < 0.001). Despite the differences in PCa detection the concordance index was 75% and 77% for overall PCa and HGPCa, respectively. Calibration for overall PCa was good. This represents the first external validation of a PCA3-based prostate cancer predictive nomogram in a North American population. Prostate 76:1019-1023, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Bioproduction of 4-vinylphenol from corn cob alkaline hydrolyzate in two-phase extractive fermentation using free or immobilized recombinant E. coli expressing pad gene.

    PubMed

    Salgado, José Manuel; Rodríguez-Solana, Raquel; Curiel, José Antonio; de Las Rivas, Blanca; Muñoz, Rosario; Domínguez, José Manuel

    2014-05-10

    In situ extractive fermentation was used to produce 4-vinyl derivatives from hydroxycinnamic acids extracted from corn cobs by recombinant Escherichia coli cells expressing Lactobacillus plantarum phenolic acid descarboxylase (PAD) gene. This microorganism mainly produced 4-vinylphenol (4VP) from p-coumaric acid (p-CA). In the first study , we observed that the concentrations of 4VP are higher than 1g/L which had a negative impact on decarboxylation of p-CA to 4VP by recombinant E. coli cells. Because of this, and in order to improve the downstream process, a two-phase aqueous-organic solvent system was developed. The results of the extractive fermentation indicated that it was possible to use hydrolyzates as aqueous phase to bioproduce 4VP, and recover simultaneously the product in the organic phase containing hexane. The detoxification of pre-treated corn cob alkaline hydrolyzate improved 4VP production up to 1003.5mg/L after 24h fermentation (QP=41.813mg/Lh). Additionally, preliminary experiments using cells immobilized in calcium alginate showed to be a good system for the biotransform of p-CA to 4VP in extractive fermentation, although the process hindered partially the recovery of 4VP in the organic phase. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Automated high-grade prostate cancer detection and ranking on whole slide images

    NASA Astrophysics Data System (ADS)

    Huang, Chao-Hui; Racoceanu, Daniel

    2017-03-01

    Recently, digital pathology (DP) has been largely improved due to the development of computer vision and machine learning. Automated detection of high-grade prostate carcinoma (HG-PCa) is an impactful medical use-case showing the paradigm of collaboration between DP and computer science: given a field of view (FOV) from a whole slide image (WSI), the computer-aided system is able to determine the grade by classifying the FOV. Various approaches have been reported based on this approach. However, there are two reasons supporting us to conduct this work: first, there is still room for improvement in terms of detection accuracy of HG-PCa; second, a clinical practice is more complex than the operation of simple image classification. FOV ranking is also an essential step. E.g., in clinical practice, a pathologist usually evaluates a case based on a few FOVs from the given WSI. Then, makes decision based on the most severe FOV. This important ranking scenario is not yet being well discussed. In this work, we introduce an automated detection and ranking system for PCa based on Gleason pattern discrimination. Our experiments suggested that the proposed system is able to perform high-accuracy detection ( 95:57% +/- 2:1%) and excellent performance of ranking. Hence, the proposed system has a great potential to support the daily tasks in the medical routine of clinical pathology.

  18. Prostate cancer survivors with a passive role preference in treatment decision-making are less satisfied with information received: Results from the PROFILES registry.

    PubMed

    Cuypers, Maarten; Lamers, Romy E D; de Vries, Marieke; Husson, Olga; Kil, Paul J M; van de Poll-Franse, Lonneke V

    2016-11-01

    To investigate decision-making role preferences and their association with the evaluation of information received in a sample of low-risk and intermediate-risk prostate cancer (Pca) survivors. Cross-sectional study involved 562 men diagnosed with low-risk or intermediate-risk Pca (median time since diagnosis, 48mo), measuring preferred decision-making role (Control Preference Scale) and the evaluation of information received (EORTC QLQ-INFO25). Analyses were performed using analysis of variance, chi-square tests, and multivariable linear regression models. Men who preferred a passive role were older and less educated than other preference groups and more often selected a noninvasive treatment option (all with P<0.001). The passive role preference group reported having received less information, judged the received information as less helpful, and indicated lower overall satisfaction with information received (all with P<0.05). Role preference groups did not differ in their desire to receive more information. Compared with nonpassive preference groups, the preference for a passive role in Pca treatment decision-making is associated with less satisfaction with the information received. Assessment of role preferences and tailored information provision could improve satisfaction with information received and perhaps may ultimately lead to improved patient participation in treatment decision-making. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Exploring factors affecting owners' trust of contractors in construction projects: a case of China.

    PubMed

    Tai, Shuangliang; Sun, Chengshuang; Zhang, Shoujian

    2016-01-01

    It has been found that a low level of trust among members of a construction project team leads to poor performance in China. Many researchers have described the challenges, consequently advocating partnering as an attractive approach for more valuable cooperation. Because substantial investments have been poured into construction projects since the year 2000, trust research will improve the performance of construction projects and will be meaningful to the Chinese construction industry. The purpose of this paper is to investigate the attributes affecting owners' trust of contractors, to understand the potential properties of these factors, and to rank the factors in order of importance. Twenty-four attributes are identified from a literature review. Supported by qualitative reviews, a questionnaire is conducted to obtain relevant data, and 168 valid responses are obtained for data analysis. Principal component analysis (PCA) is employed to find the factor structure of the identified trust attributes. By the method of PCA, the attributes are extracted into eight factors, including interaction history, information sharing and communication, contract and institution, relation-specific investment, reputation, integrity, competence, and opportunistic behaviour. The value and originality of this paper are embodied in using PCA to understand the various attribute groupings and to illuminate trust impact factors in the Chinese context. When they understand the critical factors affecting trust better, owners and contractors can devise more appropriate strategies to improve performance.

  20. Using Serological Proteome Analysis to Identify Serum Anti-Nucleophosmin 1 Autoantibody as a Potential Biomarker in European-American and African-American Patients With Prostate Cancer.

    PubMed

    Dai, Liping; Li, Jitian; Xing, Mengtao; Sanchez, Tino W; Casiano, Carlos A; Zhang, Jian-Ying

    2016-11-01

    The prostate-specific antigen (PSA) testing has been widely implemented for the early detection and management of prostate cancer (PCa). However, the lack of specificity has led to overdiagnosis, resulting in many possibly unnecessary biopsies and overtreatment. Therefore, novel serological biomarkers with high sensitivity and specificity are of vital importance needed to complement PSA testing in the early diagnosis and effective management of PCa. This is particularly critical in the context of PCa health disparities, where early detection and management could help reduce the disproportionately high PCa mortality observed in African-American men. Previous studies have demonstrated that sera from patients with PCa contain autoantibodies that react with tumor-associated antigens (TAAs). The serological proteome analysis (SERPA) approach was used to identify tumor-associated antigens (TAAs) of PCa. In evaluation study, the level of anti-NPM1 antibody was examined in sera from test cohort, validation cohort, as well as European-American (EA) and African-American (AA) men with PCa by using immunoassay. Nucleophosmin 1 (NPM1) as a 33 kDa TAA in PCa was identified and characterized by SERPA approach. Anti-NPM1 antibody level in PCa was higher than in benign prostatic hyperplasia (BPH) patients and healthy individuals. Receiver operating characteristic (ROC) curve analysis showed similar high diagnostic value for PCa in the test cohort (area under the curve (AUC):0.860) and validation cohort (AUC: 0.822) to differentiate from normal individuals and BPH. Interestingly, AUC values were significantly higher for AA PCa patients. When considering concurrent serum measurements of anti-NPM1 antibody and PSA, 97.1% PCa patients at early stage were identified correctly, while 69.2% BPH patients who had elevated PSA levels were found to be anti-NPM1 negative. Additionally, anti-NPM1 antibody levels in PCa patients at early stage significantly increased after surgery treatment. This intriguing data suggested that NPM1 can elicit autoantibody response in PCa and might be a potential biomarker for the immunodiagnosis and prognosis of PCa, and for supplementing PSA testing in distinguishing PCa from BPH. Prostate 76:1375-1386, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Fabrication of oxide dispersion strengthened bond coats with low Al 2O 3 content [Fabrication of ODS bond coats with low Al 2O 3 content

    DOE PAGES

    Bergholz, Jan; Pint, Bruce A.; Unocic, Kinga A.; ...

    2017-03-23

    Here, nanoscale oxide dispersions have long been used to increase the oxidation and wear resistance of alloys used as bond coatings in thermal barrier coatings. Their manufacturing via mechanical alloying is often accompanied by difficulties regarding their particle size, homogeneous distribution of the oxide dispersions inside the powder, involving considerable costs, due to cold welding of the powder during milling. A significant improvement in this process can be achieved by the use of process control agent (PCA) to achieve the critical balance between cold welding and fracturing, thereby enhancing the process efficiency. In this investigation, the influence of the organicmore » additive stearic acid on the manufacturing process of Al 2O 3-doped CoNiCrAlY powder was investigated. Powders were fabricated via mechanical alloying at different milling times and PCA concentrations. The results showed a decrease in particle size, without hindering the homogeneous incorporation of the oxide dispersions. Two powders manufactured with 0.5 and 1.0 wt.% PCA were deposited by high velocity oxygen fuel (HVOF) spraying. Results showed that a higher content of elongated particles in the powder with the higher PCA content led to increased surface roughness, porosity and decreased coating thickness, with areas without embedded oxide particles.« less

  2. EEG channels reduction using PCA to increase XGBoost's accuracy for stroke detection

    NASA Astrophysics Data System (ADS)

    Fitriah, N.; Wijaya, S. K.; Fanany, M. I.; Badri, C.; Rezal, M.

    2017-07-01

    In Indonesia, based on the result of Basic Health Research 2013, the number of stroke patients had increased from 8.3 ‰ (2007) to 12.1 ‰ (2013). These days, some researchers are using electroencephalography (EEG) result as another option to detect the stroke disease besides CT Scan image as the gold standard. A previous study on the data of stroke and healthy patients in National Brain Center Hospital (RS PON) used Brain Symmetry Index (BSI), Delta-Alpha Ratio (DAR), and Delta-Theta-Alpha-Beta Ratio (DTABR) as the features for classification by an Extreme Learning Machine (ELM). The study got 85% accuracy with sensitivity above 86 % for acute ischemic stroke detection. Using EEG data means dealing with many data dimensions, and it can reduce the accuracy of classifier (the curse of dimensionality). Principal Component Analysis (PCA) could reduce dimensionality and computation cost without decreasing classification accuracy. XGBoost, as the scalable tree boosting classifier, can solve real-world scale problems (Higgs Boson and Allstate dataset) with using a minimal amount of resources. This paper reuses the same data from RS PON and features from previous research, preprocessed with PCA and classified with XGBoost, to increase the accuracy with fewer electrodes. The specific fewer electrodes improved the accuracy of stroke detection. Our future work will examine the other algorithm besides PCA to get higher accuracy with less number of channels.

  3. A modified receptor model for source apportionment of heavy metal pollution in soil.

    PubMed

    Huang, Ying; Deng, Meihua; Wu, Shaofu; Japenga, Jan; Li, Tingqiang; Yang, Xiaoe; He, Zhenli

    2018-07-15

    Source apportionment is a crucial step toward reduction of heavy metal pollution in soil. Existing methods are generally based on receptor models. However, overestimation or underestimation occurs when they are applied to heavy metal source apportionment in soil. Therefore, a modified model (PCA-MLRD) was developed, which is based on principal component analysis (PCA) and multiple linear regression with distance (MLRD). This model was applied to a case study conducted in a peri-urban area in southeast China where soils were contaminated by arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb). Compared with existing models, PCA-MLRD is able to identify specific sources and quantify the extent of influence for each emission. The zinc (Zn)-Pb mine was identified as the most important anthropogenic emission, which affected approximately half area for Pb and As accumulation, and approximately one third for Cd. Overall, the influence extent of the anthropogenic emissions decreased in the order of mine (3 km) > dyeing mill (2 km) ≈ industrial hub (2 km) > fluorescent factory (1.5 km) > road (0.5 km). Although algorithm still needs to improved, the PCA-MLRD model has the potential to become a useful tool for heavy metal source apportionment in soil. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. [Research on spectra recognition method for cabbages and weeds based on PCA and SIMCA].

    PubMed

    Zu, Qin; Deng, Wei; Wang, Xiu; Zhao, Chun-Jiang

    2013-10-01

    In order to improve the accuracy and efficiency of weed identification, the difference of spectral reflectance was employed to distinguish between crops and weeds. Firstly, the different combinations of Savitzky-Golay (SG) convolutional derivation and multiplicative scattering correction (MSC) method were applied to preprocess the raw spectral data. Then the clustering analysis of various types of plants was completed by using principal component analysis (PCA) method, and the feature wavelengths which were sensitive for classifying various types of plants were extracted according to the corresponding loading plots of the optimal principal components in PCA results. Finally, setting the feature wavelengths as the input variables, the soft independent modeling of class analogy (SIMCA) classification method was used to identify the various types of plants. The experimental results of classifying cabbages and weeds showed that on the basis of the optimal pretreatment by a synthetic application of MSC and SG convolutional derivation with SG's parameters set as 1rd order derivation, 3th degree polynomial and 51 smoothing points, 23 feature wavelengths were extracted in accordance with the top three principal components in PCA results. When SIMCA method was used for classification while the previously selected 23 feature wavelengths were set as the input variables, the classification rates of the modeling set and the prediction set were respectively up to 98.6% and 100%.

  5. Neuropsychiatric Symptoms in Posterior Cortical Atrophy and Alzheimer Disease

    PubMed Central

    Crutch, Sebastian J.; Franco-Macías, Emilio; Gil-Néciga, Eulogio

    2016-01-01

    Background: Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterized by early progressive visual dysfunction in the context of relative preservation of memory and a pattern of atrophy mainly involving the posterior cortex. The aim of the present study is to characterize the neuropsychiatric profile of PCA. Methods: The Neuropsychiatric Inventory was used to assess 12 neuropsychiatric symptoms (NPS) in 28 patients with PCA and 34 patients with typical Alzheimer disease (AD) matched by age, disease duration, and illness severity. Results: The most commonly reported NPS in both groups were depression, anxiety, apathy, and irritability. However, aside from a trend toward lower rates of apathy in patients with PCA, there were no differences in the percentage of NPS presented in each group. All those patients presenting visual hallucinations in the PCA group also met diagnostic criteria for dementia with Lewy bodies (DLB). Auditory hallucinations were only present in patients meeting diagnosis criteria for DLB. Conclusion: Prevalence of the 12 NPS examined was similar between patients with PCA and AD. Hallucinations in PCA may be helpful in the differential diagnosis between PCA-AD and PCA-DLB. PMID:26404166

  6. The function of oxytocin: a potential biomarker for prostate cancer diagnosis and promoter of prostate cancer.

    PubMed

    Xu, Huan; Fu, Shi; Chen, Qi; Gu, Meng; Zhou, Juan; Liu, Chong; Chen, Yanbo; Wang, Zhong

    2017-05-09

    To measure the level of oxytocin in serum and prostate cancer (PCa) tissue and study its effect on the proliferation of PCa cells. Oxytocin level in serum was significantly increased in PCa patients compared with the no-carcinoma individuals. Additionally, the levels of oxytocin and its receptor were also elevated in the PCa tissue. However, no significant difference existed among the PCa of various Gleason grades. Western blot analysis confirmed the previous results and revealed an increased expression level of APPL1. The level of oxytocin in serum was measured by ELISA analysis. The expression of oxytocin and its receptor in prostate was analyzed by immunohistochemistry. The proliferation and apoptosis of PCa cells were assessed by the Cell Counting Kit 8 (CCK8) assay, cell cycle analysis and caspase3 activity analysis, respectively. Western blot analysis was used for the detection of PCNA, Caspase3 and APPL1 protein levels. Serum and prostatic oxytocin levels are increased in the PCa subjects. Serum oxytocin level may be a biomarker for PCa in the future. Oxytocin increases PCa growth and APPL1 expression.

  7. Effect on laryngeal adductor function of vincristine block of posterior cricoarytenoid muscle 3 to 5 months after recurrent laryngeal nerve injury.

    PubMed

    Paniello, Randal C; Park, Andrea

    2015-06-01

    It has been shown in a canine model that a single injection of vincristine into the posterior cricoarytenoid (PCA) muscle at the time of recurrent laryngeal nerve (RLN) injury effectively blocks its reinnervation and results in improved adductor strength. But clinically, such injuries are usually diagnosed weeks or months after onset. Vincristine injection does not affect a muscle that is already innervated; thus, there is a limited time frame following RLN injury during which a vincristine injection could effectively improve ultimate laryngeal adductor functional recovery. A series of delayed injections was performed in a canine model and results assessed. Animal (canine) experiment. The RLN was transected and repaired, and vincristine (0.4 mg) was injected into the PCA muscle at the time of injury (n=12) or 3, 4, and 5 months later (n=8 each study group). Six months after RLN injury, laryngeal adductor function was measured. Results of vincristine injection without RLN injury (n=6) and longer-term (12 months) follow-up for time zero injections (n=4) are also reported. The animals injected at time zero had better adductor function than non-injected controls, as reported previously, and this result was further increased at 12 months. The 3-month delay gave results similar to the time zero group. The 5-month delay group showed no vincristine benefit, and the 4-month delay group gave an intermediate result. Vincristine to the PCA had no effect on adductor function when the RLN was left intact. Plasma levels showed 19% of injected vincristine reached systemic circulation, which was cleared within 69 hours. Vincristine injection of the PCA muscle after RLN injury, which blocks this antagonist muscle from synkinetic reinnervation, leads to improved laryngeal adductor functional recovery. The window of opportunity to apply this treatment closes by 4 months after RLN injury in the canine model. Human RLN recovery follows a similar time course and can reasonably be expected to have a similar therapeutic window. © The Author(s) 2015.

  8. Effect of yokukansan, a traditional Japanese medicine, on social and aggressive behaviour of para-chloroamphetamine-injected rats.

    PubMed

    Kanno, Hitomi; Sekiguchi, Kyoji; Yamaguchi, Takuji; Terawaki, Kiyoshi; Yuzurihara, Mitsutoshi; Kase, Yoshio; Ikarashi, Yasushi

    2009-09-01

    Yokukansan, a traditional Japanese medicine, has been approved by the Ministry of Health, Labour, and Welfare of Japan as a remedy for neurosis, insomnia or night crying and irritability in children. It has recently been reported to improve behavioural and psychological symptoms of dementia, such as hallucinations, agitation, and aggressiveness in patients with some forms of senile dementia. Little is known about the mechanism underlying the effectiveness of yokukansan. Our aim was to clarify the involvement of yokukansan in serotonergic function in para-chloroamphetamine (PCA)-induced aggressive behaviour in rats. The effect of yokukansan on social interactions, including social and aggressive behaviour, was examined in PCA-injected rats. Concentration and release level of serotonin (5-HT) in the hypothalamus were measured. PCA reduced not only the 5-HT concentration but also the high K(+)-induced 5-HT release in the rat hypothalamus. Social interaction tests showed a significant decrease in social behaviour and a significant increase in aggressive behaviour in the PCA-treated rats. The decrease in social behaviour was ameliorated by the 5-HT1A agonist buspirone and further decreased by a 5-HT1A antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-hexanecarboxamide trihydrochloride (WAY-100635), whereas it was further decreased by the 5-HT2A agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), and ameliorated by the 5-HT2A antagonist ketanserin. On the other hand, the increase in aggressive behaviour was ameliorated by buspirone but not affected by WAY-100635, whereas it was enhanced by DOI and ameliorated by ketanserin. A single injection of yokukansan ameliorated the PCA-induced decrease in social behaviour but not aggressive behaviour. Chronic treatment for 14 days with yokukansan ameliorated PCA-induced abnormal behaviour, decreased social behaviour and increased aggressive behaviour, but it did not ameliorate PCA-induced decreases in the cerebral 5-HT concentration and 5-HT release. The ameliorative effects of chronic yokukansan on behaviour were counteracted by co-administration of WAY-100635. These results suggest that yokukansan might have two different effects: an acute effect on social behaviour and a chronic effect on aggressive behaviour. One of the mechanisms of these effects of yokukansan may be related to the agonistic effect on 5-HT1A receptors.

  9. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.

    PubMed

    Klein, Eric A; Cooperberg, Matthew R; Magi-Galluzzi, Cristina; Simko, Jeffry P; Falzarano, Sara M; Maddala, Tara; Chan, June M; Li, Jianbo; Cowan, Janet E; Tsiatis, Athanasios C; Cherbavaz, Diana B; Pelham, Robert J; Tenggara-Hunter, Imelda; Baehner, Frederick L; Knezevic, Dejan; Febbo, Phillip G; Shak, Steven; Kattan, Michael W; Lee, Mark; Carroll, Peter R

    2014-09-01

    Prostate tumor heterogeneity and biopsy undersampling pose challenges to accurate, individualized risk assessment for men with localized disease. To identify and validate a biopsy-based gene expression signature that predicts clinical recurrence, prostate cancer (PCa) death, and adverse pathology. Gene expression was quantified by reverse transcription-polymerase chain reaction for three studies-a discovery prostatectomy study (n=441), a biopsy study (n=167), and a prospectively designed, independent clinical validation study (n=395)-testing retrospectively collected needle biopsies from contemporary (1997-2011) patients with low to intermediate clinical risk who were candidates for active surveillance (AS). The main outcome measures defining aggressive PCa were clinical recurrence, PCa death, and adverse pathology at prostatectomy. Cox proportional hazards regression models were used to evaluate the association between gene expression and time to event end points. Results from the prostatectomy and biopsy studies were used to develop and lock a multigene-expression-based signature, called the Genomic Prostate Score (GPS); in the validation study, logistic regression was used to test the association between the GPS and pathologic stage and grade at prostatectomy. Decision-curve analysis and risk profiles were used together with clinical and pathologic characteristics to evaluate clinical utility. Of the 732 candidate genes analyzed, 288 (39%) were found to predict clinical recurrence despite heterogeneity and multifocality, and 198 (27%) were predictive of aggressive disease after adjustment for prostate-specific antigen, Gleason score, and clinical stage. Further analysis identified 17 genes representing multiple biological pathways that were combined into the GPS algorithm. In the validation study, GPS predicted high-grade (odds ratio [OR] per 20 GPS units: 2.3; 95% confidence interval [CI], 1.5-3.7; p<0.001) and high-stage (OR per 20 GPS units: 1.9; 95% CI, 1.3-3.0; p=0.003) at surgical pathology. GPS predicted high-grade and/or high-stage disease after controlling for established clinical factors (p<0.005) such as an OR of 2.1 (95% CI, 1.4-3.2) when adjusting for Cancer of the Prostate Risk Assessment score. A limitation of the validation study was the inclusion of men with low-volume intermediate-risk PCa (Gleason score 3+4), for whom some providers would not consider AS. Genes representing multiple biological pathways discriminate PCa aggressiveness in biopsy tissue despite tumor heterogeneity, multifocality, and limited sampling at time of biopsy. The biopsy-based 17-gene GPS improves prediction of the presence or absence of adverse pathology and may help men with PCa make more informed decisions between AS and immediate treatment. Prostate cancer (PCa) is often present in multiple locations within the prostate and has variable characteristics. We identified genes with expression associated with aggressive PCa to develop a biopsy-based, multigene signature, the Genomic Prostate Score (GPS). GPS was validated for its ability to predict men who have high-grade or high-stage PCa at diagnosis and may help men diagnosed with PCa decide between active surveillance and immediate definitive treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  10. Chemometrics resolution and quantification power evaluation: Application on pharmaceutical quaternary mixture of Paracetamol, Guaifenesin, Phenylephrine and p-aminophenol.

    PubMed

    Yehia, Ali M; Mohamed, Heba M

    2016-01-05

    Three advanced chemmometric-assisted spectrophotometric methods namely; Concentration Residuals Augmented Classical Least Squares (CRACLS), Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and Principal Component Analysis-Artificial Neural Networks (PCA-ANN) were developed, validated and benchmarked to PLS calibration; to resolve the severely overlapped spectra and simultaneously determine; Paracetamol (PAR), Guaifenesin (GUA) and Phenylephrine (PHE) in their ternary mixture and in presence of p-aminophenol (AP) the main degradation product and synthesis impurity of Paracetamol. The analytical performance of the proposed methods was described by percentage recoveries, root mean square error of calibration and standard error of prediction. The four multivariate calibration methods could be directly used without any preliminary separation step and successfully applied for pharmaceutical formulation analysis, showing no excipients' interference. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. The Raman spectrum character of skin tumor induced by UVB

    NASA Astrophysics Data System (ADS)

    Wu, Shulian; Hu, Liangjun; Wang, Yunxia; Li, Yongzeng

    2016-03-01

    In our study, the skin canceration processes induced by UVB were analyzed from the perspective of tissue spectrum. A home-made Raman spectral system with a millimeter order excitation laser spot size combined with a multivariate statistical analysis for monitoring the skin changed irradiated by UVB was studied and the discrimination were evaluated. Raman scattering signals of the SCC and normal skin were acquired. Spectral differences in Raman spectra were revealed. Linear discriminant analysis (LDA) based on principal component analysis (PCA) were employed to generate diagnostic algorithms for the classification of skin SCC and normal. The results indicated that Raman spectroscopy combined with PCA-LDA demonstrated good potential for improving the diagnosis of skin cancers.

  12. Online monitoring of coffee roasting by proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS): towards a real-time process control for a consistent roast profile.

    PubMed

    Wieland, Flurin; Gloess, Alexia N; Keller, Marco; Wetzel, Andreas; Schenker, Stefan; Yeretzian, Chahan

    2012-03-01

    A real-time automated process control tool for coffee roasting is presented to consistently and accurately achieve a targeted roast degree. It is based on the online monitoring of volatile organic compounds (VOC) in the off-gas of a drum roaster by proton transfer reaction time-of-flight mass spectrometry at a high time (1 Hz) and mass resolution (5,500 m/Δm at full width at half-maximum) and high sensitivity (better than parts per billion by volume). Forty-two roasting experiments were performed with the drum roaster being operated either on a low, medium or high hot-air inlet temperature (= energy input) and the coffee (Arabica from Antigua, Guatemala) being roasted to low, medium or dark roast degrees. A principal component analysis (PCA) discriminated, for each one of the three hot-air inlet temperatures, the roast degree with a resolution of better than ±1 Colorette. The 3D space of the three first principal components was defined based on 23 mass spectral profiles of VOCs and their roast degree at the end point of roasting. This provided a very detailed picture of the evolution of the roasting process and allowed establishment of a predictive model that projects the online-monitored VOC profile of the roaster off-gas in real time onto the PCA space defined by the calibration process and, ultimately, to control the coffee roasting process so as to achieve a target roast degree and a consistent roasting.

  13. Volatile-Compound Fingerprinting by Headspace-Gas-Chromatography Ion-Mobility Spectrometry (HS-GC-IMS) as a Benchtop Alternative to 1H NMR Profiling for Assessment of the Authenticity of Honey.

    PubMed

    Gerhardt, Natalie; Birkenmeier, Markus; Schwolow, Sebastian; Rohn, Sascha; Weller, Philipp

    2018-02-06

    This work describes a simple approach for the untargeted profiling of volatile compounds for the authentication of the botanical origins of honey based on resolution-optimized HS-GC-IMS combined with optimized chemometric techniques, namely PCA, LDA, and kNN. A direct comparison of the PCA-LDA models between the HS-GC-IMS and 1 H NMR data demonstrated that HS-GC-IMS profiling could be used as a complementary tool to NMR-based profiling of honey samples. Whereas NMR profiling still requires comparatively precise sample preparation, pH adjustment in particular, HS-GC-IMS fingerprinting may be considered an alternative approach for a truly fully automatable, cost-efficient, and in particular highly sensitive method. It was demonstrated that all tested honey samples could be distinguished on the basis of their botanical origins. Loading plots revealed the volatile compounds responsible for the differences among the monofloral honeys. The HS-GC-IMS-based PCA-LDA model was composed of two linear functions of discrimination and 10 selected PCs that discriminated canola, acacia, and honeydew honeys with a predictive accuracy of 98.6%. Application of the LDA model to an external test set of 10 authentic honeys clearly proved the high predictive ability of the model by correctly classifying them into three variety groups with 100% correct classifications. The constructed model presents a simple and efficient method of analysis and may serve as a basis for the authentication of other food types.

  14. Association between age-related reductions in testosterone and risk of prostate cancer-An analysis of patients' data with prostatic diseases.

    PubMed

    Wang, Kai; Chen, Xinguang; Bird, Victoria Y; Gerke, Travis A; Manini, Todd M; Prosperi, Mattia

    2017-11-01

    The relationship between serum total testosterone and prostate cancer (PCa) risk is controversial. The hypothesis that faster age-related reduction in testosterone is linked with increased PCa risk remains untested. We conducted our study at a tertiary-level hospital in southeast of the USA, and derived data from the Medical Registry Database of individuals that were diagnosed of any prostate-related disease from 2001 to 2015. Cases were those diagnosed of PCa and had one or more measurements of testosterone prior to PCa diagnosis. Controls were those without PCa and had one or more testosterone measurements. Multivariable logistic regression models for PCa risk of absolute levels (one-time measure and 5-year average) and annual change in testosterone were respectively constructed. Among a total of 1,559 patients, 217 were PCa cases, and neither one-time measure nor 5-year average of testosterone was found to be significantly associated with PCa risk. Among the 379 patients with two or more testosterone measurements, 27 were PCa cases. For every 10 ng/dL increment in annual reduction of testosterone, the risk of PCa would increase by 14% [adjusted odds ratio, 1.14; 95% confidence interval (CI), 1.03-1.25]. Compared to patients with a relatively stable testosterone, patients with an annual testosterone reduction of more than 30 ng/dL had 5.03 [95% CI: 1.53, 16.55] fold increase in PCa risk. This implies a faster age-related reduction in, but not absolute level of serum total testosterone as a risk factor for PCa. Further longitudinal studies are needed to confirm this finding. © 2017 UICC.

  15. European Randomized Study of Screening for Prostate Cancer Risk Calculator: External Validation, Variability, and Clinical Significance.

    PubMed

    Gómez-Gómez, Enrique; Carrasco-Valiente, Julia; Blanca-Pedregosa, Ana; Barco-Sánchez, Beatriz; Fernandez-Rueda, Jose Luis; Molina-Abril, Helena; Valero-Rosa, Jose; Font-Ugalde, Pilar; Requena-Tapia, Maria José

    2017-04-01

    To externally validate the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) and to evaluate its variability between 2 consecutive prostate-specific antigen (PSA) values. We prospectively catalogued 1021 consecutive patients before prostate biopsy for suspicion of prostate cancer (PCa). The risk of PCa and significant PCa (Gleason score ≥7) from 749 patients was calculated according to ERSPC-RC (digital rectal examination-based version 3 of 4) for 2 consecutive PSA tests per patient. The calculators' predictions were analyzed using calibration plots and the area under the receiver operating characteristic curve (area under the curve). Cohen kappa coefficient was used to compare the ability and variability. Of 749 patients, PCa was detected in 251 (33.5%) and significant PCa was detected in 133 (17.8%). Calibration plots showed an acceptable parallelism and similar discrimination ability for both PSA levels with an area under the curve of 0.69 for PCa and 0.74 for significant PCa. The ERSPC showed 226 (30.2%) unnecessary biopsies with the loss of 10 significant PCa. The variability of the RC was 16% for PCa and 20% for significant PCa, and a higher variability was associated with a reduced risk of significant PCa. We can conclude that the performance of the ERSPC-RC in the present cohort shows a high similitude between the 2 PSA levels; however, the RC variability value is associated with a decreased risk of significant PCa. The use of the ERSPC in our cohort detects a high number of unnecessary biopsies. Thus, the incorporation of ERSPC-RC could help the clinical decision to carry out a prostate biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories.

    PubMed

    Arthur, Rhonda; Møller, Henrik; Garmo, Hans; Holmberg, Lars; Stattin, Pår; Malmstrom, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Robinson, David; Jungner, Ingmar; Hemelrijck, Mieke Van

    2016-06-01

    Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 μg/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 μg/L compared to PSA 4.0-9.9 μg/L. Hypertriglyceridemia was also positively associated with PSA>20 μg/L. Hyperglycemic men had a greater odds of intermediate- and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Epileptic seizure detection in EEG signal with GModPCA and support vector machine.

    PubMed

    Jaiswal, Abeg Kumar; Banka, Haider

    2017-01-01

    Epilepsy is one of the most common neurological disorders caused by recurrent seizures. Electroencephalograms (EEGs) record neural activity and can detect epilepsy. Visual inspection of an EEG signal for epileptic seizure detection is a time-consuming process and may lead to human error; therefore, recently, a number of automated seizure detection frameworks were proposed to replace these traditional methods. Feature extraction and classification are two important steps in these procedures. Feature extraction focuses on finding the informative features that could be used for classification and correct decision-making. Therefore, proposing effective feature extraction techniques for seizure detection is of great significance. Principal Component Analysis (PCA) is a dimensionality reduction technique used in different fields of pattern recognition including EEG signal classification. Global modular PCA (GModPCA) is a variation of PCA. In this paper, an effective framework with GModPCA and Support Vector Machine (SVM) is presented for epileptic seizure detection in EEG signals. The feature extraction is performed with GModPCA, whereas SVM trained with radial basis function kernel performed the classification between seizure and nonseizure EEG signals. Seven different experimental cases were conducted on the benchmark epilepsy EEG dataset. The system performance was evaluated using 10-fold cross-validation. In addition, we prove analytically that GModPCA has less time and space complexities as compared to PCA. The experimental results show that EEG signals have strong inter-sub-pattern correlations. GModPCA and SVM have been able to achieve 100% accuracy for the classification between normal and epileptic signals. Along with this, seven different experimental cases were tested. The classification results of the proposed approach were better than were compared the results of some of the existing methods proposed in literature. It is also found that the time and space complexities of GModPCA are less as compared to PCA. This study suggests that GModPCA and SVM could be used for automated epileptic seizure detection in EEG signal.

  18. Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins*

    PubMed Central

    Sanchez, Tino W.; Zhang, Guangyu; Li, Jitian; Dai, Liping; Mirshahidi, Saied; Wall, Nathan R.; Yates, Clayton; Wilson, Colwick; Montgomery, Susanne; Zhang, Jian-Ying; Casiano, Carlos A.

    2016-01-01

    African American (AA) men suffer from a disproportionately high incidence and mortality of prostate cancer (PCa) compared with other racial/ethnic groups. Despite these disparities, African American men are underrepresented in clinical trials and in studies on PCa biology and biomarker discovery. We used immunoseroproteomics to profile antitumor autoantibody responses in AA and European American (EA) men with PCa, and explored differences in these responses. This minimally invasive approach detects autoantibodies to tumor-associated antigens that could serve as clinical biomarkers and immunotherapeutic agents. Sera from AA and EA men with PCa were probed by immunoblotting against PC3 cell proteins, with AA sera showing stronger immunoreactivity. Mass spectrometry analysis of immunoreactive protein spots revealed that several AA sera contained autoantibodies to a number of proteins associated with both the glycolysis and plasminogen pathways, particularly to alpha-enolase (ENO1). The proteomic data is deposited in ProteomeXchange with identifier PXD003968. Analysis of sera from 340 racially diverse men by enzyme-linked immunosorbent assays (ELISA) showed higher frequency of anti-ENO1 autoantibodies in PCa sera compared with control sera. We observed differences between AA-PCa and EA-PCa patients in their immunoreactivity against ENO1. Although EA-PCa sera reacted with higher frequency against purified ENO1 in ELISA and recognized by immunoblotting the endogenous cellular ENO1 across a panel of prostate cell lines, AA-PCa sera reacted weakly against this protein by ELISA but recognized it by immunoblotting preferentially in metastatic cell lines. These race-related differences in immunoreactivity to ENO1 could not be accounted by differential autoantibody recognition of phosphoepitopes within this antigen. Proteomic analysis revealed differences in the posttranslational modification profiles of ENO1 variants differentially recognized by AA-PCa and EA-PCa sera. These intriguing results suggest the possibility of race-related differences in the antitumor autoantibody response in PCa, and have implications for defining novel biological determinants of PCa health disparities. PMID:27742740

  19. Gabor-based kernel PCA with fractional power polynomial models for face recognition.

    PubMed

    Liu, Chengjun

    2004-05-01

    This paper presents a novel Gabor-based kernel Principal Component Analysis (PCA) method by integrating the Gabor wavelet representation of face images and the kernel PCA method for face recognition. Gabor wavelets first derive desirable facial features characterized by spatial frequency, spatial locality, and orientation selectivity to cope with the variations due to illumination and facial expression changes. The kernel PCA method is then extended to include fractional power polynomial models for enhanced face recognition performance. A fractional power polynomial, however, does not necessarily define a kernel function, as it might not define a positive semidefinite Gram matrix. Note that the sigmoid kernels, one of the three classes of widely used kernel functions (polynomial kernels, Gaussian kernels, and sigmoid kernels), do not actually define a positive semidefinite Gram matrix either. Nevertheless, the sigmoid kernels have been successfully used in practice, such as in building support vector machines. In order to derive real kernel PCA features, we apply only those kernel PCA eigenvectors that are associated with positive eigenvalues. The feasibility of the Gabor-based kernel PCA method with fractional power polynomial models has been successfully tested on both frontal and pose-angled face recognition, using two data sets from the FERET database and the CMU PIE database, respectively. The FERET data set contains 600 frontal face images of 200 subjects, while the PIE data set consists of 680 images across five poses (left and right profiles, left and right half profiles, and frontal view) with two different facial expressions (neutral and smiling) of 68 subjects. The effectiveness of the Gabor-based kernel PCA method with fractional power polynomial models is shown in terms of both absolute performance indices and comparative performance against the PCA method, the kernel PCA method with polynomial kernels, the kernel PCA method with fractional power polynomial models, the Gabor wavelet-based PCA method, and the Gabor wavelet-based kernel PCA method with polynomial kernels.

  20. In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA).

    PubMed

    Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P; Kovács, Tünde; Bai, Péter; Trencsényi, György

    2017-01-01

    The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68 Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 ( 68 Ga-NODAGA-PCA). The melanin specificity of 68 Ga-NODAGA-PCA was tested in vitro , ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68 Ga-NODAGA-PCA and 18 FDG tracers. 68 Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%<), at all cases. In vitro experiments showed that 68 Ga-NODAGA-PCA uptake of B16-F10 cells was significantly ( p ≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly ( p ≤0.01) higher 68 Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18 FDG and 68 Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly ( p ≤0.05 and p ≤0.01) higher using 68 Ga-NODAGA-PCA than the 18 FDG accumulation. Our novel radiotracer 68 Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68 Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo .

  1. In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA)

    PubMed Central

    Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P.; Kovács, Tünde; Bai, Péter; Trencsényi, György

    2017-01-01

    Purpose: The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Methods: Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 (68Ga-NODAGA-PCA). The melanin specificity of 68Ga-NODAGA-PCA was tested in vitro, ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68Ga-NODAGA-PCA and 18FDG tracers. Results: 68Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%<), at all cases. In vitro experiments showed that 68Ga-NODAGA-PCA uptake of B16-F10 cells was significantly (p≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly (p≤0.01) higher 68Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18FDG and 68Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly (p≤0.05 and p≤0.01) higher using 68Ga-NODAGA-PCA than the 18FDG accumulation. Conclusion: Our novel radiotracer 68Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo. PMID:28382139

  2. Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic behavior: a novel ex vivo and biophysical approach.

    PubMed

    Jansson, Keith H; Castillo, Deborah G; Morris, Joseph W; Boggs, Mary E; Czymmek, Kirk J; Adams, Elizabeth L; Schramm, Lawrence P; Sikes, Robert A

    2014-01-01

    Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics systems; however, PCa may utilize the extensive innervation of the prostate for glandular egress. The interaction of PCa and its nerve fibers is observed in 80% of PCa and is termed perineural invasion (PNI). PCa cells have been observed traveling through the endoneurium of nerves, although the underlying mechanisms have not been elucidated. Voltage sensitive sodium channels (VSSC) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two auxiliary beta (β) subunits with inherent cell adhesion molecule (CAM) functions. The beta-2 isoform (gene SCN2B) interacts with several neural CAMs, while interacting putatively with other prominent neural CAMs. Furthermore, beta-2 exhibits elevated mRNA and protein levels in highly metastatic and castrate-resistant PCa. When overexpressed in weakly aggressive LNCaP cells (2BECFP), beta-2 alters LNCaP cell morphology and enhances LNCaP cell metastasis associated behavior in vitro. We hypothesize that PCa cells use beta-2 as a CAM during PNI and subsequent PCa metastasis. The objective of this study was to determine the effect of beta-2 expression on PCa cell neurotropic metastasis associated behavior. We overexpressed beta-2 as a fusion protein with enhanced cyan fluorescence protein (ECFP) in weakly aggressive LNCaP cells and observed neurotropic effects utilizing our novel ex vivo organotypic spinal cord co-culture model, and performed functional assays with neural matrices and atomic force microscopy. With increased beta-2 expression, PCa cells display a trend of enhanced association with nerve axons. On laminin, a neural CAM, overexpression of beta-2 enhances PCa cell migration, invasion, and growth. 2BECFP cells exhibit marked binding affinity to laminin relative to LNECFP controls, and recombinant beta-2 ectodomain elicits more binding events to laminin than BSA control. Functional overexpression of VSSC beta subunits in PCa may mediate PCa metastatic behavior through association with neural matrices.

  3. GLS-Finder: A Platform for Fast Profiling of Glucosinolates in Brassica Vegetables.

    PubMed

    Sun, Jianghao; Zhang, Mengliang; Chen, Pei

    2016-06-01

    Mass spectrometry combined with related tandem techniques has become the most popular method for plant secondary metabolite characterization. We introduce a new strategy based on in-database searching, mass fragmentation behavior study, formula predicting for fast profiling of glucosinolates, a class of important compounds in brassica vegetables. A MATLAB script-based expert system computer program, "GLS-Finder", was developed. It is capable of qualitative and semi-quantitative analyses of glucosinolates in samples using data generated by ultrahigh-performance liquid chromatography-high-resolution accurate mass with multi-stage mass fragmentation (UHPLC-HRAM/MS(n)). A suite of bioinformatic tools was integrated into the "GLS-Finder" to perform raw data deconvolution, peak alignment, glucosinolate putative assignments, semi-quantitation, and unsupervised principal component analysis (PCA). GLS-Finder was successfully applied to identify intact glucosinolates in 49 commonly consumed Brassica vegetable samples in the United States. It is believed that this work introduces a new way of fast data processing and interpretation for qualitative and quantitative analyses of glucosinolates, where great efficacy was improved in comparison to identification manually.

  4. E-selectin ligand-1 controls circulating prostate cancer cell rolling/adhesion and metastasis

    PubMed Central

    Yasmin-Karim, Sayeda; King, Michael R.; Messing, Edward M.; Lee, Yi-Fen

    2014-01-01

    Circulating prostate cancer (PCa) cells preferentially roll and adhere on bone marrow vascular endothelial cells, where abundant E-selectin and stromal cell-derived factor 1 (SDF-1) are expressed, subsequently initiating a cascade of activation events that eventually lead to the development of metastases. To elucidate the roles of circulating PCa cells' rolling and adhesion behaviors in cancer metastases, we applied a dynamic cylindrical flow-based microchannel device that is coated with E-selectin and SDF-1, mimicking capillary endothelium. Using this device we captured a small fraction of rolling PCa cells. These rolling cells display higher static adhesion ability, more aggressive cancer phenotypes and stem-like properties. Importantly, mice received rolling PCa cells, but not floating PCa cells, developed cancer metastases. Genes coding for E-selectin ligands and genes associated with cancer stem cells and metastasis were elevated in rolling PCa cells. Knock down of E-selectin ligand 1(ESL-1), significantly impaired PCa cells' rolling capacity and reduced cancer aggressiveness. Moreover, ESL-1 activates RAS and MAP kinase signal cascade, consequently inducing the downstream targets. In summary, circulating PCa cells' rolling capacity contributes to PCa metastasis, and that is in part controlled by ESL-1. PMID:25301730

  5. Hsp70 and gama-Semino protein as possible prognostic marker of prostate cancer.

    PubMed

    Kumar, Sanjay; Gurshaney, Sanjeev; Adagunodo, Yori; Gage, Erica; Qadri, Shezreen; Sharma, Mahak; Malik, Shalie; Manne, Upender; Singh, Udai P; Singh, Rajesh; Mishra, Manoj K

    2018-06-01

    In the United States, Prostate Cancer (PCa) is the leading cause of cancer-related mortality in men. PCa resulted in abnormal growth and function of prostate gland such as secretion of high level of gamma-seminoprotein (gama-SM)/Prostate-Specific Antigen (PSA) which could be detected in the blood. Beside gama-SM protein, the levels of heat shock proteins (Hsp70) were also observed significantly high. Therefore, gama-SM and Hsp70 are unique proteins with high potential for PCa therapeutics and diagnostics. High level of Hsp70 suppresses apoptosis, thus allowing PCa cells to exist; however, depletion of Hsp70 induces apoptosis in PCa cells. Gama-SM is the most prominent biomarker for PCa screening; however, its accuracy is still questionable. Thus, a more suitable streamline biomarker for PCa screening is urgently needed. Hsp70 and gama-SM proteins could be used as a revolutionary biomarker for PCa, and could help to identify possible therapeutic target(s). In this review article we will discuss the relationship between the Hsp70 and gama-SM proteins with PCa, their potential as a dual biomarker, and the possibility for both proteins being used as therapeutic targets.

  6. Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer.

    PubMed

    Xu, S; Adisetiyo, H; Tamura, S; Grande, F; Garofalo, A; Roy-Burman, P; Neamati, N

    2015-07-14

    Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice.

  7. Knockdown of Mediator Complex Subunit 19 Suppresses the Growth and Invasion of Prostate Cancer Cells

    PubMed Central

    Zhao, Hongwei; Lv, Wei; Chen, Jian; Wan, Fengchun; Liu, Dongfu; Gao, Zhenli; Wu, Jitao

    2017-01-01

    Prostate cancer (PCa) is one of the most common cancers in elderly men. Mediator Complex Subunit 19 (Med19) is overexpressed and plays promotional roles in many cancers. However, the roles of Med19 in PCa are still obscure. In this study, by using immunohistochemical staining, we found higher expression level of Med19 in PCa tissues than in adjacent benign prostate tissues. We then knocked down the Med19 expression in PCa cell lines LNCaP and PC3 by using lentivirus siRNA. Cell proliferation, anchor-independent growth, migration, and invasion were suppressed in Med19 knockdown PCa cells. In nude mice xenograft model, we found that Med19 knockdown PCa cells formed smaller tumors with lower proliferation index than did control cells. In the mechanism study, we found that Med19 could regulate genes involved in cell proliferation, cell cycle, and epithelial-mesenchymal transition, including P27, pAKT, pPI3K, IGF1R, E-Cadherin, N-Cadherin, Vimentin, ZEB2, Snail-1 and Snail-2. Targeting Med19 in PCa cells could inhibit the PCa growth and metastasis, and might be a therapeutic option for PCa in the future. PMID:28125713

  8. Comparison of 68Ga-HBED-CC PSMA-PET/CT and multiparametric MRI for gross tumour volume detection in patients with primary prostate cancer based on slice by slice comparison with histopathology

    PubMed Central

    Zamboglou, Constantinos; Drendel, Vanessa; Jilg, Cordula A.; Rischke, Hans C.; Beck, Teresa I.; Schultze-Seemann, Wolfgang; Krauss, Tobias; Mix, Michael; Schiller, Florian; Wetterauer, Ulrich; Werner, Martin; Langer, Mathias; Bock, Michael; Meyer, Philipp T.; Grosu, Anca L.

    2017-01-01

    Purpose: The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared 68Ga-HBED-CC-PSMA PET/CT with multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material. Methodology: Seven patients with histopathologically proven primary PCa underwent 68Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and prepared for histopathology. Invasive PCa was delineated on a HE stained histologic tissue slide and matched to ex-vivo CT to obtain gross tumor volume (GTV-)histo. Ex-vivo CT including GTV-histo and MRI data were matched to in-vivo CT(PET). Consensus contours based on MRI (GTV-MRI), PSMA PET (GTV-PET) or the combination of both (GTV-union/-intersection) were created. In each in-vivo CT slice the prostate was separated into 4 equal segments and sensitivity and specificity for PSMA PET and mpMRI were assessed by comparison with histological reference material. Furthermore, the spatial overlap between GTV-histo and GTV-PET/-MRI and the Sørensen-Dice coefficient (DSC) were calculated. In the case of multifocal PCa (4/7 patients), SUV values (PSMA PET) and ADC-values (diffusion weighted MRI) were obtained for each lesion. Results: PSMA PET and mpMRI detected PCa in all patients. GTV-histo was detected in 225 of 340 segments (66.2%). Sensitivity and specificity for GTV-PET, GTV-MRI, GTV-union and GTV-intersection were 75% and 87%, 70% and 82%, 82% and 67%, 55% and 99%, respectively. GTV-histo had on average the highest overlap with GTV-union (57±22%), which was significantly higher than overlap with GTV-MRI (p=0.016) and GTV-PET (p=0.016), respectively. The mean DSC for GTV-union, GTV-PET and GTV-MRI was 0.51 (±0.18), 0.45 (±0.17) and 0.48 (±0.19), respectively. In every patient with multifocal PCa there was one lesion which had both the highest SUV and the lowest ADC-value (mean and max). Conclusion: In a slice by slice analysis with histopathology, 68Ga-HBED-CC-PSMA PET/CT and mpMRI showed high sensitivity and specificity in detection of primary PCa. A combination of both methods performed even better in terms of sensitivity (GTV-union) and specificity (GTV-intersection). A moderate to good spatial overlap with GTV-histo was observed for PSMA PET/CT and mpMRI alone which was significantly improved by GTV-union. Further studies are warranted to analyse the impact of these preliminary findings for diagnostic (multimodal guided TRUS biopsy) and therapeutic (focal therapy) strategies in primary PCa. PMID:28042330

  9. Physical activity in relation to risk of prostate cancer: a systematic review and meta-analysis.

    PubMed

    Benke, I N; Leitzmann, M F; Behrens, G; Schmid, D

    2018-05-01

    Prostate cancer (PCa) is one of the most common cancers among men, yet little is known about its modifiable risk and protective factors. This study aims to quantitatively summarize observational studies relating physical activity (PA) to PCa incidence and mortality. Published articles pertaining to PA and PCa incidence and mortality were retrieved in July 2017 using the Medline and EMBASE databases. The literature review yielded 48 cohort studies and 24 case-control studies with a total of 151 748 PCa cases. The mean age of the study participants at baseline was 61 years. In random-effects models, comparing the highest versus the lowest level of overall PA showed a summary relative risk (RR) estimate for total PCa incidence close to the null [RR = 0.99, 95% confidence interval (CI) = 0.94-1.04]. The corresponding RRs for advanced and non-advanced PCa were 0.92 (95% CI = 0.80-1.06) and 0.95 (95% CI = 0.85-1.07), respectively. We noted a statistically significant inverse association between long-term occupational activity and total PCa (RR = 0.83, 95% CI = 0.71-0.98, n studies = 13), although that finding became statistically non-significant when individual studies were removed from the analysis. When evaluated by cancer subtype, an inverse association with long-term occupational activity was noted for non-advanced/non-aggressive PCa (RR = 0.51, 95% CI = 0.37-0.71, n studies = 2) and regular recreational activity was inversely related to advanced/aggressive PCa (RR = 0.75, 95% CI = 0.60-0.95, n studies = 2), although these observations are based on a low number of studies. Moreover, PA after diagnosis was related to reduced risk of PCa mortality among survivors of PCa (summary RR based on four studies = 0.69, 95% CI = 0.55-0.85). Whether PA protects against PCa remains elusive. Further investigation taking into account the complex clinical and pathologic nature of PCa is needed to clarify the PA and PCa incidence relation. Moreover, future studies are needed to confirm whether PA after diagnosis reduces risk of PCa mortality.

  10. Characterizing the molecular features of ERG-positive tumors in primary and castration resistant prostate cancer

    PubMed Central

    Roudier, Martine P; Winters, Brian R; Coleman, Ilsa; Lam, Hung-Ming; Zhang, Xiaotun; Coleman, Roger; Chéry, Lisly; True, Lawrence D.; Higano, Celestia S.; Montgomery, Bruce; Lange, Paul H.; Snyder, Linda A.; Srivistava, Shiv; Corey, Eva; Vessella, Robert L.; Nelson, Peter S.; Üren, Aykut; Morrissey, Colm

    2017-01-01

    Background The TMPRSS2-ERG gene fusion is detected in approximately half of primary prostate cancers (PCa) yet the prognostic significance remains unclear. We hypothesized that ERG promotes the expression of common genes in primary PCa and metastatic castration-resistant PCa (CRPC), with the objective of identifying ERG-associated pathways, which may promote the transition from primary PCa to CRPC. Methods We constructed tissue microarrays (TMA) from 127 radical prostatectomy specimens, 20 LuCaP patient-derived xenografts (PDX), and 152 CRPC metastases obtained immediately at time of death. Nuclear ERG was assessed by immunohistochemistry (IHC). To characterize the molecular features of ERG-expressing PCa, a subset of IHC confirmed ERG+ or ERG-specimens including 11 radical prostatectomies, 20 LuCaP PDXs, and 45 CRPC metastases underwent gene expression analysis. Genes were ranked based on expression in primary PCa and CRPC. Common genes of interest were targeted for IHC analysis and expression compared with biochemical recurrence (BCR) status. Results IHC revealed that 43% of primary PCa, 35% of the LuCaP PDXs, and 18% of the CRPC metastases were ERG+ (12 of 48 patients [25%] had at least 1 ERG+ metastasis). Based on gene expression data and previous literature, two proteins involved in calcium signaling (NCALD, CACNA1D), a protein involved in inflammation (HLA-DMB), CD3 positive immune cells, and a novel ERG-associated protein, DCLK1 were evaluated in primary PCa and CRPC metastases. In ERG+ primary PCa, a weak association was seen with NCALD and CACNA1D protein expression. HLA-DMB expression and the presence of CD3 positive immune cells were decreased in CRPC metastases compared to primary PCa. DCLK1 was upregulated at the protein level in unpaired ERG+ primary PCa and CRPC metastases (p=0.0013 and p<0.0001, respectively). In primary PCa, ERG status or expression of targeted proteins was not associated with BCR-free survival. However for primary PCa, ERG+DCLK1+ patients exhibited shorter time to BCR (p=0.06) compared with ERG+DCLK1- patients. Conclusions This study examined ERG expression in primary PCa and CRPC. We have identified altered levels of inflammatory mediators associated with ERG expression. We determined expression of DCLK1 correlates with ERG expression and may play a role in primary PCa progression to metastatic CPRC. PMID:26990456

  11. Wavelet PCA for automatic identification of walking with and without an exoskeleton on a treadmill using pressure and accelerometer sensors.

    PubMed

    Naik, Ganesh R; Pendharkar, Gita; Nguyen, Hung T

    2016-08-01

    Nowadays portable devices with more number of sensors are used for gait assessment and monitoring for elderly and disabled. However, the problem with using multiple sensors is that if they are placed on the same platform or base, there could be cross talk between them, which could change the signal amplitude or add noise to the signal. Hence, this study uses wavelet PCA as a signal processing technique to separate the original sensor signal from the signal obtained from the sensors through the integrated unit to compare the two types of walking (with and without an exoskeleton). This comparison using wavelet PCA will enable the researchers to obtain accurate sensor data and compare and analyze the data in order to further improve the design of compact portable devices used to monitor and assess the gait in stroke or paralyzed subjects. The advantage of designing such systems is that they can also be used to assess and monitor the gait of the stroke subjects at home, which will save them time and efforts to visit the laboratory or clinic.

  12. Hyperspectral Image Denoising Using a Nonlocal Spectral Spatial Principal Component Analysis

    NASA Astrophysics Data System (ADS)

    Li, D.; Xu, L.; Peng, J.; Ma, J.

    2018-04-01

    Hyperspectral images (HSIs) denoising is a critical research area in image processing duo to its importance in improving the quality of HSIs, which has a negative impact on object detection and classification and so on. In this paper, we develop a noise reduction method based on principal component analysis (PCA) for hyperspectral imagery, which is dependent on the assumption that the noise can be removed by selecting the leading principal components. The main contribution of paper is to introduce the spectral spatial structure and nonlocal similarity of the HSIs into the PCA denoising model. PCA with spectral spatial structure can exploit spectral correlation and spatial correlation of HSI by using 3D blocks instead of 2D patches. Nonlocal similarity means the similarity between the referenced pixel and other pixels in nonlocal area, where Mahalanobis distance algorithm is used to estimate the spatial spectral similarity by calculating the distance in 3D blocks. The proposed method is tested on both simulated and real hyperspectral images, the results demonstrate that the proposed method is superior to several other popular methods in HSI denoising.

  13. Classification of prostate cancer grade using temporal ultrasound: in vivo feasibility study

    NASA Astrophysics Data System (ADS)

    Ghavidel, Sahar; Imani, Farhad; Khallaghi, Siavash; Gibson, Eli; Khojaste, Amir; Gaed, Mena; Moussa, Madeleine; Gomez, Jose A.; Siemens, D. Robert; Leveridge, Michael; Chang, Silvia; Fenster, Aaron; Ward, Aaron D.; Abolmaesumi, Purang; Mousavi, Parvin

    2016-03-01

    Temporal ultrasound has been shown to have high classification accuracy in differentiating cancer from benign tissue. In this paper, we extend the temporal ultrasound method to classify lower grade Prostate Cancer (PCa) from all other grades. We use a group of nine patients with mostly lower grade PCa, where cancerous regions are also limited. A critical challenge is to train a classifier with limited aggressive cancerous tissue compared to low grade cancerous tissue. To resolve the problem of imbalanced data, we use Synthetic Minority Oversampling Technique (SMOTE) to generate synthetic samples for the minority class. We calculate spectral features of temporal ultrasound data and perform feature selection using Random Forests. In leave-one-patient-out cross-validation strategy, an area under receiver operating characteristic curve (AUC) of 0.74 is achieved with overall sensitivity and specificity of 70%. Using an unsupervised learning approach prior to proposed method improves sensitivity and AUC to 80% and 0.79. This work represents promising results to classify lower and higher grade PCa with limited cancerous training samples, using temporal ultrasound.

  14. Settlement behavior of municipal solid waste due to internal and external environmental factors in a lysimeter.

    PubMed

    Melo, Márcio C; Caribé, Rômulo M; Ribeiro, Libânia S; Sousa, Raul B A; Monteiro, Veruschka E D; de Paiva, William

    2016-12-05

    Long-term settlement magnitude is influenced by changes in external and internal factors that control the microbiological activity in the landfill waste body. To improve the understanding of settlement phenomena, it is instructive to study lysimeters filled with MSW. This paper aims to understand the settlement behavior of MSW by correlating internal and external factors that influence waste biodegradation in a lysimeter. Thus, a lysimeter was built, instrumented and filled with MSW from the city of Campina Grande, the state of Paraíba, Brazil. Physicochemical analysis of the waste (from three levels of depth of the lysimeter) was carried out along with MSW settlement measurements. Statistical tools such as descriptive analysis and principal component analysis (PCA) were also performed. The settlement/compression, coefficient of variation and PCA results indicated the most intense rate of biodegradation in the top layer. The PCA results of intermediate and bottom levels presented fewer physicochemical and meteorological variables correlated with compression data in contrast with the top layer. It is possible to conclude that environmental conditions may influence internal indicators of MSW biodegradation, such as the settlement.

  15. Detection of circulatory microRNAs in prostate cancer.

    PubMed

    Srivastava, Anvesha; Goldberger, Helle; Afzal, Zainab; Suy, Simeng; Collins, Sean P; Kumar, Deepak

    2015-01-01

    Prostate cancer (PCa) is one of the most common cancer worldwide and accounts for 14.4 % of all new cancer cases. The clinical outcome and management of PCa can be significantly improved by use of biomarker assays for early detection, prognosis and also for prediction and monitoring of treatment response. MiRNAs are short, endogenous, single-stranded RNA molecules that play important role in regulation of gene expression and can modulate a number of cellular processes. Discovery of miRNAs in circulation has not only facilitated understanding their role in various diseases but also paved new avenues for biomarker discovery due to their ease of access and stability. The fact that a minimally invasive test based on miRNAs profiles can distinguish the presence or absence of disease illustrates immense potential of these molecules as predictive biomarkers.In this chapter, we have summarized the presumed mechanisms of miRNA release into the circulation and systematically summarized the studies of circulatory miRNAs in PCa. Also, we have mainly focused on the methodology of identification of circulatory miRNAs from biofluids.

  16. A comparison of PCA/ICA for data preprocessing in remote sensing imagery classification

    NASA Astrophysics Data System (ADS)

    He, Hui; Yu, Xianchuan

    2005-10-01

    In this paper a performance comparison of a variety of data preprocessing algorithms in remote sensing image classification is presented. These selected algorithms are principal component analysis (PCA) and three different independent component analyses, ICA (Fast-ICA (Aapo Hyvarinen, 1999), Kernel-ICA (KCCA and KGV (Bach & Jordan, 2002), EFFICA (Aiyou Chen & Peter Bickel, 2003). These algorithms were applied to a remote sensing imagery (1600×1197), obtained from Shunyi, Beijing. For classification, a MLC method is used for the raw and preprocessed data. The results show that classification with the preprocessed data have more confident results than that with raw data and among the preprocessing algorithms, ICA algorithms improve on PCA and EFFICA performs better than the others. The convergence of these ICA algorithms (for data points more than a million) are also studied, the result shows EFFICA converges much faster than the others. Furthermore, because EFFICA is a one-step maximum likelihood estimate (MLE) which reaches asymptotic Fisher efficiency (EFFICA), it computers quite small so that its demand of memory come down greatly, which settled the "out of memory" problem occurred in the other algorithms.

  17. Androgen Receptor Roles in Insulin Resistance and Obesity in Males: The Linkage of Androgen-Deprivation Therapy to Metabolic Syndrome

    PubMed Central

    Yu, I-Chen; Lin, Hung-Yun; Sparks, Janet D.; Yeh, Shuyuan

    2014-01-01

    Prostate cancer (PCa) is one of the most frequently diagnosed malignancies in men. Androgen-deprivation therapy (ADT) is the first-line treatment and fundamental management for men with advanced PCa to suppress functions of androgen/androgen receptor (AR) signaling. ADT is effective at improving cancer symptoms and prolonging survival. However, epidemiological and clinical studies support the notion that testosterone deficiency in men leads to the development of metabolic syndrome that increases cardiovascular disease risk. The underlying mechanisms by which androgen/AR signaling regulates metabolic homeostasis in men are complex, and in this review, we discuss molecular mechanisms mediated by AR signaling that link ADT to metabolic syndrome. Results derived from various AR knockout mouse models reveal tissue-specific AR signaling that is involved in regulation of metabolism. These data suggest that steps be taken early to manage metabolic complications associated with PCa patients receiving ADT, which could be accomplished using tissue-selective modulation of AR signaling and by treatment with insulin-sensitizing agents. PMID:25249645

  18. The role of serum neuron-specific enolase in patients with prostate cancer: a systematic review of the recent literature.

    PubMed

    Muoio, Barbara; Pascale, Mariarosa; Roggero, Enrico

    2018-01-01

    In this systematic review, we evaluated the value of serum concentrations of neuron-specific enolase (NSE) in patients with prostate cancer (PCa) in order to clarify the possible role of NSE in the diagnosis, management, treatment and monitoring of PCa. A comprehensive search of the recent literature was conducted to find relevant data on the role of NSE in PCa. Two hundred and eighty-two records were revealed, and 19 articles including 1,772 patients with PCa (either confirmed or suspected) were selected. After reviewing the articles, the major result was that elevated serum NSE appears to correlate with prognosis in advanced PCa, particularly in patients with progressive and metastatic castration-resistant PCa. Based on the existing literature, the role of serum NSE in PCa patients should be further evaluated.

  19. Prostate Cancer Predictive Simulation Modelling, Assessing the Risk Technique (PCP-SMART): Introduction and Initial Clinical Efficacy Evaluation Data Presentation of a Simple Novel Mathematical Simulation Modelling Method, Devised to Predict the Outcome of Prostate Biopsy on an Individual Basis.

    PubMed

    Spyropoulos, Evangelos; Kotsiris, Dimitrios; Spyropoulos, Katherine; Panagopoulos, Aggelos; Galanakis, Ioannis; Mavrikos, Stamatios

    2017-02-01

    We developed a mathematical "prostate cancer (PCa) conditions simulating" predictive model (PCP-SMART), from which we derived a novel PCa predictor (prostate cancer risk determinator [PCRD] index) and a PCa risk equation. We used these to estimate the probability of finding PCa on prostate biopsy, on an individual basis. A total of 371 men who had undergone transrectal ultrasound-guided prostate biopsy were enrolled in the present study. Given that PCa risk relates to the total prostate-specific antigen (tPSA) level, age, prostate volume, free PSA (fPSA), fPSA/tPSA ratio, and PSA density and that tPSA ≥ 50 ng/mL has a 98.5% positive predictive value for a PCa diagnosis, we hypothesized that correlating 2 variables composed of 3 ratios (1, tPSA/age; 2, tPSA/prostate volume; and 3, fPSA/tPSA; 1 variable including the patient's tPSA and the other, a tPSA value of 50 ng/mL) could operate as a PCa conditions imitating/simulating model. Linear regression analysis was used to derive the coefficient of determination (R 2 ), termed the PCRD index. To estimate the PCRD index's predictive validity, we used the χ 2 test, multiple logistic regression analysis with PCa risk equation formation, calculation of test performance characteristics, and area under the receiver operating characteristic curve analysis using SPSS, version 22 (P < .05). The biopsy findings were positive for PCa in 167 patients (45.1%) and negative in 164 (44.2%). The PCRD index was positively signed in 89.82% positive PCa cases and negative in 91.46% negative PCa cases (χ 2 test; P < .001; relative risk, 8.98). The sensitivity was 89.8%, specificity was 91.5%, positive predictive value was 91.5%, negative predictive value was 89.8%, positive likelihood ratio was 10.5, negative likelihood ratio was 0.11, and accuracy was 90.6%. Multiple logistic regression revealed the PCRD index as an independent PCa predictor, and the formulated risk equation was 91% accurate in predicting the probability of finding PCa. On the receiver operating characteristic analysis, the PCRD index (area under the curve, 0.926) significantly (P < .001) outperformed other, established PCa predictors. The PCRD index effectively predicted the prostate biopsy outcome, correctly identifying 9 of 10 men who were eventually diagnosed with PCa and correctly ruling out PCa for 9 of 10 men who did not have PCa. Its predictive power significantly outperformed established PCa predictors, and the formulated risk equation accurately calculated the probability of finding cancer on biopsy, on an individual patient basis. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Comparison between a disposable and an electronic PCA device for labor epidural analgesia.

    PubMed

    Sumikura, Hiroyuki; van de Velde, Marc; Tateda, Takeshi

    2004-01-01

    The aims of the present study were (1) to investigate if a disposable patient-controlled analgesia (PCA) device can be used for labor analgesia and (2) to evaluate the device by midwives and parturients. Forty healthy parturients were divided into two groups and received combined spinal epidural analgesia for labor pain relief. Following intrathecal administration of 3 mg ropivacaine and 1.5 microg sufentanil, either a disposable PCA device (Coopdech Syrinjector; Daiken Medical, Osaka, Japan) or an electronic PCA device (IVAC PCAM PCA Syringe Pump; Alaris, Basingstoke, UK) was connected to the epidural catheter, and 0.15% ropivacaine with sufentanil 0.75 microg/ml was used for continuous infusion and PCA. For an electronic PCA device, continuous infusion rate, bolus dose, lockout time, and hourly limit were set at 4 ml/h, 3 ml, 15 min, and 16 ml, respectively. For a disposable PCA device, continuous infusion rate, bolus dose, and an hourly limit were set at 4 ml/h, 3 ml, and 16 ml, respectively, but lockout function was not available. No differences were observed between the groups concerning demographic data, obstetric data, and outcome of labor. Anesthetic requirements (disposable, 9.7 +/- 4.7 ml/h; electronic, 8.2 +/- 4.0 ml/h) and VAS score during the delivery (disposable, 26 +/- 25; electronic, 21 +/- 22) were similar between the groups. Midwives praised the disposable PCA device as well as the electronic one. The present results imply that the disposable PCA device can be an alternative to the electronic PCA device for labor analgesia.

  1. The Association Between Calcium Channel Blocker Use and Prostate Cancer Outcome

    PubMed Central

    Poch, Michael A.; Mehedint, Diana; Green, Dawn J.; Payne-Ondracek, Rochelle; Fontham, Elizabeth T.H.; Bensen, Jeannette T.; Attwood, Kristopher; Wilding, Gregory E.; Guru, Khurshid A.; Underwood, Willie; Mohler, James L.; Heemers, Hannelore V.

    2018-01-01

    BACKGROUND Epidemiological studies indicate that calcium channel blocker (CCB) use is inversely related to prostate cancer (PCa) incidence. The association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) and outcome after RP was examined. METHODS Medication use, PCa aggressiveness and post-RP outcome were retrieved from a prospectively populated database that contains clinical and outcome for RP patients at Roswell Park Cancer Institute (RPCI) from 1993 to 2010. The database was queried for anti-hypertensive medication use at diagnosis for patients with ≥1 year follow-up. Recurrence was defined using NCCN guidelines. Chi-Square tests assessed the relationship between CCB use and PCa aggressiveness. Cox regression models compared the distribution of progression-free survival (PFS) and overall survival (OS) with adjustment for covariates. Results for association between CCB usage and PCa aggressiveness were validated using data from the population-based North Carolina-Louisiana Prostate Cancer Project (PCaP). RESULTS 48%, 37%, and 15% of RPCI’s RP patients (n = 875) had low, intermediate, and high aggressive PCa, respectively. 104 (11%) had a history of CCB use. Patients taking CCBs were more likely to be older, have a higher BMI and use additional anti-hypertensive medications. Diagnostic PSA levels, PCa aggressiveness, and margin status were similar for CCB users and non-users. PFS and OS did not differ between the two groups. Tumor aggressiveness was associated with PFS. CCB use in the PCaP study population was not associated with PCa aggressiveness. CONCLUSIONS CCB use is not associated with PCa aggressiveness at diagnosis, PFS or OS. PMID:23280547

  2. Testosterone inhibits the growth of prostate cancer xenografts in nude mice.

    PubMed

    Song, Weitao; Soni, Vikram; Soni, Samit; Khera, Mohit

    2017-09-07

    Traditional beliefs of androgen's stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells. In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice. Different serum testosterone levels were manipulated in male nude/nude athymic mice by orchiectomy or inserting different dosages of T pellets subcutaneously. PCa cells were injected subcutaneously to nude mice and tumor incidence rate and tumor growth rate of PCa xenografts were tested. The data demonstrated that low levels of serum T resulted in the highest PCa incidence rate (50%). This PCa incidence rate in mice with low T levels was significantly higher than that in mice treated with higher doses of T (24%, P < 0.01) and mice that underwent orchiectomy (8%, P < 0.001). Mice that had low serum T levels had the shortest tumor volume doubling time (112 h). This doubling time was significantly shorter than that in the high dose 5 mg T arm (158 h, P < 0.001) and in the orchiectomy arm (468 h, P < 0.001). These results indicated that low T levels are optimal for PCa cell growth. Castrate T levels, as seen after orchiectomy, are not sufficient to support PCa cell growth. Higher levels of serum T inhibited PCa cell growth.

  3. Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

    DTIC Science & Technology

    2017-10-01

    SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer (PCA) is a clinically and genetically heterogeneous and the development of a molecular classification is...AWARD NUMBER: W81XWH-16-1-0739 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH

  4. Effect on Laryngeal Adductor Function of Vincristine Block of Posterior Cricoarytenoid Muscle 3-5 Months After Recurrent Laryngeal Nerve Injury

    PubMed Central

    Paniello, Randal C.; Park, Andrea

    2015-01-01

    Objectives It has been shown, in a canine model, that a single injection of vincristine into the PCA muscle at the time of recurrent laryngeal nerve (RLN) injury effectively blocks its reinnervation and results in improved adductor strength. But clinically, such injuries are usually diagnosed weeks or months after onset. Vincristine injection does not affect a muscle that is already innervated; thus, there is a limited time frame following RLN injury during which a vincristine injection could effectively improve ultimate laryngeal adductor functional recovery. A series of delayed injections were performed in a canine model and results assessed. Study Design Animal (canine) experiment. Methods The RLN was transected and repaired, and vincristine (0.4 mg) was injected into the PCA muscle at the time of injury (n=12), or at 3, 4, and 5 months later (n=8 each study group). Six months after RLN injury, laryngeal adductor function was measured. Results of vincristine injection without RLN injury (n=6), and longer-term (12 months) follow-up for time zero injections (n=4), are also reported. Results The animals injected at time zero had better adductor function than non-injected controls, as reported previously, and this result was further increased at 12 months. The 3-month delay gave results similar to the time zero group. The 5-month delay group showed no vincristine benefit, and the 4-month delay group gave an intermediate result. Vincristine to the PCA had no effect on adductor function when the RLN was left intact. Plasma levels showed 19% of injected vincristine reached systemic circulation, which was cleared within 69 hours. Conclusions Vincristine injection of the PCA muscle after RLN injury, which blocks this functional recovery. The window of opportunity to apply this treatment closes by four months after RLN injury in the canine model. Human RLN recovery follows a similar time course and can reasonably be expected to have a similar therapeutic window. PMID:25595140

  5. Reference-tissue correction of T2-weighted signal intensity for prostate cancer detection

    NASA Astrophysics Data System (ADS)

    Peng, Yahui; Jiang, Yulei; Oto, Aytekin

    2014-03-01

    The purpose of this study was to investigate whether correction with respect to reference tissue of T2-weighted MRimage signal intensity (SI) improves its effectiveness for classification of regions of interest (ROIs) as prostate cancer (PCa) or normal prostatic tissue. Two image datasets collected retrospectively were used in this study: 71 cases acquired with GE scanners (dataset A), and 59 cases acquired with Philips scanners (dataset B). Through a consensus histology- MR correlation review, 175 PCa and 108 normal-tissue ROIs were identified and drawn manually. Reference-tissue ROIs were selected in each case from the levator ani muscle, urinary bladder, and pubic bone. T2-weighted image SI was corrected as the ratio of the average T2-weighted image SI within an ROI to that of a reference-tissue ROI. Area under the receiver operating characteristic curve (AUC) was used to evaluate the effectiveness of T2-weighted image SIs for differentiation of PCa from normal-tissue ROIs. AUC (+/- standard error) for uncorrected T2-weighted image SIs was 0.78+/-0.04 (datasets A) and 0.65+/-0.05 (datasets B). AUC for corrected T2-weighted image SIs with respect to muscle, bladder, and bone reference was 0.77+/-0.04 (p=1.0), 0.77+/-0.04 (p=1.0), and 0.75+/-0.04 (p=0.8), respectively, for dataset A; and 0.81+/-0.04 (p=0.002), 0.78+/-0.04 (p<0.001), and 0.79+/-0.04 (p<0.001), respectively, for dataset B. Correction in reference to the levator ani muscle yielded the most consistent results between GE and Phillips images. Correction of T2-weighted image SI in reference to three types of extra-prostatic tissue can improve its effectiveness for differentiation of PCa from normal-tissue ROIs, and correction in reference to the levator ani muscle produces consistent T2-weighted image SIs between GE and Phillips MR images.

  6. Laccase catalysed grafting of phenolic onto xylan to improve its applicability in films

    NASA Astrophysics Data System (ADS)

    Pei, Jicheng; Wang, Bing; Zhang, Fangdong; Li, Zhongyang; Yin, Yunbei; Zhang, Dongxu

    2015-07-01

    Xylan can be tailored for various value-added applications. However, its use in aqueous systems is hampered by its complex structure, and small molecular weight. This research aimed at improving the xylan molecular weight and changing its structure. Laccase-catalysed oxidation of 4-coumaric acid (PCA), ferulic acid (FA), syringaldehyde (SD), and vanillin (VA) onto xylan was grafted to study the changes in its structure, tensile properties, and antibacterial activities. A Fourier transform infrared (FTIR) spectrum analyser was used to observe the changes in functional groups of xylan. The results showed a band at 1635 cm-1 corresponding to the stretching vibration of conjugated carbonyl carboxy hemoglobin and a benzene ring structure were strengthened; the appearance of a new band between 1200 cm-1 and 1270 cm-1 corresponding to alkyl ethers on the aryl C-O stretching vibration was due to the fact that during the grafting process, the number of benzene ring structures increased and covalent connections occurred between phenols and xylan. The reaction mechanism for the laccase-catalysed oxidation of phenol compounds onto xylan was preliminary explored by 13C-NMR. The results showed that PCA-xylan, FA-xylan graft poly onto xylan by Cγ ester bond, SD-xylan graft poly onto xylan by ether bond and an ester bond, and VD-xylan graft poly onto xylan by ether bond. The film strength of xylan derivatives has been significantly increased, especially for the PCA-xylan derivative. The increases in tensile stress at break, tensile strength, tensile yield stress, and Young's modulus were: 24.04%, 31.30%, 55.56%, and 28.21%, respectively. After laccase/phenolics were modified, xylan had a good antibacterial effect to E. coli, Corynebacterium glutamicum, and Bacillus subtilis. The SD-xylan, FA-xylan, and PCA-xylan showed a greater efficacy against E. coli, Corynebacterium glutamicum, and Bacillus subtilis, respectively.

  7. Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

    PubMed

    Hayman, Jonathan; Phillips, Ryan; Chen, Di; Perin, Jamie; Narang, Amol K; Trieu, Janson; Radwan, Noura; Greco, Stephen; Deville, Curtiland; McNutt, Todd; Song, Daniel Y; DeWeese, Theodore L; Tran, Phuoc T

    2018-06-01

    Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men. © 2018 Wiley Periodicals, Inc.

  8. Computer-aided diagnosis of prostate cancer using a deep convolutional neural network from multiparametric MRI.

    PubMed

    Song, Yang; Zhang, Yu-Dong; Yan, Xu; Liu, Hui; Zhou, Minxiong; Hu, Bingwen; Yang, Guang

    2018-04-16

    Deep learning is the most promising methodology for automatic computer-aided diagnosis of prostate cancer (PCa) with multiparametric MRI (mp-MRI). To develop an automatic approach based on deep convolutional neural network (DCNN) to classify PCa and noncancerous tissues (NC) with mp-MRI. Retrospective. In all, 195 patients with localized PCa were collected from a PROSTATEx database. In total, 159/17/19 patients with 444/48/55 observations (215/23/23 PCas and 229/25/32 NCs) were randomly selected for training/validation/testing, respectively. T 2 -weighted, diffusion-weighted, and apparent diffusion coefficient images. A radiologist manually labeled the regions of interest of PCas and NCs and estimated the Prostate Imaging Reporting and Data System (PI-RADS) scores for each region. Inspired by VGG-Net, we designed a patch-based DCNN model to distinguish between PCa and NCs based on a combination of mp-MRI data. Additionally, an enhanced prediction method was used to improve the prediction accuracy. The performance of DCNN prediction was tested using a receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Moreover, the predicted result was compared with the PI-RADS score to evaluate its clinical value using decision curve analysis. Two-sided Wilcoxon signed-rank test with statistical significance set at 0.05. The DCNN produced excellent diagnostic performance in distinguishing between PCa and NC for testing datasets with an AUC of 0.944 (95% confidence interval: 0.876-0.994), sensitivity of 87.0%, specificity of 90.6%, PPV of 87.0%, and NPV of 90.6%. The decision curve analysis revealed that the joint model of PI-RADS and DCNN provided additional net benefits compared with the DCNN model and the PI-RADS scheme. The proposed DCNN-based model with enhanced prediction yielded high performance in statistical analysis, suggesting that DCNN could be used in computer-aided diagnosis (CAD) for PCa classification. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

  9. The History of Testosterone and the Evolution of its Therapeutic Potential.

    PubMed

    Morgentaler, Abraham; Traish, Abdulmaged

    2018-04-13

    Testosterone therapy has been controversial since its synthesis in the 1930s to the present day. Testosterone's history provides depth and context for current controversies. To review the history of testosterone therapy from its initial synthesis in the 1930s to the modern day. Expert review of the literature. Impactful events in the history of testosterone. By the 1940s there was already a fascinating literature that described the many symptomatic benefits of testosterone therapy that are recognized today. Numerous early reports suggested testosterone therapy improved angina pectoris and peripheral vascular disease. The assertion by Huggins and Hodges (Cancer Res 1941;1:293-297) in 1941 that testosterone activated prostate cancer (PCa) cast a pall for the next 70 years. The introduction of the radioimmunoassay in the 1970s shifted the diagnosis of testosterone deficiency from signs and symptoms to an undue emphasis on blood test results. The fear of PCa was the primary obstacle to the adoption of testosterone therapy for decades. Prescription rates increased as accumulated evidence showed testosterone therapy was not associated with increased PCa risks. The observation that androgenic stimulation of PCa reaches a maximum at relatively low testosterone concentrations-the saturation model-provided the theoretical framework for understanding the relation between androgens and PCa and led to multiple case series documenting reassuring results of testosterone therapy in men with PCa. Recent concerns regarding cardiovascular risks also have diminished because new evidence suggests testosterone therapy might actually be cardioprotective. In 2016 the Testosterone Trials provided high-quality evidence of multiple benefits of testosterone therapy, nearly all of which had been recognized by clinicians by 1940. If the past has any lessons for the future, it is likely that research will continue to demonstrate health benefits of testosterone therapy, while it remains one of the most controversial topics in medicine. Morgentaler A, Traish A. The History of Testosterone and the Evolution of its Therapeutic Potential. Sex Med Rev 2018;X:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  10. Exploring patterns enriched in a dataset with contrastive principal component analysis.

    PubMed

    Abid, Abubakar; Zhang, Martin J; Bagaria, Vivek K; Zou, James

    2018-05-30

    Visualization and exploration of high-dimensional data is a ubiquitous challenge across disciplines. Widely used techniques such as principal component analysis (PCA) aim to identify dominant trends in one dataset. However, in many settings we have datasets collected under different conditions, e.g., a treatment and a control experiment, and we are interested in visualizing and exploring patterns that are specific to one dataset. This paper proposes a method, contrastive principal component analysis (cPCA), which identifies low-dimensional structures that are enriched in a dataset relative to comparison data. In a wide variety of experiments, we demonstrate that cPCA with a background dataset enables us to visualize dataset-specific patterns missed by PCA and other standard methods. We further provide a geometric interpretation of cPCA and strong mathematical guarantees. An implementation of cPCA is publicly available, and can be used for exploratory data analysis in many applications where PCA is currently used.

  11. The influence of stigma on the quality of life for prostate cancer survivors.

    PubMed

    Wood, Andrew W; Barden, Sejal; Terk, Mitchell; Cesaretti, Jamie

    2017-01-01

    The purpose of the present study was to investigate the influence of stigma on prostate cancer (PCa) survivors' quality of life. Stigma for lung cancer survivors has been the focus of considerable research (Else-Quest & Jackson, 2014); however, gaps remain in understanding the experience of PCa stigma. A cross-sectional correlational study was designed to assess the incidence of PCa stigma and its influence on the quality of life of survivors. Eighty-five PCa survivors were administered survey packets consisting of a stigma measure, a PCa-specific quality of life measure, and a demographic survey during treatment of their disease. A linear regression analysis was conducted with the data received from PCa survivors. Results indicated that PCa stigma has a significant, negative influence on the quality of life for survivors (R 2 = 0.33, F(4, 80) = 11.53, p < 0.001). There were no statistically significant differences in PCa stigma based on demographic variables (e.g., race and age). Implications for physical and mental health practitioners and researchers are discussed.

  12. Motor features in posterior cortical atrophy and their imaging correlates☆

    PubMed Central

    Ryan, Natalie S.; Shakespeare, Timothy J.; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M.; Leung, Kelvin K.; Fox, Nick C.; Crutch, Sebastian J.

    2014-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. PMID:25086839

  13. Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii

    PubMed Central

    Wright, Terry W.; Malone, Jane E.; Haidaris, Constantine G.; Harber, Martha; Sant, Andrea J.; Nayak, Jennifer L.

    2016-01-01

    ABSTRACT Pneumocystis pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse Pneumocystis surface protein, designated Pneumocystis cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4+ T cells were depleted, and the mice were exposed to Pneumocystis murina. Pca1 immunization completely protected nearly all mice, similar to immunization with whole Pneumocystis organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized Pneumocystis jirovecii and Pneumocystis carinii. Potential orthologs of Pca1 have been identified in P. jirovecii. Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation. PMID:28031260

  14. Fatty acid binding protein 4 enhances prostate cancer progression by upregulating matrix metalloproteinases and stromal cell cytokine production

    PubMed Central

    Huang, Mingguo; Narita, Shintaro; Inoue, Takamitsu; Koizumi, Atsushi; Saito, Mitsuru; Tsuruta, Hiroshi; Numakura, Kazuyuki; Satoh, Shigeru; Nanjo, Hiroshi; Sasaki, Takehiko; Habuchi, Tomonori

    2017-01-01

    Fatty acid binding protein 4 (FABP4) is an abundant protein in adipocytes, and its production is influenced by high-fat diet (HFD) or obesity. The prostate stromal microenvironment induces proinflammatory cytokine production, which is key for the development and progression of prostate cancer (PCa). Here, we show that high FABP4 expression and its secretion by PCa cells directly stimulated PCa cell invasiveness by upregulating matrix metalloproteinases through phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. In addition, prostate stromal cells augmented PCa cell invasiveness by secreting interleukin-8 and -6 in response to FABP4. This was abrogated by the FABP4 specific inhibitor, BMS309403. Furthermore, a mouse xenograft experiment showed HFD enhanced PCa metastasis and invasiveness by the upregulation of FABP4 and interleukin-8. Clinically, the serum level of FABP4 was significantly associated with an aggressive type of PCa rather than obesity. Taken together, FABP4 may enhance PCa progression and invasiveness by upregulating matrix metalloproteinases and cytokine production in the PCa stromal microenvironment, especially under HFD or obesity. PMID:29340091

  15. Novel targets for prostate cancer chemoprevention

    PubMed Central

    Sarkar, Fazlul H; Li, Yiwei; Wang, Zhiwei; Kong, Dejuan

    2010-01-01

    Among many endocrine-related cancers, prostate cancer (PCa) is the most frequent male malignancy, and it is the second most common cause of cancer-related death in men in the United States. Therefore, this review focuses on summarizing the knowledge of molecular signaling pathways in PCa because, in order to better design new preventive strategies for the fight against PCa, documentation of the knowledge on the pathogenesis of PCa at the molecular level is very important. Cancer cells are known to have alterations in multiple cellular signaling pathways; indeed, the development and the progression of PCa are known to be caused by the deregulation of several selective signaling pathways such as the androgen receptor, Akt, nuclear factor-κB, Wnt, Hedgehog, and Notch. Therefore, strategies targeting these important pathways and their upstream and downstream signaling could be promising for the prevention of PCa progression. In this review, we summarize the current knowledge regarding the alterations in cell signaling pathways during the development and progression of PCa, and document compelling evidence showing that these are the targets of several natural agents against PCa progression and its metastases. PMID:20576802

  16. Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis

    PubMed Central

    Kumar, Avinash; Davuluri, Gangarao; deSilva, Rafaella Nasciemento; Engelen, Marielle PKJ; TenHave, Gabrie; Prayson, Richard; Deutz, Nicolaas EP; Dasarathy, Srinivasan

    2017-01-01

    Sarcopenia or skeletal muscle loss is a frequent, potentially reversible complication in cirrhosis that adversely affects clinical outcomes. Hyperammonemia is a consistent abnormality in cirrhosis that results in impaired skeletal muscle protein synthesis and breakdown (proteostasis). Despite availability of effective ammonia lowering therapies, whether lowering ammonia restores proteostasis and reverses muscle mass is unknown. Myotube diameter, protein synthesis and molecular responses in C2C12 murine myotubes to withdrawal of ammonium acetate following 24 h exposure to 10mM ammonium acetate were complemented by in vivo studies in the hyperammonemic portacaval anastomosis rat (PCA) and sham operated, pair-fed (SO) Sprague- Dawley rats treated with ammonia lowering therapy by L-ornithine L-aspartate and rifaximin orally for 4 weeks. We observed reduced myotube diameter, impaired protein synthesis and increased autophagy flux in response to hyperammonemia that were partially reversed following 24h and 48h withdrawal of ammonium acetate. Consistently, 4 weeks of ammonia lowering therapy resulted in significant lowering of blood and skeletal muscle ammonia, increase in lean body mass, improved grip strength and higher skeletal muscle mass, diameter and an increase in type II fibers in the treated compared to untreated PCA rats. Increased skeletal muscle myostatin expression, reduced mTORC1 function, and the hyperammonemic stress response including autophagy markers were also reversed in the PCA rats treated with ammonia lowering therapy. Despite significant improvement, molecular and functional readouts were not completely reversed by ammonia lowering measures. Conclusions Ammonia lowering therapy results in improvement in skeletal muscle phenotype, function and molecular perturbations of hyperammonemia. These preclinical studies complement previous studies on ammonia induced skeletal muscle loss and lay the foundation for prolonged ammonia lowering therapy to reverse sarcopenia of cirrhosis. PMID:28195332

  17. Exercise improves quality of life in androgen deprivation therapy-treated prostate cancer: systematic review of randomised controlled trials.

    PubMed

    Teleni, Laisa; Chan, Raymond J; Chan, Alexandre; Isenring, Elisabeth A; Vela, Ian; Inder, Warrick J; McCarthy, Alexandra L

    2016-02-01

    Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal obesity and osteoporosis. Other treatment-related side effects adversely influence quality of life (QoL) including vasomotor distress, depression, anxiety, mood swings, poor sleep quality and compromised sexual function. The objective of this study was to systematically review the nature and effects of dietary and exercise interventions on QoL, androgen deprivation symptoms and metabolic risk factors in men with PCa undergoing ADT. An electronic search of CINAHL, CENTRAL, Medline, PsychINFO and reference lists was performed to identify peer-reviewed articles published between January 2004 and December 2014 in English. Eligible study designs included randomised controlled trials (RCTs) with pre- and post-intervention data. Data extraction and assessment of methodological quality with the Cochrane approach was conducted by two independent reviewers. Seven exercise studies were identified. Exercise significantly improved QoL, but showed no effect on metabolic risk factors (weight, waist circumference, lean or fat mass, blood pressure and lipid profile). Two dietary studies were identified, both of which tested soy supplements. Soy supplementation did not improve any outcomes. No dietary counselling studies were identified. No studies evaluated androgen-deficiency symptoms (libido, erectile function, sleep quality, mood swings, depression, anxiety and bone mineral density). Evidence from RCTs indicates that exercise enhances health- and disease-specific QoL in men with PCa undergoing ADT. Further studies are required to evaluate the effect of exercise and dietary interventions on QoL, androgen deprivation symptoms and metabolic risk factors in this cohort. © 2016 Society for Endocrinology.

  18. Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer

    PubMed Central

    Xu, S; Adisetiyo, H; Tamura, S; Grande, F; Garofalo, A; Roy-Burman, P; Neamati, N

    2015-01-01

    Background: Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. Methods: We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. Results: Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. Conclusions: There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice. PMID:26103574

  19. Hypoxia induces triglycerides accumulation in prostate cancer cells and extracellular vesicles supporting growth and invasiveness following reoxygenation

    PubMed Central

    Kumar, Rahul; Dhar, Deepanshi; Agarwal, Chapla; Bergman, Bryan; Graner, Michael; Maroni, Paul; Singh, Rana P.; Agarwal, Rajesh; Deep, Gagan

    2015-01-01

    Hypoxia is an independent prognostic indicator of poor outcome in several malignancies. However, precise mechanism through which hypoxia promotes disease aggressiveness is still unclear. Here, we report that under hypoxia (1% O2), human prostate cancer (PCA) cells, and extracellular vesicles (EVs) released by these cells, are significantly enriched in triglycerides due to the activation of lipogenesis-related enzymes and signaling molecules. This is likely a survival response to hypoxic stress as accumulated lipids could support growth following reoxygenation. Consistent with this, significantly higher proliferation was observed in hypoxic PCA cells following reoxygenation associated with rapid use of accumulated lipids. Importantly, lipid utilization inhibition by CPT1 inhibitor etomoxir and shRNA-mediated CPT1-knockdown significantly compromised hypoxic PCA cell proliferation following reoxygenation. Furthermore, COX2 inhibitor celecoxib strongly reduced growth and invasiveness following hypoxic PCA cells reoxygenation, and inhibited invasiveness induced by hypoxic PCA EVs. This establishes a role for COX2 enzymatic products in the enhanced PCA growth and invasiveness. Importantly, concentration and loading of EVs secreted by PCA cells were significantly compromised under delipidized serum condition and by lipogenesis inhibitors (fatostatin and silibinin). Overall, present study highlights the biological significance of lipid accumulation in hypoxic PCA cells and its therapeutic relevance in PCA. PMID:26087400

  20. AMACR polymorphisms, dietary intake of red meat and dairy and prostate cancer risk.

    PubMed

    Wright, Jonathan L; Neuhouser, Marian L; Lin, Daniel W; Kwon, Erika M; Feng, Ziding; Ostrander, Elaine A; Stanford, Janet L

    2011-04-01

    Alpha-methylacyl CoA racemase (AMACR) is an enzyme involved in fatty acids metabolism. One of AMACRs primary substrates, phytanic acid, is principally obtained from dietary red meat/dairy, which are associated with prostate cancer (PCa) risk. AMACR is also a tumor tissue biomarker over-expressed in PCa. In this study, we explored the potential relationship between AMACR polymorphisms, red meat/dairy intake, and PCa risk. Caucasian participants from two population-based PCa case-control studies were included. AMACR single nucleotide polymorphisms (SNPs) were selected to capture variation across the gene and regulatory regions. Red meat and dairy intake was determined from food frequency questionnaires. The odds ratio (OR) of PCa (overall and by disease aggressiveness) was estimated by logistic and polytomous regression. Potential interactions between genotypes and dietary exposures were evaluated. Data from 1,309 cases and 1,267 controls were analyzed. Carriers of the variant T allele (rs2287939) had an OR of 0.81 (95% CI 0.68-0.97) for less aggressive PCa, but no alteration in risk for more aggressive PCa. Red meat consumption was positively associated with PCa risk, and the association was stronger for more aggressive disease (lowest vs. highest tertile OR=1.55, 95% CI 1.10-2.20). No effect modification of AMACR polymorphisms by either dietary red meat or dairy intake on PCa risk was observed. PCa risk varied by level of red meat intake and by one AMACR SNP, but there was no evidence for gene-environment interaction. These findings suggest that the effects of AMACR polymorphisms and red meat and dairy on PCa risk are independent. Copyright © 2010 Wiley-Liss, Inc.

  1. Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells

    PubMed Central

    Jeet, Varinder; Tevz, Gregor; Lehman, Melanie; Hollier, Brett; Nelson, Colleen

    2014-01-01

    Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa. PMID:24981110

  2. Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells.

    PubMed

    Jeet, Varinder; Tevz, Gregor; Lehman, Melanie; Hollier, Brett; Nelson, Colleen

    2014-10-01

    Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa. © 2014 The authors.

  3. DWI-associated entire-tumor histogram analysis for the differentiation of low-grade prostate cancer from intermediate-high-grade prostate cancer.

    PubMed

    Wu, Chen-Jiang; Wang, Qing; Li, Hai; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin; Zhang, Yu-Dong

    2015-10-01

    To investigate diagnostic efficiency of DWI using entire-tumor histogram analysis in differentiating the low-grade (LG) prostate cancer (PCa) from intermediate-high-grade (HG) PCa in comparison with conventional ROI-based measurement. DW images (b of 0-1400 s/mm(2)) from 126 pathology-confirmed PCa (diameter >0.5 cm) in 110 patients were retrospectively collected and processed by mono-exponential model. The measurement of tumor apparent diffusion coefficients (ADCs) was performed with using histogram-based and ROI-based approach, respectively. The diagnostic ability of ADCs from two methods for differentiating LG-PCa (Gleason score, GS ≤ 6) from HG-PCa (GS > 6) was determined by ROC regression, and compared by McNemar's test. There were 49 LG-tumor and 77 HG-tumor at pathologic findings. Histogram-based ADCs (mean, median, 10th and 90th) and ROI-based ADCs (mean) showed dominant relationships with ordinal GS of Pca (ρ = -0.225 to -0.406, p < 0.05). All above imaging indices reflected significant difference between LG-PCa and HG-PCa (all p values <0.01). Histogram 10th ADCs had dominantly high Az (0.738), Youden index (0.415), and positive likelihood ratio (LR+, 2.45) in stratifying tumor GS against mean, median and 90th ADCs, and ROI-based ADCs. Histogram mean, median, and 10th ADCs showed higher specificity (65.3%-74.1% vs. 44.9%, p < 0.01), but lower sensitivity (57.1%-71.3% vs. 84.4%, p < 0.05) than ROI-based ADCs in differentiating LG-PCa from HG-PCa. DWI-associated histogram analysis had higher specificity, Az, Youden index, and LR+ for differentiation of PCa Gleason grade than ROI-based approach.

  4. Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

    PubMed

    Giri, Veda N; Knudsen, Karen E; Kelly, William K; Abida, Wassim; Andriole, Gerald L; Bangma, Chris H; Bekelman, Justin E; Benson, Mitchell C; Blanco, Amie; Burnett, Arthur; Catalona, William J; Cooney, Kathleen A; Cooperberg, Matthew; Crawford, David E; Den, Robert B; Dicker, Adam P; Eggener, Scott; Fleshner, Neil; Freedman, Matthew L; Hamdy, Freddie C; Hoffman-Censits, Jean; Hurwitz, Mark D; Hyatt, Colette; Isaacs, William B; Kane, Christopher J; Kantoff, Philip; Karnes, R Jeffrey; Karsh, Lawrence I; Klein, Eric A; Lin, Daniel W; Loughlin, Kevin R; Lu-Yao, Grace; Malkowicz, S Bruce; Mann, Mark J; Mark, James R; McCue, Peter A; Miner, Martin M; Morgan, Todd; Moul, Judd W; Myers, Ronald E; Nielsen, Sarah M; Obeid, Elias; Pavlovich, Christian P; Peiper, Stephen C; Penson, David F; Petrylak, Daniel; Pettaway, Curtis A; Pilarski, Robert; Pinto, Peter A; Poage, Wendy; Raj, Ganesh V; Rebbeck, Timothy R; Robson, Mark E; Rosenberg, Matt T; Sandler, Howard; Sartor, Oliver; Schaeffer, Edward; Schwartz, Gordon F; Shahin, Mark S; Shore, Neal D; Shuch, Brian; Soule, Howard R; Tomlins, Scott A; Trabulsi, Edouard J; Uzzo, Robert; Vander Griend, Donald J; Walsh, Patrick C; Weil, Carol J; Wender, Richard; Gomella, Leonard G

    2018-02-01

    Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

  5. The impact of socioeconomic status on stage specific prostate cancer survival and mortality before and after introduction of PSA test in Finland.

    PubMed

    Seikkula, Heikki A; Kaipia, Antti J; Ryynänen, Heidi; Seppä, Karri; Pitkäniemi, Janne M; Malila, Nea K; Boström, Peter J

    2018-03-01

    Socioeconomic status (SES) has an impact on prostate cancer (PCa) outcomes. Men with high SES have higher incidence and lower mortality of PCa versus lower SES males. PCa cases diagnosed in Finland in 1985-2014 (N = 95,076) were identified from the Finnish Cancer Registry. Information on education level (EL) was obtained from Statistics Finland. EL was assessed with three-tiered scale: basic, upper secondary and higher education. PCa stage at diagnosis was defined as localized, metastatic or unknown. Years of diagnosis 1985-1994 were defined as pre-PSA period and thereafter as post-PSA period. We report PCa-specific survival (PCSS) and relative risks (RR) for PCa specific mortality (PCSM) among cancer cases in Finland, where healthcare is 100% publicly reimbursed and inequality in healthcare services low. Men with higher EL had markedly better 10-year PCSS: 68 versus 63% in 1985-1994 and 90 versus 85% in 1995-2004 compared to basic EL in localized PCa. The RR for PCSM among men with localized PCa and higher EL compared to basic EL was 0.76(95%confidence interval (CI) 0.66-0.88) in 1985-1994 and 0.61(95%CI 0.53-0.70) in 1995-2004. Variation in PCSS and PCSM between EL categories was evident in metastatic PCa, too. The difference in PCSM between EL categories was larger in the first 10-year post-PSA period than before that but decreased thereafter in localized PCa, suggesting PSA testing became earlier popular among men with high EL. In summary, higher SES/EL benefit PCa survival both in local and disseminated disease and the effect of EL was more pronounced in early post-PSA period. © 2017 UICC.

  6. Protocatechuic aldehyde inhibits migration and proliferation of vascular smooth muscle cells and intravascular thrombosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moon, Chang Yoon; Endocrinology, Brain Korea 21 Project for Medical Science, Institute of Endocrine Research, and Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University College of Medicine, Seoul; Ku, Cheol Ryong

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Protocatechuic aldehyde (PCA) inhibits ROS production in VSMCs. Black-Right-Pointing-Pointer PCA inhibits proliferation and migration in PDGF-induced VSMCs. Black-Right-Pointing-Pointer PCA has anti-platelet effects in ex vivo rat whole blood. Black-Right-Pointing-Pointer We report the potential therapeutic role of PCA in atherosclerosis. -- Abstract: The migration and proliferation of vascular smooth muscle cells (VSMCs) and formation of intravascular thrombosis play crucial roles in the development of atherosclerotic lesions. This study examined the effects of protocatechuic aldehyde (PCA), a compound isolated from the aqueous extract of the root of Salvia miltiorrhiza, an herb used in traditional Chinese medicine to treat a varietymore » of vascular diseases, on the migration and proliferation of VSMCs and platelets due to platelet-derived growth factor (PDGF). DNA 5-bromo-2 Prime -deoxy-uridine (BrdU) incorporation and wound-healing assays indicated that PCA significantly attenuated PDGF-induced proliferation and migration of VSMCs at a pharmacologically relevant concentration (100 {mu}M). On a molecular level, we observed down-regulation of the phosphatidylinositol 3-kinase (PI3K)/Akt and the mitogen-activated protein kinase (MAPK) pathways, both of which regulate key enzymes associated with migration and proliferation. We also found that PCA induced S-phase arrest of the VSMC cell cycle and suppressed cyclin D2 expression. In addition, PCA inhibited PDGF-BB-stimulated reactive oxygen species production in VSMCs, indicating that PCA's antioxidant properties may contribute to its suppression of PDGF-induced migration and proliferation in VSMCs. Finally, PCA exhibited an anti-thrombotic effect related to its inhibition of platelet aggregation, confirmed with an aggregometer. Together, these findings suggest a potential therapeutic role of PCA in the treatment of atherosclerosis and angioplasty-induced vascular restenosis.« less

  7. Whole milk intake is associated with prostate cancer-specific mortality among U.S. male physicians.

    PubMed

    Song, Yan; Chavarro, Jorge E; Cao, Yin; Qiu, Weiliang; Mucci, Lorelei; Sesso, Howard D; Stampfer, Meir J; Giovannucci, Edward; Pollak, Michael; Liu, Simin; Ma, Jing

    2013-02-01

    Previous studies have associated higher milk intake with greater prostate cancer (PCa) incidence, but little data are available concerning milk types and the relation between milk intake and risk of fatal PCa. We investigated the association between intake of dairy products and the incidence and survival of PCa during a 28-y follow-up. We conducted a cohort study in the Physicians' Health Study (n = 21,660) and a survival analysis among the incident PCa cases (n = 2806). Information on dairy product consumption was collected at baseline. PCa cases and deaths (n = 305) were confirmed during follow-up. The intake of total dairy products was associated with increased PCa incidence [HR = 1.12 (95% CI: 0.93, 1.35); >2.5 servings/d vs. ≤0.5 servings/d]. Skim/low-fat milk intake was positively associated with risk of low-grade, early stage, and screen-detected cancers, whereas whole milk intake was associated only with fatal PCa [HR = 1.49 (95% CI: 0.97, 2.28); ≥237 mL/d (1 serving/d) vs. rarely consumed]. In the survival analysis, whole milk intake remained associated with risk of progression to fatal disease after diagnosis [HR = 2.17 (95% CI: 1.34, 3.51)]. In this prospective cohort, higher intake of skim/low-fat milk was associated with a greater risk of nonaggressive PCa. Most importantly, only whole milk was consistently associated with higher incidence of fatal PCa in the entire cohort and higher PCa-specific mortality among cases. These findings add further evidence to suggest the potential role of dairy products in the development and prognosis of PCa.

  8. Activation of Beta-Catenin Signaling in Androgen Receptor–Negative Prostate Cancer Cells

    PubMed Central

    Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W.; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S.; Troncoso, Patricia; Maity, Sankar N.; Navone, Nora M.

    2012-01-01

    Purpose To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin–androgen receptor (AR) interaction. Experimental Design We performed beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin–mediated transcription), and sequenced the beta-catenin gene in MDA PCa 118a, MDA PCa 118b, MDA PCa 2b, and PC-3 prostate cancer (PCa) cells. We knocked down beta-catenin in AR-negative MDA PCa 118b cells and performed comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs. Results Beta-catenin nuclear accumulation and TOP-flash reporter activity were high in MDA PCa 118b but not in MDA PCa 2b or PC-3 cells. MDA PCa 118a and 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA PCa 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher’s exact test), suggesting that reduced AR expression enables Wnt/beta-catenin signaling. Conclusion We identified a previously unknown downstream target of beta-catenin, HAS2, in PCa, and found that high beta-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone-metastatic PCa. These findings may guide physicians in managing these patients. PMID:22298898

  9. Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells

    PubMed Central

    Chao, Hsueh-Ping; Deng, Qu; Jeter, Collene; Liu, Can; Honorio, Sofia; Li, Hangwen; Davis, Tammy; Suraneni, Mahipal; Laffin, Brian; Qin, Jichao; Li, Qiuhui; Yang, Tao; Whitney, Pamela; Shen, Jianjun; Huang, Jiaoti; Tang, Dean G.

    2015-01-01

    Human cancers are heterogeneous containing stem-like cancer cells operationally defined as cancer stem cells (CSCs) that possess great tumor-initiating and long-term tumor-propagating properties. In this study, we systematically dissect the phenotypic, functional and tumorigenic heterogeneity in human prostate cancer (PCa) using xenograft models and >70 patient tumor samples. In the first part, we further investigate the PSA−/lo PCa cell population, which we have recently shown to harbor self-renewing long-term tumor-propagating cells and present several novel findings. We show that discordant AR and PSA expression in both untreated and castration-resistant PCa (CRPC) results in AR+PSA+, AR+PSA−, AR−PSA−, and AR−PSA+ subtypes of PCa cells that manifest differential sensitivities to therapeutics. We further demonstrate that castration leads to a great enrichment of PSA−/lo PCa cells in both xenograft tumors and CRPC samples and systemic androgen levels dynamically regulate the relative abundance of PSA+ versus PSA−/lo PCa cells that impacts the kinetics of tumor growth. We also present evidence that the PSA−/lo PCa cells possess distinct epigenetic profiles. As the PSA−/lo PCa cell population is heterogeneous, in the second part, we employ two PSA− (Du145 and PC3) and two PSA+ (LAPC9 and LAPC4) PCa models as well as patient tumor cells to further dissect the clonogenic and tumorigenic subsets. We report that different PCa models possess distinct tumorigenic subpopulations that both commonly and uniquely express important signaling pathways that could represent therapeutic targets. Our results have important implications in understanding PCa cell heterogeneity, response to clinical therapeutics, and cellular mechanisms underlying CRPC. PMID:26246472

  10. Evidence for Masturbation and Prostate Cancer Risk: Do We Have a Verdict?

    PubMed

    Aboul-Enein, Basil H; Bernstein, Joshua; Ross, Michael W

    2016-07-01

    Prostate cancer (PCa) is one of the leading causes of cancer death in men and remains one of the most diagnosed malignancies worldwide. Ongoing public health efforts continue to promote protective factors, such as diet, physical activity, and other lifestyle modifications, against PCa development. Masturbation is a nearly universal safe sexual activity that transcends societal boundaries and geography yet continues to be met with stigma and controversy in contemporary society. Although previous studies have examined associations between sexual activity and PCa risk, anecdotal relations have been suggested regarding masturbation practice and PCa risk. To provide a summary of the published literature and examine the contemporary evidence for relations between masturbation practice and PCa risk. A survey of the current literature using seven academic electronic databases was conducted using search terms and key words associated with masturbation practice and PCa risk. The practice of masturbation and its relation to PCa risk. The literature search identified study samples (n = 16) published before October 2015. Sample inclusions varied by study type, sample size, and primary objective. Protective relations (n = 7) between ejaculation through masturbation and PCa risk were reported by 44% of the study sample. Age range emerged as a significant variable in the relation between masturbation and PCa. Findings included relations among masturbation, ejaculation frequency, and age range as individual factors of PCa risk. No universally accepted themes were identified across the study sample. Throughout the sample, there was insufficient agreement in survey design and data reporting. Potential avenues for new research include frequency of ejaculation and age range as covarying factors that could lead to more definitive statements about masturbation practice and PCa risk. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  11. Biotransformation of ferulic acid to protocatechuic acid by Corynebacterium glutamicum ATCC 21420 engineered to express vanillate O-demethylase.

    PubMed

    Okai, Naoko; Masuda, Takaya; Takeshima, Yasunobu; Tanaka, Kosei; Yoshida, Ken-Ichi; Miyamoto, Masanori; Ogino, Chiaki; Kondo, Akihiko

    2017-12-01

    Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a lignin-derived phenolic compound abundant in plant biomass. The utilization of FA and its conversion to valuable compounds is desired. Protocatechuic acid (3,4-dihydroxybenzoic acid, PCA) is a precursor of polymers and plastics and a constituent of food. A microbial conversion system to produce PCA from FA was developed in this study using a PCA-producing strain of Corynebacterium glutamicum F (ATCC 21420). C. glutamicum strain F grown at 30 °C for 48 h utilized 2 mM each of FA and vanillic acid (4-hydroxy-3-methoxybenzoic acid, VA) to produce PCA, which was secreted into the medium. FA may be catabolized by C. glutamicum through proposed (I) non-β-oxidative, CoA-dependent or (II) β-oxidative, CoA-dependent phenylpropanoid pathways. The conversion of VA to PCA is the last step in each pathway. Therefore, the vanillate O-demethylase gene (vanAB) from Corynebacterium efficiens NBRC 100395 was expressed in C. glutamicum F (designated strain FVan) cultured at 30 °C in AF medium containing FA. Strain C. glutamicum FVan converted 4.57 ± 0.07 mM of FA into 2.87 ± 0.01 mM PCA after 48 h with yields of 62.8% (mol/mol), and 6.91 mM (1064 mg/L) of PCA was produced from 16.0 mM of FA after 12 h of fed-batch biotransformation. Genomic analysis of C. glutamicum ATCC 21420 revealed that the PCA-utilization genes (pca cluster) were conserved in strain ATCC 21420 and that mutations were present in the PCA importer gene pcaK.

  12. Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry.

    PubMed

    Biggs, Colleen N; Siddiqui, Khurram M; Al-Zahrani, Ali A; Pardhan, Siddika; Brett, Sabine I; Guo, Qiu Q; Yang, Jun; Wolf, Philipp; Power, Nicholas E; Durfee, Paul N; MacMillan, Connor D; Townson, Jason L; Brinker, Jeffrey C; Fleshner, Neil E; Izawa, Jonathan I; Chambers, Ann F; Chin, Joseph L; Leong, Hon S

    2016-02-23

    Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

  13. A novel-type phosphatidylinositol phosphate-interactive, Ca-binding protein PCaP1 in Arabidopsis thaliana: stable association with plasma membrane and partial involvement in stomata closure.

    PubMed

    Nagata, Chisako; Miwa, Chika; Tanaka, Natsuki; Kato, Mariko; Suito, Momoe; Tsuchihira, Ayako; Sato, Yori; Segami, Shoji; Maeshima, Masayoshi

    2016-05-01

    The Ca(2+)-binding protein-1 (PCaP1) of Arabidopsis thaliana is a new type protein that binds to phosphatidylinositol phosphates and Ca(2+)-calmodulin complex as well as free Ca(2+). Although biochemical properties, such as binding to ligands and N-myristoylation, have been revealed, the intracellular localization, tissue and cell specificity, integrity of membrane association and physiological roles of PCaP1 are unknown. We investigated the tissue and intracellular distribution of PCaP1 by using transgenic lines expressing PCaP1 linked with a green fluorescence protein (GFP) at the carboxyl terminus of PCaP1. GFP fluorescence was obviously detected in most tissues including root, stem, leaf and flower. In these tissues, PCaP1-GFP signal was observed predominantly in the plasma membrane even under physiological stress conditions but not in other organelles. The fluorescence was detected in the cytosol when the 25-residue N-terminal sequence was deleted from PCaP1 indicating essential contribution of N-myristoylation to the plasma membrane anchoring. Fluorescence intensity of PCaP1-GFP in roots was slightly decreased in seedlings grown in medium supplemented with high concentrations of iron for 1 week and increased in those grown with copper. In stomatal guard cells, PCaP1-GFP was strictly, specifically localized to the plasma membrane at the epidermal-cell side but not at the pore side. A T-DNA insertion mutant line of PCaP1 did not show marked phenotype in a life cycle except for well growth under high CO2 conditions. However, stomata of the mutant line did not close entirely even in high osmolarity, which usually induces stomata closure. These results suggest that PCaP1 is involved in the stomatal movement, especially closure process, in leaves and response to excessive copper in root and leaf as a mineral nutrient as a physiological role.

  14. Calcium channel blocker use and risk of prostate cancer by TMPRSS2:ERG gene fusion status

    PubMed Central

    Geybels, Milan S.; McCloskey, Karen D.; Mills, Ian G.; Stanford, Janet L.

    2017-01-01

    Background Calcium channel blockers (CCBs) may affect prostate cancer (PCa) growth by various mechanisms including those related to androgens. The fusion of the androgen-regulated gene TMPRSS2 and the oncogene ERG (TMPRSS2:ERG or T2E) is common in PCa, and prostate tumors that harbor the gene fusion are believed to represent a distinct disease subtype. We studied the association of CCB use with the risk of PCa, and molecular subtypes of PCa defined by T2E status. Methods Participants were residents of King County, Washington, recruited for population-based case–control studies (1993–1996 or 2002–2005). Tumor T2E status was determined by fluorescence in situ hybridization using tumor tissue specimens from radical prostatectomy. Detailed information on use of CCBs and other variables was obtained through in-person interviews. Binomial and polytomous logistic regression were used to generate odds ratios (ORs) and 95% confidence intervals (CIs). Results The study includes 1,747 PCa patients and 1,635 age-matched controls. A subset of 563 patients treated with radical prostatectomy had T2E status determined, of which 295 were T2E positive (52%). Use of CCBs (ever vs. never) was not associated with overall PCa risk. However, among European-American men, users had a reduced risk of higher-grade PCa (Gleason scores ≥7: adjusted OR = 0.64; 95% CI: 0.44–0.95). Further, use of CCBs was associated with a reduced risk of T2E positive PCa (adjusted OR = 0.38; 95% CI: 0.19–0.78), but was not associated with T2E negative PCa. Conclusions This study found suggestive evidence that use of CCBs is associated with reduced relative risks for higher Gleason score and T2E positive PCa. Future studies of PCa etiology should consider etiologic heterogeneity as PCa subtypes may develop through different causal pathways. PMID:27753122

  15. G Protein-Coupled Estrogen Receptor-1 Is Involved in the Protective Effect of Protocatechuic Aldehyde against Endothelial Dysfunction

    PubMed Central

    Kong, Byung Soo; Cho, Yoon Hee; Lee, Eun Jig

    2014-01-01

    Protocatechuic aldehyde (PCA), a phenolic aldehyde, has therapeutic potency against atherosclerosis. Although PCA is known to inhibit the migration and proliferation of vascular smooth muscle cells and intravascular thrombosis, the underlying mechanism remains unclear. In this study, we investigated the protective effect of PCA on endothelial cells and injured vessels in vivo in association with G protein-coupled estrogen receptor-1 (GPER-1). With PCA treatment, cAMP production was increased in HUVECs, while GPER-1 expression was increased in both HUVECs and a rat aortic explant. PCA and G1, a GPER-1 agonist, reduced H2O2 stimulated ROS production in HUVECs, whereas, G15, a GPER-1 antagonist, increased ROS production further. These elevations were inhibited by co-treatment with PCA or G1. TNFα stimulated the expression of inflammatory markers (VCAM-1, ICAM-1 and CD40), phospho-NF-κB, phospho-p38 and HIF-1α; however, co-treatment with PCA or G1 down-regulated this expression significantly. Likewise, increased expression of inflammatory markers by treatment with G15 was inhibited by co-treatment with PCA. In re-endothelization, aortic ring sprouting and neointima formation assay, rat aortas treated with PCA or G1 showed accelerated re-endothelization of the endothelium and reduced sprouting and neointima formation. However, aortas from G15-treated rats showed decelerated re-endothelization and increased sprouting and neointima formation. The effects of G15 were restored by co-treatment with PCA or G1. Also, in the endothelia of these aortas, PCA and G1 increased CD31 and GPER-1 and decreased VCAM-1 and CD40 expression. In contrast, the opposite effect was observed in G15-treated endothelium. These results suggest that GPER-1 might mediate the protective effect of PCA on the endothelium. PMID:25411835

  16. G protein-coupled estrogen receptor-1 is involved in the protective effect of protocatechuic aldehyde against endothelial dysfunction.

    PubMed

    Kong, Byung Soo; Cho, Yoon Hee; Lee, Eun Jig

    2014-01-01

    Protocatechuic aldehyde (PCA), a phenolic aldehyde, has therapeutic potency against atherosclerosis. Although PCA is known to inhibit the migration and proliferation of vascular smooth muscle cells and intravascular thrombosis, the underlying mechanism remains unclear. In this study, we investigated the protective effect of PCA on endothelial cells and injured vessels in vivo in association with G protein-coupled estrogen receptor-1 (GPER-1). With PCA treatment, cAMP production was increased in HUVECs, while GPER-1 expression was increased in both HUVECs and a rat aortic explant. PCA and G1, a GPER-1 agonist, reduced H2O2 stimulated ROS production in HUVECs, whereas, G15, a GPER-1 antagonist, increased ROS production further. These elevations were inhibited by co-treatment with PCA or G1. TNFα stimulated the expression of inflammatory markers (VCAM-1, ICAM-1 and CD40), phospho-NF-κB, phospho-p38 and HIF-1α; however, co-treatment with PCA or G1 down-regulated this expression significantly. Likewise, increased expression of inflammatory markers by treatment with G15 was inhibited by co-treatment with PCA. In re-endothelization, aortic ring sprouting and neointima formation assay, rat aortas treated with PCA or G1 showed accelerated re-endothelization of the endothelium and reduced sprouting and neointima formation. However, aortas from G15-treated rats showed decelerated re-endothelization and increased sprouting and neointima formation. The effects of G15 were restored by co-treatment with PCA or G1. Also, in the endothelia of these aortas, PCA and G1 increased CD31 and GPER-1 and decreased VCAM-1 and CD40 expression. In contrast, the opposite effect was observed in G15-treated endothelium. These results suggest that GPER-1 might mediate the protective effect of PCA on the endothelium.

  17. Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry

    PubMed Central

    Al-Zahrani, Ali A.; Pardhan, Siddika; Brett, Sabine I.; Guo, Qiu Q.; Yang, Jun; Wolf, Philipp; Power, Nicholas E.; Durfee, Paul N.; MacMillan, Connor D.; Townson, Jason L.; Brinker, Jeffrey C.; Fleshner, Neil E.; Izawa, Jonathan I.; Chambers, Ann F.; Chin, Joseph L.; Leong, Hon S.

    2016-01-01

    Background Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Patients and Methods Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/μL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. Results PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. Conclusions PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer. PMID:26814433

  18. Inflammation: an important parameter in the search of prostate cancer biomarkers

    PubMed Central

    2014-01-01

    Background A more specific and early diagnostics for prostate cancer (PCa) is highly desirable. In this study, being inflammation the focus of our effort, serum protein profiles were analyzed in order to investigate if this parameter could interfere with the search of discriminating proteins between PCa and benign prostatic hyperplasia (BPH). Methods Patients with clinical suspect of PCa and candidates for trans-rectal ultrasound guided prostate biopsy (TRUS) were enrolled. Histological specimens were examined in order to grade and classify the tumor, identify BPH and detect inflammation. Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (SELDI-ToF-MS) and two-dimensional gel electrophoresis (2-DE) coupled with Liquid Chromatography-MS/MS (LC-MS/MS) were used to analyze immuno-depleted serum samples from patients with PCa and BPH. Results The comparison between PCa (with and without inflammation) and BPH (with and without inflammation) serum samples by SELDI-ToF-MS analysis did not show differences in protein expression, while changes were only observed when the concomitant presence of inflammation was taken into consideration. In fact, when samples with histological sign of inflammation were excluded, 20 significantly different protein peaks were detected. Subsequent comparisons (PCa with inflammation vs PCa without inflammation, and BPH with inflammation vs BPH without inflammation) showed that 16 proteins appeared to be modified in the presence of inflammation, while 4 protein peaks were not modified. With 2-DE analysis, comparing PCa without inflammation vs PCa with inflammation, and BPH without inflammation vs the same condition in the presence of inflammation, were identified 29 and 25 differentially expressed protein spots, respectively. Excluding samples with inflammation the comparison between PCa vs BPH showed 9 unique PCa proteins, 4 of which overlapped with those previously identified in the presence of inflammation, while other 2 were new proteins, not identified in our previous comparisons. Conclusions The present study indicates that inflammation might be a confounding parameter during the proteomic research of candidate biomarkers of PCa. These results indicate that some possible biomarker-candidate proteins are strongly influenced by the presence of inflammation, hence only a well-selected protein pattern should be considered for potential marker of PCa. PMID:24944525

  19. Can Prostate Imaging Reporting and Data System Version 2 reduce unnecessary prostate biopsies in men with PSA levels of 4-10 ng/ml?

    PubMed

    Xu, Ning; Wu, Yu-Peng; Chen, Dong-Ning; Ke, Zhi-Bin; Cai, Hai; Wei, Yong; Zheng, Qing-Shui; Huang, Jin-Bei; Li, Xiao-Dong; Xue, Xue-Yi

    2018-05-01

    To explore the value of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) for predicting prostate biopsy results in patients with prostate specific antigen (PSA) levels of 4-10 ng/ml. We retrospectively reviewed multi-parameter magnetic resonance images from 528 patients with PSA levels of 4-10 ng/ml who underwent transrectal ultrasound-guided prostate biopsies between May 2015 and May 2017. Among them, 137 were diagnosed with prostate cancer (PCa), and we further subdivided them according to pathological results into the significant PCa (S-PCa) and insignificant significant PCa (Ins-PCa) groups (121 cases were defined by surgical pathological specimen and 16 by biopsy). Age, PSA, percent free PSA, PSA density (PSAD), prostate volume (PV), and PI-RADS score were collected. Logistic regression analysis was performed to determine predictors of pathological results. Receiver operating characteristic curves were constructed to analyze the diagnostic value of PI-RADS v2 in PCa. Multivariate analysis indicated that age, PV, percent free PSA, and PI-RADS score were independent predictors of biopsy findings, while only PI-RADS score was an independent predictor of S-PCa (P < 0.05). The areas under the receiver operating characteristic curve for diagnosing PCa with respect to age, PV, percent free PSA, and PI-RADS score were 0.570, 0.430, 0.589 and 0.836, respectively. The area under the curve for diagnosing S-PCa with respect to PI-RADS score was 0.732. A PI-RADS score of 3 was the best cutoff for predicting PCa, and 4 was the best cutoff for predicting S-PCa. Thus, 92.8% of patients with PI-RADS scores of 1-2 would have avoided biopsy, but at the cost of missing 2.2% of the potential PCa cases. Similarly, 83.82% of patients with a PI-RADS score ≤ 3 would have avoided biopsy, but at the cost of missing 3.3% of the potential S-PCa cases. PI-RADS v2 could be used to reduce unnecessary prostate biopsies in patients with PSA levels of 4-10 ng/ml.

  20. Risk of prostate cancer in African-American men: Evidence of mixed effects of dietary quercetin by serum vitamin D status.

    PubMed

    Paller, C J; Kanaan, Y M; Beyene, D A; Naab, T J; Copeland, R L; Tsai, H L; Kanarek, N F; Hudson, T S

    2015-09-01

    African-American (AA) men experience higher rates of prostate cancer (PCa) and vitamin D (vitD) deficiency than white men. VitD is promoted for PCa prevention, but there is conflicting data on the association between vitD and PCa. We examined the association between serum vitD and dietary quercetin and their interaction with PCa risk in AA men. Participants included 90 AA men with PCa undergoing treatment at Howard University Hospital (HUH) and 62 controls participating in HUH's free PCa screening program. We measured serum 25-hydroxy vitD [25(OH)D] and used the 98.2 item Block Brief 2000 Food Frequency Questionnaires to measure dietary intake of quercetin and other nutrients. Case and control groups were compared using a two-sample t-test for continuous risk factors and a Fisher exact test for categorical factors. Associations between risk factors and PCa risk were examined via age-adjusted logistic regression models. Interaction effects of dietary quercetin and serum vitD on PCa status were observed. AA men (age 40-70) with normal levels of serum vitD (>30 ng/ml) had a 71% lower risk of PCa compared to AA men with vitD deficiency (OR = 0.29, 95%CI: 0.08-1.03; P = 0.055). In individuals with vitD deficiency, increased dietary quercetin showed a tendency toward lower risk of PCa (OR = 0.91, 95%CI: 0.82-1.00; P = 0.054, age-adjusted) while men with normal vitD were at elevated risk (OR = 1.23, 95%CI: 1.04-1.45). These findings suggest that AA men who are at a higher risk of PCa may benefit more from vitD intake, and supplementation with dietary quercetin may increase the risk of PCa in AA men with normal vitD levels. Further studies with larger populations are needed to better understand the impact of the interaction between sera vitD levels and supplementation with quercetin on PCa in AA men. © 2015 Wiley Periodicals, Inc.

  1. Lycopene and Risk of Prostate Cancer

    PubMed Central

    Chen, Ping; Zhang, Wenhao; Wang, Xiao; Zhao, Keke; Negi, Devendra Singh; Zhuo, Li; Qi, Mao; Wang, Xinghuan; Zhang, Xinhua

    2015-01-01

    Abstract Prostate cancer (PCa) is a common illness for aging males. Lycopene has been identified as an antioxidant agent with potential anticancer properties. Studies investigating the relation between lycopene and PCa risk have produced inconsistent results. This study aims to determine dietary lycopene consumption/circulating concentration and any potential dose–response associations with the risk of PCa. Eligible studies published in English up to April 10, 2014, were searched and identified from Pubmed, Sciencedirect Online, Wiley online library databases and hand searching. The STATA (version 12.0) was applied to process the dose–response meta-analysis. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) and to incorporate variation between studies. The linear and nonlinear dose–response relations were evaluated with data from categories of lycopene consumption/circulating concentrations. Twenty-six studies were included with 17,517 cases of PCa reported from 563,299 participants. Although inverse association between lycopene consumption and PCa risk was not found in all studies, there was a trend that with higher lycopene intake, there was reduced incidence of PCa (P = 0.078). Removal of one Chinese study in sensitivity analysis, or recalculation using data from only high-quality studies for subgroup analysis, indicated that higher lycopene consumption significantly lowered PCa risk. Furthermore, our dose–response meta-analysis demonstrated that higher lycopene consumption was linearly associated with a reduced risk of PCa with a threshold between 9 and 21 mg/day. Consistently, higher circulating lycopene levels significantly reduced the risk of PCa. Interestingly, the concentration of circulating lycopene between 2.17 and 85 μg/dL was linearly inversed with PCa risk whereas there was no linear association >85 μg/dL. In addition, greater efficacy for the circulating lycopene concentration on preventing PCa was found for studies with high quality, follow-up >10 years and where results were adjusted by the age or the body mass index. In conclusion, our novel data demonstrates that higher lycopene consumption/circulating concentration is associated with a lower risk of PCa. However, further studies are required to determine the mechanism by which lycopene reduces the risk of PCa and if there are other factors in tomato products that might potentially decrease PCa risk and progression. PMID:26287411

  2. Characterizing the molecular features of ERG-positive tumors in primary and castration resistant prostate cancer.

    PubMed

    Roudier, Martine P; Winters, Brian R; Coleman, Ilsa; Lam, Hung-Ming; Zhang, Xiaotun; Coleman, Roger; Chéry, Lisly; True, Lawrence D; Higano, Celestia S; Montgomery, Bruce; Lange, Paul H; Snyder, Linda A; Srivastava, Shiv; Corey, Eva; Vessella, Robert L; Nelson, Peter S; Üren, Aykut; Morrissey, Colm

    2016-06-01

    The TMPRSS2-ERG gene fusion is detected in approximately half of primary prostate cancers (PCa) yet the prognostic significance remains unclear. We hypothesized that ERG promotes the expression of common genes in primary PCa and metastatic castration-resistant PCa (CRPC), with the objective of identifying ERG-associated pathways, which may promote the transition from primary PCa to CRPC. We constructed tissue microarrays (TMA) from 127 radical prostatectomy specimens, 20 LuCaP patient-derived xenografts (PDX), and 152 CRPC metastases obtained immediately at time of death. Nuclear ERG was assessed by immunohistochemistry (IHC). To characterize the molecular features of ERG-expressing PCa, a subset of IHC confirmed ERG+ or ERG- specimens including 11 radical prostatectomies, 20 LuCaP PDXs, and 45 CRPC metastases underwent gene expression analysis. Genes were ranked based on expression in primary PCa and CRPC. Common genes of interest were targeted for IHC analysis and expression compared with biochemical recurrence (BCR) status. IHC revealed that 43% of primary PCa, 35% of the LuCaP PDXs, and 18% of the CRPC metastases were ERG+ (12 of 48 patients [25%] had at least one ERG+ metastasis). Based on gene expression data and previous literature, two proteins involved in calcium signaling (NCALD, CACNA1D), a protein involved in inflammation (HLA-DMB), CD3 positive immune cells, and a novel ERG-associated protein, DCLK1 were evaluated in primary PCa and CRPC metastases. In ERG+ primary PCa, a weak association was seen with NCALD and CACNA1D protein expression. HLA-DMB association with ERG was decreased and CD3 cell number association with ERG was changed from positive to negative in CRPC metastases compared to primary PCa. DCLK1 was upregulated at the protein level in unpaired ERG+ primary PCa and CRPC metastases (P = 0.0013 and P < 0.0001, respectively). In primary PCa, ERG status or expression of targeted proteins was not associated with BCR-free survival. However, for primary PCa, ERG+DCLK1+ patients exhibited shorter time to BCR (P = 0.06) compared with ERG+DCLK1- patients. This study examined ERG expression in primary PCa and CRPC. We have identified altered levels of inflammatory mediators associated with ERG expression. We determined expression of DCLK1 correlates with ERG expression and may play a role in primary PCa progression to metastatic CPRC. Prostate 76:810-822, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Activation of coagulation by a thalidomide-based regimen.

    PubMed

    Hoshi, Asuka; Matsumoto, Aya; Chung, Jihwa; Isozumi, Yu; Koyama, Takatoshi

    2011-09-01

    Combining thalidomide (Thal) with chemotherapeutic agents or steroid preparations led to improved response rates in the treatment of multiple myeloma. However, deep vein thrombosis (DVT) is one of the most serious side-effects noted with this regimen, and how a Thal-based regimen causes DVT is unclear. We investigated the procoagulant effects of Thal when combined with chemotherapeutic agents in vitro, focusing on tissue factor (TF) and phosphatidylserine. We examined the effects of the chemotherapeutic doxorubicin hydrochloride (Dox) and the steroid dexamethasone (Dex), with or without Thal. Our study used the human vascular endothelial, monocytic, and myeloma cell lines, EAhy926, THP-1, and RPMI8226, respectively. In EAhy926 and THP-1, Dex treatment increased expression of TF, which may induce procoagulant activity (PCA). Upregulation of TF mRNA correlated with activation of the Egr-1 pathway. In Thal and Dex treatments, the increase of PCA induction from phosphatidylserine exposure was modest. In contrast, Dox and Thal-Dox increased phosphatidylserine exposure in both cell types. In THP-1 cells, cell surface phosphatidylserine exposure correlated with increased PCA by Dox. Thal alone showed a modest increase in phosphatidylserine exposure in endothelial cells and monocytes. When Thal is given in combination with chemotherapies or Dex, endothelial cell and monocyte PCA may be induced through phosphatidylserine exposure, or TF expression. Induction may be protracted by Thal, which has an antiangiogenic activity. Therefore, prophylactic anticoagulant strategies should be considered in Thal-based combination regimens.

  4. Multiparametric dynamic contrast-enhanced ultrasound imaging of prostate cancer.

    PubMed

    Wildeboer, Rogier R; Postema, Arnoud W; Demi, Libertario; Kuenen, Maarten P J; Wijkstra, Hessel; Mischi, Massimo

    2017-08-01

    The aim of this study is to improve the accuracy of dynamic contrast-enhanced ultrasound (DCE-US) for prostate cancer (PCa) localization by means of a multiparametric approach. Thirteen different parameters related to either perfusion or dispersion were extracted pixel-by-pixel from 45 DCE-US recordings in 19 patients referred for radical prostatectomy. Multiparametric maps were retrospectively produced using a Gaussian mixture model algorithm. These were subsequently evaluated on their pixel-wise performance in classifying 43 benign and 42 malignant histopathologically confirmed regions of interest, using a prostate-based leave-one-out procedure. The combination of the spatiotemporal correlation (r), mean transit time (μ), curve skewness (κ), and peak time (PT) yielded an accuracy of 81% ± 11%, which was higher than the best performing single parameters: r (73%), μ (72%), and wash-in time (72%). The negative predictive value increased to 83% ± 16% from 70%, 69% and 67%, respectively. Pixel inclusion based on the confidence level boosted these measures to 90% with half of the pixels excluded, but without disregarding any prostate or region. Our results suggest multiparametric DCE-US analysis might be a useful diagnostic tool for PCa, possibly supporting future targeting of biopsies or therapy. Application in other types of cancer can also be foreseen. • DCE-US can be used to extract both perfusion and dispersion-related parameters. • Multiparametric DCE-US performs better in detecting PCa than single-parametric DCE-US. • Multiparametric DCE-US might become a useful tool for PCa localization.

  5. Estimating the leaf nitrogen content of paddy rice by using the combined reflectance and laser-induced fluorescence spectra.

    PubMed

    Yang, Jian; Du, Lin; Sun, Jia; Zhang, Zhenbing; Chen, Biwu; Shi, Shuo; Gong, Wei; Song, Shalei

    2016-08-22

    Paddy rice is one of the most important crops in China, and leaf nitrogen content (LNC) serves as a significant indictor for monitoring crop status. A reliable method is needed for precise and fast quantification of LNC. Laser-induced fluorescence (LIF) technology and reflectance spectra of crops are widely used to monitor leaf biochemical content. However, comparison between the fluorescence and reflectance spectra has been rarely investigated in the monitoring of LNC. In this study, the performance of the fluorescence and reflectance spectra for LNC estimation was discussed based on principal component analysis (PCA) and back-propagation neural network (BPNN). The combination of fluorescence and reflectance spectra was also proposed to monitor paddy rice LNC. The fluorescence and reflectance spectra exhibited a high degree of multi-collinearity. About 95.38%, and 97.76% of the total variance included in the spectra were efficiently extracted by using the first three PCs in PCA. The BPNN was implemented for LNC prediction based on new variables calculated using PCA. The experimental results demonstrated that the fluorescence spectra (R2 = 0.810, 0.804 for 2014 and 2015, respectively) are superior to the reflectance spectra (R2 = 0.721, 0.671 for 2014 and 2015, respectively) for estimating LNC based on the PCA-BPNN model. The proposed combination of fluorescence and reflectance spectra can greatly improve the accuracy of LNC estimation (R2 = 0.912, 0.890 for 2014 and 2015, respectively).

  6. Novel molecular imprinted polymers over magnetic mesoporous silica microspheres for selective and efficient determination of protocatechuic acid in Syzygium aromaticum.

    PubMed

    Xie, Lianwu; Guo, Junfang; Zhang, Yuping; Hu, Yunchu; You, Qingping; Shi, Shuyun

    2015-07-01

    Improving sites accessibility can increase the binding efficiency of molecular imprinted polymers (MIPs). In this work, we firstly synthesized MIPs over magnetic mesoporous silica microspheres (Fe3O4@mSiO2@MIPs) for the selective recognition of protocatechuic acid (PCA). The resulting Fe3O4@mSiO2@MIPs were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectrometer (FT-IR), thermo-gravimetric analysis (TGA), Brunauer-Emmett-Teller (BET), and vibration sample magnetometer (VSM), and evaluated by adsorption isotherms/kinetics and competitive adsorption. The maximum adsorption capacity of PCA on Fe3O4@mSiO2@MIPs was 17.2mg/g (2.3 times that on Fe3O4@SiO2@MIPs). In addition, Fe3O4@mSiO2@MIPs showed a short equilibrium time (140min), rapid magnetic separation (5s) and high stability (retained 94.4% after six cycles). Subsequently, Fe3O4@mSiO2@MIPs were successfully applied for the selective and efficient determination of PCA (29.3μg/g) from Syzygium aromaticum. Conclusively, we combined three advantages into Fe3O4@mSiO2@MIPs, namely, Fe3O4 core for quick separation, mSiO2 layer for enough accessible sites, and surface imprinting MIPs for fast binding and excellent selectivity, to extract PCA from complex systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Nonlinear Peculiar-Velocity Analysis and PCA

    NASA Astrophysics Data System (ADS)

    Dekel, Avishai; Eldar, Amiram; Silberman, Lior; Zehavi, Idit

    We allow for nonlinear effects in the likelihood analysis of peculiar velocities, and obtain ˜35%-lower values for the cosmological density parameter and for the amplitude of mass-density fluctuations. The power spectrum in the linear regime is assumed to be of the flat ΛCDM model (h = 0.65, n = 1) with only Ω_m free. Since the likelihood is driven by the nonlinear regime, we "break" the power spectrum at k_b˜ 0.2 (h^{-1}Mpc)^{-1} and fit a two-parameter power-law at k > k b . This allows for an unbiased fit in the linear regime. Tests using improved mock catalogs demonstrate a reduced bias and a better fit. We find for the Mark III and SFI data Ω_m = 0.35± 0.09 with σ_8Ω_m^{0.6} = 0.55± 0.10 (90% errors). When allowing deviations from ΛCDM, we find an indication for a wiggle in the power spectrum in the form of an excess near k ˜ 0.05 and a deficiency at k ˜ 0.1 (h^{-1}Mpc)^{-1} - a "cold flow" which may be related to a feature indicated from redshift surveys and the second peak in the CMB anisotropy. A χ^2 test applied to principal modes demonstrates that the nonlinear procedure improves the goodness of fit. The Principal Component Analysis (PCA) helps identifying spatial features of the data and fine-tuning the theoretical and error models. We address the potential for optimal data compression using PCA.

  8. A novel fusion method of improved adaptive LTP and two-directional two-dimensional PCA for face feature extraction

    NASA Astrophysics Data System (ADS)

    Luo, Yuan; Wang, Bo-yu; Zhang, Yi; Zhao, Li-ming

    2018-03-01

    In this paper, under different illuminations and random noises, focusing on the local texture feature's defects of a face image that cannot be completely described because the threshold of local ternary pattern (LTP) cannot be calculated adaptively, a local three-value model of improved adaptive local ternary pattern (IALTP) is proposed. Firstly, the difference function between the center pixel and the neighborhood pixel weight is established to obtain the statistical characteristics of the central pixel and the neighborhood pixel. Secondly, the adaptively gradient descent iterative function is established to calculate the difference coefficient which is defined to be the threshold of the IALTP operator. Finally, the mean and standard deviation of the pixel weight of the local region are used as the coding mode of IALTP. In order to reflect the overall properties of the face and reduce the dimension of features, the two-directional two-dimensional PCA ((2D)2PCA) is adopted. The IALTP is used to extract local texture features of eyes and mouth area. After combining the global features and local features, the fusion features (IALTP+) are obtained. The experimental results on the Extended Yale B and AR standard face databases indicate that under different illuminations and random noises, the algorithm proposed in this paper is more robust than others, and the feature's dimension is smaller. The shortest running time reaches 0.329 6 s, and the highest recognition rate reaches 97.39%.

  9. Spinal anaesthesia for a caesarean section in a patient with paraneoplastic cerebellar ataxia

    PubMed Central

    Tuna, Ayca Tas; Sahin, Fatih; Kotan, Dilcan; Erdem, Ali Fuat; Baykara, Meltem; Duzcan, Tuba

    2017-01-01

    Paraneoplastic cerebellar ataxia (PCA) is most frequently observed in gynaecological cancers, small cell lung cancer, breast cancer, Hodgkin's lymphoma, cancer testis or malignant thymoma. In the literature, there is no data related to the effects of PCA during pregnancy or reports on the effects of anaesthesia in patients with PCA. We present management of a pregnant woman with PCA who was suddenly unable to walk with PCA and for whom effective spinal anaesthesia was performed for an elective caesarean section with no complications. PMID:28515524

  10. The discrimination of honey origin using melissopalynology and Raman spectroscopy techniques coupled with multivariate analysis.

    PubMed

    Corvucci, Francesca; Nobili, Lara; Melucci, Dora; Grillenzoni, Francesca-Vittoria

    2015-02-15

    Honey traceability to food quality is required by consumers and food control institutions. Melissopalynologists traditionally use percentages of nectariferous pollens to discriminate the botanical origin and the entire pollen spectrum (presence/absence, type and quantities and association of some pollen types) to determinate the geographical origin of honeys. To improve melissopalynological routine analysis, principal components analysis (PCA) was used. A remarkable and innovative result was that the most significant pollens for the traditional discrimination of the botanical and geographical origin of honeys were the same as those individuated with the chemometric model. The reliability of assignments of samples to honey classes was estimated through explained variance (85%). This confirms that the chemometric model properly describes the melissopalynological data. With the aim to improve honey discrimination, FT-microRaman spectrography and multivariate analysis were also applied. Well performing PCA models and good agreement with known classes were achieved. Encouraging results were obtained for botanical discrimination. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Multimodal Broadband Vibrational Sum Frequency Generation (MM-BB-V-SFG) Spectrometer and Microscope.

    PubMed

    Lee, Christopher M; Kafle, Kabindra; Huang, Shixin; Kim, Seong H

    2016-01-14

    A broadband sum frequency generation (BB-SFG) spectrometer with multimodal (MM) capabilities was constructed, which could be routinely reconfigured for tabletop experiments in reflection, transmission, and total internal reflection (TIR) geometries, as well as microscopic imaging. The system was constructed using a Ti:sapphire amplifier (800 nm, pulse width = 85 fs, repetition rate = 2 kHz), an optical parameter amplification (OPA) system for production of broadband IR pulses tunable between 1000 and 4000 cm(-1), and two Fabry-Pérot etalons arranged in series for production of narrowband 800 nm pulses. The key feature allowing the MM operation was the nearly collinear alignment of the visible (fixed, 800 nm) and infrared (tunable, 1000-4000 cm(-1)) pulses which were spatially separated. Physical insights discussed in this paper include the comparison of spectral bandwidth produced with 40 and 85 fs pump beams, the improvement of spectral resolution using etalons, the SFG probe volume in bulk analysis, the normalization of SFG signals, the stitching of multiple spectral segments, and the operation in different modes for air/liquid and adsorbate/solid interfaces, bulk samples, as well as spectral imaging combined with principle component analysis (PCA). The SFG spectral features obtained with the MM-BB-SFG system were compared with those obtained with picosecond-scanning-SFG system and high-resolution BB-SFG system (HR-BB-SFG) for dimethyl sulfoxide, α-pinene, and various samples containing cellulose (purified commercial products, Cladophora cell wall, cotton and flax fibers, and onion epidermis cell wall).

  12. Prostate-cancer diagnosis by non-invasive prostatic Zinc mapping using X-Ray Fluorescence (XRF)

    NASA Astrophysics Data System (ADS)

    Cortesi, Marco

    At present, the major screening tools (PSA, DRE, TRUS) for prostate cancer lack sensitivity and specificity, and none can distinguish between low-grade indolent cancer and high-grade lethal one. The situation calls for the promotion of alternative approaches, with better detection sensitivity and specificity, to provide more efficient selection of patients to biopsy and with possible guidance of the biopsy needles. The prime objective of the present work was the development of a novel non-invasive method and tool for promoting detection, localization, diagnosis and follow-up of PCa. The method is based on in-vivo imaging of Zn distribution in the peripheral zone of the prostate, by a trans-rectal X-ray fluorescence (XRF) probe. Local Zn levels, measured in 1--4 mm3 fresh tissue biopsy segments from an extensive clinical study involving several hundred patients, showed an unambiguous correlation with the histological classification of the tissue (Non-Cancer or PCa), and a systematic positive correlation of its depletion level with the cancer-aggressiveness grade (Gleason classification). A detailed analysis of computer-simulated Zn-concentration images (with input parameters from clinical data) disclosed the potential of the method to provide sensitive and specific detection and localization of the lesion, its grade and extension. Furthermore, it also yielded invaluable data on some requirements, such as the image resolution and counting-statistics, requested from a trans-rectal XRF probe for in-vivo recording of prostatic-Zn maps in patients. By means of systematic table-top experiments on prostate-phantoms comprising tumor-like inclusions, followed by dedicated Monte Carlo simulations, the XRF-probe and its components have been designed and optimized. Multi-parameter analysis of the experimental data confirmed the simulation estimations of the XRF detection system in terms of: delivered dose, counting statistics, scanning resolution, target-volume size and the accuracy of locating at various depths of small-volume tumor-like inclusions in tissue-phantoms. The clinical study, the Monte Carlo simulations and the analysis of Zn-map images provided essential information and promising vision on the potential performance of the Zn-based PCa detection concept. Simulations focusing on medical-probe design and its performance at permissible radiation doses yielded positive results - confirmed by a series of systematic laboratory experiments with a table-top XRF system.

  13. Infrared imaging spectroscopy and chemometric tools for in situ analysis of an imiquimod pharmaceutical preparation presented as cream

    NASA Astrophysics Data System (ADS)

    Carneiro, Renato Lajarim; Poppi, Ronei Jesus

    2014-01-01

    In the present work the homogeneity of a pharmaceutical formulation presented as a cream was studied using infrared imaging spectroscopy and chemometric methodologies such as principal component analysis (PCA) and multivariate curve resolution with alternating least squares (MCR-ALS). A cream formulation, presented as an emulsion, was prepared using imiquimod as the active pharmaceutical ingredient (API) and the excipients: water, vaseline, an emulsifier and a carboxylic acid in order to dissolve the API. After exposure at 45 °C during 3 months to perform accelerated stability test, the presence of some crystals was observed, indicating homogeneity problems in the formulation. PCA exploratory analysis showed that the crystal composition was different from the composition of the emulsion, since the score maps presented crystal structures in the emulsion. MCR-ALS estimated the spectra of the crystals and the emulsion. The crystals presented amine and C-H bands, suggesting that the precipitate was a salt formed by carboxylic acid and imiquimod. These results indicate the potential of infrared imaging spectroscopy in conjunction with chemometric methodologies as an analytical tool to ensure the quality of cream formulations in the pharmaceutical industry.

  14. Discrimination of complex mixtures by a colorimetric sensor array: coffee aromas.

    PubMed

    Suslick, Benjamin A; Feng, Liang; Suslick, Kenneth S

    2010-03-01

    The analysis of complex mixtures presents a difficult challenge even for modern analytical techniques, and the ability to discriminate among closely similar such mixtures often remains problematic. Coffee provides a readily available archetype of such highly multicomponent systems. The use of a low-cost, sensitive colorimetric sensor array for the detection and identification of coffee aromas is reported. The color changes of the sensor array were used as a digital representation of the array response and analyzed with standard statistical methods, including principal component analysis (PCA) and hierarchical clustering analysis (HCA). PCA revealed that the sensor array has exceptionally high dimensionality with 18 dimensions required to define 90% of the total variance. In quintuplicate runs of 10 commercial coffees and controls, no confusions or errors in classification by HCA were observed in 55 trials. In addition, the effects of temperature and time in the roasting of green coffee beans were readily observed and distinguishable with a resolution better than 10 degrees C and 5 min, respectively. Colorimetric sensor arrays demonstrate excellent potential for complex systems analysis in real-world applications and provide a novel method for discrimination among closely similar complex mixtures.

  15. Atomic-scale phase composition through multivariate statistical analysis of atom probe tomography data.

    PubMed

    Keenan, Michael R; Smentkowski, Vincent S; Ulfig, Robert M; Oltman, Edward; Larson, David J; Kelly, Thomas F

    2011-06-01

    We demonstrate for the first time that multivariate statistical analysis techniques can be applied to atom probe tomography data to estimate the chemical composition of a sample at the full spatial resolution of the atom probe in three dimensions. Whereas the raw atom probe data provide the specific identity of an atom at a precise location, the multivariate results can be interpreted in terms of the probabilities that an atom representing a particular chemical phase is situated there. When aggregated to the size scale of a single atom (∼0.2 nm), atom probe spectral-image datasets are huge and extremely sparse. In fact, the average spectrum will have somewhat less than one total count per spectrum due to imperfect detection efficiency. These conditions, under which the variance in the data is completely dominated by counting noise, test the limits of multivariate analysis, and an extensive discussion of how to extract the chemical information is presented. Efficient numerical approaches to performing principal component analysis (PCA) on these datasets, which may number hundreds of millions of individual spectra, are put forward, and it is shown that PCA can be computed in a few seconds on a typical laptop computer.

  16. Spectral discrimination of bleached and healthy submerged corals based on principal components analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Holden, H.; LeDrew, E.

    1997-06-01

    Remote discrimination of substrate types in relatively shallow coastal waters has been limited by the spatial and spectral resolution of available sensors. An additional limiting factor is the strong attenuating influence of the water column over the substrate. As a result, there have been limited attempts to map submerged ecosystems such as coral reefs based on spectral characteristics. Both healthy and bleached corals were measured at depth with a hand-held spectroradiometer, and their spectra compared. Two separate principal components analyses (PCA) were performed on two sets of spectral data. The PCA revealed that there is indeed a spectral difference basedmore » on health. In the first data set, the first component (healthy coral) explains 46.82%, while the second component (bleached coral) explains 46.35% of the variance. In the second data set, the first component (bleached coral) explained 46.99%; the second component (healthy coral) explained 36.55%; and the third component (healthy coral) explained 15.44 % of the total variance in the original data. These results are encouraging with respect to using an airborne spectroradiometer to identify areas of bleached corals thus enabling accurate monitoring over time.« less

  17. Discrimination of Complex Mixtures by a Colorimetric Sensor Array: Coffee Aromas

    PubMed Central

    Suslick, Benjamin A.; Feng, Liang; Suslick, Kenneth S.

    2010-01-01

    The analysis of complex mixtures presents a difficult challenge even for modern analytical techniques, and the ability to discriminate among closely similar such mixtures often remains problematic. Coffee provides a readily available archetype of such highly multicomponent systems. The use of a low-cost, sensitive colorimetric sensor array for the detection and identification of coffee aromas is reported. The color changes of the sensor array were used as a digital representation of the array response and analyzed with standard statistical methods, including principal component analysis (PCA) and hierarchical clustering analysis (HCA). PCA revealed that the sensor array has exceptionally high dimensionality with 18 dimensions required to define 90% of the total variance. In quintuplicate runs of 10 commercial coffees and controls, no confusions or errors in classification by HCA were observed in 55 trials. In addition, the effects of temperature and time in the roasting of green coffee beans were readily observed and distinguishable with a resolution better than 10 °C and 5 min, respectively. Colorimetric sensor arrays demonstrate excellent potential for complex systems analysis in real-world applications and provide a novel method for discrimination among closely similar complex mixtures. PMID:20143838

  18. Unsteady 3D flow simulations in cranial arterial tree

    NASA Astrophysics Data System (ADS)

    Grinberg, Leopold; Anor, Tomer; Madsen, Joseph; Karniadakis, George

    2008-11-01

    High resolution unsteady 3D flow simulations in major cranial arteries have been performed. Two cases were considered: 1) a healthy volunteer with a complete Circle of Willis (CoW); and 2) a patient with hydrocephalus and an incomplete CoW. Computation was performed on 3344 processors of the new half petaflop supercomputer in TACC. Two new numerical approaches were developed and implemented: 1) a new two-level domain decomposition method, which couples continuous and discontinuous Galerkin discretization of the computational domain; and 2) a new type of outflow boundary conditions, which imposes, in an accurate and computationally efficient manner, clinically measured flow rates. In the first simulation, a geometric model of 65 cranial arteries was reconstructed. Our simulation reveals a high degree of asymmetry in the flow at the left and right parts of the CoW and the presence of swirling flow in most of the CoW arteries. In the second simulation, one of the main findings was a high pressure drop at the right anterior communicating artery (PCA). Due to the incompleteness of the CoW and the pressure drop at the PCA, the right internal carotid artery supplies blood to most regions of the brain.

  19. A Biomimetic Sensor for the Classification of Honeys of Different Floral Origin and the Detection of Adulteration

    PubMed Central

    Zakaria, Ammar; Shakaff, Ali Yeon Md; Masnan, Maz Jamilah; Ahmad, Mohd Noor; Adom, Abdul Hamid; Jaafar, Mahmad Nor; Ghani, Supri A.; Abdullah, Abu Hassan; Aziz, Abdul Hallis Abdul; Kamarudin, Latifah Munirah; Subari, Norazian; Fikri, Nazifah Ahmad

    2011-01-01

    The major compounds in honey are carbohydrates such as monosaccharides and disaccharides. The same compounds are found in cane-sugar concentrates. Unfortunately when sugar concentrate is added to honey, laboratory assessments are found to be ineffective in detecting this adulteration. Unlike tracing heavy metals in honey, sugar adulterated honey is much trickier and harder to detect, and traditionally it has been very challenging to come up with a suitable method to prove the presence of adulterants in honey products. This paper proposes a combination of array sensing and multi-modality sensor fusion that can effectively discriminate the samples not only based on the compounds present in the sample but also mimic the way humans perceive flavours and aromas. Conversely, analytical instruments are based on chemical separations which may alter the properties of the volatiles or flavours of a particular honey. The present work is focused on classifying 18 samples of different honeys, sugar syrups and adulterated samples using data fusion of electronic nose (e-nose) and electronic tongue (e-tongue) measurements. Each group of samples was evaluated separately by the e-nose and e-tongue. Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were able to separately discriminate monofloral honey from sugar syrup, and polyfloral honey from sugar and adulterated samples using the e-nose and e-tongue. The e-nose was observed to give better separation compared to e-tongue assessment, particularly when LDA was applied. However, when all samples were combined in one classification analysis, neither PCA nor LDA were able to discriminate between honeys of different floral origins, sugar syrup and adulterated samples. By applying a sensor fusion technique, the classification for the 18 different samples was improved. Significant improvement was observed using PCA, while LDA not only improved the discrimination but also gave better classification. An improvement in performance was also observed using a Probabilistic Neural Network classifier when the e-nose and e-tongue data were fused. PMID:22164046

  20. A biomimetic sensor for the classification of honeys of different floral origin and the detection of adulteration.

    PubMed

    Zakaria, Ammar; Shakaff, Ali Yeon Md; Masnan, Maz Jamilah; Ahmad, Mohd Noor; Adom, Abdul Hamid; Jaafar, Mahmad Nor; Ghani, Supri A; Abdullah, Abu Hassan; Aziz, Abdul Hallis Abdul; Kamarudin, Latifah Munirah; Subari, Norazian; Fikri, Nazifah Ahmad

    2011-01-01

    The major compounds in honey are carbohydrates such as monosaccharides and disaccharides. The same compounds are found in cane-sugar concentrates. Unfortunately when sugar concentrate is added to honey, laboratory assessments are found to be ineffective in detecting this adulteration. Unlike tracing heavy metals in honey, sugar adulterated honey is much trickier and harder to detect, and traditionally it has been very challenging to come up with a suitable method to prove the presence of adulterants in honey products. This paper proposes a combination of array sensing and multi-modality sensor fusion that can effectively discriminate the samples not only based on the compounds present in the sample but also mimic the way humans perceive flavours and aromas. Conversely, analytical instruments are based on chemical separations which may alter the properties of the volatiles or flavours of a particular honey. The present work is focused on classifying 18 samples of different honeys, sugar syrups and adulterated samples using data fusion of electronic nose (e-nose) and electronic tongue (e-tongue) measurements. Each group of samples was evaluated separately by the e-nose and e-tongue. Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were able to separately discriminate monofloral honey from sugar syrup, and polyfloral honey from sugar and adulterated samples using the e-nose and e-tongue. The e-nose was observed to give better separation compared to e-tongue assessment, particularly when LDA was applied. However, when all samples were combined in one classification analysis, neither PCA nor LDA were able to discriminate between honeys of different floral origins, sugar syrup and adulterated samples. By applying a sensor fusion technique, the classification for the 18 different samples was improved. Significant improvement was observed using PCA, while LDA not only improved the discrimination but also gave better classification. An improvement in performance was also observed using a Probabilistic Neural Network classifier when the e-nose and e-tongue data were fused.

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